0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.","title":"International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration."},{"docid":"MED-3953","text":"An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.","title":"An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration."},{"docid":"MED-4143","text":"In this study, we hoped to provide valuable clinical information on yersiniosis for clinicians. Two thousand six hundred stool samples were collected from in- and outpatients with diarrhea, which were tested with both culture method and real-time polymerase chain reaction (RT-PCR). In total, 188 positive samples were detected by RT-PCR (178) and culture method (160), while the incidence was about 7.23%. The detection rate of RT-PCR was significantly higher than culture method and a higher incidence in autumn-winter was also noticeably identified than in spring-summer. Infection sources mostly focused on unboiled foods (101) and pets (45), while clinical manifestation mainly presented as gastroenteritis (156), pseudoappendicitis (32), and extraintestinal complications (46). The morbidity of extraintestinal complications in adults was significantly higher than in children and it was the same for high-risk patients between adults over the age of 60 years (4.7%) and children under the age of 3 years (1.4%), whereas the constituent ratio of children versus adults with yersiniosis in different systems was not significant. Of 160 isolates tested for antimicrobial susceptibility, the majority were susceptible to third-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, whereas only a small portion was susceptible to the first-generation cephalosporins and penicillins. During autumn-winter months, clinicians should pay more attention to clinical manifestation, early diagnosis, and treatment with susceptible antibiotics of yersiniosis and its complications, targeting high-risk patients.","title":"Yersinia enterocolitica infection in diarrheal patients."},{"docid":"MED-3316","text":"BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.","title":"An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study."},{"docid":"MED-3320","text":"OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.","title":"Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry."},{"docid":"MED-2274","text":"Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.","title":"Cherry Consumption and the Risk of Recurrent Gout Attacks"},{"docid":"MED-2801","text":"Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.","title":"Curcumin and obesity."},{"docid":"MED-5293","text":"Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.","title":"A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010"},{"docid":"MED-5326","text":"The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.","title":"Red meat and colon cancer: should we become vegetarians, or can we make meat safer?"},{"docid":"MED-5332","text":"The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.","title":"Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age."},{"docid":"MED-3312","text":"BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.","title":"Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S."},{"docid":"MED-5338","text":"Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.","title":"Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease"},{"docid":"MED-2361","text":"The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.","title":"Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York."},{"docid":"MED-1122","text":"OBJECTIVES: patients with rheumatoid arthritis (RA) are reported to have in their sera raised levels of antibody specific to Proteus mirabilis. The aim of the study was to verify this and to determine an explanation for it by investigating the frequency of P. mirabilis urinary tract infection in RA patients and matched controls. METHODS: freshly voided urine was examined for the presence, number and identity of infecting bacteria. The levels of antibody in blood and in urine of the IgM, IgA and IgG classes to the common O serotypes of P. mirabilis and the antigens to which they reacted were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: analysis of urine from 76 patients with RA and 48 age- and gender-matched healthy controls showed that only two (4%) of the control urines but 25 (33%) of those from the RA patients were infected. The commonest infecting organism in the RA patients' urine was Proteus mirabilis which occurred twice as frequently as Escherichia coli. Proteus mirabilis was found in 52% of the infected urines of the RA patients and was always detected as a pure growth and usually in insignificant (< 10(4)/ml) numbers. It is highly improbable that this finding was the outcome of differences in age, physical ability or medication between the RA and control patient groups. Comparison of antibody levels to P. mirabilis by ELISA showed RA patients had raised (P < 0.0001, P = 0.001, P = 0.0063) levels of IgA, IgG and IgM respectively in their sera and raised (P < 0.0001, P < 0.0001, P = 0.0001) levels of IgG, IgM and IgA respectively in their urine compared with the control group. It was not possible to detect an antibody reacting to a P. mirabilis antigen that was specific to the RA patients. CONCLUSION: the results confirm that RA patients have raised levels of antibody to P. mirabilis not only in blood but also in urine and suggest that this arises because RA patients have an asymptomatic, non-significant P. mirabilis bacteriuria more frequently or more prolonged than control patients. This may be the trigger for their RA condition.","title":"Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Proteus mirabilis bacteriuria more frequently than healthy con..."}],"string":"[\n {\n \"docid\": \"MED-3302\",\n \"text\": \"In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.\",\n \"title\": \"A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States.\"\n },\n {\n \"docid\": \"MED-3952\",\n \"text\": \"Endothelial anti-inflammatory effects of açaí (Ac) and red muscadine grape (Gp) polyphenolics have not been extensively investigated. It was hypothesized that polyphenolics from Ac and Gp exert comparable protective effects in human vascular endothelial cells (HUVEC) upon inflammatory stress. Furthermore, this study investigated whether microRNAs relevant to endothelial function might be regulated by Ac and Gp. Results showed that Ac and Gp (5-20 mg gallic acid equivalent/L) protected HUVEC against glucose-induced oxidative stress and inflammation. Glucose-induced expression of interleukin-6 and -8 was down-regulated by Ac and Gp at mRNA and protein levels. Upon lipopolysaccharide (LPS; 1 μg/L)-induced inflammation, Ac and Gp inhibited gene expression of adhesion molecules and NF-κB activation to similar extents, although Gp was more effective in decreasing PECAM-1 and ICAM-1 protein. Of the screened microRNAs, only microRNA-126 expression was found to be modulated by Ac and Gp as the underlying mechanism to inhibit gene and protein expression of VCAM-1.\",\n \"title\": \"Polyphenolics from açaí ( Euterpe oleracea Mart.) and red muscadine grape (Vitis rotundifolia ) protect human umbilical vascular Endothelial cell...\"\n },\n {\n \"docid\": \"MED-1441\",\n \"text\": \"Most ethnic foods and cooking practices have incorporated the use of spices and other food additives. Many common spices have crossed cultural boundaries and appear in multiple ethnic cuisines. Recent studies have demonstrated that many of these ingredients possess antimicrobial properties against common food spoilage microorganisms. We developed a laboratory exercise that promotes the use of scientific methodology to evaluate the effectiveness of salsa components at inhibiting the growth of undesirable microorganisms. Tomato, onion, garlic, cilantro, and jalapeño were tested for antimicrobial properties against a representative fungus, Saccharomyces cerevisiae, and the common food spoilage bacteria Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Each component was ethanol extracted and a modification of the Kirby-Bauer method of antimicrobial sensitivity was employed. Garlic demonstrated the greatest inhibitory effects against all organisms tested. Onion demonstrated a slight inhibition of all four organisms, while cilantro showed some inhibition of all three bacteria but no effect against the fungus. Jalapeño may have slightly inhibited E. coli and S. aureus, as evidenced by a consistently measured increase in the zone of inhibition that was not statistically significant when compared to that of the control. Following the initial exercise, students were given the opportunity to repeat the exercise using other spices such as cinnamon, clove, nutmeg, and coriander. Student learning outcomes were evaluated using preliminary and secondary surveys, mainly focusing on definitions of science and hypothesis as well as the process of science. Students enjoyed this exercise and met the learning goals of understanding the process and methodology of science, as well as the interdisciplinarity inherent in the sciences. Student learning was evidenced by an increase in the number of correct responses on the secondary survey in comparison to the preliminary.\",\n \"title\": \"The Science of Salsa: Antimicrobial Properties of Salsa Components to Learn Scientific Methodology\"\n },\n {\n \"docid\": \"MED-5327\",\n \"text\": \"OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.\",\n \"title\": \"The association between dietary patterns and mental health in early adolescence.\"\n },\n {\n \"docid\": \"MED-4853\",\n \"text\": \"OBJECTIVE: To demonstrate the effects of a very low-fat, vegan diet on patients with rheumatoid arthritis (RA). DESIGN: Single-blind dietary intervention study. SUBJECTS AND STUDY INTERVENTIONS: This study evaluated the influence of a 4-week, very low-fat (approximately 10%), vegan diet on 24 free-living subjects with RA, average age, 56 +/- 11 years old. OUTCOME MEASUREMENTS: Prestudy and poststudy assessment of RA symptomatology was performed by a rheumatologist blind to the study design. Biochemical measures and 4-day diet data were also collected. Subjects met weekly for diet instruction, compliance monitoring, and progress assessments. RESULTS: There were significant (p < 0.001) decreases in fat (69%), protein (24%), and energy (22%), and a significant increase in carbohydrate (55%) intake. All measures of RA symptomatology decreased significantly (p < 0.05), except for duration of morning stiffness (p > 0.05). Weight also decreased significantly (p < 0.001). At 4 weeks, C-reactive protein decreased 16% (ns, p > 0.05), RA factor decreased 10% (ns, p > 0.05), while erythrocyte sedimentation rate was unchanged (p > 0.05). CONCLUSION: This study showed that patients with moderate-to-severe RA, who switch to a very low-fat, vegan diet can experience significant reductions in RA symptoms.\",\n \"title\": \"Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-2819\",\n \"text\": \"OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.\",\n \"title\": \"Biological actions of curcumin on articular chondrocytes.\"\n },\n {\n \"docid\": \"MED-2825\",\n \"text\": \"Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\",\n \"title\": \"Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric.\"\n },\n {\n \"docid\": \"MED-2812\",\n \"text\": \"Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Molecular mechanisms of curcumin action: gene expression.\"\n },\n {\n \"docid\": \"MED-1990\",\n \"text\": \"BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.) 2009 Massachusetts Medical Society\",\n \"title\": \"Intensive versus conventional glucose control in critically ill patients.\"\n },\n {\n \"docid\": \"MED-3308\",\n \"text\": \"An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.\",\n \"title\": \"Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry.\"\n },\n {\n \"docid\": \"MED-3294\",\n \"text\": \"In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.\",\n \"title\": \"Emerging and re-emerging swine viruses.\"\n },\n {\n \"docid\": \"MED-4631\",\n \"text\": \"BACKGROUND: Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA. METHODS: Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period. RESULTS: Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs 217%) and lower formation of leukotriene B(4) (34% vs 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6-8 of the experiment. CONCLUSION: A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.\",\n \"title\": \"Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-3288\",\n \"text\": \"In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.\",\n \"title\": \"Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue.\"\n },\n {\n \"docid\": \"MED-4855\",\n \"text\": \"OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs)--of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS: The three studies (287 patients and a median trial-duration of 3 months)--all supported by the manufacturer (Hyben-Vital International)--showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients. CONCLUSIONS: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.\",\n \"title\": \"Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?--a meta-analysis of randomized controlled trials.\"\n },\n {\n \"docid\": \"MED-2364\",\n \"text\": \"We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.\",\n \"title\": \"Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides.\"\n },\n {\n \"docid\": \"MED-2814\",\n \"text\": \"Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin in various cancers.\"\n },\n {\n \"docid\": \"MED-4854\",\n \"text\": \"In a controlled clinical trial we have recently shown that patients with rheumatoid arthritis (RA) improved after fasting for 7-10 d and that the improvement could be sustained through 3.5 months with a vegan diet and 9 months with a lactovegetarian diet. Other studies have indicated that the inflammatory process in RA can be reduced through manipulation of dietary fatty acids. A switch to a vegetarian diet significantly alters the intake of fatty acids. Therefore, we have analysed the changes in fatty acid profiles of the plasma phospholipid fraction and related these changes to disease activity. The concentrations of the fatty acids 20:3n-6 and 20:4n-6 were significantly reduced after 3.5 months with a vegan diet (P < 0.0001 and P < 0.01 respectively), but the concentration increased to baseline values with a lactovegetarian diet. The concentration of 20:5n-3 was significantly reduced after the vegan diet (P < 0.0001) and the lactovegetarian diet periods (P < 0.01). There was no significant difference in fatty acid concentrations between diet responders and diet non-responders after the vegan or lactovegetarian diet periods. Our results indicate that the changes in the fatty acid profiles cannot explain the clinical improvement.\",\n \"title\": \"Changes in plasma phospholipid fatty acids and their relationship to disease activity in rheumatoid arthritis patients treated with a vegetarian diet.\"\n },\n {\n \"docid\": \"MED-2273\",\n \"text\": \"Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.\",\n \"title\": \"Purine-rich foods intake and recurrent gout attacks\"\n },\n {\n \"docid\": \"MED-1443\",\n \"text\": \"SUMMARY BACKGROUND: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti-inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo. METHODS: 40 volunteers were enrolled in this monocentric,randomized,placebo-controlled double-blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV-B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place-bo.The effect of the test substances on the UV-induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non-irradiated skin. RESULTS: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV-induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent. CONCLUSIONS: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.\",\n \"title\": \"Anti-inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test.\"\n },\n {\n \"docid\": \"MED-4088\",\n \"text\": \"The influence of a 3-week vegetarian diet and fasting on serum concentration of peroxides, lipids, apolipoproteins, and plasma fibrinogen was studied in ten middle-aged fibromyalgia/fibrositis patients (eight women, two men). Mean serum peroxide concentration (estimated as thiobarbituric acid reacting substances) was reduced from 3.60 +/- 0.14 to 2.82 +/- 0.15 umol/l (p = 0.01) and plasma fibrinogen from 3.33 +/- 0.25 to 2.74 +/- 0.15 g/l (p = 0.02). Serum total cholesterol fell from 6.61 +/- 0.50 to 4.83 +/- 0.35 mmol/l (p < 0.0001), apolipoprotein B from 1.77 +/- 0.14 to 1.31 +/- 0.11 g/l (p < 0.0001), and apolipoprotein A from 1.41 +/- 0.09 to 1.23 +/- 0.05 g/l (p = 0.03). High density lipoprotein cholesterol concentration also decreased somewhat (from 1.26 +/- 0.09 to 1.07 +/- 0.04 mmol/l, p = 0.03) An atherogenic index, reflecting the balance between low and high density lipoproteins, was reduced by 31% (from 5.74 +/- 0.79 to 3.97 +/- 0.60, p = 0.02). The results suggest that vegetarian diet/fasting may have a beneficial influence on the concentration of serum peroxides and plasma fibrinogen concentration, and on the serum level of several lipoprotein-related coronary risk factors.\",\n \"title\": \"Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3-week vegetarian diet.\"\n },\n {\n \"docid\": \"MED-3944\",\n \"text\": \"Dietary interventions involving antioxidants are of interest for reducing inflammation, improving joint motion, and altering pain perception. We evaluated the effect of oral consumption of a fruit and berry blend on pain and range of motion (ROM). This open-label clinical pilot study involved 14 study participants with limitations in ROM that was associated with pain and affected daily living. Participants included but were not limited to those with age-related osteoarthritis. Study participants consumed 120 mL MonaVie Active® fruit juice, predominantly containing açai pulp (Euterpe oleracea Mart.) and other fruit concentrates, daily for 12 weeks. Study participants were assessed at baseline and 2, 4, 8, and 12 weeks by structured nurse interviews, pain and activities of daily living (ADL) questionnaires, blood samples, and ROM assessment. Pain was scored by using a visual analogue scale. ROM was assessed by using dual digital inclinometry as recommended by American Medical Association guidelines. Consumption of the juice resulted in significant pain reduction, improved ROM measures, and improvement in ADLs. Serum antioxidant status, as monitored by the cell-based antioxidant protection in erythrocytes (CAP-e) assay, was improved within 2 weeks and continued to improve throughout the 12 weeks of study participation (P<.01). The inflammatory marker C-reactive protein was reduced at 12 weeks, but this change did not reach statistical significance. Lipid peroxidation decreased mildly at 12 weeks. The antioxidant status, as measured by the CAP-e bioassay, showed the best correlation with improvements in physical well-being (pain, ROM, and ADL). The significant association among increased antioxidant status, improved ROM, and pain reduction warrants further study.\",\n \"title\": \"Pain Reduction and Improvement in Range of Motion After Daily Consumption of an Açai (Euterpe oleracea Mart.) Pulp–Fortified Polyphenolic-Rich Fruit and Berry Juice Blend\"\n },\n {\n \"docid\": \"MED-2363\",\n \"text\": \"We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.\",\n \"title\": \"A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis.\"\n },\n {\n \"docid\": \"MED-5322\",\n \"text\": \"BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.\",\n \"title\": \"Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting.\"\n },\n {\n \"docid\": \"MED-2810\",\n \"text\": \"Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \\\"Curecumin\\\".\",\n \"title\": \"Curcumin as \\\"Curecumin\\\": from kitchen to clinic.\"\n },\n {\n \"docid\": \"MED-5324\",\n \"text\": \"Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.\",\n \"title\": \"Effects of a high-fat meal on pulmonary function in healthy subjects.\"\n },\n {\n \"docid\": \"MED-5011\",\n \"text\": \"AV119 is a patented blend of two sugars from avocado that can induce human beta-defensin-2 production by normal human keratinocytes. In this study, we analysed the effect of AV119 on growth and invasiveness of Malassezia furfur, a dimorphic, lipid-dependent yeast that is part of the normal human cutaneous commensal flora. The ability to modulate the expression of the proinflammatory and immunomodulatory cytokines in normal human keratinocytes was also investigated. Microbiological assay demonstrated that this sugar induced the aggregation of yeast cells and inhibited the invasiveness of M. furfur, without affecting its growth. Real-time PCR analysis demonstrated that AV119 was able to modulate the HBD-2 response in treated keratinocytes, reaching a maximum after 48-h treatment, and to induce the recovery of a satisfactory proinflammatory response in human keratinocytes. As AV119 can induce aggregation of yeast cells, thus inhibiting their penetration into the keratinocytes, the sugar could be used in the preparation of cosmetics or pharmacological drugs to inhibit colonization of the skin by pathogenic strains of M. furfur.\",\n \"title\": \"Effects of AV119, a natural sugar from avocado, on Malassezia furfur invasiveness and on the expression of HBD-2 and cytokines in human keratinocytes.\"\n },\n {\n \"docid\": \"MED-2079\",\n \"text\": \"Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (-8.78%, -13.72% and -20.80%, respectively; P<.05) compared with baseline period, while high-density lipoprotein cholesterol remained unchanged. Strawberry supplementation also significant decreased serum malondialdehyde, urinary 8-OHdG and isoprostanes levels (-31.40%, -29.67%, -27.90%, respectively; P<.05). All the parameters returned to baseline values after the washout period. A significant increase in plasma total antioxidant capacity measured by both ferric reducing ability of plasma and oxygen radical absorbance capacity assays and vitamin C levels (+24.97%, +41.18%, +41.36%, respectively; P<.05) was observed after strawberry consumption. Moreover, the spontaneous and oxidative hemolysis were significant reduced (-31.7% and -39.03%, respectively; P<.05), compared to the baseline point, which remained stable after the washout period. Finally, strawberry intake significant decrease (P<.05) the number of activated platelets, compared to both baseline and washout values. Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk. Copyright © 2014 Elsevier Inc. All rights reserved.\",\n \"title\": \"One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans.\"\n },\n {\n \"docid\": \"MED-4856\",\n \"text\": \"OBJECTIVE: To investigate if standardised powder made from rose-hip (Rosa canina) can reduce the symptom score in patients with rheumatoid arthritis. METHODS: In a double-blind placebo-controlled trial, patients with rheumatoid arthritis (RA) according to ARA/ACR criteria were randomised to treatment with capsulated rose-hip powder 5g daily or matching placebo for 6 months at two outpatient clinics in Berlin and Copenhagen. Primary outcome variable was Health Assessment Questionnaire (HAQ) at 6 months, secondary outcome included DAS-28, physician's global evaluation of disease activity, RAQoL, SF-12 and concomitant pain medication. RESULTS: In a total of 89 patients (90% female, mean age 56.6+11.3 years, mean disease duration 12.8+9.6 years) HAQ-DI in the rose-hip group improved by 0.105+/-0.346, whereas in the placebo group it worsened by 0.039+/-0.253 (p adjusted=0.032). In the HAQ Patient Pain Scale no significant differences were observed between both groups. In the HAQ Patient Global Scale a trend was seen favouring rose-hip (p=0.078). The DAS-28 score yielded improvement in the rose-hip group of 0.89+/-1.32 and in the placebo group of 0.34+/-1.27 (p=0.056) indicating moderate clinical relevance. The Physicians Global Scale demonstrated more improvement in the rose-hip compared to the placebo group (p=0.012). RAQoL and SF-12 physical score improved significantly in the rose-hip group compared to placebo, whereas SF-12 mental score remained unchanged. Intake of pain medication was not different between the groups. Per-protocol analysis confirmed these results. CONCLUSION: The results indicate that patients with RA may benefit from additional treatment with rose hip powder. Copyright 2009 Elsevier GmbH. All rights reserved.\",\n \"title\": \"Rose hip herbal remedy in patients with rheumatoid arthritis - a randomised controlled trial.\"\n },\n {\n \"docid\": \"MED-5337\",\n \"text\": \"PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.\",\n \"title\": \"Intensive lifestyle changes may affect the progression of prostate cancer.\"\n },\n {\n \"docid\": \"MED-2805\",\n \"text\": \"Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.\",\n \"title\": \"Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation\"\n },\n {\n \"docid\": \"MED-2815\",\n \"text\": \"Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin, a component of turmeric: from farm to pharmacy.\"\n },\n {\n \"docid\": \"MED-2802\",\n \"text\": \"OBJECTIVE: The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis. STUDY DESIGN AND SETTING: The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand. METHODS: One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded. RESULTS: Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively). CONCLUSIONS: C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.\",\n \"title\": \"Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis.\"\n },\n {\n \"docid\": \"MED-4103\",\n \"text\": \"Patients with rheumatoid arthritis (RA) have been described as having significantly low serum potassium concentrations than that in healthy subjects. We assessed the therapeutic efficacy and tolerability of oral potassium supplement dissolved in grape juice in female hypokalemic patients with active RA. Thirty-two hypokalemic patients with active RA were investigated in a parallel, randomized design. In addition to their usual medication, the control group received placebo and the intervention group received 6000 mg chloride potassium dissolved in grape juice on 28 consecutive days. The primary outcome parameter was the change of pain on a visual analog scale (VAS). The American College of Rheumatology (ACR) percent response criteria and Disease Activity Score 28 (DAS28, 28-joint count) and the European League Against Rheumatism (EULAR) moderate response were assessed. Mean age was 48.6 +/- 6 years. In the potassium group, 43.75% (7/16) of the patients met the criteria of 33% lower pain intensity compared with 6.25% (1/16) in the placebo group (P < .02) at day 28. Also, 31.25% (5/16) of the patients in the intervention group achieved moderate responses, according to the EULAR criteria. The corresponding percentage for patients receiving placebo was 6.25% (1/16) (P < .05). Potassium supplements appeared to decrease pain intensity. PERSPECTIVE: This article reports a trial evaluating the effect of potassium supplementation in the treatment of pain in hypokalemic patients with rheumatoid arthritis. The elevated serum cortisol and potassium values in the treatment group correlate negatively with patient's assessment of pain intensity, reflecting an anti-pain effect for potassium supplementation.\",\n \"title\": \"A pilot study of potassium supplementation in the treatment of hypokalemic patients with rheumatoid arthritis: a randomized, double-blinded, placeb...\"\n },\n {\n \"docid\": \"MED-1116\",\n \"text\": \"Molecular mimicry is one of the pathological mechanisms proposed to explain the association between microorganisms and autoimmune diseases. This review deals with the association between bacteria and rheumatic diseases with a special emphasis on rheumatoid arthritis where upper urinary tract infection by Proteus mirabilis is the possible cause of this severe, arthritic condition. Prospective trials involving anti-Proteus therapy should be carried out.\",\n \"title\": \"Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity.\"\n },\n {\n \"docid\": \"MED-2813\",\n \"text\": \"The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to \\\"get back to our roots.\\\"\",\n \"title\": \"Curcumin: getting back to the roots.\"\n },\n {\n \"docid\": \"MED-4852\",\n \"text\": \"OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.\",\n \"title\": \"Self-reported food intolerance and mucosal reactivity after rectal food protein challenge in patients with rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-4844\",\n \"text\": \"Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r(2) 0.877, P<0.001 for eight countries). The statistical correlations for meat and offal were almost as high as those for their fat. Similar correlations were found for temporal changes in indices of effects of RA in several European countries between 1968 and 1978 as more meat was added to the national diets, although the correlations were higher for meat than for fat. It is hypothesized that meat and offal may be a major factor contributing to the inflammation in RA. In the present short review, the author examines some of the data that associate meat consumption with RA and the possible factors, e.g. fat, Fe and nitrite, which may contribute to the inflammation.\",\n \"title\": \"The role of meat in the expression of rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-1442\",\n \"text\": \"We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h2 from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype–phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.\",\n \"title\": \"Genetic Analysis of Chemosensory Traits in Human Twins\"\n },\n {\n \"docid\": \"MED-1127\",\n \"text\": \"Rheumatoid arthritis is a crippling and disabling joint disease affecting over 20 million people. It occurs predominantly in women and smokers, and affects the HLA-DR1/4 individuals who carry the \\\"shared epitope\\\" of amino acids EQRRAA. The cause of this disease was investigated by the methods of the philosopher of science Karl Popper who suggested that scientific research should be based on bold conjectures and critical refutations. The \\\"Popper sequences\\\" generate new facts which then change or alter the original problem. The new facts must then be explained by any new theory. Using the \\\"molecular mimicry\\\" model, it was found that Proteus bacteria possess an amino acid sequence ESRRAL in haemolysin which resembles the, shared epitope, and another sequence in urease which resembles type XI collagen. Antibodies to Proteus bacteria have been found in 14 different countries. It would appear that rheumatoid arthritis is caused by an upper urinary tract infection by Proteus bacteria. Anti-Proteus therapy should be assessed in the management of this disease separately or in conjunction with existing modalities of therapy.\",\n \"title\": \"Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper.\"\n },\n {\n \"docid\": \"MED-1996\",\n \"text\": \"Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.\",\n \"title\": \"Childhood obesity and type 2 diabetes mellitus.\"\n },\n {\n \"docid\": \"MED-3318\",\n \"text\": \"Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.\",\n \"title\": \"Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium\"\n },\n {\n \"docid\": \"MED-4139\",\n \"text\": \"Pigs are the major animal reservoir for Yersinia enterocolitica strains, which are potentially pathogenic for humans. The goals of this study were (i) to estimate the individual animal and on-farm prevalences of Y. enterocolitica in hogs based on tonsil samples collected during National Animal Health Monitoring System Swine 2002 study and (ii) to use these data with data previously published for fecal samples to determine on-farm risk factors for Y. enterocolitica. Tonsil swabs (1,218) and fecal samples (2,847) were collected on 124 farms located in the top 17 pork-producing states. Ten percent of tonsils (122 of 1,218 samples) were positive in irgasan-tiracillin-chlorate (ITC) enrichment broth by real-time PCR, but only 5.6% of samples (68 of 1,218) were positive after subculture on the more selective cefsulodin-irgasan-novobiocin (CIN) agar. For tonsils, the on-farm prevalence based on real-time PCR detection of the ail gene in ITC enrichment broth cultures was 32% (32 of 100 premises sampled); the prevalence based on subculture in CIN agar was 19.6% (20 of 102 premises). Results of bacteriological isolation and real-time PCR analysis of tonsils and feces were combined to estimate prevalence (individual animal and farm), which was subsequently correlated with 40 farm management practices. Four factors and their accompanying odds ratios (ORs) were identified in the final regression model: location in a central state (OR = 0.3), vaccination for Escherichia coli (OR = 3.0), percentage of deaths due to scours (OR = 3.5), and presence of meat or bone meal in grower-finisher diet (OR = 4.1).\",\n \"title\": \"Prevalence of Yersinia enterocolitica in market weight hogs in the United States.\"\n },\n {\n \"docid\": \"MED-3317\",\n \"text\": \"Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.\",\n \"title\": \"Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain.\"\n },\n {\n \"docid\": \"MED-4134\",\n \"text\": \"Yersinia enterocolitica is considered an important food-borne pathogen impacting the pork production and processing industry in the United States. Since this bacterium is a commensal of swine, the primary goal of this study was to determine the prevalence of pathogenic Y. enterocolitica in pigs in the United Sates using feces as the sample source. A total of 2,793 fecal samples were tested for its presence in swine. Fecal samples were collected from late finisher pigs from 77 production sites in the 15 eastern and midwestern pork-producing states over a period of 27 weeks (6 September 2000 to 20 March 2001). The prevalence of ail-positive Y. enterocolitica was determined in samples using both a fluorogenic 5′ nuclease PCR assay and a culture method. The mean prevalence was 13.10% (366 of 2,793 fecal samples tested) when both PCR- and culture-positive results were combined. Forty-one of 77 premises (53.25%) contained at least one fecal sample positive for the ail sequence. The PCR assay indicated a contamination rate of 12.35% (345/2,793) compared to 4.08% (114/2,793) by the culture method. Of the 345 PCR-positive samples, 252 were culture negative, while of the 114 culture-positive samples, 21 were PCR negative. Among 77 premises, the PCR assay revealed a significantly (P < 0.05) higher percentage (46.75%, n = 36 sites) of samples positive for the pathogen (ail sequence) than the culture method (22.08%, n = 17 sites). Thus, higher sensitivity, with respect to number of samples and sites identified as positive for the PCR method compared with the culture method for detecting pathogenic Y. enterocolitica, was demonstrated in this study. The results support the hypothesis that swine are a reservoir for Y. enterocolitica strains potentially pathogenic for humans.\",\n \"title\": \"Prevalence of Pathogenic Yersinia enterocolitica Strains in Pigs in the United States\"\n },\n {\n \"docid\": \"MED-2809\",\n \"text\": \"Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.\",\n \"title\": \"Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials\"\n },\n {\n \"docid\": \"MED-2822\",\n \"text\": \"Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.\",\n \"title\": \"A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-2354\",\n \"text\": \"A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.\",\n \"title\": \"A unique natural human IgG antibody with anti-alpha-galactosyl specificity\"\n },\n {\n \"docid\": \"MED-1121\",\n \"text\": \"Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age. Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies. Patients with RA especially during the early stages of the disease could benefit from Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments.\",\n \"title\": \"Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection\"\n },\n {\n \"docid\": \"MED-2221\",\n \"text\": \"Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.\",\n \"title\": \"The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?\"\n },\n {\n \"docid\": \"MED-2353\",\n \"text\": \"Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.\",\n \"title\": \"Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits\"\n },\n {\n \"docid\": \"MED-2080\",\n \"text\": \"Beyond obvious functions in haemostasis and thrombosis, platelets are considered to be essential in proinflammatory surroundings such as atherosclerosis, allergy, rheumatoid arthritis and even cancer. In atherosclerosis, platelets facilitate the recruitment of inflammatory cells towards the lesion sites and release a plethora of inflammatory mediators, thereby enriching and boosting the inflammatory milieu. Platelets do so by interacting with endothelial cells, circulating leukocytes (monocytes, neutrophils, dendritic cells, T-cells) and progenitor cells. This cross-talk enforces leukocyte activation, adhesion and transmigration. Furthermore, platelets are known to function in innate host defense through the release of antimicrobial peptides and the expression of pattern recognition receptors. In severe sepsis, platelets are able to trigger the formation of neutrophil extracellular traps (NETs), which bind and clear pathogens. The present antiplatelet therapies that target key pathways of platelet activation and aggregation therefore hold the potential to modulate platelet-derived immune functions by reducing cellular interactions of platelets with other immune components and by reducing the secretion of inflammatory proteins into the milieu. The objective of this review is to update and discuss the current perceptions of the platelet immune constituents and their prospect as therapeutic targets in an atherosclerotic setting.\",\n \"title\": \"Platelets in atherosclerosis.\"\n },\n {\n \"docid\": \"MED-1993\",\n \"text\": \"Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.\",\n \"title\": \"Type 2 diabetes mellitus in children and adolescents\"\n },\n {\n \"docid\": \"MED-2820\",\n \"text\": \"Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.\",\n \"title\": \"Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis\"\n },\n {\n \"docid\": \"MED-4131\",\n \"text\": \"In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.\",\n \"title\": \"Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens.\"\n },\n {\n \"docid\": \"MED-4142\",\n \"text\": \"Swine confinement buildings in eastern Canada are enclosed and equipped with modern production systems to manage waste. Bioaerosols of these swine confinement buildings could be contaminated by human pathogens and antimicrobial resistant bacteria which could colonize exposed workers. We therefore wanted to analyze bioaerosols of swine confinement buildings and nasal flora of Canadian hog producers to evaluate possible colonization with human pathogens and tetracycline-resistant bacteria. Culturable and non-culturable human pathogens and tet genes were investigated in the bioaerosols of 18 barns. The nasal passages of 35 hog producers were sampled and total DNA was extracted from the calcium-alginate swabs to detect, by PCR, Campylobacter, C. perfringens, Enterococcus, E. coli, Y. enterocolitica, tetA/tetC, tetG and ribosomal protection protein genes. Airborne culturable C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were present in the bioaerosols of 16, 17, 11 and 6 of the 18 facilities. Aerosolized total (culturable/non culturable) Campylobacter, C. perfringens, Enterococcus, E. coli and Y. enterocolitica were detected in 10, 6, 15, 18 and 2 barns, respectively. Tet genes were found in isolates of culturable human pathogens. TetA/tetC, tetG and ribosomal protection protein genes were detected in the bioaerosols of all 18 studied buildings. Campylobacter, C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were found respectively in 4, 9, 17, 14 and one nasal flora of workers. One and 10 workers were positive for tetA/tetC and tetG genes, respectively. In swine confinement buildings, hog producers are exposed to aerosolized human pathogens and tetracycline-resistant bacteria that can contaminate the nasal flora. Copyright © 2010 Elsevier GmbH. All rights reserved.\",\n \"title\": \"Human pathogens and tetracycline-resistant bacteria in bioaerosols of swine confinement buildings and in nasal flora of hog producers.\"\n },\n {\n \"docid\": \"MED-4845\",\n \"text\": \"Fasting is an effective treatment for rheumatoid arthritis, but most patients relapse on reintroduction of food. The effect of fasting followed by one year of a vegetarian diet was assessed in a randomised, single-blind controlled trial. 27 patients were allocated to a four-week stay at a health farm. After an initial 7-10 day subtotal fast, they were put on an individually adjusted gluten-free vegan diet for 3.5 months. The food was then gradually changed to a lactovegetarian diet for the remainder of the study. A control group of 26 patients stayed for four weeks at a convalescent home, but ate an ordinary diet throughout the whole study period. After four weeks at the health farm the diet group showed a significant improvement in number of tender joints, Ritchie's articular index, number of swollen joints, pain score, duration of morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and a health assessment questionnaire score. In the control group, only pain score improved score. In the control group, only pain score improved significantly. The benefits in the diet group were still present after one year, and evaluation of the whole course showed significant advantages for the diet group in all measured indices. This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis.\",\n \"title\": \"Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-5090\",\n \"text\": \"OBJECTIVE: To examine associations between the prevalence of degenerative arthritis and soft tissue disorders and consumption of meat and other foods among participants in the Adventist Health Study. METHODS: Unconditional logistic regression analysis is used to examine cross-sectional associations, adjusting for the effects of age, smoking, alcohol consumption, body mass index, use of sex hormones and parity. RESULTS: The prevalence of degenerative arthritis and soft tissue disorders was 22.60 percent. Women had a higher prevalence than men and prevalence increased greatly with age. Smoking, higher body mass index, never use of contraceptive pills, and current hormone replacement therapy are associated with a higher prevalence of these disorders on multivariate analysis. Multivariate OR's comparing consumption of meat < 1/week; >or= 1/week; with the reference being no meat, were 1.31(95% CI: 1.21,1.43) and 1.49(1.31, 1.70) in women; and 1.19 (95% CI: 1.05,1.34) and 1.43(1.20, 1.70) in men. Dairy fat and fruit consumption were weakly associated with increased risk. There were protective associations with nut and salad consumption. CONCLUSIONS: Greater meat consumption is associated with a higher prevalence of degenerative arthritis and soft tissue disorders in both male and female subjects of this population, as is hormone replacement therapy in women.\",\n \"title\": \"Associations between meat consumption and the prevalence of degenerative arthritis and soft tissue disorders in the adventist health study, Califor...\"\n },\n {\n \"docid\": \"MED-4422\",\n \"text\": \"OBJECTIVES: To test the efficacy and safety of oral L-citrulline supplementation in improving erection hardness in patients with mild erectile dysfunction (ED). L-arginine supplementation improves nitric oxide-mediated vasodilation and endothelial function; however, oral administration has been hampered by extensive presystemic metabolism. In contrast, L-citrulline escapes presystemic metabolism and is converted to L-arginine, thus setting the rationale for oral L-citrulline supplementation as a donor for the L-arginine/nitric oxide pathway of penile erection. METHODS: In the present single-blind study, men with mild ED (erection hardness score of 3) received a placebo for 1 month and L-citrulline, 1.5 g/d, for another month. The erection hardness score, number of intercourses per month, treatment satisfaction, and adverse events were recorded. RESULTS: A total of 24 patients, mean age 56.5 ± 9.8 years, were entered and concluded the study without adverse events. The improvement in the erection hardness score from 3 (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01). The mean number of intercourses per month increased from 1.37 ± 0.93 at baseline to 1.53 ± 1.00 at the end of the placebo phase (P = .57) and 2.3 ± 1.37 at the end of the treatment phase (P < .01). All patients reporting an erection hardness score improvement from 3 to 4 reported being very satisfied. CONCLUSIONS: Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychologically fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction.\"\n },\n {\n \"docid\": \"MED-1118\",\n \"text\": \"OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.\",\n \"title\": \"Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet.\"\n },\n {\n \"docid\": \"MED-2360\",\n \"text\": \"Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.\",\n \"title\": \"STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness.\"\n },\n {\n \"docid\": \"MED-1123\",\n \"text\": \"OBJECTIVES: To provide a state of the art of economic analyses applied to rheumatoid arthritis (RA). METHODS: A systematic literature review on economic consequences and pharmacoeconomic issues of RA was performed. RESULTS: 127 valid articles were examined in this review. Generally, the financial impact of RA is substantial for health-care systems and society worldwide, although differences exist among national economies. Both direct and indirect (i.e. loss of productivity) costs contribute to economic burden of RA and must be taken into account when estimating overall impact to society. Disease severity, disease activity, age and socioeconomic status have been found to be the most relevant predictors of cost increase in RA. Moreover, introduction of biological anti-rheumatic agents has significantly raised direct medical costs in certain patients, but has also led to marked improvements in reducing disease activity, joint damage, and productivity loss in many of these patients. RA has also a significant impact on all aspects of quality of life; recent publications on health utility scores showed RA to be one of the diseases associated with poorest quality of life. CONCLUSIONS: RA represents a clinical and economic burden for healthcare systems. Although attributable RA costs have been extensively evaluated over the last decades, several issues, especially concerning the use of expensive therapies, must be addressed and frequently updated. Future research should also provide health economic evidence from usual practice settings, and on the economic impact of different therapeutic approaches to pursue specific clinical targets in individual patients.\",\n \"title\": \"Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-4349\",\n \"text\": \"Inflammation is a pathological condition underlying a number of diseases including cardiovascular diseases, cancer, and chronic inflammatory diseases. In addition, healthy, obese subjects also express markers of inflammation in their blood. Diet provides a variety of nutrients as well as non-nutritive bioactive constituents which modulate immunomodulatory and inflammatory processes. Epidemiological data suggest that dietary patterns strongly affect inflammatory processes. Primarily the intake of fruit and vegetables as well as of whole wheat is inversely associated with the risk of inflammation. In addition to observational studies there are also data from human intervention studies suggesting an anti-inflammatory potential of these plant foods. At the level of bioactive compounds occurring in plant foods, primarily carotenoids and flavonoids seem to modulate inflammatory as well as immunological processes. In conclusion, there is convincing evidence that plant foods and non-nutritive constituents associated with these foods modulate immunological and inflammatory processes. By means of anti-inflammatory activities a plant-based diet may contribute to the lower risk of cardiovascular diseases and cancer. A high intake of vegetables, fruit, and whole wheat as recommended by all international nutrition authorities provides a wide spectrum of bioactive compounds at health-promoting concentrations.\",\n \"title\": \"Anti-inflammatory effects of plant-based foods and of their constituents.\"\n },\n {\n \"docid\": \"MED-5339\",\n \"text\": \"Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.\",\n \"title\": \"Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat.\"\n },\n {\n \"docid\": \"MED-4140\",\n \"text\": \"A survey of 788 pigs from 120 farms was conducted to determine the within-farm prevalence of pathogenic Yersinia enterocolitica and a questionnaire of management conditions was mailed to the farms afterwards. A univariate statistical analysis with carriage and shedding as outcomes was conducted with random-effects logistic regression with farm as a clustering factor. Variables with a P value <0·15 were included into the respective multivariate random-effects logistic regression model. The use of municipal water was discovered to be a protective factor against carriage and faecal shedding of the pathogen. Organic production and buying feed from a certain feed manufacturer were also protective against total carriage. Tonsillar carriage, a different feed manufacturer, fasting pigs before transport to the slaughterhouse, higher-level farm health classification, and snout contacts between pigs were risk factors for faecal shedding. We concluded that differences in management can explain different prevalences of Y. enterocolitica between farms.\",\n \"title\": \"Factors related to the prevalence of pathogenic Yersinia enterocolitica on pig farms.\"\n },\n {\n \"docid\": \"MED-2272\",\n \"text\": \"To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.\",\n \"title\": \"Consumption of cherries lowers plasma urate in healthy women.\"\n },\n {\n \"docid\": \"MED-3943\",\n \"text\": \"The health benefits associated with pomegranate juice have led to the development of pomegranate extracts as botanical dietary supplements. Pomegranates contain hydrolyzable tannins in the form of punicalagins and punicalin as well as tannin-based complex oligomers that account for much of the antioxidant activity in juice. The content of ellagic acid has been used to standardize most pomegranate extract dietary supplements marketed. However, supplements can be adulterated with ellagic acid from less expensive plant sources and undercut this method of standardization. To compare the phytochemical contents and antioxidant activities of commercially available pomegranate extract dietary supplements beyond their content of ellagic acid, a total of 27 different supplements in the form of capsules, tablets, and soft gels were studied. Total phenolics were measured using both gallic acid equivalent (GAE) and ellagic acid equivalent (EAE) assays. Punicalagins, punicalin, and ellagic acid contents were determined by HPLC, whereas antioxidant capacity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay. Of the 27 supplements tested, only 5 had the typical pomegranate tannin profile by HPLC, 17 had ellagic acid as the predominant chemical with minor or no detectable pomegranate tannins, and 5 had no detectable tannins or ellagic acid. Therefore, standardization of pomegranate extract supplements based on their ellagic acid content does not guarantee pomegranate supplement authenticity. Future research is needed to assess the health impact of substituting ellagic acid for the complex mix of phytochemicals in a pomegranate extract dietary supplement.\",\n \"title\": \"Absence of pomegranate ellagitannins in the majority of commercial Pomegranate extracts: implications for standardization and quality control.\"\n },\n {\n \"docid\": \"MED-2082\",\n \"text\": \"BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S...\"\n },\n {\n \"docid\": \"MED-3949\",\n \"text\": \"In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.\",\n \"title\": \"Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia.\"\n },\n {\n \"docid\": \"MED-5335\",\n \"text\": \"Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.\",\n \"title\": \"Does a vegan diet reduce risk for Parkinson's disease?\"\n },\n {\n \"docid\": \"MED-1444\",\n \"text\": \"Coriander (Coriandrum sativum L.), a herbal plant, belonging to the family Apiceae, is valued for its culinary and medicinal uses. All parts of this herb are in use as flavoring agent and/or as traditional remedies for the treatment of different disorders in the folk medicine systems of different civilizations. The plant is a potential source of lipids (rich in petroselinic acid) and an essential oil (high in linalool) isolated from the seeds and the aerial parts. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb, which include anti-microbial, anti-oxidant, anti-diabetic, anxiolytic, anti-epileptic, anti-depressant, anti-mutagenic, anti-inflammatory, anti-dyslipidemic, anti-hypertensive, neuro-protective and diuretic. Interestingly, coriander also possessed lead-detoxifying potential. This review focuses on the medicinal uses, detailed phytochemistry, and the biological activities of this valuable herb to explore its potential uses as a functional food for the nutraceutical industry. Copyright © 2012 John Wiley & Sons, Ltd.\",\n \"title\": \"Coriander (Coriandrum sativum L.): a potential source of high-value components for functional foods and nutraceuticals--a review.\"\n },\n {\n \"docid\": \"MED-2085\",\n \"text\": \"A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.\",\n \"title\": \"Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables.\"\n },\n {\n \"docid\": \"MED-2076\",\n \"text\": \"BACKGROUND: Berries are a particularly rich source of polyphenols. They also contain other bioactive substances, such as vitamin C. Previous studies indicated that the consumption of polyphenol-rich foods (eg, cocoa, tea, and red wine) may induce beneficial changes in pathways related to cardiovascular health. Whether the consumption of berries has similar effects is unknown. OBJECTIVE: We aimed to investigate the effects of berry consumption on hemostatic function, serum lipids, and blood pressure (BP). DESIGN: Middle-aged unmedicated subjects (n = 72) with cardiovascular risk factors consumed moderate amounts of berry or control products for 8 wk in a single-blind, randomized, placebo-controlled intervention trial. RESULTS: Berry consumption inhibited platelet function as measured with a platelet function analyzer (using collagen and ADP as platelet activator) [changes: 11% and -1.4% in the berry and control groups, respectively; P = 0.018, analysis of covariance (ANCOVA)]. Plasma biomarkers of platelet activation, coagulation, and fibrinolysis did not change during the intervention. Serum HDL-cholesterol concentrations increased significantly more (P = 0.006, ANCOVA) in the berry than in the control group (5.2% and 0.6%, respectively), but total cholesterol and triacylglycerol remained unchanged. Systolic BP decreased significantly (P = 0.050, ANCOVA); the decrease mostly occurred in subjects with high baseline BP (7.3 mm Hg in highest tertile; P = 0.024, ANCOVA). Polyphenol and vitamin C concentrations in plasma increased, whereas other nutritional biomarkers (ie, folate, tocopherols, sodium, and potassium) were unaffected. CONCLUSION: The consumption of moderate amounts of berries resulted in favorable changes in platelet function, HDL cholesterol, and BP. The results indicate that regular consumption of berries may play a role in the prevention of cardiovascular disease.\",\n \"title\": \"Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol.\"\n },\n {\n \"docid\": \"MED-2352\",\n \"text\": \"BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.\",\n \"title\": \"Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose.\"\n },\n {\n \"docid\": \"MED-2356\",\n \"text\": \"Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.\",\n \"title\": \"The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose\"\n },\n {\n \"docid\": \"MED-3307\",\n \"text\": \"OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.\",\n \"title\": \"Mortality in workers employed in pig abattoirs and processing plants.\"\n },\n {\n \"docid\": \"MED-2365\",\n \"text\": \"Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).\",\n \"title\": \"An association between tick bite reactions and red meat allergy in humans.\"\n },\n {\n \"docid\": \"MED-2816\",\n \"text\": \"Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.\",\n \"title\": \"Plant-derived health: the effects of turmeric and curcuminoids.\"\n },\n {\n \"docid\": \"MED-5330\",\n \"text\": \"Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.\",\n \"title\": \"Effect of a single high-fat meal on endothelial function in healthy subjects.\"\n },\n {\n \"docid\": \"MED-2800\",\n \"text\": \"The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.\",\n \"title\": \"Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management\"\n },\n {\n \"docid\": \"MED-5363\",\n \"text\": \"OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.\",\n \"title\": \"Dietary patterns and depressive symptoms among Japanese men and women.\"\n },\n {\n \"docid\": \"MED-4133\",\n \"text\": \"BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.\",\n \"title\": \"Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study.\"\n },\n {\n \"docid\": \"MED-1986\",\n \"text\": \"BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up.\",\n \"title\": \"Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935.\"\n },\n {\n \"docid\": \"MED-3464\",\n \"text\": \"The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.\",\n \"title\": \"Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women.\"\n },\n {\n \"docid\": \"MED-3947\",\n \"text\": \"Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.\",\n \"title\": \"Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells.\"\n },\n {\n \"docid\": \"MED-2362\",\n \"text\": \"The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)\",\n \"title\": \"Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G...\"\n },\n {\n \"docid\": \"MED-4407\",\n \"text\": \"Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects. Copyright © 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Addition of açaí (Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice.\"\n },\n {\n \"docid\": \"MED-5334\",\n \"text\": \"Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.\",\n \"title\": \"Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study.\"\n },\n {\n \"docid\": \"MED-4520\",\n \"text\": \"Evidence suggests that endothelial dysfunction is on the causal pathway for both atherogenesis and destabilization of established plaques. In this review, the role of flow-mediated dilatation (FMD) as a non-invasive method to assess endothelial function is discussed. Technical modifications and development of analysis software have significantly improved the variability of the method. Following a strict standardized protocol enables reproducible measurements to be achieved and export of the technique from specialized laboratories to population studies and multicentre settings. Endothelial function assessed by FMD has been shown to be affected by cardiovascular risk factors, to be related to structural arterial disease and to cardiovascular outcome, validating its use for studying the pathophysiology of arterial disease. Numerous studies have also demonstrated that it is responsive to physiological and pharmacological interventions. Flow-mediated dilatation provides unique opportunities in drug development programmes to assess an early rapidly responsive signal of risk or benefit, complementing endpoints of structural arterial disease and cardiovascular outcomes that take much longer and are more expensive.\",\n \"title\": \"Assessment of atherosclerosis: the role of flow-mediated dilatation.\"\n },\n {\n \"docid\": \"MED-4087\",\n \"text\": \"Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.\",\n \"title\": \"Fibromyalgia and nutrition, what do we know?\"\n },\n {\n \"docid\": \"MED-4141\",\n \"text\": \"To study the origin and spread of Yersinia enterocolitica among pigs, fecal and blood samples were repeatedly taken on a fattening farm. A few piglets were found to be already infected on breeding farms. After the piglets were mixed, the infection spread through the whole unit. Eventually, all the pigs excreted the pathogen.\",\n \"title\": \"Piglets Are a Source of Pathogenic Yersinia enterocolitica on Fattening-Pig Farms\"\n },\n {\n \"docid\": \"MED-4843\",\n \"text\": \"We have previously reported that significant improvement may be obtained in rheumatoid arthritis patients by fasting followed by a vegetarian diet for one year. The present study was carried out to examine to what extent biochemical and immunological variables changed during the clinical trial of fasting and vegetarian diet. For the patients who were randomised to the vegetarian diet there was a significant decrease in platelet count, leukocyte count, calprotectin, total IgG, IgM rheumatoid factor (RF), C3-activation products, and the complement components C3 and C4 after one month of treatment. None of the measured parameters changed significantly during this period in the group of omnivores. The course of 14 of 15 measured variables favored the vegetarians compared with the omnivores, but the difference was only significant for leukocyte count, IgM RF, and the complement components C3 and C4. Most of the laboratory variables declined considerably in the vegetarians who improved according to clinical variables, indicating a substantial reduction in inflammatory activity. The leukocyte count, however, decreased in the vegetarians irrespective of the clinical results. Thus, the decline in leukocyte count may be attributed to vegetarian diet per se and not to the reduction in disease activity. The results of the present study are in accordance with the findings from the clinical trial, namely that dietary treatment can reduce the disease activity in some patients with rheumatoid arthritis.\",\n \"title\": \"Changes in laboratory variables in rheumatoid arthritis patients during a trial of fasting and one-year vegetarian diet.\"\n },\n {\n \"docid\": \"MED-4132\",\n \"text\": \"Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.\",\n \"title\": \"Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic...\"\n },\n {\n \"docid\": \"MED-2804\",\n \"text\": \"Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.\",\n \"title\": \"Epidemiology of OA\"\n },\n {\n \"docid\": \"MED-2807\",\n \"text\": \"In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.\",\n \"title\": \"Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients.\"\n },\n {\n \"docid\": \"MED-4104\",\n \"text\": \"BACKGROUND: Although vegan diets improve diabetes management, little is known about the nutrient profiles or diet quality of individuals with type 2 diabetes who adopt a vegan diet. OBJECTIVE: To assess the changes in nutrient intake and dietary quality among participants following a low-fat vegan diet or the 2003 American Diabetes Association dietary recommendations. DESIGN: A 22-week randomized, controlled clinical trial examining changes in nutrient intake and diet quality. SUBJECTS/SETTING: Participants with type 2 diabetes (n=99) in a free-living setting. RESEARCH DESIGN AND METHODS: Participants were randomly assigned to a low-fat vegan diet or a 2003 American Diabetes Association recommended diet. MAIN OUTCOME MEASURES: Nutrient intake and Alternate Healthy Eating Index (AHEI) scores were collected at baseline and 22 weeks. STATISTICAL ANALYSES PERFORMED: Between-group t tests were calculated for changes between groups and paired comparison t tests were calculated for changes within-group. Pearson's correlation assessed relationship of AHEI score to hemoglobin A1c and body weight changes. RESULTS: Both groups reported significant decreases in energy, protein, fat, cholesterol, vitamin D, selenium, and sodium intakes. The vegan group also significantly reduced reported intakes of vitamin B-12 and calcium, and significantly increased carbohydrate, fiber, total vitamin A activity, beta carotene, vitamins K and C, folate, magnesium, and potassium. The American Diabetes Association recommended diet group also reported significant decreases in carbohydrate and iron, but reported no significant increases. The vegan group significantly improved its AHEI score (P<0.0001), while the American Diabetes Association recommended diet group did not (P=0.7218). The difference in AHEI score at 22 weeks between groups was significant (P<0.0001). With both groups combined, AHEI score was negatively correlated with both changes in hemoglobin A1c value (r=-0.24, P=0.016) and weight (r=-0.27, P=0.007). CONCLUSIONS: Vegan diets increase intakes of carbohydrate, fiber, and several micronutrients, in contrast with the American Diabetes Association recommended diet. The vegan group improved its AHEI score whereas the American Diabetes Association recommended diet group's AHEI score remained unchanged.\",\n \"title\": \"Changes in nutrient intake and dietary quality among participants with type 2 diabetes following a low-fat vegan diet or a conventional diabetes di...\"\n },\n {\n \"docid\": \"MED-4138\",\n \"text\": \"Yersinia enterocolitica is a zoonotic agent that causes gastrointestinal disease in humans, as well as reactive arthritis and erythema nodosum. Enteropathogenic Yersinia are the etiological agents for yersiniosis, which can be acquired through the consumption of contaminated foods. As porcine animals are the main carriers of Y. enterocolitica, food safety measures to minimize human infection are of increasing interest to the scientific and medical community. In this review, we examine why it is imperative that information on the reservoirs, prevalence, virulence, and ability of this pathogen to survive in different environments is further investigated to provide rational measures to prevent or decrease associated disease risks.\",\n \"title\": \"Yersinia enterocolitica: a brief review of the issues relating to the zoonotic pathogen, public health challenges, and the pork production chain.\"\n },\n {\n \"docid\": \"MED-2797\",\n \"text\": \"Osteoarthritis (OA) has long been considered a \\\"wear and tear\\\" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an \\\"inflammatory\\\" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.\",\n \"title\": \"Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!).\"\n },\n {\n \"docid\": \"MED-4130\",\n \"text\": \"We investigated characteristics of Yersinia enterocolitica infection in Ontario finisher pig herds. Our specific objectives were to estimate or test: prevalence of Y. enterocolitica shedding in finisher pigs, bioserotype distribution, agreement between the herd-level tests based on sampling pig and pooled fecal samples, whether bioserotypes cluster by farms, and whether Y. enterocolitica-positive herds cluster spatially. In total, 3747 fecal samples were collected from 100 farms over the years 2001, 2002, and 2004 (250 total herd visits). Fecal samples were tested by culture and positive isolates were biotyped and serotyped. Apparent pig-level prevalence of Y. enterocolitica was 1.8%, 3.2%, and 12.5% in 2001, 2002, and 2004, respectively. Estimated true pig-level prevalence of Y. enterocolitica was 5.1%, 9.1%, and 35.1% in 2001, 2002, and 2004, respectively. Herd-level prevalence was 16.3%, 17.9%, and 37.5% in 2001, 2002, and 2004, respectively. In all years, the most common bioserotype was 4, O:3, followed by bioserotype 2, O:5,27. Kappa between herd-level status based on pig and pooled samples ranged between 0.51 and 0.68 for biotype 1A and bioserotype 4, O:3, respectively. For 4, O:3, a significant bias in discordant pairs was detected, indicating that pig samples were more sensitive than pooled samples in declaring a herd as positive. Farms tended to be repeatedly positive with the same bioserotype, but positive study farms did not cluster spatially (suggesting lack of between herd transmission and lack of a common geographic risk factor). Copyright 2009 Elsevier B.V. All rights reserved.\",\n \"title\": \"Prevalence of Yersinia enterocolitica shedding and bioserotype distribution in Ontario finisher pig herds in 2001, 2002, and 2004.\"\n },\n {\n \"docid\": \"MED-2278\",\n \"text\": \"OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.\",\n \"title\": \"Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats.\"\n },\n {\n \"docid\": \"MED-4630\",\n \"text\": \"Arachidonic acid (AA)-derived eicosanoids belong to a complex family of lipid mediators that regulate a wide variety of physiological responses and pathological processes. They are produced by various cell types through distinct enzymatic pathways and act on target cells via specific G-protein-coupled receptors. Although originally recognized for their capacity to elicit biological responses such as vascular homeostasis, protection of the gastric mucosa and platelet aggregation, eicosanoids are now understood to regulate immunopathological processes ranging from inflammatory responses to chronic tissue remodelling, cancer, asthma, rheumatoid arthritis and autoimmune disorders. Here, we review the major properties of eicosanoids and their expanding roles in biology and medicine.\",\n \"title\": \"Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology.\"\n },\n {\n \"docid\": \"MED-3852\",\n \"text\": \"Recently two groups of compounds with diphenolic structure, the lignans and the isoflavonic phytoestrogens, were detected and identified in human urine and other biological fluids. These compounds are of great biological interest because they exhibit both in vitro and in vivo weak estrogenic and sometimes also antiestrogenic activities and many plant lignans have been shown to have anticarcinogenic, antiviral, antifungal and other interesting biological effects. The compounds found in relatively large amounts (10-1000 times more than estrogens) in urine are modified by intestinal bacteria from plant lignans and phytoestrogens, which are present in fiber-rich food such as grain and beans. They bind with low affinity to estrogen receptors and preliminary results suggest that they may induce production of sex hormone binding globulin (SHBG) in the liver and in this way may influence sex hormone metabolism and biological effects. Five compounds, the lignans enterolactone (Enl), enterodiol (End) and the isoflavonic phytoestrogen metabolites daidzein (Da), equol (Eq) and O-desmethylangolensin (O-Dma) were measured in urine by gas chromatography-mass spectrometry (selected ion monitoring) using deuterated internal standards in 5 groups of women (total number 53). The members of three dietary groups (omnivores, lactovegetarians and macrobiotics) were living in Boston and of two groups in Helsinki (omnivores and lactovegetarians). Until now measurements have been carried out in 94 72-h samples. The highest mean excretion of the most abundant compound, enterolactone, was found in the macrobiotic group and the lowest in the omnivoric groups. Total mean 24-h excretion of enterolactone was 17,680 nmol in the macrobiotics, 4,170 nmol in the Boston lactovegetarians, 3,650 nmol in the Helsinki lactovegetarians, 2,460 nmol in the Helsinki omnivores and 2,050 nmol in the Boston omnivores. The other diphenols followed approximately the same pattern. In an earlier study the lowest excretion of enterolactone (1,040 nmol/24 h) was found in a group of postmenopausal apparently healthy breast cancer patients living in Boston. It is concluded that further studies are necessary to elucidate the possible role of these compounds in cancer and other diseases. However, the evidence obtained until now seems to justify the conclusion that these compounds may be among the dietary factors affording protection against hormone-dependent cancers in vegetarians and semivegetarians.\",\n \"title\": \"Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual ...\"\n },\n {\n \"docid\": \"MED-3314\",\n \"text\": \"OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.\",\n \"title\": \"Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC).\"\n },\n {\n \"docid\": \"MED-1126\",\n \"text\": \"Lignans are a class of secondary plant metabolites produced by oxidative dimerization of two phenylpropanoid units. Although their molecular backbone consists only of two phenylpropane (C6-C3) units, lignans show an enormous structural diversity. There is a growing interest in lignans and their synthetic derivatives due to applications in cancer chemotherapy and various other pharmacological effects. This review deals with lignans possessing anticancer, antioxidant, antimicrobial, anti-inflammatory and immunosuppressive activities, and comprises the data reported in more than 100 peer-reviewed articles, so as to highlight the recently reported bioactive lignans that could be a first step towards the development of potential new therapeutic agents.\",\n \"title\": \"An update on bioactive plant lignans.\"\n },\n {\n \"docid\": \"MED-1987\",\n \"text\": \"OBJECTIVE: Over the last 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guideline, \\\"Management of Type 2 Diabetes Mellitus in Children and Adolescents,\\\" and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline's recommendations. METHODS: A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary literature search was conducted relating to the screening and treatment of T2DM's comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treatment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were considered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. RESULTS: Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclusion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 studies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic review. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information.\",\n \"title\": \"Management of type 2 diabetes mellitus in children and adolescents.\"\n },\n {\n \"docid\": \"MED-4846\",\n \"text\": \"The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.\",\n \"title\": \"Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-3313\",\n \"text\": \"INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.\",\n \"title\": \"Occupational toxicology of asbestos-related malignancies.\"\n },\n {\n \"docid\": \"MED-5341\",\n \"text\": \"The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.\",\n \"title\": \"Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro.\"\n },\n {\n \"docid\": \"MED-2366\",\n \"text\": \"Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.\",\n \"title\": \"A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis.\"\n },\n {\n \"docid\": \"MED-3292\",\n \"text\": \"The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.\",\n \"title\": \"The Restriction of Zoonotic PERV Transmission by Human APOBEC3G\"\n },\n {\n \"docid\": \"MED-4137\",\n \"text\": \"Swine have been identified as the primary reservoir of pathogenic Yersinia enterocolitica (YE), but little research has focused on the epidemiology of YE at the farm level. The objective of this study was to describe the prevalence of YE in different production phases on swine farms. In this cross-sectional study, individual pigs on eight swine operations were sampled for the presence of YE. On each farm, both feces and oral-pharyngeal swabs were collected from pigs in five different production phases: gestating, farrowing, suckling, nursery, and finishing. A pig was considered positive if either sample tested positive. Samples were cultured with cold enrichment followed by isolation on selective media plates. Presumptive isolates were confirmed as YE and assayed for the presence of ail with a multiplex PCR. Of the 2,349 pigs sampled, 120 (5.1%) tested positive, and of those, 51 were ail positive (42.5% of YE isolates). On all farms, there was a trend of increasing prevalence as pigs mature. Less than 1% of suckling piglets tested positive for YE. Only 1.4% (44.4% of which were ail positive) of nursery pigs tested positive, but 10.7% (48.1% of which were ail positive) of finishing pigs harbored YE. Interestingly, gestating sows had the second highest prevalence of YE at 9.1% (26.7% of which were ail positive), yet YE was never detected from the farrowing sows. These results represent the first on-farm description of YE in U.S. herds and provide the initial step for designing future studies of YE.\",\n \"title\": \"Prevalence of Yersinia enterocolitica in different phases of production on swine farms.\"\n },\n {\n \"docid\": \"MED-2083\",\n \"text\": \"Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. This study evaluated whether commercial grape, orange and grapefruit juices, taken daily, reduce ex vivo platelet activity. In a randomized cross-over design, ten healthy human subjects (ages 26-58 y, five of each gender) drank 5-7.5 mL/(kg. d) of purple grape juice, orange juice or grapefruit juice for 7-10 d each. Platelet aggregation (whole blood impedance aggregometry, Chronolog Model #590) at baseline was compared to results after consumption of each juice. Drinking purple grape juice for one week reduced the whole blood platelet aggregation response to 1 mg/L of collagen by 77% (from 17.9 +/- 2.3 to 4.0 +/- 6.8 ohms, P = 0.0002). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.\",\n \"title\": \"Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation.\"\n },\n {\n \"docid\": \"MED-5010\",\n \"text\": \"Phytochemicals are recognized as playing an important role in cancer prevention by fruits and vegetables. The avocado is a widely grown and consumed fruit that is high in nutrients and low in calories, sodium, and fats. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with chloroform from avocado fruits target multiple signaling pathways and increase intracellular reactive oxygen leading to apoptosis. This review summarizes the reported phytochemicals in avocado fruit and discusses their molecular mechanisms and targets. These studies suggest that individual and combinations of phytochemicals from the avocado fruit may offer an advantageous dietary strategy in cancer prevention.\",\n \"title\": \"Chemopreventive characteristics of avocado fruit.\"\n },\n {\n \"docid\": \"MED-3310\",\n \"text\": \"We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.\",\n \"title\": \"A new type of Hypersensitivity Pneumonitis: salami brusher's disease.\"\n },\n {\n \"docid\": \"MED-4317\",\n \"text\": \"Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.\",\n \"title\": \"Intestinal iron absorption: regulation by dietary & systemic factors.\"\n },\n {\n \"docid\": \"MED-3951\",\n \"text\": \"INTRODUCTION: This case report describes a patient who developed rhabdomyolysis temporally associated with the use of a mislabeled acai berry dietary supplement. METHODS AND RESULTS: The authors describe a 22-year-old man presenting with rhabdomyolysis approximately 2 weeks after starting a weight-loss dietary supplement. His medical history was significant only for hypertension treated with amlodipine. The diagnosis of rhabdomyolysis was confirmed (creatine kinase, 84,000 IU/L, positive urine myoglobin) with other potential causes ruled out. The signs and symptoms of the patient gradually resolved and he was discharged on hospital day 5. Assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 3, indicating a possible relationship between the supplement and rhabdomyolysis. Although the product was labeled and promoted as containing acai berry and additional ingredients, there was no acai berry found on analysis. CONCLUSION: Clinicians should be aware that all dietary supplements may vary in uniformity and contain unknown contaminants.\",\n \"title\": \"Rhabdomyolysis associated with the use of a mislabeled \\\"acai berry\\\" dietary supplement.\"\n },\n {\n \"docid\": \"MED-2359\",\n \"text\": \"INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"Anti-Gal titers in healthy adults and inflammatory bowel disease patients.\"\n },\n {\n \"docid\": \"MED-1988\",\n \"text\": \"PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.\",\n \"title\": \"Pediatrician's role in screening and treatment: bullying, prediabetes, oral health.\"\n },\n {\n \"docid\": \"MED-4628\",\n \"text\": \"BACKGROUND & AIMS: Dietary arachidonic acid, an n-6 polyunsaturated fatty acid (n-6 PUFA), might be involved in the etiology of ulcerative colitis (UC). We performed a prospective cohort study to determine whether high levels of arachidonic acid in adipose tissue samples (which reflects dietary intake) are associated with UC. METHODS: We analyzed data collected from 57,053 men and women in the EPIC-Denmark Prospective Cohort Study from 1993 to 1997. Adipose tissue biopsy samples were collected from gluteal regions at the beginning of the study, the cohort was monitored over subsequent years, and participants who developed UC were identified. A subcohort of 2510 randomly selected participants were used as controls. Concentrations of arachidonic acid were measured in adipose tissue samples. In the analysis, arachidonic acid levels were divided into quartiles; relative risks (RR) were calculated and adjusted for smoking, use of aspirin and nonsteroidal anti-inflammatory drugs, and levels of n-3 PUFAs. RESULTS: A total of 34 subjects (56% men) developed incident UC at a median age of 58.8 years (range, 50.0-69.0 years). Those in the highest quartile for arachidonic acid concentrations in adipose tissue had an RR for UC of 4.16 (95% confidence interval [CI]: 1.56-11.04); a trend per 0.1% increase in arachidonic acid of 1.77 in RR was observed (95% CI: 1.38-2.27). The fraction attributed the highest levels of arachidonic acid was 40.3%. CONCLUSIONS: Individuals with the highest relative concentrations of arachidonic acid in adipose tissue have a significantly greater risk of developing UC. Dietary modifications might therefore prevent UC or reduce disease symptoms. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"An association between dietary arachidonic acid, measured in adipose tissue, and ulcerative colitis.\"\n },\n {\n \"docid\": \"MED-2817\",\n \"text\": \"Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin in inflammatory diseases.\"\n },\n {\n \"docid\": \"MED-4135\",\n \"text\": \"Yersinia enterocolitica are ubiquitous, being isolated frequently from soil, water, animals, and a variety of foods. They comprise a biochemically heterogeneous group that can survive and grow at refrigeration temperatures. The ability to propagate at refrigeration temperatures is of considerable significance in food hygiene. Virulent strains of Yersinia invade mammalian cells such as HeLa cells in tissue culture. Two chromosomal genes, inv and ail, were identified for cell invasion of mammalian. The pathogen can cause diarrhoea, appendicitis and post-infection arthritis may occur in a small proportion of cases. The most common transmission route of pathogenic Y. enterocolitica is thought to be fecal-oral via contaminated food. Direct person-to-person contact is rare. Occasionally, pathogenic Y. enterocolitica has been detected in vegetables and environmental water; thus, vegetables and untreated water are also potential sources of human yersiniosis. However, the isolation rates of pathogenic Y. enterocolitica have been low, which may be due to the limited sensitivity of the detection methods. To identify other possible transmission vehicles, different food items should be studied more extensively. Many factors related to the epidemiology of Y. enterocolitica, such as sources, transmission routes, and predominating genotypes remain obscure because of the low sensitivity of detection methods.\",\n \"title\": \"Behavior of Yersinia enterocolitica in Foods\"\n },\n {\n \"docid\": \"MED-4851\",\n \"text\": \"The notion that dietary factors may influence rheumatoid arthritis (RA) has been a part of the folklore of the disease, but scientific support for this has been sparse. In a controlled, single-blind trial we tested the effect of fasting for 7-10 d, then consuming an individually adjusted, gluten-free, vegan diet for 3.5 mo, and then consuming an individually adjusted lactovegetarian diet for 9 mo on patients with RA. For all clinical variables and most laboratory variables measured, the 27 patients in the fasting and vegetarian diet groups improved significantly compared with the 26 patients in the control group who followed their usual omnivorous diet throughout the study period. One year after the patients completed the trial, they were reexamined. Compared with baseline, the improvements measured were significantly greater in the vegetarians who previously benefited from the diet (diet responders) than in diet nonresponders and omnivores. The beneficial effect could not be explained by patients' psychologic characteristics, antibody activity against food antigens, or changes in concentrations of prostaglandin and leukotriene precursors. However, the fecal flora differed significantly between samples collected at time points at which there was substantial clinical improvement and time points at which there were no or only minor improvements. In summary, the results show that some patients with RA can benefit from a fasting period followed by a vegetarian diet. Thus, dietary treatment may be a valuable adjunct to the ordinary therapeutic armamentarium for RA.\",\n \"title\": \"Rheumatoid arthritis treated with vegetarian diets.\"\n },\n {\n \"docid\": \"MED-2077\",\n \"text\": \"Cardiovascular diseases are one of the leading causes of morbidity and mortality in industrialized countries, and although many processes play a role in the development of vascular disease, thrombosis is the primary event that precipitates stroke and acute coronary syndromes. The blood platelets are of significant importance in medicine. These cells are involved in many physiological processes, particularly haemostasis through their ability to aggregate and form clots in response to activation. In addition, these dynamic cells display activities that extend beyond thrombosis, including an important role in initiating and sustaining vascular inflammation. The expansion of knowledge from basic and clinical research has highlighted the critical position of platelets in several inflammatory diseases such as arthritis and atherosclerosis. Platelets are emerging as important mediators of inflammation and provide important signals to mediate phenotype of other blood and vascular cells. The important role of platelets in arterial thrombosis and the onset of acute myocardial infarction after atherosclerotic plaque rupture make inhibition of platelet aggregation a critical step in preventing thrombotic events associated with stroke, heart attack, and peripheral arterial thrombosis. However, the use of platelet inhibitors for thrombosis prevention must seek a delicate balance between inhibiting platelet activation and an associated increased bleeding risk. The aim of this review is to up-date the knowledge on platelets physiology and dysfunction in pathologies, such as diabetes mellitus, hypercholesterolemia, and hypertension, emphasizing the link between platelets and the inflammation-related atherosclerosis. The review evaluates the opportunities offered by the novel platelet inhibitors to efficiently alleviate the thrombotic events. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Platelet dysfunction in vascular pathologies and how can it be treated.\"\n },\n {\n \"docid\": \"MED-4629\",\n \"text\": \"In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.\",\n \"title\": \"Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?\"\n },\n {\n \"docid\": \"MED-5342\",\n \"text\": \"Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.\",\n \"title\": \"Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults\"\n },\n {\n \"docid\": \"MED-2355\",\n \"text\": \"Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.\",\n \"title\": \"Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)\"\n },\n {\n \"docid\": \"MED-1120\",\n \"text\": \"Molecular mimicry is a hallmark of the pathogenesis of rheumatic fever where the streptococcal group A carbohydrate epitope, N-acetyl glucosamine, and the a-helical coiled-coil streptococcal M protein structurally mimic cardiac myosin in the human disease, rheumatic carditis, and in animal models immunized with streptococcal M protein and cardiac myosin. Recent studies have unraveled the potential pathogenic mechanisms by which the immune response against the group A streptococcus attacks the rheumatic valve leading to chronic rheumatic heart disease. Both B- and T-cell responses are involved in the process, and evidence for the hypotheses of molecular mimicry and epitope spreading are reviewed.\",\n \"title\": \"Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease.\"\n },\n {\n \"docid\": \"MED-1130\",\n \"text\": \"The beneficial effect of a 1-yr vegetarian diet in RA has recently been demonstrated in a clinical trial. We have analysed stool samples of the 53 RA patients by using direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. Based on repeated clinical assessments disease improvement indices were constructed for the patients. At each time point during the intervention period the patients in the diet group were then assigned either to a group with a high improvement index (HI) or a group with a low improvement index (LI). Significant alteration in the intestinal flora was observed when the patients changed from omnivorous to vegan diet. There was also a significant difference between the periods with vegan and lactovegetarian diets. The faecal flora from patients with HI and LI differed significantly from each other at 1 and 13 months during the diet. This finding of an association between intestinal flora and disease activity may have implications for our understanding of how diet can affect RA.\",\n \"title\": \"Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet.\"\n },\n {\n \"docid\": \"MED-5325\",\n \"text\": \"Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.\",\n \"title\": \"Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)\"\n },\n {\n \"docid\": \"MED-1128\",\n \"text\": \"Rheumatoid arthritis (RA) is a chronic inflammatory arthritic and potentially disabling condition, mainly affecting women of middle age and having characteristic clinical features. Various microbial agents were implicated in the causation of RA. Extensive literature based on the results of various genetic, microbiological, molecular, and immunological studies carried out by independent research groups supports the role of Proteus mirabilis bacteria in the etiopathogenesis of RA. New diagnostic markers and criteria and the use of a novel therapeutic protocol in the form of antibiotic and dietary measures are suggested to be used together with current treatments in the management of RA. Prospective longitudinal studies with the use of antimicrobial measures in patients with RA are required to establish the therapeutic benefit of this microbe-disease association.\",\n \"title\": \"Rheumatoid arthritis is linked to Proteus--the evidence.\"\n },\n {\n \"docid\": \"MED-5328\",\n \"text\": \"Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.\",\n \"title\": \"Vegetarian diets and incidence of diabetes in the Adventist Health Study-2\"\n },\n {\n \"docid\": \"MED-1129\",\n \"text\": \"Molecular mimicry between streptococci and heart components has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). In this review, we present data from cellular autoimmune responses, focusing on the interactions between HLA class II molecules, streptococcal peptides and heart tissue proteins and T-cell receptor (TCR) usage. HLA-DR7DR53 associated with DQ molecules seem to be related with the development of valvular lesions in severe RHD patients. DR7DR53 molecules were also involved in the recognition of an immunodominant M5 peptide in these patients. T cells infiltrating RHD hearts displayed several oligoclonal expansions. Intralesional T-cell clones presenting identical TCR-BVBJ AVAJ and -CDR3 sequences were able to recognize several antigens with little or low homology, showing an intramolecular degenerate pattern of antigen recognition. Peripheral blood mononuclear cells of rheumatic fever (RF) patients produced proinflammatory cytokines, and intralesional mononuclear cells from severe RHD patients produced predominantly Th1-type cytokines. These results illustrate the complex mechanisms leading to heart tissue damage in RF/RHD patients. Copyright 2004 S. Karger AG, Basel\",\n \"title\": \"Rheumatic fever: from sore throat to autoimmune heart lesions.\"\n },\n {\n \"docid\": \"MED-5323\",\n \"text\": \"This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.\",\n \"title\": \"Endocrine-disrupting chemicals and obesity development in humans: a review.\"\n },\n {\n \"docid\": \"MED-5340\",\n \"text\": \"In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.\",\n \"title\": \"Renal function parameters of Thai vegans compared with non-vegans.\"\n },\n {\n \"docid\": \"MED-2803\",\n \"text\": \"Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.\",\n \"title\": \"Dietary polyphenols and mechanisms of osteoarthritis.\"\n },\n {\n \"docid\": \"MED-2276\",\n \"text\": \"A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.\",\n \"title\": \"Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans.\"\n },\n {\n \"docid\": \"MED-5333\",\n \"text\": \"BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.\",\n \"title\": \"Vegetarian diet affects genes of oxidative metabolism and collagen synthesis.\"\n },\n {\n \"docid\": \"MED-3305\",\n \"text\": \"BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.\",\n \"title\": \"Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres.\"\n },\n {\n \"docid\": \"MED-2368\",\n \"text\": \"BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.\",\n \"title\": \"Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques.\"\n },\n {\n \"docid\": \"MED-1991\",\n \"text\": \"The objective of this article is to review the epidemiologic literature examining the role of plant foods and plant-based diets in the prevention of childhood obesity. Available data suggest a protective effect of ready-to-eat cereal on risk of obesity, although prospective studies are still needed. Studies on fruit and vegetables; grains other than cereal; high-protein foods, including beans, legumes, and soy; fiber; and plant-based dietary patterns are inconsistent or generally null. The evidence base is limited, and most studies are fraught with methodologic limitations, including cross-sectional design, inadequate adjustment for potential confounders, and lack of consideration of reporting errors, stage of growth, and genetic influences. Well-designed prospective studies are needed. The lack of evidence showing an association between plant-based diets and childhood obesity does not mean that such diets should not be encouraged. Plant foods are highlighted in the Dietary Guidelines for Americans, and children do not meet the current recommendations for most plant foods. Although the advice to consume a plant-based, low-energy-dense diet is sound, ethical questions arise concerning the relatively high price of these diets in the United States and the way in which such diets are perceived in other parts of the world. Reducing the burden of childhood obesity, eliminating health disparities, and preventing the further spread of the disease around the globe will require not only policy interventions to ensure that plant foods are affordable and accessible to children of all income levels but also awareness of sociocultural norms that affect consumption.\",\n \"title\": \"Plant foods and plant-based diets: protective against childhood obesity?\"\n },\n {\n \"docid\": \"MED-2369\",\n \"text\": \"Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.\",\n \"title\": \"Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose\"\n },\n {\n \"docid\": \"MED-2821\",\n \"text\": \"The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.\",\n \"title\": \"Turmeric (curcumin) remedies gastroprotective action\"\n },\n {\n \"docid\": \"MED-1131\",\n \"text\": \"To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.\",\n \"title\": \"Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet.\"\n },\n {\n \"docid\": \"MED-2808\",\n \"text\": \"Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.\",\n \"title\": \"Death by design: where curcumin sensitizes drug-resistant tumours.\"\n },\n {\n \"docid\": \"MED-4848\",\n \"text\": \"We have previously reported that a significant improvement can be obtained in rheumatoid arthritis patients by fasting followed by an individually adjusted vegetarian diet for one year. The patients who changed their diet could be divided into diet responders and diet nonresponders. After the clinical trial the patients were free to change diet or medication and after approximately one year they were asked to attend a new clinical examination. We compared the change from baseline (i.e. at the time of study entry) to the time of the follow-up examination for diet responders, diet nonresponders and controls who ate an omnivorous diet. The following variables favoured diet responders: pain score, duration of morning stiffness, Stanford Health Assessment Questionnaire index, number of tender joints, Ritchie's articular index, number of swollen joints, ESR and platelet count [corrected]. The difference between the three groups were significant for all the clinical variables, except for grip strength. There was no significant difference between the groups with regard to laboratory or anthropometric variables. At the time of the follow-up examination all diet responders but only half of the diet nonresponders still followed a diet. Our findings indicate that a group of patients with rheumatoid arthritis benefit from dietary manipulations and that the improvement can be sustained through a two-year period.\",\n \"title\": \"Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet.\"\n },\n {\n \"docid\": \"MED-4318\",\n \"text\": \"Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.\",\n \"title\": \"Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal.\"\n },\n {\n \"docid\": \"MED-5329\",\n \"text\": \"OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.\",\n \"title\": \"Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet.\"\n },\n {\n \"docid\": \"MED-3311\",\n \"text\": \"OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants.\"\n },\n {\n \"docid\": \"MED-3941\",\n \"text\": \"The effects of açai polyphenolics on the antiproliferation and induction of apoptosis in HL-60 human leukemia cells were investigated. Interactions between anthocyanins and non-anthocyanin-polyphenolics in both their glycosidic and their aglycone forms were also investigated to determine additive or nonadditive responses. Polyphenolic fractions at 0.17-10.7 microM were found to reduce cell proliferation from 56 to 86% likely due to caspase-3 activation (apoptosis). Anthocyanin and polyphenolic fractions were nonadditive in their contribution to the cell antiproliferation activity. At equimolar concentrations, the glycosidic forms of phenolic acids and flavonoids induced a higher magnitude of change in cell parameters (proliferation and apoptosis) than their respective aglycone forms, while the opposite trend was observed for anthocyanin aglycones. This study demonstrated that açai offers a rich source of bioactive polyphenolics and confirmed the importance of investigating whole food systems when evaluating the potential health benefits of individual phytochemical compounds.\",\n \"title\": \"Açai (Euterpe oleracea Mart.) polyphenolics in their glycoside and aglycone forms induce apoptosis of HL-60 leukemia cells.\"\n },\n {\n \"docid\": \"MED-2357\",\n \"text\": \"Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.\",\n \"title\": \"Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression\"\n },\n {\n \"docid\": \"MED-4847\",\n \"text\": \"Clinical experience suggests that fasting followed by vegetarian diet may help patients with rheumatoid arthritis (RA). We reviewed the available scientific evidence, because patients frequently ask for dietary advice, and exclusive pharmacological treatment of RA is often not satisfying. Fasting studies in RA were searched in MEDLINE and by checking references in relevant reports. The results of the controlled studies which reported follow-up data for at least three months after fasting were quantitatively pooled. Thirty-one reports of fasting studies in patients with RA were found. Only four controlled studies investigated the effects of fasting and subsequent diets for at least three months. The pooling of these studies showed a statistically and clinically significant beneficial long-term effect. Thus, available evidence suggests that fasting followed by vegetarian diets might be useful in the treatment of RA. More randomised long-term studies are needed to confirm this view by methodologically convincing data.\",\n \"title\": \"Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review.\"\n },\n {\n \"docid\": \"MED-1994\",\n \"text\": \"PURPOSE OF REVIEW: The prevalence of obesity in youth is increasing alarmingly among children and adolescents in the United States. The problem falls disproportionately on African-American and Hispanic children. Many of the metabolic and cardiovascular complications associated with obesity are already present during childhood and are closely linked to the concomitant insulin resistance/hyperinsulinemia and degree of obesity. Moreover, these co-morbidities persist into adulthood. RECENT FINDINGS: The progression from normal glucose tolerance to type 2 diabetes mellitus involves an intermediate stage known as prediabetes or impaired glucose regulation. Prediabetes is characterized by peripheral insulin-resistance and impaired glucose sensitivity of first-phase insulin secretion. On the other hand, in overt type 2 diabetes mellitus beta-cell failure becomes fully manifested. Progression from prediabetes to type 2 diabetes mellitus in youth is characterized by marked weight gain and further reduction in insulin secretion and insulin resistance. SUMMARY: Reverting obesity through lifestyle modification, that involves nutrition education, behavior modification and exercise, is an important step to prevent the progression to diabetes.\",\n \"title\": \"Prediabetes and type 2 diabetes in youth: an emerging epidemic disease?\"\n },\n {\n \"docid\": \"MED-1998\",\n \"text\": \"The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.\",\n \"title\": \"The early treatment of type 2 diabetes.\"\n },\n {\n \"docid\": \"MED-4084\",\n \"text\": \"Experiences with food intake, diet manipulations and fast were registered in rheumatic patients. The study was a questionnaire-based survey in which 742 patients participated. It comprised 290 patients with rheumatoid arthritis, 51 patients with juvenile rheumatoid arthritis, 87 patients with ankylosing spondylitis, 51 patients with psoriatic arthropathy, 65 patients with primary fibromyalgia and 34 patients with osteoarthritis. One third of the patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthropathy reported aggravation of disease symptoms after intake of certain foods while 43% of the patients with juvenile rheumatoid arthritis and 42% of the patients with primary fibromyalgia stated the same. Twenty-six percent of the patients with juvenile rheumatoid arthritis and 23% of the patients with rheumatoid arthritis, ankylosing spondylitis and primary fibromyalgia had previously tried certain diets in the attempt to alleviate disease symptoms, whereas 13% of the patients with psoriatic arthropathy and 10% with osteoarthritis had tried diet therapy. Less pain and stiffness were reported by 46% of the patients and 36% reported reduced joint swelling. Similar beneficial effects of diet were also reported in other rheumatic disease groups. Fifteen percent of the patients with rheumatoid arthritis and ankylosing spondylitis had been through a fasting period. Less pain and stiffness were reported by 2/3 of the patients in both groups and half of the patients in both groups reported a reduced number of swollen joints.\",\n \"title\": \"Diet and disease symptoms in rheumatic diseases--results of a questionnaire based survey.\"\n },\n {\n \"docid\": \"MED-4128\",\n \"text\": \"Various methods have been described in the literature for the detection of virulent Yersinia enterocolitica in pigs. The risk factors for pig herd contamination have yet to be determined. The objective of this study was to validate a sensitive method for the detection of Y. enterocolitica and to describe the distribution of the bacteria in pigs at slaughter from conventional and alternative (\\\"organic\\\") housing systems. First, samples were collected from tonsils, caecum with caecal contents, and the caecal lymph nodes of 60 slaughter pigs. These samples were used to compare the sensitivity of six different laboratory culture methods either in common use or described in the literature with that of a polymerase chain reaction with two primer pairs (multiplex PCR). Then, only PCR was used to examine tonsils, caecum and caecal lymph nodes from two groups of slaughter pigs: 210 from six conventional fattening farms and 200 from three with alternative housing. The results of the multiplex PCR were positive in 28 cases. All culture methods proved inferior to PCR in sensitivity. In the second part of the study, PCR detected 36 (18%) positive pigs from alternative housing and 60 (29%) from conventional housing (p<0.05). The highest rate of Y. enterocolitica contamination was found in tonsils (11% alternative, 22% conventional; p<0.05), followed by caecum (5%, 11%) and lymph nodes (2%, 7%). The housing system appears to be one important factor in the prevalence of this common pathogen in pig herds, as we found important differences between the two systems studied here. In the conventional system, the main risk factors appeared to be sourcing pigs from different pig suppliers, use of commercial feed and transportation to slaughter.\",\n \"title\": \"Validation of a method for the detection of virulent Yersinia enterocolitica and their distribution in slaughter pigs from conventional and alterna...\"\n },\n {\n \"docid\": \"MED-4433\",\n \"text\": \"BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.\",\n \"title\": \"Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund.\"\n },\n {\n \"docid\": \"MED-1124\",\n \"text\": \"The effect of an uncooked extreme vegan diet on fecal microflora was studied by direct stool sample gas-liquid chromatography (GLC) of bacterial cellular fatty acids and by quantitative bacterial culture by using classical microbiological techniques of isolation, identification, and enumeration of different bacterial species. Eighteen volunteers were divided randomly into two groups. The test group received an uncooked vegan diet for 1 month and a conventional diet of mixed Western type for the other month of the study. The control group consumed a conventional diet throughout the study period. Stool samples were collected. Bacterial cellular fatty acids were extracted directly from the stool samples and measured by GLC. Computerized analysis of the resulting fatty acid profiles was performed. Such a profile represents all bacterial cellular fatty acids in a sample and thus reflects its microflora and can be used to detect changes, differences, or similarities of bacterial flora between individual samples or sample groups. GLC profiles changed significantly in the test group after the induction and discontinuation of the vegan diet but not in the control group at any time, whereas quantitative bacterial culture did not detect any significant change in fecal bacteriology in either of the groups. The results suggest that an uncooked extreme vegan diet alters the fecal bacterial flora significantly when it is measured by direct stool sample GLC of bacterial fatty acids.\",\n \"title\": \"An uncooked vegan diet shifts the profile of human fecal microflora: computerized analysis of direct stool sample gas-liquid chromatography profiles of bacterial cellular fatty acids.\"\n },\n {\n \"docid\": \"MED-3535\",\n \"text\": \"Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.\",\n \"title\": \"Cherries and health: a review.\"\n },\n {\n \"docid\": \"MED-2823\",\n \"text\": \"Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.\",\n \"title\": \"Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies\"\n },\n {\n \"docid\": \"MED-3295\",\n \"text\": \"Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.\",\n \"title\": \"Cancer and Noncancer Mortality Among American Seafood Workers\"\n },\n {\n \"docid\": \"MED-3321\",\n \"text\": \"Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.\",\n \"title\": \"Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry.\"\n },\n {\n \"docid\": \"MED-5009\",\n \"text\": \"OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.\",\n \"title\": \"Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials.\"\n },\n {\n \"docid\": \"MED-5303\",\n \"text\": \"IMPORTANCE: Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN: We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS: US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE: From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.\",\n \"title\": \"The state of US health, 1990-2010: burden of diseases, injuries, and risk factors.\"\n },\n {\n \"docid\": \"MED-4850\",\n \"text\": \"Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.\",\n \"title\": \"Antioxidants in vegan diet and rheumatic disorders.\"\n },\n {\n \"docid\": \"MED-1997\",\n \"text\": \"The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.\",\n \"title\": \"Vegetarian diets and childhood obesity prevention.\"\n },\n {\n \"docid\": \"MED-4136\",\n \"text\": \"BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.\",\n \"title\": \"Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10...\"\n },\n {\n \"docid\": \"MED-2799\",\n \"text\": \"Objective: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1ß (IL1ß), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFα and IL1ß were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. Conclusion: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.\",\n \"title\": \"Synovial tissue inflammation in early and late osteoarthritis\"\n },\n {\n \"docid\": \"MED-3306\",\n \"text\": \"OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.\",\n \"title\": \"Farming, growing up on a farm, and haematological cancer mortality.\"\n },\n {\n \"docid\": \"MED-1999\",\n \"text\": \"Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.\",\n \"title\": \"Strategies for preventing type 2 diabetes: an update for clinicians\"\n },\n {\n \"docid\": \"MED-3950\",\n \"text\": \"The Açaí (Acai) fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.\",\n \"title\": \"Polysaccharides Isolated from Açaí Fruit Induce Innate Immune Responses\"\n },\n {\n \"docid\": \"MED-2078\",\n \"text\": \"Platelet hyperactivity is one of the most important factors responsible for the incidence of cardiovascular disease. There are many nutritive and non-nutritive compounds present in the diet which may affect platelet function in various ways. Recent discovery of anti-platelet factors in plants, vegetables and fruits provides a new dietary means for a long-term strategy to favorably modify human blood platelet activity. This review summarises the effects of these dietary components on human platelet function both in vitro and in vivo.\",\n \"title\": \"Dietary components and human platelet activity.\"\n },\n {\n \"docid\": \"MED-2811\",\n \"text\": \"Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.\",\n \"title\": \"Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations.\"\n },\n {\n \"docid\": \"MED-1985\",\n \"text\": \"The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.\",\n \"title\": \"Attained height of lacto-ovo vegetarian children and adolescents.\"\n },\n {\n \"docid\": \"MED-2351\",\n \"text\": \"Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.\",\n \"title\": \"Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum.\"\n },\n {\n \"docid\": \"MED-2818\",\n \"text\": \"Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.\",\n \"title\": \"Curcumin: the story so far.\"\n },\n {\n \"docid\": \"MED-3315\",\n \"text\": \"PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"A pilot case-cohort study of liver and pancreatic cancers in poultry workers.\"\n },\n {\n \"docid\": \"MED-3942\",\n \"text\": \"Background The purpose of this study was to evaluate the effect of açai fruit pulp on risk factors for metabolic disorders in overweight subjects. The açaí palm (Euterpe oleracea Mart.), which is native to South America, produces a small, black-purple fruit which is edible. The fruit has recently become popular as a functional food due to its antioxidant potential. Although several studies have been conducted in vitro and with animals, little is known about the potential health benefits in humans aside from an increase in plasma anti-oxidant capacity. Metabolic syndrome is a condition which is defined by a cluster of risk factors for cardiovascular disease and/or type-2 diabetes. Preliminary studies indicate that a reduction in reactive oxygen species can assist in the normalization of the metabolic pathways involved in this syndrome. Methods This was an open label pilot study conducted with 10 overweight adults (BMI ≥ 25 kg/m2 and ≤ 30 kg/m2) who took 100 g açai pulp twice daily for 1 month. The study endpoints included levels of fasting plasma glucose, insulin, cholesterol, triglycerides, exhaled (breath) nitric oxide metabolites (eNO) and plasma levels of high sensitivity C-reactive protein (hs-CRP). The response of blood glucose, blood pressure and eNO to a standardized meal was determined at baseline and following the 30 day treatment. Results Compared to baseline, there were reductions in fasting glucose and insulin levels following the 30 day treatment (both p < 0.02). There was also a reduction in total cholesterol (p = 0.03), as well as borderline significant reductions in LDL-cholesterol and the ratio of total cholesterol to HDL-cholesterol (both p = 0.051). Compared to baseline, treatment with açai ameliorated the post-prandial increase in plasma glucose following the standardized meal, measured as the area under the curve (p = 0.047). There was no effect on blood pressure, hs-CRP or eNO. Conclusion In this uncontrolled pilot study, consumption of açai fruit pulp reduced levels of selected markers of metabolic disease risk in overweight adults, indicating that further studies are warranted.\",\n \"title\": \"Effects of Açai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: A pilot study\"\n },\n {\n \"docid\": \"MED-4849\",\n \"text\": \"We tested the effects of an uncooked vegan diet, rich in lactobacilli, in rheumatoid patients randomized into diet and control groups. The intervention group experienced subjective relief of rheumatic symptoms during intervention. A return to an omnivorous diet aggravated symptoms. Half of the patients experienced adverse effects (nausea, diarrhoea) during the diet and stopped the experiment prematurely. Indicators of rheumatic disease activity did not differ statistically between groups. The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and pain on movement). However, a composite index showed a higher number of patients with 3-5 improved disease activity measures in the intervention group. Stepwise regression analysis associated a decrease in the disease activity (measured as change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll-rich drinks, increase in fibre intake, and no need for gold, methotrexate or steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid arthritis. Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis.\",\n \"title\": \"Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis.\"\n },\n {\n \"docid\": \"MED-4316\",\n \"text\": \"The intestinal absorption of the essential trace element iron and its mobilization from storage sites in the body are controlled by systemic signals that reflect tissue iron requirements. Recent advances have indicated that the liver-derived peptide hepcidin plays a central role in this process by repressing iron release from intestinal enterocytes, macrophages and other body cells. When iron requirements are increased, hepcidin levels decline and more iron enters the plasma. It has been proposed that the level of circulating diferric transferrin, which reflects tissue iron levels, acts as a signal to alter hepcidin expression. In the liver, the proteins HFE, transferrin receptor 2 and hemojuvelin may be involved in mediating this signal as disruption of each of these molecules decreases hepcidin expression. Patients carrying mutations in these molecules or in hepcidin itself develop systemic iron loading (or hemochromatosis) due to their inability to down regulate iron absorption. Hepcidin is also responsible for the decreased plasma iron or hypoferremia that accompanies inflammation and various chronic diseases as its expression is stimulated by pro-inflammatory cytokines such as interleukin 6. The mechanisms underlying the regulation of hepcidin expression and how it acts on cells to control iron release are key areas of ongoing research. IUBMB Life, 57: 499-503, 2005.\",\n \"title\": \"Systemic regulation of intestinal iron absorption.\"\n },\n {\n \"docid\": \"MED-3946\",\n \"text\": \"The fruit of Euterpe oleraceae, commonly known as acai, has been demonstrated to exhibit significantly high antioxidant capacity in vitro, especially for superoxide and peroxyl scavenging, and, therefore, may have possible health benefits. In this study, the antioxidant capacities of freeze-dried acai fruit pulp/skin powder (OptiAcai) were evaluated by different assays with various free radical sources. It was found to have exceptional activity against superoxide in the superoxide scavenging (SOD) assay, the highest of any food reported to date against the peroxyl radical as measured by the oxygen radical absorbance capacity assay with fluorescein as the fluorescent probe (ORACFL), and mild activity against both the peroxynitrite and hydroxyl radical by the peroxynitrite averting capacity (NORAC) and hydroxyl radical averting capacity (HORAC) assays, respectively. The SOD of acai was 1614 units/g, an extremely high scavenging capacity for O2*-, by far the highest of any fruit or vegetable tested to date. Total phenolics were also tested as comparison. In the total antioxidant (TAO) assay, antioxidants in acai were differentiated into \\\"slow-acting\\\" and \\\"fast-acting\\\" components. An assay measuring inhibition of reactive oxygen species (ROS) formation in freshly purified human neutrophils showed that antioxidants in acai are able to enter human cells in a fully functional form and to perform an oxygen quenching function at very low doses. Furthermore, other bioactivities related to anti-inflammation and immune functions were also investigated. Acai was found to be a potential cyclooxygenase (COX)-1 and COX-2 inhibitor. It also showed a weak effect on lipopolysaccharide (LPS)-induced nitric oxide but no effect on either lymphocyte proliferation and phagocytic capacity.\",\n \"title\": \"Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai).\"\n },\n {\n \"docid\": \"MED-5331\",\n \"text\": \"A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.\",\n \"title\": \"Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland.\"\n },\n {\n \"docid\": \"MED-4085\",\n \"text\": \"The effect of a strict, low-salt, uncooked vegan diet rich in lactobacteria on symptoms in 18 fibromyalgia patients during and after a 3-month intervention period in an open, non-randomized controlled study was evaluated. As control 15 patients continued their omnivorous diet. The groups did not differ significantly from each other in the beginning of the study in any other parameters except in pain and urine sodium. The results revealed significant improvements in Visual analogue scale of pain (VAS) (p=0.005), joint stiffness (p=0.001), quality of sleep (p=0.0001), Health assessment questionnaire (HAQ) (p=0.031), General health questionnaire (GHQ) (p=0.021), and a rheumatologist's own questionnaire (p=0.038). The majority of patients were overweight to some extent at the beginning of the study and shifting to a vegan food caused a significant reduction in body mass index (BMI) (p=0.0001). Total serum cholesterol showed a statistically significant lowering (p=0.003). Urine sodium dropped to 1/3 of the beginning values (p=0.0001) indicating good diet compliance. It can be concluded that vegan diet had beneficial effects on fibromyalgia symptoms at least in the short run.\",\n \"title\": \"Vegan diet alleviates fibromyalgia symptoms.\"\n },\n {\n \"docid\": \"MED-1125\",\n \"text\": \"Genetic, molecular and biological studies indicate that rheumatoid arthritis (RA), a severe arthritic disorder affecting approximately 1% of the population in developed countries, is caused by an upper urinary tract infection by the microbe, Proteus mirabilis. Elevated levels of specific antibodies against Proteus bacteria have been reported from 16 different countries. The pathogenetic mechanism involves six stages triggered by cross-reactive autoantibodies evoked by Proteus infection. The causative amino acid sequences of Proteus namely, ESRRAL and IRRET, contain arginine doublets which can be acted upon by peptidyl arginine deiminase thereby explaining the early appearance of anti-citrullinated protein antibodies in patients with RA. Consequently, RA patients should be treated early with anti-Proteus antibiotics as well as biological agents to avoid irreversible joint damages. © 2013 APMIS. Published by John Wiley & Sons Ltd.\",\n \"title\": \"Rheumatoid arthritis is caused by a Proteus urinary tract infection.\"\n },\n {\n \"docid\": \"MED-1992\",\n \"text\": \"Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.\",\n \"title\": \"Prediabetes: A high-risk state for developing diabetes\"\n },\n {\n \"docid\": \"MED-4129\",\n \"text\": \"Pigs are considered as a major reservoir of human pathogenic Yersinia enterocolitica and a source of human yersiniosis. However, the transmission route of Y. enterocolitica from farm to pork is still unclear. The transmission of pathogenic Y. enterocolitica from pigs to carcasses and pluck sets was investigated by collecting samples from 364 individual ear-tagged pigs on the farm and at the slaughterhouse. In addition, isolated strains were analyzed, using pulsed-field gel electrophoresis. Isolation of similar genotypes of pathogenic Y. enterocolitica 4/O:3 in animals on the farm and at the slaughterhouse and in carcasses shows that carcass contamination originates from the strains a pig carries during the fattening period. Direct contamination from the carrier pig to its subsequent pluck set is also the primary contamination route for pluck sets, but cross-contamination appears to have a larger impact on pluck set contamination than on carcasses. In this study, the within-farm prevalence of pathogenic Y. enterocolitica varied from 0% to 100%, indicating specific farm factors affect the prevalence of Y. enterocolitica in pigs. The association of farm factors with the high prevalence of pathogenic Y. enterocolitica on farms was studied for the first time, using correlation and two-level logistic regression analyses. Specific farm factors, i.e. drinking from a nipple, absence of coarse feed or bedding for slaughter pigs, and no access of pest animals to pig house, were associated with a high prevalence of pathogenic Y. enterocolitica 4/O:3.\",\n \"title\": \"Contamination of carcasses with human pathogenic Yersinia enterocolitica 4/O:3 originates from pigs infected on farms.\"\n },\n {\n \"docid\": \"MED-2824\",\n \"text\": \"Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \\\"curry powder\\\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \\\"old-age\\\" disease such as cancer requires an \\\"age-old\\\" treatment.\",\n \"title\": \"Curcumin and cancer: an \\\"old-age\\\" disease with an \\\"age-old\\\" solution.\"\n },\n {\n \"docid\": \"MED-2367\",\n \"text\": \"Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.\",\n \"title\": \"Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes.\"\n },\n {\n \"docid\": \"MED-3945\",\n \"text\": \"The pomegranate fruit ( Punica granatum ) has become an international high-value crop for the production of commercial pomegranate juice (PJ). The perceived consumer value of PJ is due in large part to its potential health benefits based on a significant body of medical research conducted with authentic PJ. To establish criteria for authenticating PJ, a new International Multidimensional Authenticity Specifications (IMAS) algorithm was developed through consideration of existing databases and comprehensive chemical characterization of 45 commercial juice samples from 23 different manufacturers in the United States. In addition to analysis of commercial juice samples obtained in the United States, data from other analyses of pomegranate juice and fruits including samples from Iran, Turkey, Azerbaijan, Syria, India, and China were considered in developing this protocol. There is universal agreement that the presence of a highly constant group of six anthocyanins together with punicalagins characterizes polyphenols in PJ. At a total sugar concentration of 16 degrees Brix, PJ contains characteristic sugars including mannitol at >0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.\",\n \"title\": \"International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration.\"\n },\n {\n \"docid\": \"MED-3953\",\n \"text\": \"An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.\",\n \"title\": \"An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration.\"\n },\n {\n \"docid\": \"MED-4143\",\n \"text\": \"In this study, we hoped to provide valuable clinical information on yersiniosis for clinicians. Two thousand six hundred stool samples were collected from in- and outpatients with diarrhea, which were tested with both culture method and real-time polymerase chain reaction (RT-PCR). In total, 188 positive samples were detected by RT-PCR (178) and culture method (160), while the incidence was about 7.23%. The detection rate of RT-PCR was significantly higher than culture method and a higher incidence in autumn-winter was also noticeably identified than in spring-summer. Infection sources mostly focused on unboiled foods (101) and pets (45), while clinical manifestation mainly presented as gastroenteritis (156), pseudoappendicitis (32), and extraintestinal complications (46). The morbidity of extraintestinal complications in adults was significantly higher than in children and it was the same for high-risk patients between adults over the age of 60 years (4.7%) and children under the age of 3 years (1.4%), whereas the constituent ratio of children versus adults with yersiniosis in different systems was not significant. Of 160 isolates tested for antimicrobial susceptibility, the majority were susceptible to third-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, whereas only a small portion was susceptible to the first-generation cephalosporins and penicillins. During autumn-winter months, clinicians should pay more attention to clinical manifestation, early diagnosis, and treatment with susceptible antibiotics of yersiniosis and its complications, targeting high-risk patients.\",\n \"title\": \"Yersinia enterocolitica infection in diarrheal patients.\"\n },\n {\n \"docid\": \"MED-3316\",\n \"text\": \"BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.\",\n \"title\": \"An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study.\"\n },\n {\n \"docid\": \"MED-3320\",\n \"text\": \"OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.\",\n \"title\": \"Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry.\"\n },\n {\n \"docid\": \"MED-2274\",\n \"text\": \"Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.\",\n \"title\": \"Cherry Consumption and the Risk of Recurrent Gout Attacks\"\n },\n {\n \"docid\": \"MED-2801\",\n \"text\": \"Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin and obesity.\"\n },\n {\n \"docid\": \"MED-5293\",\n \"text\": \"Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.\",\n \"title\": \"A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010\"\n },\n {\n \"docid\": \"MED-5326\",\n \"text\": \"The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.\",\n \"title\": \"Red meat and colon cancer: should we become vegetarians, or can we make meat safer?\"\n },\n {\n \"docid\": \"MED-5332\",\n \"text\": \"The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.\",\n \"title\": \"Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age.\"\n },\n {\n \"docid\": \"MED-3312\",\n \"text\": \"BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.\",\n \"title\": \"Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S.\"\n },\n {\n \"docid\": \"MED-5338\",\n \"text\": \"Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.\",\n \"title\": \"Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease\"\n },\n {\n \"docid\": \"MED-2361\",\n \"text\": \"The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.\",\n \"title\": \"Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York.\"\n },\n {\n \"docid\": \"MED-1122\",\n \"text\": \"OBJECTIVES: patients with rheumatoid arthritis (RA) are reported to have in their sera raised levels of antibody specific to Proteus mirabilis. The aim of the study was to verify this and to determine an explanation for it by investigating the frequency of P. mirabilis urinary tract infection in RA patients and matched controls. METHODS: freshly voided urine was examined for the presence, number and identity of infecting bacteria. The levels of antibody in blood and in urine of the IgM, IgA and IgG classes to the common O serotypes of P. mirabilis and the antigens to which they reacted were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: analysis of urine from 76 patients with RA and 48 age- and gender-matched healthy controls showed that only two (4%) of the control urines but 25 (33%) of those from the RA patients were infected. The commonest infecting organism in the RA patients' urine was Proteus mirabilis which occurred twice as frequently as Escherichia coli. Proteus mirabilis was found in 52% of the infected urines of the RA patients and was always detected as a pure growth and usually in insignificant (< 10(4)/ml) numbers. It is highly improbable that this finding was the outcome of differences in age, physical ability or medication between the RA and control patient groups. Comparison of antibody levels to P. mirabilis by ELISA showed RA patients had raised (P < 0.0001, P = 0.001, P = 0.0063) levels of IgA, IgG and IgM respectively in their sera and raised (P < 0.0001, P < 0.0001, P = 0.0001) levels of IgG, IgM and IgA respectively in their urine compared with the control group. It was not possible to detect an antibody reacting to a P. mirabilis antigen that was specific to the RA patients. CONCLUSION: the results confirm that RA patients have raised levels of antibody to P. mirabilis not only in blood but also in urine and suggest that this arises because RA patients have an asymptomatic, non-significant P. mirabilis bacteriuria more frequently or more prolonged than control patients. This may be the trigger for their RA condition.\",\n \"title\": \"Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Proteus mirabilis bacteriuria more frequently than healthy con...\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-933","text":"A case of occult coeliac disease (CD) presenting with recurrent monoarthritis in a boy aged 11 years is reported. The case is unique due to the association of occult untreated CD and arthritis in childhood. Peripheral or axial arthritis as a first manifestation of occult CD has been described in adult patients, with an interval between the arthritis and CD of up to 15 years. In our case the interval between the appearance of arthritis and the diagnosis of CD was 2 years. The boy was asymptomatic for bowel disease and his nutritional status was normal. The diagnosis of CD was established using anti-gliadin (AGA) and anti-endomysium (EMA) antibody tests and was confirmed by small bowel biopsy. The introduction of a gluten-free diet resulted in the persistent remission of arthritis. As the treatment of CD-associated arthritis is based on dietary therapy, physicians should be alert to the possibility of occult CD in any child with arthritis of unclear origin.","title":"Recurrent monoarthritis in an 11-year-old boy with occult coeliac disease. Successful and stable remission after gluten-free diet."},{"docid":"MED-4080","text":"Background Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases. While microbiological fecal culture analysis is now increasingly used, little is known about the relationship of changes in intestinal flora, dietary patterns and clinical outcome in specific diseases. To clarify the role of microbiological culture analysis we aimed to evaluate whether in patients with rheumatoid arthritis (RA) or fibromyalgia (FM) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome. Methods During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA (n = 16) or FM (n = 35) were included in the study. According to predefined clinical criteria and the subjects' choice the patients received a mostly vegetarian Mediterranean diet (n = 21; mean age 50.9 +/-13.3 y) or participated in an intermittent modified 8-day fasting therapy (n = 30; mean age 53.7 +/- 9.4 y). Quantitative aerob and anaerob bacterial flora, stool pH and concentrations of secretory immunoglobulin A (sIgA) were analysed from stool samples at the beginning, at the end of the 2-week hospital stay and at a 3-months follow-up. Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients. Results We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups, nor were significant differences found in the analysis of sIgA and stool ph. Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA (p = 0.09). Clinical outcome was not related to alterations in the intestinal flora. Conclusion Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM. The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques. The potential benefit of fasting treatment in RA and FM should be further tested in randomised trials.","title":"Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study"},{"docid":"MED-4114","text":"Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.","title":"Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..."},{"docid":"MED-2788","text":"Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.","title":"Clinical utility of curcumin extract."},{"docid":"MED-2284","text":"In 1999, drug manufacturers introduced a class of NSAIDs called COX-2 inhibitors or coxibs. The drugs were avidly promoted directly to the consumers and became bestsellers from the start. Arthritis sufferers were eager to take medications that eased joint pain with less risk of causing gastrointestinal pain, bleeding and other side-effects. In the year after their introduction, doctors wrote over 100 million prescriptions for celecoxib (Celebrex) and rofecoxib (Vioxx). Celebrex is the sixth best-selling drug, with sales of more than US$ 4 billion since its debut in 1999. Vioxx had sales of US$ 2.6 billion in 2001. However, the coxibs increase the risk of heart attacks and strokes, and their price, in the USA, is obscene. The manufacturers faced a possibly complicit, toothless and bloodless FDA, and used every maneuvering to fleece the patients. We must now reflect on attitudes that we thought only belong to the tobacco industry. Fortunately, safe and active alternatives exist.","title":"COX-2 inhibitors: a story of greed, deception and death."},{"docid":"MED-716","text":"Throughout evolution sunlight produced vitamin D in the skin has been critically important for health. Vitamin D, known as the sunshine vitamin, is actually a hormone. Once it is produced in the skin or ingested from the diet it is converted sequentially in the liver and kidneys to its biologically active form 1,25-dihydroxyvitamin D. This hormone interacts with its receptor in the small intestine to increase the efficiency of intestinal calcium and phosphate absorption for the maintenance of the skeleton throughout life. Vitamin D deficiency during the first few years of life results in a flattened pelvis making it difficult for childbirth. Vitamin D deficiency causes osteopenia and osteoporosis increasing risk of fracture. Essentially every tissue and cell in the body has a vitamin D receptor. Therefore vitamin D deficiency has been linked to increased risk for preeclampsia, requiring a Cesarean section for birthing, multiple sclerosis, rheumatoid arthritis, type I diabetes, type II diabetes, heart disease, dementia, deadly cancers and infectious diseases. Therefore sensible sun exposure along with vitamin D supplementation of at least 2000 IU/d for adults and 1000 IU/d for children is essential to maximize their health.","title":"VITAMIN D: A D-LIGHTFUL SOLUTION FOR HEALTH"},{"docid":"MED-1730","text":"The United States (US) Environmental Protection Agency (EPA) and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. To examine potential health risks in humans, we searched and reviewed the literature to evaluate whether exposure to glyphosate is associated causally with non-cancer health risks in humans. We also reviewed biomonitoring studies of glyphosate to allow for a more comprehensive discussion of issues related to exposure assessment and misclassification. Cohort, case-control and cross-sectional studies on glyphosate and non-cancer outcomes evaluated a variety of endpoints, including non-cancer respiratory conditions, diabetes, myocardial infarction, reproductive and developmental outcomes, rheumatoid arthritis, thyroid disease, and Parkinson's disease. Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0. Because accurate exposure measurement is crucial for valid results, it is recommended that pesticide-specific exposure algorithms be developed and validated. Copyright © 2011 Elsevier Inc. All rights reserved.","title":"Epidemiologic studies of glyphosate and non-cancer health outcomes: a review."},{"docid":"MED-2791","text":"Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.","title":"Bioavailability of curcumin: problems and promises."},{"docid":"MED-1167","text":"Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. Copyright © 2013 Elsevier Inc. All rights reserved.","title":"Pesticides and human chronic diseases: evidences, mechanisms, and perspectives."},{"docid":"MED-2777","text":"BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.","title":"The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994."},{"docid":"MED-2827","text":"Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.","title":"Soy protein may alleviate osteoarthritis symptoms."},{"docid":"MED-4612","text":"Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.","title":"Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."},{"docid":"MED-3577","text":"PROBLEM/CONDITION: During the twenty first century, growth in the number of older adults (persons aged > or =65 years) in the United States will produce an unprecedented increase in the number of persons at risk for costly age-associated chronic diseases and other health conditions and injuries. REPORTING PERIOD: 1995-1996. DESCRIPTION OF SYSTEMS: This report uses data from CDC's National Center for Health Statistics (NCHS) to report on leading causes of death in 1996 (from the National Vital Statistics System), major causes of hospitalization (1996 National Hospital Discharge Survey [NHDSI), and major chronic conditions (1995 National Health Interview Survey [NHIS]). The National Vital Statistics System compiles information regarding all death certificates filed in the United States. NHDS is an annual probability sample of discharges from nonfederal, short-stay hospitals. NHIS is an ongoing annual cross-sectional household survey of the U.S. civilian, noninstitutionalized population. In addition, health-care expenditures for older adults are examined by using information obtained from published reports from the U.S. Health Care Financing Administration (HCFA) and health-services literature. RESULTS: The leading causes of death among adults aged > or =65 years were heart disease (1,808 deaths/100,000 population), malignant neoplasms (1,131/100,000), and cerebrovascular disease (415/100,000). Several leading causes of mortality among older adults differed by race, with deaths caused by Alzheimer's disease more frequent among whites and deaths caused by diabetes, kidney diseases, septicemia, and hypertension more frequent among blacks. Rates of hospitalization and length of hospital stays increased with age. Hospitalizations for heart disease represented the highest proportion of all discharges among older adults (23%). Discharge rates for malignant neoplasms, stroke, and pneumonia were similar for adults aged > or =65 years and, as with heart disease, were higher for men than for women. However, the rate of hospitalization for fractures among women exceeded the rate among men. Arthritis was the most prevalent chronic condition among adults aged > or =65 years (48.9/100 adults), followed by hypertension (40.3/100) and heart disease (28.6/100). In 1995, adults aged > or =65 years comprised 13% of the population but accounted for 35% of total personal health care dollars spent ($310 billion), and real per capita personal health-care expenditure for this age group increased at an average annual rate of 5.8% during 1985-1995. Projections for future medical expenditures for older adults vary; however, all project substantial increases after the year 2000. Hip fracture, dementia, and urinary incontinence are discussed as examples of prevalent and costly health conditions among older adults that differ in potential for prevention. These conditions were selected because they result in substantial medical and social costs and they differ in potential for prevention. INTERPRETATION: The higher prevalence of serious and costly health conditions among adults aged > or =65 years highlights the importance of implementing preventive health measures in this population. PUBLIC HEALTH ACTIONS: Data regarding causes of morbidity, mortality, and health-care expenditures among older adults provide information for measuring the effectiveness of public health efforts to reduce modifiable risk factors for morbidity and mortality in this population.","title":"Surveillance for morbidity and mortality among older adults--United States, 1995-1996."},{"docid":"MED-957","text":"Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to \"negative\" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)","title":"Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powde..."},{"docid":"MED-1394","text":"BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).","title":"Primary prevention of cardiovascular disease with a Mediterranean diet."},{"docid":"MED-2123","text":"Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.","title":"Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth"},{"docid":"MED-4679","text":"OBJECTIVES The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The κ statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage ≥2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage ≥2. The prime determinant of height velocity was pubertal status. CONCLUSIONS In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.","title":"Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls"},{"docid":"MED-5025","text":"Gel filtration chromatography, ultra-filtration, and solid-phase extraction silica gel clean-up were evaluated for their ability to remove microcystins selectively from extracts of cyanobacteria Spirulina samples after using the reversed-phase octadecylsilyl ODS cartridge for subsequent analysis by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The reversed-phase ODS cartridge/silica gel combination were effective and the optimal wash and elution conditions were: H(2)O (wash), 20% methanol in water (wash), and 90% methanol in water (elution) for the reversed-phase ODS cartridge, followed by 80% methanol in water elution in the silica gel cartridge. The presence of microcystins in 36 kinds of cyanobacteria Spirulina health food samples obtained from various retail outlets in China were detected by LC-MS/MS, and 34 samples (94%) contained microcystins ranging from 2 to 163 ng g(-1) (mean = 14 +/- 27 ng g(-1)), which were significantly lower than microcystins present in blue green alga products previously reported. MC-RR - which contains two molecules of arginine (R) - (in 94.4% samples) was the predominant microcystin, followed by MC-LR - where L is leucine - (30.6%) and MC-YR - where Y is tyrose - (27.8%). The possible potential health risks from chronic exposure to microcystins from contaminated cyanobacteria Spirulina health food should not be ignored, even if the toxin concentrations were low. The method presented herein is proposed to detect microcystins present in commercial cyanobacteria Spirulina samples.","title":"Detection of the hepatotoxic microcystins in 36 kinds of cyanobacteria Spirulina food products in China."},{"docid":"MED-818","text":"Lepidium meyenii (Maca) is a plant that grows at over 4000 meters above sea level in the central Peruvian Andes. The hypocotyls of this plant are traditionally consumed for their nutritional and medicinal properties. The aim of this study was to determine the health status based on a health related quality of life (HRQL) questionnaire (SF-20) and serum levels of interleukin 6 (IL-6) in subjects that are maca consumers. For this, a cross-sectional study was designed to be performed in 50 subjects from Junin (4100 m): 27 subjects were maca consumers and 23 were non-consumers. The SF-20 survey is used to obtain a summary measure of health status. The stand up from a chair and sit down (SUCSD) test (to assess lower-extremity function), hemoglobin measurement, blood pressure, sexual hormone levels, serum IL-6 levels and the score of chronic mountain sickness (CMS) were evaluated. Testosterone/estradiol ratio (P≪0.05), IL-6 (P<0.05) and CMS score were lower, whereas the health status score was higher, in maca consumers when compared to non-consumers (P<0.01). A greater proportion of maca consumers successfully completed the SUCSD test compared to non-consumers (P<0.01), showing a significant association with lower values of serum IL-6 (P<0.05). In conclusion, consumption of maca was associated with low serum IL-6 levels and in turn with better health status scores in the SF-20 survey and low chronic mountain sickness scores.","title":"Role of maca (Lepidium meyenii) consumption on serum interleukin-6 levels and health status in populations living in the Peruvian central Andes over 4000 m of altitude"},{"docid":"MED-1606","text":"Background: Plant-based and fiber-rich diets high in vegetables, fruit, and whole grains are recommended to prevent cancer and chronic conditions associated with renal cell carcinoma (RCC), such as obesity, hypertension, and diabetes. Diet may play a role in the etiology of RCC directly and/or indirectly. Objective: In a large prospective cohort of US men and women, we comprehensively investigated dietary intake and food sources of fiber in relation to RCC risk. Design: Participants of the NIH-AARP Diet and Health Study (n = 491,841) completed a self-administered questionnaire of demographics, diet, lifestyle, and medical history. Over 9 (mean) years of follow-up we identified 1816 incident cases of RCC. HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Results: Total dietary fiber intake was associated with a significant 15–20% lower risk of RCC in the 2 highest quintiles compared with the lowest (P-trend = 0.005). Intakes of legumes, whole grains, and cruciferous vegetables were also associated with a 16–18% reduced risk of RCC. Conversely, refined grain intake was positively associated with RCC risk in a comparison of quintile 5 with quintile 1 (HR: 1.19; 95% CI: 1.02, 1.39; P-trend = 0.04). The inverse association between fiber intake and RCC was consistent among participants who never smoked, had a body mass index [BMI (in kg/m2)] <30, and did not report a history of diabetes or hypertension. Conclusions: Intake of fiber and fiber-rich plant foods was associated with a significantly lower risk of RCC in this large US cohort. This trial was registered at clinicaltrials.gov as NCT00340015.","title":"Intake of fiber and fiber-rich plant foods is associated with a lower risk of renal cell carcinoma in a large US cohort"},{"docid":"MED-5276","text":"Background: Cellular changes lead to coronary artery endothelial dysfunction (ED) and precede plaque formation. Clinical events, such as unstable angina and acute coronary syndromes, are common consequences of ED. Coronary artery ED, as characterized by Rb-82 PE, is a perfusion abnormality at rest, which improves following stress. In risk factor modification studies, particularly in cholesterol-lowering trials, coronary artery ED has been demonstrated to be reversible. Other studies have correlated low fat diet modification with improvement in coronary artery disease.Purpose: This study evaluates changes in myocardial perfusion following meals with low versus high TG content, and its influence on post prandial serum TG.Methods: With a randomized, double blind placebo controlled, cross over design, we investigated 19 patients (10 with ED and 9 with normal perfusion) with Rb-82 PET for myocardial blood flow at rest and with adenosine stress. PET images and serum triglycerides were obtained before and after an olestra (OA) meal (2.7g TG, 44g olestra) and a high-fat meal (46.7g TG). Meals were matched for carbohydrate, protein, and cholesterol content.Results: Myocardial perfusion (uCi/cc) increased 11 - 12% following the OA meal compared to the high-fat meal in patients with ED. For all patients combined, serum TG increased significantly (p < 0.01) in the non-OA group with the median change from baseline to 170.0 mg/dl, compared to 21.5 mg/dl in the OA group during the 6 hours following the meal.Conclusions: A single olestra meal significantly diminishes post prandial serum TG levels and improves myocardial perfusion in patients with endothelial disease.","title":"8:45-90:00. The Influence of a High Fat Meal Compared to an Olestra Meal on Coronary Artery Endothelial Dysfunction by Rubidium (Rb)-82 Positron Em..."},{"docid":"MED-5109","text":"The objective of this research was to evaluate the effects of 2 levels of raw milk somatic cell count (SCC) on the composition of Prato cheese and on the microbiological and sensory changes of Prato cheese throughout ripening. Two groups of dairy cows were selected to obtain low-SCC (<200,000 cells/mL) and high-SCC (>700,000 cells/mL) milks, which were used to manufacture 2 vats of cheese. The pasteurized milk was evaluated according to the pH, total solids, fat, total protein, lactose, standard plate count, coliforms at 45 degrees C, and Salmonella spp. The cheese composition was evaluated 2 d after manufacture. Lactic acid bacteria, psychrotrophic bacteria, and yeast and mold counts were carried out after 3, 9, 16, 32, and 51 d of storage. Salmonella spp., Listeria monocytogenes, and coagulase-positive Staphylococcus counts were carried out after 3, 32, and 51 d of storage. A 2 x 5 factorial design with 4 replications was performed. Sensory evaluation of the cheeses from low- and high-SCC milks was carried out for overall acceptance by using a 9-point hedonic scale after 8, 22, 35, 50, and 63 d of storage. The somatic cell levels used did not affect the total protein and salt:moisture contents of the cheeses. The pH and moisture content were higher and the clotting time was longer for cheeses from high-SCC milk. Both cheeses presented the absence of Salmonella spp. and L. monocytogenes, and the coagulase-positive Staphylococcus count was below 1 x 10(2) cfu/g throughout the storage time. The lactic acid bacteria count decreased significantly during the storage time for the cheeses from both low- and high-SCC milks, but at a faster rate for the cheese from high-SCC milk. Cheeses from high-SCC milk presented lower psychrotrophic bacteria counts and higher yeast and mold counts than cheeses from low-SCC milk. Cheeses from low-SCC milk showed better overall acceptance by the consumers. The lower overall acceptance of the cheeses from high-SCC milk may be associated with texture and flavor defects, probably caused by the higher proteolysis of these cheeses.","title":"Microbial and sensory changes throughout the ripening of Prato cheese made from milk with different levels of somatic cells."},{"docid":"MED-3182","text":"OBJECTIVE: Review of human cysticercosis in Canada, to estimate the magnitude of the disease and to describe the pattern of disease expression in this country. METHODS: MEDLINE and manual search of case reports and case series of patients with cysticercosis diagnosed in Canada. ed data included year of diagnosis, citizenship status, clinical manifestations, and form of cysticercosis. FINDINGS: A total of 21 articles reporting 60 patients were found. Forty (67%) of these patients were diagnosed in the past two decades. Most cases came from Ontario (n=43) and Quebec (n=14). Immigrants accounted for 96% of the 28 cases in whom citizenship information was available. Neurocysticercosis was observed in 55 patients, and isolated compromise of striated muscles in the remaining five. Seizures was the primary or sole manifestation of the disease in 72% of patients, and most of them had parenchymal brain cysticerci (either viable cysts or calcifications). Two of seven patients were positive for Taenia eggs. In no case were household contacts of the patients investigated for taeniasis. CONCLUSIONS: An increasing number of patients with cysticercosis have been reported from Canada in the past two decades, suggesting that the prevalence of this parasitic disease may be on the rise. While most cases occur in immigrants, it is possible that at least some of these patients had acquired the disease in Canada.","title":"A review of cases of human cysticercosis in Canada."},{"docid":"MED-1840","text":"OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.","title":"Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P."},{"docid":"MED-1190","text":"The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.","title":"High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae."},{"docid":"MED-334","text":"OBJECTIVE: Among plant foods, grain products, legumes, and seeds are important sources of phosphorus (P). Current data on P content and absorbability of P from these foods are lacking. Measurement of in vitro digestible P (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected foods and to compare the amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP content of 21 foods and drinks of plant origin were measured by inductively coupled plasma optical emission spectrometry. In DP analysis, samples were digested enzymatically in principle in the same way as in the alimentary canal before P analyses. The most popular national brands were chosen for analysis. RESULTS: The highest amount of TP (667 mg/100 g) was found in sesame seeds with hull, which also had the lowest percentage of DP (6%) to TP. Instead, in cola drinks and beer, the percentage of DP to TP was 87 to 100% (13 to 22 mg/100 g). In cereal products, the highest TP content (216 mg/100 g) and DP proportion (100%) were present in industrial muffins, which contain sodium phosphate as a leavening agent. Legumes contained an average DP content of 83 mg/100 g (38% of TP). CONCLUSION: Absorbability of P may differ substantially among different plant foods. Despite high TP content, legumes may be a relatively poor P source. In foods containing phosphate additives, the proportion of DP is high, which supports previous conclusions of the effective absorbability of P from P additives. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.","title":"Differences among total and in vitro digestible phosphorus content of plant foods and beverages."},{"docid":"MED-1523","text":"Peppermint oil is easily available as a constituent of medicines. A near fatal case due to ingestion of toxic dose of oral peppermint oil is being reported. The patient came in a comatosed state and was in shock. She was managed with mechanical ventilation and ionotropes. Her vital parameters reached normal within 8 hours and became conscious by 24 hours. The side effects of peppermint oil are considered to be mild but this case report warns that ingestion of oral toxic doses of peppermint oil could be dangerous.","title":"A near fatal case of high dose peppermint oil ingestion- Lessons learnt"},{"docid":"MED-1473","text":"To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.","title":"Mechanism of free fatty acid-induced insulin resistance in humans."},{"docid":"MED-5057","text":"High fructose corn syrup (HFCS) has become an increasingly common food ingredient in the last 40 years. However, there is concern that HFCS consumption increases the risk for obesity and other adverse health outcomes compared to other caloric sweeteners. The most commonly used types of HFCS (HFCS-42 and HFCS-55) are similar in composition to sucrose (table sugar), consisting of roughly equal amounts of fructose and glucose. The primary difference is that these monosaccharides exist free in solution in HFCS, but in disaccharide form in sucrose. The disaccharide sucrose is easily cleaved in the small intestine, so free fructose and glucose are absorbed from both sucrose and HFCS. The advantage to food manufacturers is that the free monosaccharides in HFCS provide better flavor enhancement, stability, freshness, texture, color, pourability, and consistency in foods in comparison to sucrose. Because the composition of HFCS and sucrose is so similar, particularly on absorption by the body, it appears unlikely that HFCS contributes more to obesity or other conditions than sucrose does. Nevertheless, few studies have evaluated the potentially differential effect of various sweeteners, particularly as they relate to health conditions such as obesity, which develop over relatively long periods of time. Improved nutrient databases are needed to analyze food consumption in epidemiologic studies, as are more strongly designed experimental studies, including those on the mechanism of action and relationship between fructose dose and response. At the present time, there is insufficient evidence to ban or otherwise restrict use of HFCS or other fructose-containing sweeteners in the food supply or to require the use of warning labels on products containing HFCS. Nevertheless, dietary advice to limit consumption of all added caloric sweeteners, including HFCS, is warranted.","title":"The effects of high fructose syrup."},{"docid":"MED-2740","text":"To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.","title":"FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States."}],"string":"[\n {\n \"docid\": \"MED-933\",\n \"text\": \"A case of occult coeliac disease (CD) presenting with recurrent monoarthritis in a boy aged 11 years is reported. The case is unique due to the association of occult untreated CD and arthritis in childhood. Peripheral or axial arthritis as a first manifestation of occult CD has been described in adult patients, with an interval between the arthritis and CD of up to 15 years. In our case the interval between the appearance of arthritis and the diagnosis of CD was 2 years. The boy was asymptomatic for bowel disease and his nutritional status was normal. The diagnosis of CD was established using anti-gliadin (AGA) and anti-endomysium (EMA) antibody tests and was confirmed by small bowel biopsy. The introduction of a gluten-free diet resulted in the persistent remission of arthritis. As the treatment of CD-associated arthritis is based on dietary therapy, physicians should be alert to the possibility of occult CD in any child with arthritis of unclear origin.\",\n \"title\": \"Recurrent monoarthritis in an 11-year-old boy with occult coeliac disease. Successful and stable remission after gluten-free diet.\"\n },\n {\n \"docid\": \"MED-4080\",\n \"text\": \"Background Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases. While microbiological fecal culture analysis is now increasingly used, little is known about the relationship of changes in intestinal flora, dietary patterns and clinical outcome in specific diseases. To clarify the role of microbiological culture analysis we aimed to evaluate whether in patients with rheumatoid arthritis (RA) or fibromyalgia (FM) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome. Methods During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA (n = 16) or FM (n = 35) were included in the study. According to predefined clinical criteria and the subjects' choice the patients received a mostly vegetarian Mediterranean diet (n = 21; mean age 50.9 +/-13.3 y) or participated in an intermittent modified 8-day fasting therapy (n = 30; mean age 53.7 +/- 9.4 y). Quantitative aerob and anaerob bacterial flora, stool pH and concentrations of secretory immunoglobulin A (sIgA) were analysed from stool samples at the beginning, at the end of the 2-week hospital stay and at a 3-months follow-up. Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients. Results We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups, nor were significant differences found in the analysis of sIgA and stool ph. Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA (p = 0.09). Clinical outcome was not related to alterations in the intestinal flora. Conclusion Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM. The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques. The potential benefit of fasting treatment in RA and FM should be further tested in randomised trials.\",\n \"title\": \"Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study\"\n },\n {\n \"docid\": \"MED-4114\",\n \"text\": \"Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.\",\n \"title\": \"Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an...\"\n },\n {\n \"docid\": \"MED-2788\",\n \"text\": \"Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.\",\n \"title\": \"Clinical utility of curcumin extract.\"\n },\n {\n \"docid\": \"MED-2284\",\n \"text\": \"In 1999, drug manufacturers introduced a class of NSAIDs called COX-2 inhibitors or coxibs. The drugs were avidly promoted directly to the consumers and became bestsellers from the start. Arthritis sufferers were eager to take medications that eased joint pain with less risk of causing gastrointestinal pain, bleeding and other side-effects. In the year after their introduction, doctors wrote over 100 million prescriptions for celecoxib (Celebrex) and rofecoxib (Vioxx). Celebrex is the sixth best-selling drug, with sales of more than US$ 4 billion since its debut in 1999. Vioxx had sales of US$ 2.6 billion in 2001. However, the coxibs increase the risk of heart attacks and strokes, and their price, in the USA, is obscene. The manufacturers faced a possibly complicit, toothless and bloodless FDA, and used every maneuvering to fleece the patients. We must now reflect on attitudes that we thought only belong to the tobacco industry. Fortunately, safe and active alternatives exist.\",\n \"title\": \"COX-2 inhibitors: a story of greed, deception and death.\"\n },\n {\n \"docid\": \"MED-716\",\n \"text\": \"Throughout evolution sunlight produced vitamin D in the skin has been critically important for health. Vitamin D, known as the sunshine vitamin, is actually a hormone. Once it is produced in the skin or ingested from the diet it is converted sequentially in the liver and kidneys to its biologically active form 1,25-dihydroxyvitamin D. This hormone interacts with its receptor in the small intestine to increase the efficiency of intestinal calcium and phosphate absorption for the maintenance of the skeleton throughout life. Vitamin D deficiency during the first few years of life results in a flattened pelvis making it difficult for childbirth. Vitamin D deficiency causes osteopenia and osteoporosis increasing risk of fracture. Essentially every tissue and cell in the body has a vitamin D receptor. Therefore vitamin D deficiency has been linked to increased risk for preeclampsia, requiring a Cesarean section for birthing, multiple sclerosis, rheumatoid arthritis, type I diabetes, type II diabetes, heart disease, dementia, deadly cancers and infectious diseases. Therefore sensible sun exposure along with vitamin D supplementation of at least 2000 IU/d for adults and 1000 IU/d for children is essential to maximize their health.\",\n \"title\": \"VITAMIN D: A D-LIGHTFUL SOLUTION FOR HEALTH\"\n },\n {\n \"docid\": \"MED-1730\",\n \"text\": \"The United States (US) Environmental Protection Agency (EPA) and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. To examine potential health risks in humans, we searched and reviewed the literature to evaluate whether exposure to glyphosate is associated causally with non-cancer health risks in humans. We also reviewed biomonitoring studies of glyphosate to allow for a more comprehensive discussion of issues related to exposure assessment and misclassification. Cohort, case-control and cross-sectional studies on glyphosate and non-cancer outcomes evaluated a variety of endpoints, including non-cancer respiratory conditions, diabetes, myocardial infarction, reproductive and developmental outcomes, rheumatoid arthritis, thyroid disease, and Parkinson's disease. Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0. Because accurate exposure measurement is crucial for valid results, it is recommended that pesticide-specific exposure algorithms be developed and validated. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"Epidemiologic studies of glyphosate and non-cancer health outcomes: a review.\"\n },\n {\n \"docid\": \"MED-2791\",\n \"text\": \"Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.\",\n \"title\": \"Bioavailability of curcumin: problems and promises.\"\n },\n {\n \"docid\": \"MED-1167\",\n \"text\": \"Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. Copyright © 2013 Elsevier Inc. All rights reserved.\",\n \"title\": \"Pesticides and human chronic diseases: evidences, mechanisms, and perspectives.\"\n },\n {\n \"docid\": \"MED-2777\",\n \"text\": \"BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.\",\n \"title\": \"The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994.\"\n },\n {\n \"docid\": \"MED-2827\",\n \"text\": \"Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.\",\n \"title\": \"Soy protein may alleviate osteoarthritis symptoms.\"\n },\n {\n \"docid\": \"MED-4612\",\n \"text\": \"Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.\",\n \"title\": \"Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.\"\n },\n {\n \"docid\": \"MED-3577\",\n \"text\": \"PROBLEM/CONDITION: During the twenty first century, growth in the number of older adults (persons aged > or =65 years) in the United States will produce an unprecedented increase in the number of persons at risk for costly age-associated chronic diseases and other health conditions and injuries. REPORTING PERIOD: 1995-1996. DESCRIPTION OF SYSTEMS: This report uses data from CDC's National Center for Health Statistics (NCHS) to report on leading causes of death in 1996 (from the National Vital Statistics System), major causes of hospitalization (1996 National Hospital Discharge Survey [NHDSI), and major chronic conditions (1995 National Health Interview Survey [NHIS]). The National Vital Statistics System compiles information regarding all death certificates filed in the United States. NHDS is an annual probability sample of discharges from nonfederal, short-stay hospitals. NHIS is an ongoing annual cross-sectional household survey of the U.S. civilian, noninstitutionalized population. In addition, health-care expenditures for older adults are examined by using information obtained from published reports from the U.S. Health Care Financing Administration (HCFA) and health-services literature. RESULTS: The leading causes of death among adults aged > or =65 years were heart disease (1,808 deaths/100,000 population), malignant neoplasms (1,131/100,000), and cerebrovascular disease (415/100,000). Several leading causes of mortality among older adults differed by race, with deaths caused by Alzheimer's disease more frequent among whites and deaths caused by diabetes, kidney diseases, septicemia, and hypertension more frequent among blacks. Rates of hospitalization and length of hospital stays increased with age. Hospitalizations for heart disease represented the highest proportion of all discharges among older adults (23%). Discharge rates for malignant neoplasms, stroke, and pneumonia were similar for adults aged > or =65 years and, as with heart disease, were higher for men than for women. However, the rate of hospitalization for fractures among women exceeded the rate among men. Arthritis was the most prevalent chronic condition among adults aged > or =65 years (48.9/100 adults), followed by hypertension (40.3/100) and heart disease (28.6/100). In 1995, adults aged > or =65 years comprised 13% of the population but accounted for 35% of total personal health care dollars spent ($310 billion), and real per capita personal health-care expenditure for this age group increased at an average annual rate of 5.8% during 1985-1995. Projections for future medical expenditures for older adults vary; however, all project substantial increases after the year 2000. Hip fracture, dementia, and urinary incontinence are discussed as examples of prevalent and costly health conditions among older adults that differ in potential for prevention. These conditions were selected because they result in substantial medical and social costs and they differ in potential for prevention. INTERPRETATION: The higher prevalence of serious and costly health conditions among adults aged > or =65 years highlights the importance of implementing preventive health measures in this population. PUBLIC HEALTH ACTIONS: Data regarding causes of morbidity, mortality, and health-care expenditures among older adults provide information for measuring the effectiveness of public health efforts to reduce modifiable risk factors for morbidity and mortality in this population.\",\n \"title\": \"Surveillance for morbidity and mortality among older adults--United States, 1995-1996.\"\n },\n {\n \"docid\": \"MED-957\",\n \"text\": \"Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to \\\"negative\\\" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)\",\n \"title\": \"Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powde...\"\n },\n {\n \"docid\": \"MED-1394\",\n \"text\": \"BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).\",\n \"title\": \"Primary prevention of cardiovascular disease with a Mediterranean diet.\"\n },\n {\n \"docid\": \"MED-2123\",\n \"text\": \"Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.\",\n \"title\": \"Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth\"\n },\n {\n \"docid\": \"MED-4679\",\n \"text\": \"OBJECTIVES The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The κ statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage ≥2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage ≥2. The prime determinant of height velocity was pubertal status. CONCLUSIONS In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.\",\n \"title\": \"Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls\"\n },\n {\n \"docid\": \"MED-5025\",\n \"text\": \"Gel filtration chromatography, ultra-filtration, and solid-phase extraction silica gel clean-up were evaluated for their ability to remove microcystins selectively from extracts of cyanobacteria Spirulina samples after using the reversed-phase octadecylsilyl ODS cartridge for subsequent analysis by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The reversed-phase ODS cartridge/silica gel combination were effective and the optimal wash and elution conditions were: H(2)O (wash), 20% methanol in water (wash), and 90% methanol in water (elution) for the reversed-phase ODS cartridge, followed by 80% methanol in water elution in the silica gel cartridge. The presence of microcystins in 36 kinds of cyanobacteria Spirulina health food samples obtained from various retail outlets in China were detected by LC-MS/MS, and 34 samples (94%) contained microcystins ranging from 2 to 163 ng g(-1) (mean = 14 +/- 27 ng g(-1)), which were significantly lower than microcystins present in blue green alga products previously reported. MC-RR - which contains two molecules of arginine (R) - (in 94.4% samples) was the predominant microcystin, followed by MC-LR - where L is leucine - (30.6%) and MC-YR - where Y is tyrose - (27.8%). The possible potential health risks from chronic exposure to microcystins from contaminated cyanobacteria Spirulina health food should not be ignored, even if the toxin concentrations were low. The method presented herein is proposed to detect microcystins present in commercial cyanobacteria Spirulina samples.\",\n \"title\": \"Detection of the hepatotoxic microcystins in 36 kinds of cyanobacteria Spirulina food products in China.\"\n },\n {\n \"docid\": \"MED-818\",\n \"text\": \"Lepidium meyenii (Maca) is a plant that grows at over 4000 meters above sea level in the central Peruvian Andes. The hypocotyls of this plant are traditionally consumed for their nutritional and medicinal properties. The aim of this study was to determine the health status based on a health related quality of life (HRQL) questionnaire (SF-20) and serum levels of interleukin 6 (IL-6) in subjects that are maca consumers. For this, a cross-sectional study was designed to be performed in 50 subjects from Junin (4100 m): 27 subjects were maca consumers and 23 were non-consumers. The SF-20 survey is used to obtain a summary measure of health status. The stand up from a chair and sit down (SUCSD) test (to assess lower-extremity function), hemoglobin measurement, blood pressure, sexual hormone levels, serum IL-6 levels and the score of chronic mountain sickness (CMS) were evaluated. Testosterone/estradiol ratio (P≪0.05), IL-6 (P<0.05) and CMS score were lower, whereas the health status score was higher, in maca consumers when compared to non-consumers (P<0.01). A greater proportion of maca consumers successfully completed the SUCSD test compared to non-consumers (P<0.01), showing a significant association with lower values of serum IL-6 (P<0.05). In conclusion, consumption of maca was associated with low serum IL-6 levels and in turn with better health status scores in the SF-20 survey and low chronic mountain sickness scores.\",\n \"title\": \"Role of maca (Lepidium meyenii) consumption on serum interleukin-6 levels and health status in populations living in the Peruvian central Andes over 4000 m of altitude\"\n },\n {\n \"docid\": \"MED-1606\",\n \"text\": \"Background: Plant-based and fiber-rich diets high in vegetables, fruit, and whole grains are recommended to prevent cancer and chronic conditions associated with renal cell carcinoma (RCC), such as obesity, hypertension, and diabetes. Diet may play a role in the etiology of RCC directly and/or indirectly. Objective: In a large prospective cohort of US men and women, we comprehensively investigated dietary intake and food sources of fiber in relation to RCC risk. Design: Participants of the NIH-AARP Diet and Health Study (n = 491,841) completed a self-administered questionnaire of demographics, diet, lifestyle, and medical history. Over 9 (mean) years of follow-up we identified 1816 incident cases of RCC. HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Results: Total dietary fiber intake was associated with a significant 15–20% lower risk of RCC in the 2 highest quintiles compared with the lowest (P-trend = 0.005). Intakes of legumes, whole grains, and cruciferous vegetables were also associated with a 16–18% reduced risk of RCC. Conversely, refined grain intake was positively associated with RCC risk in a comparison of quintile 5 with quintile 1 (HR: 1.19; 95% CI: 1.02, 1.39; P-trend = 0.04). The inverse association between fiber intake and RCC was consistent among participants who never smoked, had a body mass index [BMI (in kg/m2)] <30, and did not report a history of diabetes or hypertension. Conclusions: Intake of fiber and fiber-rich plant foods was associated with a significantly lower risk of RCC in this large US cohort. This trial was registered at clinicaltrials.gov as NCT00340015.\",\n \"title\": \"Intake of fiber and fiber-rich plant foods is associated with a lower risk of renal cell carcinoma in a large US cohort\"\n },\n {\n \"docid\": \"MED-5276\",\n \"text\": \"Background: Cellular changes lead to coronary artery endothelial dysfunction (ED) and precede plaque formation. Clinical events, such as unstable angina and acute coronary syndromes, are common consequences of ED. Coronary artery ED, as characterized by Rb-82 PE, is a perfusion abnormality at rest, which improves following stress. In risk factor modification studies, particularly in cholesterol-lowering trials, coronary artery ED has been demonstrated to be reversible. Other studies have correlated low fat diet modification with improvement in coronary artery disease.Purpose: This study evaluates changes in myocardial perfusion following meals with low versus high TG content, and its influence on post prandial serum TG.Methods: With a randomized, double blind placebo controlled, cross over design, we investigated 19 patients (10 with ED and 9 with normal perfusion) with Rb-82 PET for myocardial blood flow at rest and with adenosine stress. PET images and serum triglycerides were obtained before and after an olestra (OA) meal (2.7g TG, 44g olestra) and a high-fat meal (46.7g TG). Meals were matched for carbohydrate, protein, and cholesterol content.Results: Myocardial perfusion (uCi/cc) increased 11 - 12% following the OA meal compared to the high-fat meal in patients with ED. For all patients combined, serum TG increased significantly (p < 0.01) in the non-OA group with the median change from baseline to 170.0 mg/dl, compared to 21.5 mg/dl in the OA group during the 6 hours following the meal.Conclusions: A single olestra meal significantly diminishes post prandial serum TG levels and improves myocardial perfusion in patients with endothelial disease.\",\n \"title\": \"8:45-90:00. The Influence of a High Fat Meal Compared to an Olestra Meal on Coronary Artery Endothelial Dysfunction by Rubidium (Rb)-82 Positron Em...\"\n },\n {\n \"docid\": \"MED-5109\",\n \"text\": \"The objective of this research was to evaluate the effects of 2 levels of raw milk somatic cell count (SCC) on the composition of Prato cheese and on the microbiological and sensory changes of Prato cheese throughout ripening. Two groups of dairy cows were selected to obtain low-SCC (<200,000 cells/mL) and high-SCC (>700,000 cells/mL) milks, which were used to manufacture 2 vats of cheese. The pasteurized milk was evaluated according to the pH, total solids, fat, total protein, lactose, standard plate count, coliforms at 45 degrees C, and Salmonella spp. The cheese composition was evaluated 2 d after manufacture. Lactic acid bacteria, psychrotrophic bacteria, and yeast and mold counts were carried out after 3, 9, 16, 32, and 51 d of storage. Salmonella spp., Listeria monocytogenes, and coagulase-positive Staphylococcus counts were carried out after 3, 32, and 51 d of storage. A 2 x 5 factorial design with 4 replications was performed. Sensory evaluation of the cheeses from low- and high-SCC milks was carried out for overall acceptance by using a 9-point hedonic scale after 8, 22, 35, 50, and 63 d of storage. The somatic cell levels used did not affect the total protein and salt:moisture contents of the cheeses. The pH and moisture content were higher and the clotting time was longer for cheeses from high-SCC milk. Both cheeses presented the absence of Salmonella spp. and L. monocytogenes, and the coagulase-positive Staphylococcus count was below 1 x 10(2) cfu/g throughout the storage time. The lactic acid bacteria count decreased significantly during the storage time for the cheeses from both low- and high-SCC milks, but at a faster rate for the cheese from high-SCC milk. Cheeses from high-SCC milk presented lower psychrotrophic bacteria counts and higher yeast and mold counts than cheeses from low-SCC milk. Cheeses from low-SCC milk showed better overall acceptance by the consumers. The lower overall acceptance of the cheeses from high-SCC milk may be associated with texture and flavor defects, probably caused by the higher proteolysis of these cheeses.\",\n \"title\": \"Microbial and sensory changes throughout the ripening of Prato cheese made from milk with different levels of somatic cells.\"\n },\n {\n \"docid\": \"MED-3182\",\n \"text\": \"OBJECTIVE: Review of human cysticercosis in Canada, to estimate the magnitude of the disease and to describe the pattern of disease expression in this country. METHODS: MEDLINE and manual search of case reports and case series of patients with cysticercosis diagnosed in Canada. ed data included year of diagnosis, citizenship status, clinical manifestations, and form of cysticercosis. FINDINGS: A total of 21 articles reporting 60 patients were found. Forty (67%) of these patients were diagnosed in the past two decades. Most cases came from Ontario (n=43) and Quebec (n=14). Immigrants accounted for 96% of the 28 cases in whom citizenship information was available. Neurocysticercosis was observed in 55 patients, and isolated compromise of striated muscles in the remaining five. Seizures was the primary or sole manifestation of the disease in 72% of patients, and most of them had parenchymal brain cysticerci (either viable cysts or calcifications). Two of seven patients were positive for Taenia eggs. In no case were household contacts of the patients investigated for taeniasis. CONCLUSIONS: An increasing number of patients with cysticercosis have been reported from Canada in the past two decades, suggesting that the prevalence of this parasitic disease may be on the rise. While most cases occur in immigrants, it is possible that at least some of these patients had acquired the disease in Canada.\",\n \"title\": \"A review of cases of human cysticercosis in Canada.\"\n },\n {\n \"docid\": \"MED-1840\",\n \"text\": \"OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.\",\n \"title\": \"Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P.\"\n },\n {\n \"docid\": \"MED-1190\",\n \"text\": \"The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.\",\n \"title\": \"High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae.\"\n },\n {\n \"docid\": \"MED-334\",\n \"text\": \"OBJECTIVE: Among plant foods, grain products, legumes, and seeds are important sources of phosphorus (P). Current data on P content and absorbability of P from these foods are lacking. Measurement of in vitro digestible P (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected foods and to compare the amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP content of 21 foods and drinks of plant origin were measured by inductively coupled plasma optical emission spectrometry. In DP analysis, samples were digested enzymatically in principle in the same way as in the alimentary canal before P analyses. The most popular national brands were chosen for analysis. RESULTS: The highest amount of TP (667 mg/100 g) was found in sesame seeds with hull, which also had the lowest percentage of DP (6%) to TP. Instead, in cola drinks and beer, the percentage of DP to TP was 87 to 100% (13 to 22 mg/100 g). In cereal products, the highest TP content (216 mg/100 g) and DP proportion (100%) were present in industrial muffins, which contain sodium phosphate as a leavening agent. Legumes contained an average DP content of 83 mg/100 g (38% of TP). CONCLUSION: Absorbability of P may differ substantially among different plant foods. Despite high TP content, legumes may be a relatively poor P source. In foods containing phosphate additives, the proportion of DP is high, which supports previous conclusions of the effective absorbability of P from P additives. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.\",\n \"title\": \"Differences among total and in vitro digestible phosphorus content of plant foods and beverages.\"\n },\n {\n \"docid\": \"MED-1523\",\n \"text\": \"Peppermint oil is easily available as a constituent of medicines. A near fatal case due to ingestion of toxic dose of oral peppermint oil is being reported. The patient came in a comatosed state and was in shock. She was managed with mechanical ventilation and ionotropes. Her vital parameters reached normal within 8 hours and became conscious by 24 hours. The side effects of peppermint oil are considered to be mild but this case report warns that ingestion of oral toxic doses of peppermint oil could be dangerous.\",\n \"title\": \"A near fatal case of high dose peppermint oil ingestion- Lessons learnt\"\n },\n {\n \"docid\": \"MED-1473\",\n \"text\": \"To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.\",\n \"title\": \"Mechanism of free fatty acid-induced insulin resistance in humans.\"\n },\n {\n \"docid\": \"MED-5057\",\n \"text\": \"High fructose corn syrup (HFCS) has become an increasingly common food ingredient in the last 40 years. However, there is concern that HFCS consumption increases the risk for obesity and other adverse health outcomes compared to other caloric sweeteners. The most commonly used types of HFCS (HFCS-42 and HFCS-55) are similar in composition to sucrose (table sugar), consisting of roughly equal amounts of fructose and glucose. The primary difference is that these monosaccharides exist free in solution in HFCS, but in disaccharide form in sucrose. The disaccharide sucrose is easily cleaved in the small intestine, so free fructose and glucose are absorbed from both sucrose and HFCS. The advantage to food manufacturers is that the free monosaccharides in HFCS provide better flavor enhancement, stability, freshness, texture, color, pourability, and consistency in foods in comparison to sucrose. Because the composition of HFCS and sucrose is so similar, particularly on absorption by the body, it appears unlikely that HFCS contributes more to obesity or other conditions than sucrose does. Nevertheless, few studies have evaluated the potentially differential effect of various sweeteners, particularly as they relate to health conditions such as obesity, which develop over relatively long periods of time. Improved nutrient databases are needed to analyze food consumption in epidemiologic studies, as are more strongly designed experimental studies, including those on the mechanism of action and relationship between fructose dose and response. At the present time, there is insufficient evidence to ban or otherwise restrict use of HFCS or other fructose-containing sweeteners in the food supply or to require the use of warning labels on products containing HFCS. Nevertheless, dietary advice to limit consumption of all added caloric sweeteners, including HFCS, is warranted.\",\n \"title\": \"The effects of high fructose syrup.\"\n },\n {\n \"docid\": \"MED-2740\",\n \"text\": \"To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.\",\n \"title\": \"FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States.\"\n }\n]"}}},{"rowIdx":388,"cells":{"query_id":{"kind":"string","value":"PLAIN-3155"},"query":{"kind":"string","value":"Avoiding Epilepsy Through Diet"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-1981","text":"The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.","title":"Antibiotic resistance-the need for global solutions."},{"docid":"MED-1980","text":"Enterobacterial strains producing clavulanic-acid-inhibited extended-spectrum β-lactamases (ESBLs) are increasingly reported worldwide. Conventional detection of ESBL production remains time-consuming (24 to 48 h). Therefore, the ESBL NDP (Nordmann/Dortet/Poirel) test was developed for a rapid identification of ESBLs in Enterobacteriaceae. This biochemical test was based on the in vitro detection of a cephalosporin (cefotaxime) hydrolysis that is inhibited by tazobactam addition. The ESBL activity was evidenced by a color change (red to yellow) of a pH indicator (red phenol) due to carboxyl-acid formation resulting from cefotaxime hydrolysis that was reversed by addition of tazobactam (positive test). The ESBL NDP test was applied to cultured strains (215 ESBL producers and 40 ESBL nonproducers). Its sensitivity and specificity were 92.6% and 100%, respectively. Its sensitivity (100%) was excellent for detection of CTX-M producers. A few ESBL producers (n = 16) that remained susceptible to cefotaxime were not detected. The test was also evaluated on spiked blood cultures and showed excellent sensitivity and specificity (100% for both). The test was rapid (less than 1 h) and cost-effective. It can be implemented in any health care facility and is well adapted for infection control purposes in particular.","title":"Rapid Detection of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae"},{"docid":"MED-2748","text":"The consumption of fresh produce is frequently associated with outbreaks of human norovirus (hNoV) disease. To prevent the contamination of fresh produce with hNoV, knowledge of the possible introduction sources of the viruses, such as water, is needed to be able to implement appropriate and efficient preventive measures. Contaminated water used to reconstitute pesticides could be a relevant source of infectious hNoV, determined by the initial level of virus contamination and the persistence of these viruses in reconstituted pesticides. We studied the persistence of hNoV GI.4, hNoV GII.4 and murine norovirus (MNV-1), the only culturable norovirus, in eight different pesticides after 0 and 2h. Virus concentrations were determined by reverse transcriptase PCR, and infectivity of MNV-1 was determined by endpoint dilutions followed by maximum likelihood estimations. MNV-1 was found to remain infectious in seven of the eight tested pesticides at the highest concentration applied in practice. In the presence of the insecticide Vertimec, MNV-1 infectivity decreased rapidly with a 1.9 log(10)-unit reduction at timepoint T(0). Also, the concentration of NoV GI.4 RNA decreased considerably with a 1.7 log(10)-unit reduction; whereas the detected PCR fragment of hNoV GII.4 remained stable. Assuming a similar persistence of infectious MNV-1 and hNoV we can conclude that water containing hNoV used to dilute pesticides may be an important source of infectious hNoV in fresh produce chains. The application of pesticides may therefore not only be a chemical hazard, but also a microbiological hazard for public health. The inclusion of antiviral substances in reconstituted pesticides may be appropriate to reduce the virological health risk posed by the application of pesticides. Copyright © 2012 Elsevier B.V. All rights reserved.","title":"Persistence of human norovirus in reconstituted pesticides--pesticide application as a possible source of viruses in fresh produce chains."},{"docid":"MED-4131","text":"In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.","title":"Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens."},{"docid":"MED-2744","text":"Homicide disproportionately affects persons aged 10-24 years in the United States and consistently ranks in the top three leading causes of death in this age group, resulting in approximately 4,800 deaths and an estimated $9 billion in lost productivity and medical costs in 2010. To investigate trends in homicide among persons aged 10-24 years for the period 1981-2010, CDC analyzed National Vital Statistics System data on deaths caused by homicide of persons in this age group and examined trends by sex, age, race/ethnicity, and mechanism of injury. This report describes the results of that analysis, which indicated that homicide rates varied substantially during the study period, with a sharp rise from 1985 to 1993 followed by a decline that has slowed since 1999. During the period 2000-2010, rates declined for all groups, although the decline was significantly slower for males compared with females and for blacks compared with Hispanics and persons of other racial/ethnic groups. By mechanism of injury, the decline for firearm homicides from 2000 to 2010 was significantly slower than for nonfirearm homicides. The homicide rate among persons aged 10-24 years in 2010 was 7.5 per 100,000, the lowest in the 30-year study period. Primary prevention strategies remain critical, particularly among groups at increased risk for homicide.","title":"Homicide rates among persons aged 10-24 years - United States, 1981-2010."},{"docid":"MED-2745","text":"The current study was undertaken to acquire data on contamination of chicken parts with Salmonella at retail and to acquire data on cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation. Whole raw chickens (n = 31) were obtained from local retail stores and cut into two wings, two breasts without skin or bones, two thighs, and two drumsticks. Data for cross-contamination were obtained by cutting up a sterile, cooked chicken breast with the same board and knife used to cut up the raw chicken. The board, knife, and latex gloves used by the food handler were not rinsed or washed before cutting up the sterile, cooked chicken breast, thus providing a worst-case scenario for cross-contamination. Standard curves for the concentration of Salmonella bacteria in 400 ml of buffered peptone water after 6 h of incubation of chicken parts as a function of the initial log number of Salmonella bacteria inoculated onto chicken parts were developed and used to enumerate Salmonella bacteria. Standard curves were not affected by the type of chicken part but did differ (P < 0.05) among the five isolates of Salmonella examined. Consequently, Salmonella bacteria were enumerated on naturally contaminated chicken parts using a standard curve developed with the serotype of Salmonella that was isolated from the original sample. The prevalence of contamination was 3 % (4 of 132), whereas the incidence of cross-contamination was 1.8 % (1 of 57). The positive chicken parts were a thigh from chicken 4, which contained 3 CFU of Salmonella enterica serotype Kentucky, and both wings, one thigh, and one cooked breast portion from chicken 15, which all contained 1 CFU of serotype 8,20:-:z(6). These results indicated that the poultry industry is providing consumers in the studied area with chicken that has a low prevalence and low number of Salmonella bacteria at retail and that has a low incidence and low level of cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation under a worst-case scenario.","title":"Initial contamination of chicken parts with Salmonella at retail and cross-contamination of cooked chicken with Salmonella from raw chicken during ..."},{"docid":"MED-2736","text":"Campylobacter represents the leading cause of gastroenteritis in Europe. Campylobacteriosis is mainly due to C. jejuni and C. coli. Poultry meat is the main source of contamination, and cross-contaminations in the consumer's kitchen appear to be the important route for exposure. The aim of this study was to examine the transfer of Campylobacter from naturally contaminated raw poultry products to a cooked chicken product via the cutting board and to determine the characteristics of the involved isolates. This study showed that transfer occurred in nearly 30% of the assays and that both the C. jejuni and C. coli species were able to transfer. Transfer seems to be linked to specific isolates: some were able to transfer during separate trials while others were not. No correlation was found between transfer and adhesion to inert surfaces, but more than 90% of the isolates presented moderate or high adhesion ability. All tested isolates had the ability to adhere and invade Caco-2 cells, but presented high variability between isolates. Our results highlighted the occurrence of Campylobacter cross-contamination via the cutting board in the kitchen. Moreover, they provided new interesting data to be considered in risk assessment studies. Copyright © 2013 Elsevier B.V. All rights reserved.","title":"Characterization of Campylobacter spp. transferred from naturally contaminated chicken legs to cooked chicken slices via a cutting board."},{"docid":"MED-2741","text":"Overcrowding stress is a reality in the poultry industry. Chickens exposed to long-term stressful situations present a reduction of welfare and immunosuppression. We designed this experiment to analyse the effects from overcrowding stress of 16 birds/m(2) on performance parameters, serum corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA and IgG levels, intestinal integrity, macrophage activity and experimental Salmonella Enteritidis invasion. The results of this study indicate that overcrowding stress decreased performance parameters, induced enteritis and decreased macrophage activity and the relative bursa weight in broiler chickens. When the chickens were similarly stressed and infected with Salmonella Enteritidis, there was an increase in feed conversion and a decrease in plasma IgG levels in the stressed and Salmonella-infected birds. We observed moderate enteritis throughout the duodenum of chickens stressed and infected with Salmonella. The overcrowding stress decreased the macrophage phagocytosis intensity and increased Salmonella Enteritidis counts in the livers of birds challenged with the pathogenic bacterium. Overcrowding stress via the hypothalamic-pituitary-adrenal axis that is associated with an increase in corticosterone and enteritis might influence the quality of the intestinal immune barrier and the integrity of the small intestine. This effect allowed pathogenic bacteria to migrate through the intestinal mucosa, resulting in inflammatory infiltration and decreased nutrient absorption. The data strengthen the hypothesis that control of the welfare of chickens and avoidance of stress from overcrowding in poultry production are relevant factors for the maintenance of intestinal integrity, performance and decreased susceptibility to Salmonella infection.","title":"Overcrowding stress decreases macrophage activity and increases Salmonella Enteritidis invasion in broiler chickens."},{"docid":"MED-2742","text":"A national telephone survey was conducted of 1,620 randomly selected U.S. residents who spoke English, were at least 18 years old, and resided in households with kitchen facilities. Respondents were interviewed about their recognition of foodborne pathogens, foods at risk for transmitting infection, knowledge of safe food handling, and food-handling practices. One-third of the respondents who prepared meals reported unsafe food hygiene practices: e.g., they did not wash hands or take precautions to prevent cross-contamination from raw meat. Unsafe practices were reported more often by men, adults 18 to 29 years of age, and occasional food preparers than by women, persons 30 years old or older, and frequent food preparers. Respondents who identified a food vehicle for Salmonella spp. were more likely to report washing their hands and cleaning cutting boards after preparing raw meat and poultry. The results raise concerns about consumer food-handling practices. The influence of food safety training, food-handling experience, and age on food-handling practices should be studied further. Awareness of a food vehicle for Salmonella spp., for example, may indicate knowledge of the etiology of foodborne disease that promotes safe food handling. Understanding the factors associated with safe food handling will assist in development of effective safe-food instruction programs.","title":"Consumer knowledge of foodborne microbial hazards and food-handling practices."},{"docid":"MED-4672","text":"Neurocysticercosis cases were identified in 1991 in an Orthodox Jewish community. Transmission was linked to tapeworm-infected immigrant housekeepers from countries where Taenia solium is endemic. To evaluate the extent of and risks for locally acquired cysticercosis, a seroprevalence survey was conducted in 9% of the households in this community. Cysticercosis antibodies were detected in 23 (1.3%) of 1,789 persons from 612 families. All 23 seropositive persons were asymptomatic, and no intracerebral lesions were found for the 21 seropositive persons who underwent brain imaging. Seropositivity was associated with female sex (relative risk [RR] = 2.45, P = 0.049), hiring a domestic worker for child care duties (RR = 3.79, P = 0.05), and with employees from Central America (RR = 2.70, P = 0.0001). Exposure to T. solium in this community is unexpectedly high. Widespread employment of domestic workers from endemic regions and high employee turnover contributes to exposure risk.","title":"Seroprevalence of cysticercosis in an Orthodox Jewish community."},{"docid":"MED-2673","text":"Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.","title":"Determination of microbial transglutaminase in meat and meat products."},{"docid":"MED-2749","text":"Noroviruses are the leading cause of foodborne illness in the United States. To better guide interventions, we analyzed 2,922 foodborne disease outbreaks for which norovirus was the suspected or confirmed cause, which had been reported to the Foodborne Disease Outbreak Surveillance System of the Centers for Disease Control and Prevention during 2001–2008. On average, 365 foodborne norovirus outbreaks were reported annually, resulting in an estimated 10,324 illnesses, 1,247 health care provider visits, 156 hospitalizations, and 1 death. In 364 outbreaks attributed to a single commodity, leafy vegetables (33%), fruits/nuts (16%), and mollusks (13%) were implicated most commonly. Infected food handlers were the source of 53% of outbreaks and may have contributed to 82% of outbreaks. Most foods were likely contaminated during preparation and service, except for mollusks, and occasionally, produce was contaminated during production and processing. Interventions to reduce the frequency of foodborne norovirus outbreaks should focus on food workers and production of produce and shellfish.","title":"Epidemiology of Foodborne Norovirus Outbreaks, United States, 2001–2008"},{"docid":"MED-4136","text":"BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.","title":"Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10..."},{"docid":"MED-3884","text":"Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to beta-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen.","title":"The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective."},{"docid":"MED-2746","text":"Foods prepared in the kitchen can become cross-contaminated with Campylobacter by contacting raw products, particularly skinned poultry. We measured the percent transfer rate from naturally contaminated poultry legs purchased in supermarkets. Transfer of Campylobacter from skin (n = 43) and from meat (n = 12) to high-density polyethylene cutting board surfaces was quantitatively assessed after contact times of 1 and 10 min. The percent transfer rate was defined as the ratio between the number of Campylobacter cells counted on the cutting board surface and the initial numbers of Campylobacter naturally present on the skin (i.e., the sum of Campylobacter cells on the skin and board). Qualitative transfer occurred in 60.5% (95% confidence interval, 45.5 to 75.4) of the naturally contaminated legs studied and reached 80.6% (95% confidence interval, 63.0 to 98.2) in the subpopulation of legs that were in contact with the surface for 10 min. The percent transfer rate varied from 5 x 10(-2)% to 35.7% and was observed as being significantly different (Kruskall-Wallis test, P < 0.025) and inversely related to the initial counts on poultry skin. This study provides quantitative data describing the evolution of the proportion of Campylobacter organisms transferred from naturally contaminated poultry under kitchen conditions. We emphasize the linear relationship between the initial load of Campylobacter on the skin and the value of the percent transfer rate. This work confirms the need for modeling transfer as a function of initial load of Campylobacter on leg skin, the weight of poultry pieces, and the duration of contact between the skin and surface.","title":"Campylobacter transfer from naturally contaminated chicken thighs to cutting boards is inversely related to initial load."},{"docid":"MED-2743","text":"In June 2012, the Oregon Health Authority and the Washington State Department of Health noted an increase in the number of Salmonella enterica serotype Heidelberg clinical isolates sharing an identical pulsed-field gel electrophoresis (PFGE) pattern. In 2004, this pattern had been linked to chicken from Foster Farms by the Washington State Department of Health; preliminary 2012 interviews with infected persons also indicated exposure to Foster Farms chicken. On August 2, 2012, CDC's PulseNet* detected a cluster of 19 Salmonella Heidelberg clinical isolates matching the outbreak pattern. This report summarizes the investigation by CDC, state and local health departments, the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS), and the Food and Drug Administration (FDA) and reinforces the importance of safe food handling to prevent illness. A total of 134 cases from 13 states were identified, including 33 patients who were hospitalized. This multifaceted investigation used standard epidemiologic and laboratory data along with patient shopper card purchase information, and PFGE data from the retail meat component of the National Antimicrobial Resistance Monitoring System (NARMS)†, a relatively novel tool in outbreak investigation, to link the outbreak strain to chicken from Foster Farms.","title":"Outbreak of Salmonella Heidelberg infections linked to a single poultry producer -- 13 states, 2012-2013."},{"docid":"MED-3889","text":"Contamination of retail chicken meat by Extended Spectrum Beta-Lactamase (ESBL) producing bacteria likely contributes to the increasing incidence of infections with these bacteria in humans. This study aimed to compare the prevalence and load of ESBL positive isolates between organic and conventional retail chicken meat samples, and to compare the distribution of ESBL genes, strain genotypes and co-resistance. In 2010, 98 raw chicken breasts (n=60 conventional; n=38 organic) were collected from 12 local stores in the Netherlands. Prevalence of ESBL producing micro-organisms was 100% on conventional and 84% on organic samples (p<0.001). Median loads of ESBL producing micro-organisms were 80 (range <20-1360) in conventional, and <20 (range 0-260) CFU/25 g in organic samples (p=0.001). The distribution of ESBL genes in conventional samples and organic samples was 42% versus 56%, respectively (N.S.), for CTX-M-1, 20% versus 42% (N.S.) for TEM-52, and 23% versus 3% (p<0.001) for SHV-12. CTX-M-2 (7%), SHV-2 (5%) and TEM-20 (3%) were exclusively found in conventional samples. Co-resistance rates of ESBL positive isolates were not different between conventional and organic samples (co-trimoxazole 56%, ciprofloxacin 14%, and tobramycin 2%), except for tetracycline, 73% and 46%, respectively, p<0.001). Six of 14 conventional meat samples harbored 4 MLST types also reported in humans and 5 of 10 organic samples harbored 3 MLST types also reported in humans (2 ST10, 2 ST23, ST354). In conclusion, the majority of organic chicken meat samples were also contaminated with ESBL producing E. coli, and the ESBL genes and strain types were largely the same as in conventional meat samples. Copyright © 2011 Elsevier B.V. All rights reserved.","title":"Comparison of ESBL contamination in organic and conventional retail chicken meat."},{"docid":"MED-1983","text":"Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has developed resistance to beta-lactam antibiotics and has been isolated at low population numbers in retail meat products. The objectives of this study were to estimate the potential transfer of MRSA from contaminated retail pork products to food contact surfaces and to estimate the potential for human exposure to MRSA by contact with those contaminated surfaces. Pork loins, bacon, and fresh pork sausage were inoculated with a four-strain mixed MRSA culture over a range of populations from approximately 4 to 8 log, vacuum packaged, and stored for 2 weeks at 5°C to simulate normal packaging and distribution. Primary transfer was determined by placing inoculated products on knife blades, cutting boards, and a human skin model (pork skin) for 5 min. Secondary transfer was determined by placing an inoculated product on the contact surface, removing it, and then placing the secondary contact surface on the initial contact surface. A pork skin model was used to simulate transfer to human skin by placing it into contact with the contact surface. The percentages of transfer for primary transfer from the inoculated products to the cutting board ranged from 39 to 49%, while the percentages of transfer to the knife ranged from 17 to 42%. The percentages of transfer from the inoculated products to the pork skin ranged from 26 to 36%. The secondary transfer percentages ranged from 2.2 to 5.2% across all products and contact surfaces. Statistical analysis showed no significant differences in the amounts of transfer between transfer surfaces and across cell concentrations.","title":"Transfer of methicillin-resistant Staphylococcus aureus from retail pork products onto food contact surfaces and the potential for consumer exposure."},{"docid":"MED-1979","text":"Methicillin-resistant Staphylococcus aureus (MRSA) is a major global public health concern and could be a food safety issue. Recurrent reports have documented that pig herds are an important reservoir for MRSA, specifically the livestock-associated sequence type 398. The high prevalence of MRSA in pig primary production facilities and the frequent detection of MRSA of the same types in pork and pig meat products raise the question of underlying mechanisms behind the introduction and transmission of MRSA along the pork production chain. A comprehensive review of current literature on the worldwide presence of livestock-associated MRSA in various steps of the pork production chain revealed that the slaughter process plays a decisive role in MRSA transmission from farm to fork. Superficial heat treatments such as scalding and flaming during the slaughter process can significantly reduce the burden of MRSA on the carcasses. However, recontamination with MRSA might occur via surface treating machinery, as a result of fecal contamination at evisceration, or via increased human handling during meat processing. By optimizing processes for carcass decontamination and avoiding recontamination by effective cleaning and personal hygiene management, transmission of MRSA from pig to pork can be minimized.","title":"From pig to pork: methicillin-resistant Staphylococcus aureus in the pork production chain."},{"docid":"MED-5169","text":"Fourteen sites evenly divided between the household kitchen and bathroom were monitored on a weekly basis for numbers of faecal coliforms, total coliforms and heterotrophic plate count bacteria. The first 10 weeks comprised the control period, hypochlorite cleaning products were introduced into the household during the second 10 weeks, and a strict cleaning regimen using hypochlorite products was implemented during the last 10 weeks. The kitchen was more heavily contaminated than the bathroom, with the toilet seat being the least contaminated site. The highest concentrations of all three classes of bacteria were found on sites that were moist environments and/or were frequently touched; these included the sponge/dishcloth, the kitchen sink drain area, the bath sink drain area, and the kitchen faucet handle(s). The implementation of a cleaning regimen with common household hypochlorite products resulted in the significant reduction of all three classes of bacteria at these four sites and other household sites.","title":"Reduction of faecal coliform, coliform and heterotrophic plate count bacteria in the household kitchen and bathroom by disinfection with hypochlori..."},{"docid":"MED-1982","text":"In a study of 40 methicillin-resistant Staphylococcus aureus (MRSA) carriers, hand contamination was equally likely after contact with commonly examined skin sites and commonly touched environmental surfaces in patient rooms (40% vs 45%). These findings suggest that contaminated surfaces may be an important source of MRSA transmission.","title":"Contamination of hands with methicillin-resistant Staphylococcus aureus after contact with environmental surfaces and after contact with the skin o..."},{"docid":"MED-1978","text":"Context Nearly 80% of antibiotics in the United States are sold for use in livestock feeds. The manure produced by these livestock contains antibiotic-resistant bacteria, resistance genes, and antibiotics, and is subsequently applied to crop fields where it may put community members at risk for antibiotic-resistant infections. Objective To assess the association between individual exposure to swine and dairy/veal industrial agriculture and risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Design, Setting, and Participants A population-based, nested case-control study of Geisinger primary care patients in Pennsylvania from 2005–2010. Incident MRSA cases were identified using electronic health records, classified as community-associated or healthcare-associated, and frequency-matched to randomly selected controls and patients with skin and soft tissue infection. Nutrient management plans were used to create two exposure variables: seasonal crop field manure application and number of livestock at the operation. In a sub-study we collected 200 isolates from patients stratified by location of diagnosis and proximity to livestock operations. Main outcome measures Community-associated MRSA, healthcare associated-MRSA, and skin and soft tissue infection status (with no history of MRSA) compared to controls. Results From 446,480 patients, 1539 community-associated MRSA, 1335 healthcare-associated MRSA, 2895 skin and soft tissue infection cases, and 2914 controls were included. After adjustment for MRSA risk factors, the highest quartile of swine crop field exposure was significantly associated with community-associated MRSA, healthcare-associated MRSA, and skin and soft tissue infection case status (adjusted odds ratio, 1.38 [95% CI, 1.13–1.69], 1.30 [95% CI, 1.05–1.61], and 1.37 [95% CI, 1.18–1.60], respectively); and there was a trend of increasing odds across quartiles for each outcome (all P for trend ≤0.01). There were similar but weaker associations of swine operations with community-associated MRSA and skin and soft tissue infection. Molecular testing of 200 isolates identified 31 unique spa types, none of which corresponded to CC398, but some have been previously found in swine. Conclusion Proximity to swine manure application to crop fields and livestock operations each was associated with MRSA and skin and soft tissue infection. These findings contribute to the growing concern about the potential public health impacts of high-density livestock production.","title":"High-density livestock operations, crop field application of manure, and risk of community-associated methicillin-resistant Staphylococcus aureus infection, Pennsylvania, USA"},{"docid":"MED-1977","text":"Reports have documented colonization of swine in Europe, North America and more recently in China with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA). Contamination of pig farmers, veterinarians and abattoir workers with these strains has been observed. However, although contamination levels of 10% of retail pork were reported from the Netherlands and Canada, there are limited data of contamination rates of workers handling raw meat. We investigated the rates of MRSA contamination of local butchers working in wet markets, where recently slaughtered pigs are cut up. Nasal swabs collected from 300 pork butchers at markets throughout Hong Kong were enriched in brain heart infusion broth with 5% salt and cultured on MRSASelect(®) . Isolates were confirmed as Staphylococcus aureus and susceptibility testing performed. The presence of mecA was confirmed, SCCmec and spa type determined and relatedness investigated by PFGE. Subjects completed a questionnaire on MRSA carriage risk factors. Seventeen samples (5.6%) yielded MRSA, 15 harbouring SCCmec IVb. Ten strains were t899 (CC9), previously reported from local pig carcasses. Five strains were healthcare associated: SCCmec type II, t701(CC6), colonizing two subjects at the same establishment, and single isolates of t008 (CC8), t002 (CC5) and t123 (CC45). The remaining isolates were t359 (CC97), previously reported from buffaloes, and t375 (CC5), reported from bovine milk. None of these butchers reported recent hospitalization or a healthcare worker in the family. Two had recently received antibiotics, one for a skin infection. Four reported wound infections within the last year. All were exposed to meat for >9 h per day. Carriage of MRSA was higher in butchers than in the general community. Although five strains were probably of healthcare origin, the high incidence of t899 (CC9) suggests that cross-contamination from pork occurs frequently. Washing of hands after touching raw pork is advised. © 2012 Blackwell Verlag GmbH.","title":"Colonization of butchers with livestock-associated methicillin-resistant Staphylococcus aureus."},{"docid":"MED-2747","text":"Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998–2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.","title":"Attribution of Foodborne Illnesses, Hospitalizations, and Deaths to Food Commodities by using Outbreak Data, United States, 1998–2008"},{"docid":"MED-3880","text":"A common approach to reducing microbial contamination has been the implementation of a Hazard Analysis and Critical Control Point (HACCP) program to prevent or reduce contamination during production. One example is the Pathogen Reduction HACCP program implemented by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). This program consisted of a staged implementation between 1996 and 2000 to reduce microbial contamination on meat and poultry products. Of the commodities regulated by FSIS, one of the largest observed reductions was for Salmonella contamination on broiler chicken carcasses. Nevertheless, how this reduction might have influenced the total number of salmonellosis cases in the United States has not been assessed. This study incorporates information from public health surveillance and surveys of the poultry slaughter industry into a model that estimates the number of broiler-related salmonellosis cases through time. The model estimates that-following the 56% reduction in the proportion of contaminated broiler carcasses observed between 1995 and 2000-approximately 190,000 fewer annual salmonellosis cases (attributed to broilers) occurred in 2000 compared with 1995. The uncertainty bounds for this estimate range from approximately 37,000 to 500,000 illnesses. Estimated illnesses prevented, due to the more modest reduction in contamination of 13% between 2000 and 2007, were not statistically significant. An analysis relating the necessary magnitude of change in contamination required for detection via human surveillance also is provided.","title":"Estimating changes in public health following implementation of hazard analysis and critical control point in the United States broiler slaughter i..."},{"docid":"MED-2740","text":"To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.","title":"FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States."},{"docid":"MED-2672","text":"To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.","title":"Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks."},{"docid":"MED-3886","text":"The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.","title":"Mechanisms of antimicrobial resistance in bacteria."},{"docid":"MED-3887","text":"Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.","title":"Food Animals and Antimicrobials: Impacts on Human Health"},{"docid":"MED-3888","text":"BACKGROUND: Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices. METHODS: We analyzed the incidence of human SE infection during 1996-2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with rates of SE isolation from processed chickens and egg products; shell eggs are not routinely tested. We also compared molecular subtyping patterns of SE isolated from humans and chickens. RESULTS: Since the period 1996-1999, the incidence of human SE infection in FoodNet has increased by 44%. This change is mirrored in passive national surveillance data. The greatest relative increases were in young children, older adults, and FoodNet sites in the southern United States. The proportion of patients with SE infection who reported recent international travel has decreased in recent years, whereas the proportion of chickens from which SE was isolated has increased. Similar molecular subtypes of SE are commonly isolated from humans and chickens. CONCLUSIONS: Most SE infections in the United States are acquired from domestic sources, and the problem is growing. Chicken and eggs are likely major sources of SE. Continued close attention to surveillance data is needed to monitor the impact of recent regulatory control measures.","title":"Salmonella enterica serotype Enteritidis: increasing incidence of domestically acquired infections."},{"docid":"MED-2671","text":"Microbiology of meats has been a subject of great concern in food science and public health in recent years. Although many articles have been devoted to the microbiology of beef, pork, and poultry meats, much less has been written about microbiology of lamb meat and even less on restructured lamb meat. This article presents data on microbiology and shelf-life of fresh lamb meat; restructured meat products, restructured lamb meat products, bacteriology of restructured meat products, and important foodborne pathogens such as Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential use of sodium and potassium lactates to control foodborne pathogens in meats and restructured lamb meat is reviewed This article should be of interest to all meat scientists, food scientists, and public health microbiologists who are concerned with the safety of meats in general and lamb meat in particular.","title":"Microbiology of fresh and restructured lamb meat: a review."},{"docid":"MED-2738","text":"Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers.","title":"Trends in U.S. consumers' safe handling and consumption of food and their risk perceptions, 1988 through 2010."},{"docid":"MED-3882","text":"Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) β-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n=18), food animals at slaughter (n=16), and retail meats (n=13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion.","title":"Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and h..."},{"docid":"MED-4132","text":"Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.","title":"Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic..."},{"docid":"MED-3891","text":"Escherichia coli isolates were recovered from the National Antimicrobial Resistance Monitoring System retail meat program and examined for antimicrobial susceptibility. Retail meat samples (n = 11,921) from four U.S. states collected during 2002 to 2008, consisting of 2,988 chicken breast, 2,942 ground turkey, 2,991 ground beef, and 3,000 pork chop samples, were analyzed. A total of 8,286 E. coli isolates were recovered. The greatest numbers of samples contaminated with the organism were chicken (83.5%) and turkey (82.0%), followed by beef (68.9%) and pork (44.0%). Resistance was most common to tetracycline (50.3%), followed by streptomycin (34.6%), sulfamethoxazole-sulfisoxazole (31.6%), ampicillin (22.5%), gentamicin (18.6%), kanamycin (8.4%), amoxicillin-clavulanic acid (6.4%), and cefoxitin (5.2%). Less than 5% of the isolates had resistance to trimethoprim, ceftriaxone, ceftiofur, nalidixic acid, chloramphenicol, and ciprofloxacin. All isolates were susceptible to amikacin. Compared to beef and pork isolates, the poultry meat isolates had a greater percentage of resistance to all tested drugs, with the exception of chloramphenicol, to which pork isolates had the most resistance. More than half of the turkey isolates (56%) were resistant to multidrugs (≥3 classes) compared to 38.9% of chicken, 17.3% of pork, and 9.3% of beef isolates. The blaCMY gene was present in all ceftriaxone- and ceftiofur-resistant isolates. The cmlA, flo, and catI genes were present in 45%, 43%, and 40% of chloramphenicol-resistant isolates, respectively. Most nalidixic acid-resistant isolates (98.5%) had a gyrA mutation in S83 or D87 or both, whereas only 6.7% had a parC mutation in either S80 or E84. The results showed that E. coli was commonly present in the retail meats, and antimicrobial resistance profiles differed according to the animal origin of the isolates.","title":"Comparison of the Prevalences and Antimicrobial Resistances of Escherichia coli Isolates from Different Retail Meats in the United States, 2002 to 2008"},{"docid":"MED-3892","text":"Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.","title":"Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model"}],"string":"[\n {\n \"docid\": \"MED-1981\",\n \"text\": \"The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Antibiotic resistance-the need for global solutions.\"\n },\n {\n \"docid\": \"MED-1980\",\n \"text\": \"Enterobacterial strains producing clavulanic-acid-inhibited extended-spectrum β-lactamases (ESBLs) are increasingly reported worldwide. Conventional detection of ESBL production remains time-consuming (24 to 48 h). Therefore, the ESBL NDP (Nordmann/Dortet/Poirel) test was developed for a rapid identification of ESBLs in Enterobacteriaceae. This biochemical test was based on the in vitro detection of a cephalosporin (cefotaxime) hydrolysis that is inhibited by tazobactam addition. The ESBL activity was evidenced by a color change (red to yellow) of a pH indicator (red phenol) due to carboxyl-acid formation resulting from cefotaxime hydrolysis that was reversed by addition of tazobactam (positive test). The ESBL NDP test was applied to cultured strains (215 ESBL producers and 40 ESBL nonproducers). Its sensitivity and specificity were 92.6% and 100%, respectively. Its sensitivity (100%) was excellent for detection of CTX-M producers. A few ESBL producers (n = 16) that remained susceptible to cefotaxime were not detected. The test was also evaluated on spiked blood cultures and showed excellent sensitivity and specificity (100% for both). The test was rapid (less than 1 h) and cost-effective. It can be implemented in any health care facility and is well adapted for infection control purposes in particular.\",\n \"title\": \"Rapid Detection of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae\"\n },\n {\n \"docid\": \"MED-2748\",\n \"text\": \"The consumption of fresh produce is frequently associated with outbreaks of human norovirus (hNoV) disease. To prevent the contamination of fresh produce with hNoV, knowledge of the possible introduction sources of the viruses, such as water, is needed to be able to implement appropriate and efficient preventive measures. Contaminated water used to reconstitute pesticides could be a relevant source of infectious hNoV, determined by the initial level of virus contamination and the persistence of these viruses in reconstituted pesticides. We studied the persistence of hNoV GI.4, hNoV GII.4 and murine norovirus (MNV-1), the only culturable norovirus, in eight different pesticides after 0 and 2h. Virus concentrations were determined by reverse transcriptase PCR, and infectivity of MNV-1 was determined by endpoint dilutions followed by maximum likelihood estimations. MNV-1 was found to remain infectious in seven of the eight tested pesticides at the highest concentration applied in practice. In the presence of the insecticide Vertimec, MNV-1 infectivity decreased rapidly with a 1.9 log(10)-unit reduction at timepoint T(0). Also, the concentration of NoV GI.4 RNA decreased considerably with a 1.7 log(10)-unit reduction; whereas the detected PCR fragment of hNoV GII.4 remained stable. Assuming a similar persistence of infectious MNV-1 and hNoV we can conclude that water containing hNoV used to dilute pesticides may be an important source of infectious hNoV in fresh produce chains. The application of pesticides may therefore not only be a chemical hazard, but also a microbiological hazard for public health. The inclusion of antiviral substances in reconstituted pesticides may be appropriate to reduce the virological health risk posed by the application of pesticides. Copyright © 2012 Elsevier B.V. All rights reserved.\",\n \"title\": \"Persistence of human norovirus in reconstituted pesticides--pesticide application as a possible source of viruses in fresh produce chains.\"\n },\n {\n \"docid\": \"MED-4131\",\n \"text\": \"In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.\",\n \"title\": \"Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens.\"\n },\n {\n \"docid\": \"MED-2744\",\n \"text\": \"Homicide disproportionately affects persons aged 10-24 years in the United States and consistently ranks in the top three leading causes of death in this age group, resulting in approximately 4,800 deaths and an estimated $9 billion in lost productivity and medical costs in 2010. To investigate trends in homicide among persons aged 10-24 years for the period 1981-2010, CDC analyzed National Vital Statistics System data on deaths caused by homicide of persons in this age group and examined trends by sex, age, race/ethnicity, and mechanism of injury. This report describes the results of that analysis, which indicated that homicide rates varied substantially during the study period, with a sharp rise from 1985 to 1993 followed by a decline that has slowed since 1999. During the period 2000-2010, rates declined for all groups, although the decline was significantly slower for males compared with females and for blacks compared with Hispanics and persons of other racial/ethnic groups. By mechanism of injury, the decline for firearm homicides from 2000 to 2010 was significantly slower than for nonfirearm homicides. The homicide rate among persons aged 10-24 years in 2010 was 7.5 per 100,000, the lowest in the 30-year study period. Primary prevention strategies remain critical, particularly among groups at increased risk for homicide.\",\n \"title\": \"Homicide rates among persons aged 10-24 years - United States, 1981-2010.\"\n },\n {\n \"docid\": \"MED-2745\",\n \"text\": \"The current study was undertaken to acquire data on contamination of chicken parts with Salmonella at retail and to acquire data on cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation. Whole raw chickens (n = 31) were obtained from local retail stores and cut into two wings, two breasts without skin or bones, two thighs, and two drumsticks. Data for cross-contamination were obtained by cutting up a sterile, cooked chicken breast with the same board and knife used to cut up the raw chicken. The board, knife, and latex gloves used by the food handler were not rinsed or washed before cutting up the sterile, cooked chicken breast, thus providing a worst-case scenario for cross-contamination. Standard curves for the concentration of Salmonella bacteria in 400 ml of buffered peptone water after 6 h of incubation of chicken parts as a function of the initial log number of Salmonella bacteria inoculated onto chicken parts were developed and used to enumerate Salmonella bacteria. Standard curves were not affected by the type of chicken part but did differ (P < 0.05) among the five isolates of Salmonella examined. Consequently, Salmonella bacteria were enumerated on naturally contaminated chicken parts using a standard curve developed with the serotype of Salmonella that was isolated from the original sample. The prevalence of contamination was 3 % (4 of 132), whereas the incidence of cross-contamination was 1.8 % (1 of 57). The positive chicken parts were a thigh from chicken 4, which contained 3 CFU of Salmonella enterica serotype Kentucky, and both wings, one thigh, and one cooked breast portion from chicken 15, which all contained 1 CFU of serotype 8,20:-:z(6). These results indicated that the poultry industry is providing consumers in the studied area with chicken that has a low prevalence and low number of Salmonella bacteria at retail and that has a low incidence and low level of cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation under a worst-case scenario.\",\n \"title\": \"Initial contamination of chicken parts with Salmonella at retail and cross-contamination of cooked chicken with Salmonella from raw chicken during ...\"\n },\n {\n \"docid\": \"MED-2736\",\n \"text\": \"Campylobacter represents the leading cause of gastroenteritis in Europe. Campylobacteriosis is mainly due to C. jejuni and C. coli. Poultry meat is the main source of contamination, and cross-contaminations in the consumer's kitchen appear to be the important route for exposure. The aim of this study was to examine the transfer of Campylobacter from naturally contaminated raw poultry products to a cooked chicken product via the cutting board and to determine the characteristics of the involved isolates. This study showed that transfer occurred in nearly 30% of the assays and that both the C. jejuni and C. coli species were able to transfer. Transfer seems to be linked to specific isolates: some were able to transfer during separate trials while others were not. No correlation was found between transfer and adhesion to inert surfaces, but more than 90% of the isolates presented moderate or high adhesion ability. All tested isolates had the ability to adhere and invade Caco-2 cells, but presented high variability between isolates. Our results highlighted the occurrence of Campylobacter cross-contamination via the cutting board in the kitchen. Moreover, they provided new interesting data to be considered in risk assessment studies. Copyright © 2013 Elsevier B.V. All rights reserved.\",\n \"title\": \"Characterization of Campylobacter spp. transferred from naturally contaminated chicken legs to cooked chicken slices via a cutting board.\"\n },\n {\n \"docid\": \"MED-2741\",\n \"text\": \"Overcrowding stress is a reality in the poultry industry. Chickens exposed to long-term stressful situations present a reduction of welfare and immunosuppression. We designed this experiment to analyse the effects from overcrowding stress of 16 birds/m(2) on performance parameters, serum corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA and IgG levels, intestinal integrity, macrophage activity and experimental Salmonella Enteritidis invasion. The results of this study indicate that overcrowding stress decreased performance parameters, induced enteritis and decreased macrophage activity and the relative bursa weight in broiler chickens. When the chickens were similarly stressed and infected with Salmonella Enteritidis, there was an increase in feed conversion and a decrease in plasma IgG levels in the stressed and Salmonella-infected birds. We observed moderate enteritis throughout the duodenum of chickens stressed and infected with Salmonella. The overcrowding stress decreased the macrophage phagocytosis intensity and increased Salmonella Enteritidis counts in the livers of birds challenged with the pathogenic bacterium. Overcrowding stress via the hypothalamic-pituitary-adrenal axis that is associated with an increase in corticosterone and enteritis might influence the quality of the intestinal immune barrier and the integrity of the small intestine. This effect allowed pathogenic bacteria to migrate through the intestinal mucosa, resulting in inflammatory infiltration and decreased nutrient absorption. The data strengthen the hypothesis that control of the welfare of chickens and avoidance of stress from overcrowding in poultry production are relevant factors for the maintenance of intestinal integrity, performance and decreased susceptibility to Salmonella infection.\",\n \"title\": \"Overcrowding stress decreases macrophage activity and increases Salmonella Enteritidis invasion in broiler chickens.\"\n },\n {\n \"docid\": \"MED-2742\",\n \"text\": \"A national telephone survey was conducted of 1,620 randomly selected U.S. residents who spoke English, were at least 18 years old, and resided in households with kitchen facilities. Respondents were interviewed about their recognition of foodborne pathogens, foods at risk for transmitting infection, knowledge of safe food handling, and food-handling practices. One-third of the respondents who prepared meals reported unsafe food hygiene practices: e.g., they did not wash hands or take precautions to prevent cross-contamination from raw meat. Unsafe practices were reported more often by men, adults 18 to 29 years of age, and occasional food preparers than by women, persons 30 years old or older, and frequent food preparers. Respondents who identified a food vehicle for Salmonella spp. were more likely to report washing their hands and cleaning cutting boards after preparing raw meat and poultry. The results raise concerns about consumer food-handling practices. The influence of food safety training, food-handling experience, and age on food-handling practices should be studied further. Awareness of a food vehicle for Salmonella spp., for example, may indicate knowledge of the etiology of foodborne disease that promotes safe food handling. Understanding the factors associated with safe food handling will assist in development of effective safe-food instruction programs.\",\n \"title\": \"Consumer knowledge of foodborne microbial hazards and food-handling practices.\"\n },\n {\n \"docid\": \"MED-4672\",\n \"text\": \"Neurocysticercosis cases were identified in 1991 in an Orthodox Jewish community. Transmission was linked to tapeworm-infected immigrant housekeepers from countries where Taenia solium is endemic. To evaluate the extent of and risks for locally acquired cysticercosis, a seroprevalence survey was conducted in 9% of the households in this community. Cysticercosis antibodies were detected in 23 (1.3%) of 1,789 persons from 612 families. All 23 seropositive persons were asymptomatic, and no intracerebral lesions were found for the 21 seropositive persons who underwent brain imaging. Seropositivity was associated with female sex (relative risk [RR] = 2.45, P = 0.049), hiring a domestic worker for child care duties (RR = 3.79, P = 0.05), and with employees from Central America (RR = 2.70, P = 0.0001). Exposure to T. solium in this community is unexpectedly high. Widespread employment of domestic workers from endemic regions and high employee turnover contributes to exposure risk.\",\n \"title\": \"Seroprevalence of cysticercosis in an Orthodox Jewish community.\"\n },\n {\n \"docid\": \"MED-2673\",\n \"text\": \"Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.\",\n \"title\": \"Determination of microbial transglutaminase in meat and meat products.\"\n },\n {\n \"docid\": \"MED-2749\",\n \"text\": \"Noroviruses are the leading cause of foodborne illness in the United States. To better guide interventions, we analyzed 2,922 foodborne disease outbreaks for which norovirus was the suspected or confirmed cause, which had been reported to the Foodborne Disease Outbreak Surveillance System of the Centers for Disease Control and Prevention during 2001–2008. On average, 365 foodborne norovirus outbreaks were reported annually, resulting in an estimated 10,324 illnesses, 1,247 health care provider visits, 156 hospitalizations, and 1 death. In 364 outbreaks attributed to a single commodity, leafy vegetables (33%), fruits/nuts (16%), and mollusks (13%) were implicated most commonly. Infected food handlers were the source of 53% of outbreaks and may have contributed to 82% of outbreaks. Most foods were likely contaminated during preparation and service, except for mollusks, and occasionally, produce was contaminated during production and processing. Interventions to reduce the frequency of foodborne norovirus outbreaks should focus on food workers and production of produce and shellfish.\",\n \"title\": \"Epidemiology of Foodborne Norovirus Outbreaks, United States, 2001–2008\"\n },\n {\n \"docid\": \"MED-4136\",\n \"text\": \"BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.\",\n \"title\": \"Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10...\"\n },\n {\n \"docid\": \"MED-3884\",\n \"text\": \"Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to beta-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen.\",\n \"title\": \"The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective.\"\n },\n {\n \"docid\": \"MED-2746\",\n \"text\": \"Foods prepared in the kitchen can become cross-contaminated with Campylobacter by contacting raw products, particularly skinned poultry. We measured the percent transfer rate from naturally contaminated poultry legs purchased in supermarkets. Transfer of Campylobacter from skin (n = 43) and from meat (n = 12) to high-density polyethylene cutting board surfaces was quantitatively assessed after contact times of 1 and 10 min. The percent transfer rate was defined as the ratio between the number of Campylobacter cells counted on the cutting board surface and the initial numbers of Campylobacter naturally present on the skin (i.e., the sum of Campylobacter cells on the skin and board). Qualitative transfer occurred in 60.5% (95% confidence interval, 45.5 to 75.4) of the naturally contaminated legs studied and reached 80.6% (95% confidence interval, 63.0 to 98.2) in the subpopulation of legs that were in contact with the surface for 10 min. The percent transfer rate varied from 5 x 10(-2)% to 35.7% and was observed as being significantly different (Kruskall-Wallis test, P < 0.025) and inversely related to the initial counts on poultry skin. This study provides quantitative data describing the evolution of the proportion of Campylobacter organisms transferred from naturally contaminated poultry under kitchen conditions. We emphasize the linear relationship between the initial load of Campylobacter on the skin and the value of the percent transfer rate. This work confirms the need for modeling transfer as a function of initial load of Campylobacter on leg skin, the weight of poultry pieces, and the duration of contact between the skin and surface.\",\n \"title\": \"Campylobacter transfer from naturally contaminated chicken thighs to cutting boards is inversely related to initial load.\"\n },\n {\n \"docid\": \"MED-2743\",\n \"text\": \"In June 2012, the Oregon Health Authority and the Washington State Department of Health noted an increase in the number of Salmonella enterica serotype Heidelberg clinical isolates sharing an identical pulsed-field gel electrophoresis (PFGE) pattern. In 2004, this pattern had been linked to chicken from Foster Farms by the Washington State Department of Health; preliminary 2012 interviews with infected persons also indicated exposure to Foster Farms chicken. On August 2, 2012, CDC's PulseNet* detected a cluster of 19 Salmonella Heidelberg clinical isolates matching the outbreak pattern. This report summarizes the investigation by CDC, state and local health departments, the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS), and the Food and Drug Administration (FDA) and reinforces the importance of safe food handling to prevent illness. A total of 134 cases from 13 states were identified, including 33 patients who were hospitalized. This multifaceted investigation used standard epidemiologic and laboratory data along with patient shopper card purchase information, and PFGE data from the retail meat component of the National Antimicrobial Resistance Monitoring System (NARMS)†, a relatively novel tool in outbreak investigation, to link the outbreak strain to chicken from Foster Farms.\",\n \"title\": \"Outbreak of Salmonella Heidelberg infections linked to a single poultry producer -- 13 states, 2012-2013.\"\n },\n {\n \"docid\": \"MED-3889\",\n \"text\": \"Contamination of retail chicken meat by Extended Spectrum Beta-Lactamase (ESBL) producing bacteria likely contributes to the increasing incidence of infections with these bacteria in humans. This study aimed to compare the prevalence and load of ESBL positive isolates between organic and conventional retail chicken meat samples, and to compare the distribution of ESBL genes, strain genotypes and co-resistance. In 2010, 98 raw chicken breasts (n=60 conventional; n=38 organic) were collected from 12 local stores in the Netherlands. Prevalence of ESBL producing micro-organisms was 100% on conventional and 84% on organic samples (p<0.001). Median loads of ESBL producing micro-organisms were 80 (range <20-1360) in conventional, and <20 (range 0-260) CFU/25 g in organic samples (p=0.001). The distribution of ESBL genes in conventional samples and organic samples was 42% versus 56%, respectively (N.S.), for CTX-M-1, 20% versus 42% (N.S.) for TEM-52, and 23% versus 3% (p<0.001) for SHV-12. CTX-M-2 (7%), SHV-2 (5%) and TEM-20 (3%) were exclusively found in conventional samples. Co-resistance rates of ESBL positive isolates were not different between conventional and organic samples (co-trimoxazole 56%, ciprofloxacin 14%, and tobramycin 2%), except for tetracycline, 73% and 46%, respectively, p<0.001). Six of 14 conventional meat samples harbored 4 MLST types also reported in humans and 5 of 10 organic samples harbored 3 MLST types also reported in humans (2 ST10, 2 ST23, ST354). In conclusion, the majority of organic chicken meat samples were also contaminated with ESBL producing E. coli, and the ESBL genes and strain types were largely the same as in conventional meat samples. Copyright © 2011 Elsevier B.V. All rights reserved.\",\n \"title\": \"Comparison of ESBL contamination in organic and conventional retail chicken meat.\"\n },\n {\n \"docid\": \"MED-1983\",\n \"text\": \"Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has developed resistance to beta-lactam antibiotics and has been isolated at low population numbers in retail meat products. The objectives of this study were to estimate the potential transfer of MRSA from contaminated retail pork products to food contact surfaces and to estimate the potential for human exposure to MRSA by contact with those contaminated surfaces. Pork loins, bacon, and fresh pork sausage were inoculated with a four-strain mixed MRSA culture over a range of populations from approximately 4 to 8 log, vacuum packaged, and stored for 2 weeks at 5°C to simulate normal packaging and distribution. Primary transfer was determined by placing inoculated products on knife blades, cutting boards, and a human skin model (pork skin) for 5 min. Secondary transfer was determined by placing an inoculated product on the contact surface, removing it, and then placing the secondary contact surface on the initial contact surface. A pork skin model was used to simulate transfer to human skin by placing it into contact with the contact surface. The percentages of transfer for primary transfer from the inoculated products to the cutting board ranged from 39 to 49%, while the percentages of transfer to the knife ranged from 17 to 42%. The percentages of transfer from the inoculated products to the pork skin ranged from 26 to 36%. The secondary transfer percentages ranged from 2.2 to 5.2% across all products and contact surfaces. Statistical analysis showed no significant differences in the amounts of transfer between transfer surfaces and across cell concentrations.\",\n \"title\": \"Transfer of methicillin-resistant Staphylococcus aureus from retail pork products onto food contact surfaces and the potential for consumer exposure.\"\n },\n {\n \"docid\": \"MED-1979\",\n \"text\": \"Methicillin-resistant Staphylococcus aureus (MRSA) is a major global public health concern and could be a food safety issue. Recurrent reports have documented that pig herds are an important reservoir for MRSA, specifically the livestock-associated sequence type 398. The high prevalence of MRSA in pig primary production facilities and the frequent detection of MRSA of the same types in pork and pig meat products raise the question of underlying mechanisms behind the introduction and transmission of MRSA along the pork production chain. A comprehensive review of current literature on the worldwide presence of livestock-associated MRSA in various steps of the pork production chain revealed that the slaughter process plays a decisive role in MRSA transmission from farm to fork. Superficial heat treatments such as scalding and flaming during the slaughter process can significantly reduce the burden of MRSA on the carcasses. However, recontamination with MRSA might occur via surface treating machinery, as a result of fecal contamination at evisceration, or via increased human handling during meat processing. By optimizing processes for carcass decontamination and avoiding recontamination by effective cleaning and personal hygiene management, transmission of MRSA from pig to pork can be minimized.\",\n \"title\": \"From pig to pork: methicillin-resistant Staphylococcus aureus in the pork production chain.\"\n },\n {\n \"docid\": \"MED-5169\",\n \"text\": \"Fourteen sites evenly divided between the household kitchen and bathroom were monitored on a weekly basis for numbers of faecal coliforms, total coliforms and heterotrophic plate count bacteria. The first 10 weeks comprised the control period, hypochlorite cleaning products were introduced into the household during the second 10 weeks, and a strict cleaning regimen using hypochlorite products was implemented during the last 10 weeks. The kitchen was more heavily contaminated than the bathroom, with the toilet seat being the least contaminated site. The highest concentrations of all three classes of bacteria were found on sites that were moist environments and/or were frequently touched; these included the sponge/dishcloth, the kitchen sink drain area, the bath sink drain area, and the kitchen faucet handle(s). The implementation of a cleaning regimen with common household hypochlorite products resulted in the significant reduction of all three classes of bacteria at these four sites and other household sites.\",\n \"title\": \"Reduction of faecal coliform, coliform and heterotrophic plate count bacteria in the household kitchen and bathroom by disinfection with hypochlori...\"\n },\n {\n \"docid\": \"MED-1982\",\n \"text\": \"In a study of 40 methicillin-resistant Staphylococcus aureus (MRSA) carriers, hand contamination was equally likely after contact with commonly examined skin sites and commonly touched environmental surfaces in patient rooms (40% vs 45%). These findings suggest that contaminated surfaces may be an important source of MRSA transmission.\",\n \"title\": \"Contamination of hands with methicillin-resistant Staphylococcus aureus after contact with environmental surfaces and after contact with the skin o...\"\n },\n {\n \"docid\": \"MED-1978\",\n \"text\": \"Context Nearly 80% of antibiotics in the United States are sold for use in livestock feeds. The manure produced by these livestock contains antibiotic-resistant bacteria, resistance genes, and antibiotics, and is subsequently applied to crop fields where it may put community members at risk for antibiotic-resistant infections. Objective To assess the association between individual exposure to swine and dairy/veal industrial agriculture and risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Design, Setting, and Participants A population-based, nested case-control study of Geisinger primary care patients in Pennsylvania from 2005–2010. Incident MRSA cases were identified using electronic health records, classified as community-associated or healthcare-associated, and frequency-matched to randomly selected controls and patients with skin and soft tissue infection. Nutrient management plans were used to create two exposure variables: seasonal crop field manure application and number of livestock at the operation. In a sub-study we collected 200 isolates from patients stratified by location of diagnosis and proximity to livestock operations. Main outcome measures Community-associated MRSA, healthcare associated-MRSA, and skin and soft tissue infection status (with no history of MRSA) compared to controls. Results From 446,480 patients, 1539 community-associated MRSA, 1335 healthcare-associated MRSA, 2895 skin and soft tissue infection cases, and 2914 controls were included. After adjustment for MRSA risk factors, the highest quartile of swine crop field exposure was significantly associated with community-associated MRSA, healthcare-associated MRSA, and skin and soft tissue infection case status (adjusted odds ratio, 1.38 [95% CI, 1.13–1.69], 1.30 [95% CI, 1.05–1.61], and 1.37 [95% CI, 1.18–1.60], respectively); and there was a trend of increasing odds across quartiles for each outcome (all P for trend ≤0.01). There were similar but weaker associations of swine operations with community-associated MRSA and skin and soft tissue infection. Molecular testing of 200 isolates identified 31 unique spa types, none of which corresponded to CC398, but some have been previously found in swine. Conclusion Proximity to swine manure application to crop fields and livestock operations each was associated with MRSA and skin and soft tissue infection. These findings contribute to the growing concern about the potential public health impacts of high-density livestock production.\",\n \"title\": \"High-density livestock operations, crop field application of manure, and risk of community-associated methicillin-resistant Staphylococcus aureus infection, Pennsylvania, USA\"\n },\n {\n \"docid\": \"MED-1977\",\n \"text\": \"Reports have documented colonization of swine in Europe, North America and more recently in China with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA). Contamination of pig farmers, veterinarians and abattoir workers with these strains has been observed. However, although contamination levels of 10% of retail pork were reported from the Netherlands and Canada, there are limited data of contamination rates of workers handling raw meat. We investigated the rates of MRSA contamination of local butchers working in wet markets, where recently slaughtered pigs are cut up. Nasal swabs collected from 300 pork butchers at markets throughout Hong Kong were enriched in brain heart infusion broth with 5% salt and cultured on MRSASelect(®) . Isolates were confirmed as Staphylococcus aureus and susceptibility testing performed. The presence of mecA was confirmed, SCCmec and spa type determined and relatedness investigated by PFGE. Subjects completed a questionnaire on MRSA carriage risk factors. Seventeen samples (5.6%) yielded MRSA, 15 harbouring SCCmec IVb. Ten strains were t899 (CC9), previously reported from local pig carcasses. Five strains were healthcare associated: SCCmec type II, t701(CC6), colonizing two subjects at the same establishment, and single isolates of t008 (CC8), t002 (CC5) and t123 (CC45). The remaining isolates were t359 (CC97), previously reported from buffaloes, and t375 (CC5), reported from bovine milk. None of these butchers reported recent hospitalization or a healthcare worker in the family. Two had recently received antibiotics, one for a skin infection. Four reported wound infections within the last year. All were exposed to meat for >9 h per day. Carriage of MRSA was higher in butchers than in the general community. Although five strains were probably of healthcare origin, the high incidence of t899 (CC9) suggests that cross-contamination from pork occurs frequently. Washing of hands after touching raw pork is advised. © 2012 Blackwell Verlag GmbH.\",\n \"title\": \"Colonization of butchers with livestock-associated methicillin-resistant Staphylococcus aureus.\"\n },\n {\n \"docid\": \"MED-2747\",\n \"text\": \"Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998–2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.\",\n \"title\": \"Attribution of Foodborne Illnesses, Hospitalizations, and Deaths to Food Commodities by using Outbreak Data, United States, 1998–2008\"\n },\n {\n \"docid\": \"MED-3880\",\n \"text\": \"A common approach to reducing microbial contamination has been the implementation of a Hazard Analysis and Critical Control Point (HACCP) program to prevent or reduce contamination during production. One example is the Pathogen Reduction HACCP program implemented by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). This program consisted of a staged implementation between 1996 and 2000 to reduce microbial contamination on meat and poultry products. Of the commodities regulated by FSIS, one of the largest observed reductions was for Salmonella contamination on broiler chicken carcasses. Nevertheless, how this reduction might have influenced the total number of salmonellosis cases in the United States has not been assessed. This study incorporates information from public health surveillance and surveys of the poultry slaughter industry into a model that estimates the number of broiler-related salmonellosis cases through time. The model estimates that-following the 56% reduction in the proportion of contaminated broiler carcasses observed between 1995 and 2000-approximately 190,000 fewer annual salmonellosis cases (attributed to broilers) occurred in 2000 compared with 1995. The uncertainty bounds for this estimate range from approximately 37,000 to 500,000 illnesses. Estimated illnesses prevented, due to the more modest reduction in contamination of 13% between 2000 and 2007, were not statistically significant. An analysis relating the necessary magnitude of change in contamination required for detection via human surveillance also is provided.\",\n \"title\": \"Estimating changes in public health following implementation of hazard analysis and critical control point in the United States broiler slaughter i...\"\n },\n {\n \"docid\": \"MED-2740\",\n \"text\": \"To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.\",\n \"title\": \"FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States.\"\n },\n {\n \"docid\": \"MED-2672\",\n \"text\": \"To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.\",\n \"title\": \"Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks.\"\n },\n {\n \"docid\": \"MED-3886\",\n \"text\": \"The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.\",\n \"title\": \"Mechanisms of antimicrobial resistance in bacteria.\"\n },\n {\n \"docid\": \"MED-3887\",\n \"text\": \"Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.\",\n \"title\": \"Food Animals and Antimicrobials: Impacts on Human Health\"\n },\n {\n \"docid\": \"MED-3888\",\n \"text\": \"BACKGROUND: Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices. METHODS: We analyzed the incidence of human SE infection during 1996-2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with rates of SE isolation from processed chickens and egg products; shell eggs are not routinely tested. We also compared molecular subtyping patterns of SE isolated from humans and chickens. RESULTS: Since the period 1996-1999, the incidence of human SE infection in FoodNet has increased by 44%. This change is mirrored in passive national surveillance data. The greatest relative increases were in young children, older adults, and FoodNet sites in the southern United States. The proportion of patients with SE infection who reported recent international travel has decreased in recent years, whereas the proportion of chickens from which SE was isolated has increased. Similar molecular subtypes of SE are commonly isolated from humans and chickens. CONCLUSIONS: Most SE infections in the United States are acquired from domestic sources, and the problem is growing. Chicken and eggs are likely major sources of SE. Continued close attention to surveillance data is needed to monitor the impact of recent regulatory control measures.\",\n \"title\": \"Salmonella enterica serotype Enteritidis: increasing incidence of domestically acquired infections.\"\n },\n {\n \"docid\": \"MED-2671\",\n \"text\": \"Microbiology of meats has been a subject of great concern in food science and public health in recent years. Although many articles have been devoted to the microbiology of beef, pork, and poultry meats, much less has been written about microbiology of lamb meat and even less on restructured lamb meat. This article presents data on microbiology and shelf-life of fresh lamb meat; restructured meat products, restructured lamb meat products, bacteriology of restructured meat products, and important foodborne pathogens such as Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential use of sodium and potassium lactates to control foodborne pathogens in meats and restructured lamb meat is reviewed This article should be of interest to all meat scientists, food scientists, and public health microbiologists who are concerned with the safety of meats in general and lamb meat in particular.\",\n \"title\": \"Microbiology of fresh and restructured lamb meat: a review.\"\n },\n {\n \"docid\": \"MED-2738\",\n \"text\": \"Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers.\",\n \"title\": \"Trends in U.S. consumers' safe handling and consumption of food and their risk perceptions, 1988 through 2010.\"\n },\n {\n \"docid\": \"MED-3882\",\n \"text\": \"Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) β-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n=18), food animals at slaughter (n=16), and retail meats (n=13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion.\",\n \"title\": \"Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and h...\"\n },\n {\n \"docid\": \"MED-4132\",\n \"text\": \"Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.\",\n \"title\": \"Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic...\"\n },\n {\n \"docid\": \"MED-3891\",\n \"text\": \"Escherichia coli isolates were recovered from the National Antimicrobial Resistance Monitoring System retail meat program and examined for antimicrobial susceptibility. Retail meat samples (n = 11,921) from four U.S. states collected during 2002 to 2008, consisting of 2,988 chicken breast, 2,942 ground turkey, 2,991 ground beef, and 3,000 pork chop samples, were analyzed. A total of 8,286 E. coli isolates were recovered. The greatest numbers of samples contaminated with the organism were chicken (83.5%) and turkey (82.0%), followed by beef (68.9%) and pork (44.0%). Resistance was most common to tetracycline (50.3%), followed by streptomycin (34.6%), sulfamethoxazole-sulfisoxazole (31.6%), ampicillin (22.5%), gentamicin (18.6%), kanamycin (8.4%), amoxicillin-clavulanic acid (6.4%), and cefoxitin (5.2%). Less than 5% of the isolates had resistance to trimethoprim, ceftriaxone, ceftiofur, nalidixic acid, chloramphenicol, and ciprofloxacin. All isolates were susceptible to amikacin. Compared to beef and pork isolates, the poultry meat isolates had a greater percentage of resistance to all tested drugs, with the exception of chloramphenicol, to which pork isolates had the most resistance. More than half of the turkey isolates (56%) were resistant to multidrugs (≥3 classes) compared to 38.9% of chicken, 17.3% of pork, and 9.3% of beef isolates. The blaCMY gene was present in all ceftriaxone- and ceftiofur-resistant isolates. The cmlA, flo, and catI genes were present in 45%, 43%, and 40% of chloramphenicol-resistant isolates, respectively. Most nalidixic acid-resistant isolates (98.5%) had a gyrA mutation in S83 or D87 or both, whereas only 6.7% had a parC mutation in either S80 or E84. The results showed that E. coli was commonly present in the retail meats, and antimicrobial resistance profiles differed according to the animal origin of the isolates.\",\n \"title\": \"Comparison of the Prevalences and Antimicrobial Resistances of Escherichia coli Isolates from Different Retail Meats in the United States, 2002 to 2008\"\n },\n {\n \"docid\": \"MED-3892\",\n \"text\": \"Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.\",\n \"title\": \"Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-5251","text":"Dietary habits have been rarely associated with seizure frequency in patients with epilepsy. We report a case of a man with a partial symptomatic epilepsy whose daily habit of heavy coffee drinking was associated with an increased seizure frequency. This patient witnessed a dramatic decrease in the frequency of his seizures after stopping coffee ingestion. Caffeine is a global stimulant and the reduction of its intake may help in the treatment of epilepsy.","title":"Heavy coffee drinking and epilepsy."},{"docid":"MED-3178","text":"Neurocysticercosis (NCC) is the most frequent parasitic disease of the human brain. Modern imaging studies, CT and MRI, have defined the diagnosis and characterization of the disease. Through these studies the therapeutic approach for each case may be individualized with the aid of antihelmintics, steroids, symptomatic medicines, or surgery. The use of one or various therapeutic measures largely depends on the peculiar combination of number, location, and biological stage of lesions as well as the degree of inflammatory response to the parasites. Although there is not a typical clinical picture of NCC, epilepsy is the most frequent manifestation of parenchymal NCC, whereas hydrocephalus is the most frequent manifestation of meningeal NCC. Eradication of cysticercosis is an attainable goal by public education and sanitary improvement in endemic areas.","title":"Clinical manifestations, diagnosis, and treatment of neurocysticercosis."},{"docid":"MED-301","text":"Epilepsy or seizure disorder is one of the most common neurological diseases in humans. Although genetic mutations in ion channels and receptors and some other risk factors such as brain injury are linked to epileptogenesis, the underlying cause for the majority of epilepsy cases remains unknown. Gene-environment interactions are thought to play a critical role in the etiology of epilepsy. Exposure to environmental chemicals is an important risk factor. Methylmercury (MeHg) is a prominent environmental neurotoxicant, which targets primarily the central nervous system (CNS). Patients or animals with acute or chronic MeHg poisoning often display epileptic seizures or show increased susceptibility to seizures, suggesting that MeHg exposure may be associated with epileptogenesis. This mini-review highlights the effects of MeHg exposure, especially developmental exposure, on the susceptibility of humans and animals to seizures, and discusses the potential role of low level MeHg exposure in epileptogenesis. This review also proposes that a preferential effect of MeHg on the inhibitory GABAergic system, leading to disinhibition of excitatory glutamatergic function, may be one of the potential mechanisms underlying MeHg-induced changes in seizure susceptibility.","title":"Methylmercury: A Potential Environmental Risk Factor Contributing to Epileptogenesis"},{"docid":"MED-3170","text":"Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.","title":"Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study"},{"docid":"MED-4391","text":"Cancer is a leading cause of death worldwide. There are a lot of cancer causing agents which are divided as physical carcinogens, chemical carcinogens and biological carcinogens. But most of the carcinogens or causes of cancer are related to our lifestyle like diet, habit, occupation, radiation and some infection, etc. Chemoprevention is highly necessary to prevent cancer related preterm death. For this besides avoiding the causes of cancer we should concentrate ourselves on our diet. Because, numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents and recently attention has been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals. In this study, we tried to describe lifestyle related causes of cancer and the molecular basis of cancer prevention through the phytochemicals.","title":"Lifestyle related causes of cancer and chemoprevention through phytonutrients."},{"docid":"MED-3527","text":"BACKGROUND: : Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. REVIEWER'S CONCLUSIONS: : Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.","title":"Melatonin for the prevention and treatment of jet lag."},{"docid":"MED-3204","text":"Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.","title":"Management of grapefruit-drug interactions."},{"docid":"MED-1679","text":"BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.","title":"Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an..."},{"docid":"MED-2437","text":"BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and METHODS: This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. RESULTS: The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. CONCLUSION: Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.","title":"Diet and breast cancer: understanding risks and benefits."},{"docid":"MED-2527","text":"BACKGROUND: One of the major issues in controlling serum cholesterol through dietetic intervention appears to be the need to improve patient adherence. AIMS: To explore the many questions regarding barriers to, and motivators for, cholesterol-lowering diet adherence. METHODS: We surveyed French general practitioners' dietetic practices for patients with hypercholesterolaemia, and looked at their patients' attitudes towards such an approach. RESULTS: We analysed 234 doctors' personal questionnaires and 356 patient self-survey questionnaires. Patients' reasons for not complying with the prescribed diet included: 'already having satisfactory food habits' (34.7%), 'unwillingness to suffer nutritional deprivation' (33.3%), 'difficulties to conciliate a diet with family life' (27.8%) and 'taking cholesterol-lowering drugs' (22.2%). Despite a generally good understanding by patients of doctors' recommendations, some discrepancies were seen between their respective declarations. While doctors largely thought that patients needed more explanation on why and how a diet can lower cholesterol (and avoid taking drugs), only 39.4% of patients declared needing this kind of information. Other discrepancies were observed concerning barriers to, and motivators for, patient adherence. Moreover, some dietetic rules appeared to be more difficult to comply with than others, e.g. 82.6% patients remembered they should 'eat more fish' but only 51.3% actually did so. Finally, physicians, as well as patients, displayed a lack of confidence in lipid-lowering diet efficiency. CONCLUSION: Improving patient education, especially concerning their perception of risk, as well as increasing the involvement of dieticians, are motivators to explore in order to improve adherence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.","title":"Cross-analysis of dietary prescriptions and adherence in 356 hypercholesterolaemic patients."},{"docid":"MED-4451","text":"Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.","title":"Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish."},{"docid":"MED-1748","text":"Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly precise log-normal distribution in the plasma samples while non-plasma (cord blood) control sample was found to be free of plant DNA.","title":"Complete Genes May Pass from Food to Human Blood"},{"docid":"MED-3545","text":"Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.","title":"Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial"},{"docid":"MED-1552","text":"OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.","title":"Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies."},{"docid":"MED-5134","text":"This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.","title":"Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition."},{"docid":"MED-3181","text":"OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.","title":"Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil."},{"docid":"MED-2014","text":"BACKGROUND: Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. SPECIFIC AIM: We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). METHODS: This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. RESULTS: Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. CONCLUSION: While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.","title":"Characteristics of patients who avoid wheat and/or gluten in the absence of Celiac disease."},{"docid":"MED-1595","text":"Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.","title":"Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels."},{"docid":"MED-3154","text":"Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1 - to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. Although it naturally follows that infection risk should in some way be linked to acute and chronic exercise-induced alterations in immunity, attempts thus far to measure this association have been unsuccessful. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Some attempts have been made through chemical or nutritional means (e.g., indomethacin, glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune changes after intensive exercise to lower the risk of infection. No consistent relationship between nutritional interventions, exercise immunology, and alteration in URTI risk has yet been established.","title":"Is infection risk linked to exercise workload?"},{"docid":"MED-3179","text":"OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.","title":"Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study."},{"docid":"MED-4972","text":"Heterocyclic amines (HCAs), compounds formed when meat is cooked at high temperatures particularly through pan frying, grilling, or barbequing, pose a potential carcinogenic risk to the public. It is unclear whether there is any level at which consumption of HCAs can be considered safe. Efforts to measure these compounds mainly include cooking studies under laboratory conditions and some measurement of home-cooked foods, but analysis of commercially cooked foods has been minimal. Attempts to estimate exposure of the public to these compounds must take into consideration dining outside the home, which could result in significant exposure for some individuals. We surveyed at least 9 locations each of 7 popular chain restaurants (McDonald's, Burger King, Chick-fil-A, Chili's, TGI Friday's, Outback Steakhouse, and Applebee's) in California, collecting one or two entrees from each location. Entrees were analyzed for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using high-performance liquid chromatography tandem mass spectrometry. All 100 samples contained PhIP. Concentrations were variable within and between entrees and ranged from 0.08 to 43.2 ng/g. When factoring in the weight of the entrees, absolute levels of PhIP reached over 1,000 ng for some entrees. Potential strategies for reducing exposure include the avoidance of meats cooked using methods that are known to form PhIP.","title":"Detection of PhIP in grilled chicken entrées at popular chain restaurants throughout California."},{"docid":"MED-5133","text":"We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.","title":"[Floppy baby with macrocytic anemia and vegan mother]."},{"docid":"MED-1851","text":"The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.","title":"Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link?"},{"docid":"MED-3523","text":"Melatonin, which is contained in certain vegetables, may have an influence on circulatory melatonin concentrations. This study examined the effects of the consumption of vegetables on 6-sulfatoxymelatonin concentrations in morning urine. Ninety-four healthy women aged 24-55 were recruited through a city public health center in Japan. The women randomly allocated to the intervention group were requested to consume high amounts of six selected vegetables, with a target of 350 g/day for 65 days, while those in the control group were asked to avoid the same six vegetables during the same period. First-void morning urine was collected before and at the end of the intervention period, and creatinine-adjusted 6-sulfatoxymelatonin concentrations were measured. At the end of the intervention period, daily mean intake of melatonin from the six vegetables was 1288.0 ng in the intervention group and 5.3 ng in the control group. In the intervention group, the mean concentration of 6-sulfatoxymelatonin changed from 48.1 [95% confidence interval (CI): 40.4-57.2] ng/mg creatinine to 49.6 (95% CI: 42.8-57.3) ng/mg creatinine across the intervention period. In the control group, the mean concentration of 6-sulfatoxymelatonin changed from 55.5 (95% CI: 48.7-63.2) ng/mg creatinine to 50.8 (95% CI: 44.0-58.7) ng/mg creatinine across the intervention period. A comparison of the two groups with regard to the changes in the 6-sulfatoxymelatonin concentrations across the intervention period showed a significant difference (P = 0.03). The results indicate that increased consumption of vegetables raises circulatory melatonin concentrations.","title":"Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration."},{"docid":"MED-4511","text":"BACKGROUND: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. METHODS: Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. RESULTS: 49 subjects were tested. Most subjects (10th to 90th percentile) had followed this diet 23-49 months. 6 subjects had serum B12 concentrations <147 pmol/l (200 pg/ml). 37 subjects (76%) had serum B12 concentrations <221 pmol/l (300 pg/ml). 23 subjects (47%) had abnormal urinary MMA concentrations above or equal to 4.0 microg/mg creatinine. Sublingual cyanocobalamin and nutritional yeast, but not probiotic supplements, significantly reduced group mean MMA concentrations (tablet p < 0.01; yeast p < 0.05, probiotic > 0.20). CONCLUSIONS: The urinary MMA assay is effective for identifying early metabolic cobalamin deficiency. People following the Hallelujah diet and other raw-food vegetarian diets should regularly monitor their urinary MMA levels, consume a sublingual cobalamin supplement, or consume cobalamin in their food.","title":"Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements."},{"docid":"MED-5272","text":"Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.","title":"Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial..."},{"docid":"MED-1333","text":"New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.","title":"Insulin secretion as a determinant of pancreatic cancer risk."},{"docid":"MED-3177","text":"Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.","title":"Neurocysticercosis: the enigmatic disease."},{"docid":"MED-1540","text":"A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.","title":"Vegetarian diets: what do we know of their effects on common chronic diseases?"},{"docid":"MED-4327","text":"Hyperphosphatemia and hyperparathyroidism, frequently observed in patients with endstage renal disease, are associated with renal osteodystrophy, organ calcification, cardiovascular disease and sudden death. Restriction of dietary protein and phosphorus is beneficial in slowing the progression of renal failure. Dietary phosphorus restriction must be prescribed at all stages of renal failure in adults. It may be achieved by decreasing protein intake and avoiding foods rich in phosphorus. An average of 60-80% of the phosphorus intake is absorbed in the gut in dialysis patients. If phosphate binders are employed, the phosphorus absorbed from the diet may be reduced to 40%. Conventional hemodialysis with a high-flux, high-efficiency dialyzer removes approximately 30 mmol (900 mg) phosphorus during each dialysis performed three times weekly. Therefore, 750 mg of phosphorus intake should be the critical value above which a positive balance of phosphorus may occur. This value corresponds to a protein diet of 45-50 g/day or 0.8 g/kg body weight/day for a 60 kg patient. Target levels should become 9.2-9.6 mg/dl for calcium, 2.5-5.5 mg/dl for phosphorus, <55 mg2/dl2 for the calcium-phosphorus product, and 100-200 pg/ml for intact parathyroid hormone.","title":"Phosphate restriction in diet therapy."}],"string":"[\n {\n \"docid\": \"MED-5251\",\n \"text\": \"Dietary habits have been rarely associated with seizure frequency in patients with epilepsy. We report a case of a man with a partial symptomatic epilepsy whose daily habit of heavy coffee drinking was associated with an increased seizure frequency. This patient witnessed a dramatic decrease in the frequency of his seizures after stopping coffee ingestion. Caffeine is a global stimulant and the reduction of its intake may help in the treatment of epilepsy.\",\n \"title\": \"Heavy coffee drinking and epilepsy.\"\n },\n {\n \"docid\": \"MED-3178\",\n \"text\": \"Neurocysticercosis (NCC) is the most frequent parasitic disease of the human brain. Modern imaging studies, CT and MRI, have defined the diagnosis and characterization of the disease. Through these studies the therapeutic approach for each case may be individualized with the aid of antihelmintics, steroids, symptomatic medicines, or surgery. The use of one or various therapeutic measures largely depends on the peculiar combination of number, location, and biological stage of lesions as well as the degree of inflammatory response to the parasites. Although there is not a typical clinical picture of NCC, epilepsy is the most frequent manifestation of parenchymal NCC, whereas hydrocephalus is the most frequent manifestation of meningeal NCC. Eradication of cysticercosis is an attainable goal by public education and sanitary improvement in endemic areas.\",\n \"title\": \"Clinical manifestations, diagnosis, and treatment of neurocysticercosis.\"\n },\n {\n \"docid\": \"MED-301\",\n \"text\": \"Epilepsy or seizure disorder is one of the most common neurological diseases in humans. Although genetic mutations in ion channels and receptors and some other risk factors such as brain injury are linked to epileptogenesis, the underlying cause for the majority of epilepsy cases remains unknown. Gene-environment interactions are thought to play a critical role in the etiology of epilepsy. Exposure to environmental chemicals is an important risk factor. Methylmercury (MeHg) is a prominent environmental neurotoxicant, which targets primarily the central nervous system (CNS). Patients or animals with acute or chronic MeHg poisoning often display epileptic seizures or show increased susceptibility to seizures, suggesting that MeHg exposure may be associated with epileptogenesis. This mini-review highlights the effects of MeHg exposure, especially developmental exposure, on the susceptibility of humans and animals to seizures, and discusses the potential role of low level MeHg exposure in epileptogenesis. This review also proposes that a preferential effect of MeHg on the inhibitory GABAergic system, leading to disinhibition of excitatory glutamatergic function, may be one of the potential mechanisms underlying MeHg-induced changes in seizure susceptibility.\",\n \"title\": \"Methylmercury: A Potential Environmental Risk Factor Contributing to Epileptogenesis\"\n },\n {\n \"docid\": \"MED-3170\",\n \"text\": \"Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.\",\n \"title\": \"Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study\"\n },\n {\n \"docid\": \"MED-4391\",\n \"text\": \"Cancer is a leading cause of death worldwide. There are a lot of cancer causing agents which are divided as physical carcinogens, chemical carcinogens and biological carcinogens. But most of the carcinogens or causes of cancer are related to our lifestyle like diet, habit, occupation, radiation and some infection, etc. Chemoprevention is highly necessary to prevent cancer related preterm death. For this besides avoiding the causes of cancer we should concentrate ourselves on our diet. Because, numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents and recently attention has been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals. In this study, we tried to describe lifestyle related causes of cancer and the molecular basis of cancer prevention through the phytochemicals.\",\n \"title\": \"Lifestyle related causes of cancer and chemoprevention through phytonutrients.\"\n },\n {\n \"docid\": \"MED-3527\",\n \"text\": \"BACKGROUND: : Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. REVIEWER'S CONCLUSIONS: : Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.\",\n \"title\": \"Melatonin for the prevention and treatment of jet lag.\"\n },\n {\n \"docid\": \"MED-3204\",\n \"text\": \"Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.\",\n \"title\": \"Management of grapefruit-drug interactions.\"\n },\n {\n \"docid\": \"MED-1679\",\n \"text\": \"BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.\",\n \"title\": \"Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an...\"\n },\n {\n \"docid\": \"MED-2437\",\n \"text\": \"BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and METHODS: This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. RESULTS: The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. CONCLUSION: Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.\",\n \"title\": \"Diet and breast cancer: understanding risks and benefits.\"\n },\n {\n \"docid\": \"MED-2527\",\n \"text\": \"BACKGROUND: One of the major issues in controlling serum cholesterol through dietetic intervention appears to be the need to improve patient adherence. AIMS: To explore the many questions regarding barriers to, and motivators for, cholesterol-lowering diet adherence. METHODS: We surveyed French general practitioners' dietetic practices for patients with hypercholesterolaemia, and looked at their patients' attitudes towards such an approach. RESULTS: We analysed 234 doctors' personal questionnaires and 356 patient self-survey questionnaires. Patients' reasons for not complying with the prescribed diet included: 'already having satisfactory food habits' (34.7%), 'unwillingness to suffer nutritional deprivation' (33.3%), 'difficulties to conciliate a diet with family life' (27.8%) and 'taking cholesterol-lowering drugs' (22.2%). Despite a generally good understanding by patients of doctors' recommendations, some discrepancies were seen between their respective declarations. While doctors largely thought that patients needed more explanation on why and how a diet can lower cholesterol (and avoid taking drugs), only 39.4% of patients declared needing this kind of information. Other discrepancies were observed concerning barriers to, and motivators for, patient adherence. Moreover, some dietetic rules appeared to be more difficult to comply with than others, e.g. 82.6% patients remembered they should 'eat more fish' but only 51.3% actually did so. Finally, physicians, as well as patients, displayed a lack of confidence in lipid-lowering diet efficiency. CONCLUSION: Improving patient education, especially concerning their perception of risk, as well as increasing the involvement of dieticians, are motivators to explore in order to improve adherence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.\",\n \"title\": \"Cross-analysis of dietary prescriptions and adherence in 356 hypercholesterolaemic patients.\"\n },\n {\n \"docid\": \"MED-4451\",\n \"text\": \"Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.\",\n \"title\": \"Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.\"\n },\n {\n \"docid\": \"MED-1748\",\n \"text\": \"Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly precise log-normal distribution in the plasma samples while non-plasma (cord blood) control sample was found to be free of plant DNA.\",\n \"title\": \"Complete Genes May Pass from Food to Human Blood\"\n },\n {\n \"docid\": \"MED-3545\",\n \"text\": \"Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.\",\n \"title\": \"Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial\"\n },\n {\n \"docid\": \"MED-1552\",\n \"text\": \"OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.\",\n \"title\": \"Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies.\"\n },\n {\n \"docid\": \"MED-5134\",\n \"text\": \"This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.\",\n \"title\": \"Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition.\"\n },\n {\n \"docid\": \"MED-3181\",\n \"text\": \"OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.\",\n \"title\": \"Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil.\"\n },\n {\n \"docid\": \"MED-2014\",\n \"text\": \"BACKGROUND: Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. SPECIFIC AIM: We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). METHODS: This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. RESULTS: Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. CONCLUSION: While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.\",\n \"title\": \"Characteristics of patients who avoid wheat and/or gluten in the absence of Celiac disease.\"\n },\n {\n \"docid\": \"MED-1595\",\n \"text\": \"Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.\",\n \"title\": \"Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels.\"\n },\n {\n \"docid\": \"MED-3154\",\n \"text\": \"Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1 - to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. Although it naturally follows that infection risk should in some way be linked to acute and chronic exercise-induced alterations in immunity, attempts thus far to measure this association have been unsuccessful. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Some attempts have been made through chemical or nutritional means (e.g., indomethacin, glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune changes after intensive exercise to lower the risk of infection. No consistent relationship between nutritional interventions, exercise immunology, and alteration in URTI risk has yet been established.\",\n \"title\": \"Is infection risk linked to exercise workload?\"\n },\n {\n \"docid\": \"MED-3179\",\n \"text\": \"OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.\",\n \"title\": \"Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study.\"\n },\n {\n \"docid\": \"MED-4972\",\n \"text\": \"Heterocyclic amines (HCAs), compounds formed when meat is cooked at high temperatures particularly through pan frying, grilling, or barbequing, pose a potential carcinogenic risk to the public. It is unclear whether there is any level at which consumption of HCAs can be considered safe. Efforts to measure these compounds mainly include cooking studies under laboratory conditions and some measurement of home-cooked foods, but analysis of commercially cooked foods has been minimal. Attempts to estimate exposure of the public to these compounds must take into consideration dining outside the home, which could result in significant exposure for some individuals. We surveyed at least 9 locations each of 7 popular chain restaurants (McDonald's, Burger King, Chick-fil-A, Chili's, TGI Friday's, Outback Steakhouse, and Applebee's) in California, collecting one or two entrees from each location. Entrees were analyzed for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using high-performance liquid chromatography tandem mass spectrometry. All 100 samples contained PhIP. Concentrations were variable within and between entrees and ranged from 0.08 to 43.2 ng/g. When factoring in the weight of the entrees, absolute levels of PhIP reached over 1,000 ng for some entrees. Potential strategies for reducing exposure include the avoidance of meats cooked using methods that are known to form PhIP.\",\n \"title\": \"Detection of PhIP in grilled chicken entrées at popular chain restaurants throughout California.\"\n },\n {\n \"docid\": \"MED-5133\",\n \"text\": \"We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.\",\n \"title\": \"[Floppy baby with macrocytic anemia and vegan mother].\"\n },\n {\n \"docid\": \"MED-1851\",\n \"text\": \"The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.\",\n \"title\": \"Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link?\"\n },\n {\n \"docid\": \"MED-3523\",\n \"text\": \"Melatonin, which is contained in certain vegetables, may have an influence on circulatory melatonin concentrations. This study examined the effects of the consumption of vegetables on 6-sulfatoxymelatonin concentrations in morning urine. Ninety-four healthy women aged 24-55 were recruited through a city public health center in Japan. The women randomly allocated to the intervention group were requested to consume high amounts of six selected vegetables, with a target of 350 g/day for 65 days, while those in the control group were asked to avoid the same six vegetables during the same period. First-void morning urine was collected before and at the end of the intervention period, and creatinine-adjusted 6-sulfatoxymelatonin concentrations were measured. At the end of the intervention period, daily mean intake of melatonin from the six vegetables was 1288.0 ng in the intervention group and 5.3 ng in the control group. In the intervention group, the mean concentration of 6-sulfatoxymelatonin changed from 48.1 [95% confidence interval (CI): 40.4-57.2] ng/mg creatinine to 49.6 (95% CI: 42.8-57.3) ng/mg creatinine across the intervention period. In the control group, the mean concentration of 6-sulfatoxymelatonin changed from 55.5 (95% CI: 48.7-63.2) ng/mg creatinine to 50.8 (95% CI: 44.0-58.7) ng/mg creatinine across the intervention period. A comparison of the two groups with regard to the changes in the 6-sulfatoxymelatonin concentrations across the intervention period showed a significant difference (P = 0.03). The results indicate that increased consumption of vegetables raises circulatory melatonin concentrations.\",\n \"title\": \"Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration.\"\n },\n {\n \"docid\": \"MED-4511\",\n \"text\": \"BACKGROUND: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. METHODS: Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. RESULTS: 49 subjects were tested. Most subjects (10th to 90th percentile) had followed this diet 23-49 months. 6 subjects had serum B12 concentrations <147 pmol/l (200 pg/ml). 37 subjects (76%) had serum B12 concentrations <221 pmol/l (300 pg/ml). 23 subjects (47%) had abnormal urinary MMA concentrations above or equal to 4.0 microg/mg creatinine. Sublingual cyanocobalamin and nutritional yeast, but not probiotic supplements, significantly reduced group mean MMA concentrations (tablet p < 0.01; yeast p < 0.05, probiotic > 0.20). CONCLUSIONS: The urinary MMA assay is effective for identifying early metabolic cobalamin deficiency. People following the Hallelujah diet and other raw-food vegetarian diets should regularly monitor their urinary MMA levels, consume a sublingual cobalamin supplement, or consume cobalamin in their food.\",\n \"title\": \"Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements.\"\n },\n {\n \"docid\": \"MED-5272\",\n \"text\": \"Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.\",\n \"title\": \"Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial...\"\n },\n {\n \"docid\": \"MED-1333\",\n \"text\": \"New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.\",\n \"title\": \"Insulin secretion as a determinant of pancreatic cancer risk.\"\n },\n {\n \"docid\": \"MED-3177\",\n \"text\": \"Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.\",\n \"title\": \"Neurocysticercosis: the enigmatic disease.\"\n },\n {\n \"docid\": \"MED-1540\",\n \"text\": \"A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.\",\n \"title\": \"Vegetarian diets: what do we know of their effects on common chronic diseases?\"\n },\n {\n \"docid\": \"MED-4327\",\n \"text\": \"Hyperphosphatemia and hyperparathyroidism, frequently observed in patients with endstage renal disease, are associated with renal osteodystrophy, organ calcification, cardiovascular disease and sudden death. Restriction of dietary protein and phosphorus is beneficial in slowing the progression of renal failure. Dietary phosphorus restriction must be prescribed at all stages of renal failure in adults. It may be achieved by decreasing protein intake and avoiding foods rich in phosphorus. An average of 60-80% of the phosphorus intake is absorbed in the gut in dialysis patients. If phosphate binders are employed, the phosphorus absorbed from the diet may be reduced to 40%. Conventional hemodialysis with a high-flux, high-efficiency dialyzer removes approximately 30 mmol (900 mg) phosphorus during each dialysis performed three times weekly. Therefore, 750 mg of phosphorus intake should be the critical value above which a positive balance of phosphorus may occur. This value corresponds to a protein diet of 45-50 g/day or 0.8 g/kg body weight/day for a 60 kg patient. Target levels should become 9.2-9.6 mg/dl for calcium, 2.5-5.5 mg/dl for phosphorus, <55 mg2/dl2 for the calcium-phosphorus product, and 100-200 pg/ml for intact parathyroid hormone.\",\n \"title\": \"Phosphate restriction in diet therapy.\"\n }\n]"}}},{"rowIdx":389,"cells":{"query_id":{"kind":"string","value":"41001"},"query":{"kind":"string","value":"Abraham Lincoln lost a Senate race to Stephen A. Douglas."},"positive_passages":{"kind":"list like","value":[{"docid":"Abraham_Lincoln","text":"Abraham Lincoln ( -LSB- ˈeɪbrəhæm_ˈlIŋkən -RSB- February 12 , 1809 -- April 15 , 1865 ) was an American politician and lawyer who served as the 16th President of the United States from March 1861 until his assassination in April 1865 . Lincoln led the United States through its Civil War -- its bloodiest war and perhaps its greatest moral , constitutional , and political crisis . In doing so , he preserved the Union , paved the way to the abolition of slavery , strengthened the federal government , and modernized the economy . Born in Hodgenville , Kentucky , Lincoln grew up on the western frontier in Kentucky and Indiana . Largely self-educated , he became a lawyer in Illinois , a Whig Party leader , and was elected to the Illinois House of Representatives , in which he served for eight years . Elected to the United States House of Representatives in 1846 , Lincoln promoted rapid modernization of the economy through banks , tariffs , and railroads . Because he had originally agreed not to run for a second term in Congress , and because his opposition to the Mexican -- American War was unpopular among Illinois voters , Lincoln returned to Springfield and resumed his successful law practice . Reentering politics in 1854 , he became a leader in building the new Republican Party , which had a statewide majority in Illinois . In 1858 , while taking part in a series of highly publicized debates with his opponent and rival , Democrat Stephen A. Douglas , Lincoln spoke out against the expansion of slavery , but lost the U.S. Senate race to Douglas . In 1860 , Lincoln secured the Republican Party presidential nomination as a moderate from a swing state . Though he gained very little support in the slaveholding states of the South , he swept the North and was elected president in 1860 . Lincoln 's victory prompted seven southern slave states to form the Confederate States of America before he moved into the White House -- no compromise or reconciliation was found regarding slavery and secession . Subsequently , on April 12 , 1861 , a Confederate attack on Fort Sumter inspired the North to enthusiastically rally behind the Union . As the leader of the moderate faction of the Republican Party , Lincoln confronted Radical Republicans , who demanded harsher treatment of the South , War Democrats , who called for more compromise , anti-war Democrats ( called Copperheads ) , who despised him , and irreconcilable secessionists , who plotted his assassination . Politically , Lincoln fought back by pitting his opponents against each other , by carefully planned political patronage , and by appealing to the American people with his powers of oratory . His Gettysburg Address became an iconic endorsement of the principles of nationalism , republicanism , equal rights , liberty , and democracy . Lincoln initially concentrated on the military and political dimensions of the war . His primary goal was to reunite the nation . He suspended habeas corpus , leading to the controversial ex parte Merryman decision , and he averted potential British intervention in the war by defusing the Trent Affair in late 1861 . Lincoln closely supervised the war effort , especially the selection of top generals , including his most successful general , Ulysses S. Grant . He also made major decisions on Union war strategy , including a naval blockade that shut down the South 's normal trade , moves to take control of Kentucky and Tennessee , and using gunboats to gain control of the southern river system . Lincoln tried repeatedly to capture the Confederate capital at Richmond ; each time a general failed , Lincoln substituted another , until finally Grant succeeded . As the war progressed , his complex moves toward ending slavery included the Emancipation Proclamation of 1863 ; Lincoln used the U.S. Army to protect escaped slaves , encouraged the border states to outlaw slavery , and pushed through Congress the Thirteenth Amendment to the United States Constitution , which permanently outlawed slavery . An exceptionally astute politician deeply involved with power issues in each state , Lincoln reached out to the War Democrats and managed his own re-election campaign in the 1864 presidential election . Anticipating the war 's conclusion , Lincoln pushed a moderate view of Reconstruction , seeking to reunite the nation speedily through a policy of generous reconciliation in the face of lingering and bitter divisiveness . On April 14 , 1865 , five days after the surrender of Confederate commanding general Robert E. Lee , Lincoln was assassinated by John Wilkes Booth , a Confederate sympathizer . Lincoln has been consistently ranked both by scholars and the public as among the greatest U.S. presidents .","title":""}],"string":"[\n {\n \"docid\": \"Abraham_Lincoln\",\n \"text\": \"Abraham Lincoln ( -LSB- ˈeɪbrəhæm_ˈlIŋkən -RSB- February 12 , 1809 -- April 15 , 1865 ) was an American politician and lawyer who served as the 16th President of the United States from March 1861 until his assassination in April 1865 . Lincoln led the United States through its Civil War -- its bloodiest war and perhaps its greatest moral , constitutional , and political crisis . In doing so , he preserved the Union , paved the way to the abolition of slavery , strengthened the federal government , and modernized the economy . Born in Hodgenville , Kentucky , Lincoln grew up on the western frontier in Kentucky and Indiana . Largely self-educated , he became a lawyer in Illinois , a Whig Party leader , and was elected to the Illinois House of Representatives , in which he served for eight years . Elected to the United States House of Representatives in 1846 , Lincoln promoted rapid modernization of the economy through banks , tariffs , and railroads . Because he had originally agreed not to run for a second term in Congress , and because his opposition to the Mexican -- American War was unpopular among Illinois voters , Lincoln returned to Springfield and resumed his successful law practice . Reentering politics in 1854 , he became a leader in building the new Republican Party , which had a statewide majority in Illinois . In 1858 , while taking part in a series of highly publicized debates with his opponent and rival , Democrat Stephen A. Douglas , Lincoln spoke out against the expansion of slavery , but lost the U.S. Senate race to Douglas . In 1860 , Lincoln secured the Republican Party presidential nomination as a moderate from a swing state . Though he gained very little support in the slaveholding states of the South , he swept the North and was elected president in 1860 . Lincoln 's victory prompted seven southern slave states to form the Confederate States of America before he moved into the White House -- no compromise or reconciliation was found regarding slavery and secession . Subsequently , on April 12 , 1861 , a Confederate attack on Fort Sumter inspired the North to enthusiastically rally behind the Union . As the leader of the moderate faction of the Republican Party , Lincoln confronted Radical Republicans , who demanded harsher treatment of the South , War Democrats , who called for more compromise , anti-war Democrats ( called Copperheads ) , who despised him , and irreconcilable secessionists , who plotted his assassination . Politically , Lincoln fought back by pitting his opponents against each other , by carefully planned political patronage , and by appealing to the American people with his powers of oratory . His Gettysburg Address became an iconic endorsement of the principles of nationalism , republicanism , equal rights , liberty , and democracy . Lincoln initially concentrated on the military and political dimensions of the war . His primary goal was to reunite the nation . He suspended habeas corpus , leading to the controversial ex parte Merryman decision , and he averted potential British intervention in the war by defusing the Trent Affair in late 1861 . Lincoln closely supervised the war effort , especially the selection of top generals , including his most successful general , Ulysses S. Grant . He also made major decisions on Union war strategy , including a naval blockade that shut down the South 's normal trade , moves to take control of Kentucky and Tennessee , and using gunboats to gain control of the southern river system . Lincoln tried repeatedly to capture the Confederate capital at Richmond ; each time a general failed , Lincoln substituted another , until finally Grant succeeded . As the war progressed , his complex moves toward ending slavery included the Emancipation Proclamation of 1863 ; Lincoln used the U.S. Army to protect escaped slaves , encouraged the border states to outlaw slavery , and pushed through Congress the Thirteenth Amendment to the United States Constitution , which permanently outlawed slavery . An exceptionally astute politician deeply involved with power issues in each state , Lincoln reached out to the War Democrats and managed his own re-election campaign in the 1864 presidential election . Anticipating the war 's conclusion , Lincoln pushed a moderate view of Reconstruction , seeking to reunite the nation speedily through a policy of generous reconciliation in the face of lingering and bitter divisiveness . On April 14 , 1865 , five days after the surrender of Confederate commanding general Robert E. Lee , Lincoln was assassinated by John Wilkes Booth , a Confederate sympathizer . Lincoln has been consistently ranked both by scholars and the public as among the greatest U.S. presidents .\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"L/D","text":"L/D may refer to : Learning and development , in human resource management Lift-to-drag ratio , in aerodynamics Lincoln -- Douglas debates , a series of seven debates in 1858 between Abraham Lincoln , the Republican candidate for the Senate in Illinois , and Senator Stephen Douglas , the Democratic Party candidate","title":""},{"docid":"United_States_Senate_elections,_1858_and_1859","text":"The United States Senate elections of 1858 and 1859 were elections which had the Republican Party gain five additional seats in the United States Senate , but the Democrats retained their majority . That majority would erode in 1860 with the secession of the southern states leading up to the Civil War . In Illinois , incumbent Stephen A. Douglas ( D ) and challenger Abraham Lincoln held a series of seven debates , known as the `` Lincoln -- Douglas debates . '' As this election was prior to ratification of the seventeenth amendment , Senators were chosen by State legislatures .","title":""},{"docid":"Abraham_Lincoln's_Peoria_speech","text":"Abraham Lincoln 's Peoria speech was made in Peoria , Illinois on October 16 , 1854 . The speech , with its specific arguments against slavery , was an important step in Abraham Lincoln 's political ascension . The 1854 Kansas-Nebraska Act , written to form the territories of Kansas and Nebraska , was designed by Stephen A. Douglas , then the chairman of the Senate Committee on Territories . The Act included language that allowed settlers to decide whether they would or would not accept slavery in their region . Lincoln saw this as a repeal of the 1820 Missouri Compromise which had outlawed slavery above the 36 ° 30 ' parallel .","title":""},{"docid":"Pardon_Tillinghast","text":"Pardon Tillinghast ( 1625 -- 1718 ) was an early settler of Providence , Rhode Island , a public official there , and a pastor of the Baptist Church of Providence . A cooper by profession , he immigrated to New England about 1645 , and became a successful merchant . Later in life he became a clergyman , serving without compensation for nearly four decades . He died in 1718 aged about 96 , and was buried in a family cemetery on Benefit Street in Providence that remains extant . Among his thousands of descendants are many of great prominence , including Continental Congress delegate Samuel Ward ; Julia Ward Howe who wrote the Battle Hymn of the Republic ; and Stephen Arnold Douglas who was involved in a series of famed debates with Abraham Lincoln in 1858 , prior to a Senate race , and later lost to him in the 1860 presidential election .","title":""},{"docid":"The_Lincoln–Douglas_Debates_(1994_reenactments)","text":"The 1994 reenactments of the Lincoln -- Douglas Debates took place between August 20 and October 15 , 1994 and were facilitated and aired by C-SPAN . They featured historical reenactors presenting , in their entireties , the series of seven debates between Abraham Lincoln and Stephen A. Douglas that took place during the 1858 U.S. Senate campaign in Illinois . The debate reenactments were held in the same seven cities as were the 1858 debates , and were performed on dates very close to the anniversaries of the original debates . They were broadcast live on C-SPAN , and have been rebroadcast periodically ever since .","title":""},{"docid":"1860_Republican_National_Convention","text":"The 1860 Republican National Convention , also known as the 2nd Republican National Convention , was a nominating convention of the Republican Party of the United States , held in Chicago , Illinois , from May 16 to 18 , 1860 . The gathering nominated former U.S. Representative Abraham Lincoln of Illinois for President of the United States and Senator Hannibal Hamlin of Maine for Vice President . Lincoln 's nomination was a surprise , as the favorite before the convention had been former Governor of New York and U.S. Senator William H. Seward . Lincoln 's campaign manager , David Davis , is credited for Lincoln 's victory over Thurlow Weed , Seward 's campaign manager . Lincoln-Hamlin went on to defeat three other major tickets that year , including Democratic nominee Stephen A. Douglas , U.S. Senator from Illinois .","title":""},{"docid":"Stephen_A._Douglas","text":"Stephen Arnold Douglas ( April 23 , 1813 -- June 3 , 1861 ) was an American politician from Illinois and the designer of the Kansas -- Nebraska Act . He was a U.S. representative , a U.S. senator , and the Democratic Party nominee for president in the 1860 election , losing to Republican Abraham Lincoln . Douglas had previously defeated Lincoln in a Senate contest , noted for the famous Lincoln-Douglas debates of 1858 . He was nicknamed the `` Little Giant '' because he was short in physical stature , but a forceful and dominant figure in politics . ( His height is given in various sources as being in the range of 5 ft to 5 ft ; five feet four is reported most often . ) Douglas was well known as a resourceful party leader , and an adroit , ready , skillful tactician in debate and passage of legislation . He was a champion of the Young America movement which sought to modernize politics and replace the agrarian and strict constructionist orthodoxies of the past . Douglas was a leading proponent of democracy , and believed in the principle of popular sovereignty : that the majority of citizens should decide contentious issues such as slavery and territorial expansion . As chairman of the Committee on Territories , Douglas dominated the Senate from 1850 to 1859 . He was largely responsible for the Compromise of 1850 that apparently settled slavery issues ; however , in 1854 he reopened the slavery question with the Kansas -- Nebraska Act , which opened some previously prohibited territories to slavery under popular sovereignty . Opposition to this led to the formation of the Republican Party . Douglas initially endorsed the Dred Scott decision of 1857 . But during the 1858 Senate campaign , he argued its effect could be negated by popular sovereignty . He also opposed the efforts of President James Buchanan and his Southern allies to enact a Federal slave code and impose the Lecompton Constitution on Kansas . In 1860 , the conflict over slavery led to the split in the Democratic Party in the 1860 Convention . Hardline pro-slavery Southerners rejected Douglas , and nominated their own candidate , Vice President John C. Breckinridge , while the Northern Democrats nominated Douglas . Douglas deeply believed in democracy , arguing the will of the people should always be decisive . When civil war came in April 1861 , he rallied his supporters to the Union cause with all his energies , but he died of typhoid fever a few weeks later .","title":""},{"docid":"Archibald_Williams_(judge)","text":"Archibald Williams ( June 10 , 1801 -- September 21 , 1863 ) was a United States federal judge . Born in Montgomery County , Kentucky , Williams read law to enter the bar in 1828 . He was in private practice in Quincy , Illinois beginning in 1829 . He was the United States Attorney for the District of Illinois from 1849 to 1853 . He served in both the Illinois House of Representatives and the Illinois State Senate . On March 8 , 1861 , Williams was nominated by President Abraham Lincoln to a new seat on the United States District Court for the District of Kansas created by 12 Stat . 126 . He was confirmed by the United States Senate on March 12 , 1861 , and received his commission the same day . Williams served in that capacity until his death , in 1863 , in Quincy , Illinois . Archibald Williams 's historical significance was based on his close friendship with Abraham Lincoln , the 16th President of the United States , who issued the Emancipation Proclamation freeing the slaves . Lincoln was from Springfield , Illinois , and Williams was from Quincy , Illinois , a port city on the Mississippi River along the western border of the state . The two men were close political allies in the Whig Party and , later on , in the newly founded Republican Party . They first met when serving in the Illinois state legislature in the early 1830 's . They were compatriots for 29 years . Archibald Williams led the life of a political party workhorse , first for the Whig Party and then the Republicans . He served in the Illinois state legislature , made two unsuccessful runs for the U.S. Senate as a Whig , played a leading role at the Illinois state Constitutional Convention of 1847 , chaired many important political meetings in Quincy , Illinois , attended many state political party conventions , made an unsuccessful run for the U.S. House of Representatives , and in 1858 campaigned in Illinois for his friend Abraham Lincoln . In all recorded instances , Archibald Williams gave Abraham Lincoln his true and unwavering support . Archibald Williams died in 1863 . By that time , Abraham Lincoln was President of the United States and the leader of the Northern states during the American Civil War . Birth and Early Life Archibald Williams was born in Montgomery County , Kentucky , on June 10 , 1801 . He was the son of John Williams and Amelia Gill Williams . He grew up in Kentucky , qualified to be a lawyer in the neighboring state of Tennessee , and then moved west with some of his brothers and sisters to Quincy , Illinois . As a young attorney , he rode circuit , going from county court to county court arguing legal cases . He was particularly noted for taking cases on appeal , and he argued many cases before the Illinois state Supreme Court . He married Nancy Kemp , who also had come from Kentucky , on July 28 , 1831 . They had nine children , but only five grew up to be adults . For several months in early 1832 he served as a volunteer in the Black Hawk War against Native Americans . In the fall of 1832 he strongly supported Henry Clay for President of the United States . At the Illinois State Legislature Archibald Williams was elected to the Illinois state Senate in 1832 . He studied and reported on School Financing to the state Senate , arguing for local control of schools rather than establishing a statewide system . Later in his legislative career , he labeled the Illinois Internal Improvements program `` Infernal Improvements '' due to its financial difficulties leading to bankruptcy . Abraham Lincoln was elected to the state legislature in 1834 . Archibald Williams and Lincoln became good friends and both subsequently joined the Whig Party . Lincoln was said to have seen Archibald Williams as a great `` reasoner . '' The two men were described as `` sitting next to each other in the southeast corner of the statehouse . '' It was noted : `` Lincoln did not hesitate to consult Williams at all times , and the two men were often associated in legal work . '' Twice the Whig Candidate for U.S. Senator Archibald Williams ran for the United States Senate as a Whig in 1836 and in 1842 . At those times the selection of U.S. senators was made by both houses of the state legislature . Lincoln voted for Archibald Williams the first time he ran for U.S. Senator in 1836 . The second time Archibald Williams ran , in 1842 , Lincoln was no longer in the state legislature and thus could not vote for his friend . In both instances , Archibald Williams was not elected . Witnessed Abraham Lincoln 's Admission to U.S. Courts Abraham Lincoln was admitted to practice law in the United States Circuit Court on December 3 , 1839 . U.S Court Judge Nathaniel Pope presided over the ceremony . A Quincy , Illinois , newspaper noted that Archibald Williams was present at the ceremony . Presided Over Whig Party State Conventions in Illinois Archibald Williams presided over a Whig Party state convention meeting in Springfield , Illinois , in 1843 . Abraham Lincoln attended the convention and was elected a Whig Party presidential elector for the 1844 presidential election . Unfortunately for the Whigs , Democrat James K. Polk of Tennessee won the presidential election . In June of 1844 , Archibald Williams was elected president of an Illinois state Whig Party convention in Peoria , Illinois . Abraham Lincoln spoke to the convention in support of the United States charging higher tariffs on imported goods , a major Whig position at the time . Supported African Colonization of Freed Slaves Along with Abraham Lincoln , Archibald Williams in the 1840 's supported the African colonization of freed slaves by joining the Illinois colonization society . Although opposed to slavery , both men believed Southerners should be allowed to keep their slaves but also should be urged to free their slaves voluntarily and return them to Africa . This was thought to be a reasonable and non-coercive solution to the slavery problem . The Mormon Problem in Illinois Joining with his friend and fellow Quincy lawyer Orville Browning , Archibald Williams in 1840 helped to defend Mormon leader Joseph Smith from being extradited to Missouri to face possible execution for alleged crimes . Joseph Smith was the founder of the Church of Latter Day Saints ( Mormons ) , and he and his church were unpopular because of the voting power of his supporters and their belief in men having multiple wives . Thanks to Browning 's and Williams 's arguments in court , Smith was not extradited to Missouri but remained in Illinois and founded a Mormon colony at Nauvoo , Illinois . Four years later , in 1844 , Smith and his brother Hyrum were murdered by a mob while incarcerated in the jail at Carthage , Illinois . Williams and Browning switched sides and helped to defend in court the accused murderers of Joseph and Hyrum Smith . The murderers were all found not-guilty . Shortly afterward , Archibald Williams chaired a meeting in Quincy , Illinois , that sought to arrange for a peaceful departure of the Mormons from Illinois to the far western state of Utah . Archibald Williams appointed a delegation of Quincy citizens that traveled to Nauvoo and convinced the new Mormon leader , Brigham Young , to leave Illinois for Utah in an orderly manner . Brigham Young said the Mormons could not leave immediately , but when `` grass grows and water runs , '' both signs of spring . The following spring the Mormons peacefully left Illinois for Utah , traveling mainly by wagon train . The Illinois Constitutional Convention of 1847 Archibald Williams was elected to the Illinois state Constitutional Convention of 1847 as a Whig . The convention met in the state capitol in Springfield , Illinois , and proceeded to write an improved state constitution . Williams was elected in a Democratic district against a Democratic candidate . Although the Democrats had a majority of the delegates to the convention , the Whigs could break away Democratic votes when they needed them and ended up dominating the convention . A historian noted : `` James W. Singleton of Mount Sterling , Archibald Williams of Quincy , and David M. Woodson of Carrollton aggressively upheld the Whig cause against the attacks of various capable Democratic opponents . '' At the constitutional convention , Archibald Williams and the Whig Party supported the rights of property , strict voting requirements in state elections , and allowing the state legislature to override the governor 's veto by a majority vote rather than a two-thirds vote . Two issues were sent to the state 's voters - one calling for the creation of an Illinois state bank and the other limiting the immigration into Illinois of freed slaves from the slave states . The voters of Illinois rejected the idea of an Illinois state bank but approved limiting the immigration of freed slaves . Archibald Williams gave a major speech at the constitutional convention opposing the idea that the Illinois Supreme Court should meet at various locations throughout the state rather than only in the state capital of Springfield . After the constitutional convention adjourned , the voters of Illinois approved the new constitution by a ratio of almost 4 to 1 . The Constitutional Convention of 1847 was a landmark in the legal and political career of Archibald Williams . He succeeded in furthering the ideals and policies of the Whig Party against stiff Democratic Party opposition . He was three months in Springfield , the state capital , meeting and working with many of the leading politicians and government officials from throughout the state . It helped to make him a significant figure in Illinois political and governmental history . The `` Lincoln Letter '' to Archibald Williams In the 1848 presidential election , Abraham Lincoln was backing General Zachary Taylor , a Mexican War hero , for the Whig Party nomination . A problem developed when Orville H. Browning , a Whig Party leader in Quincy , Illinois , supported the nomination of past Whig Party favorite Henry Clay . On April 30 , 1848 , Abraham Lincoln wrote a letter to Archibald Williams urging him to support Zachary Taylor and , if possible , also enlist the support of Browning . The letter read : Washington , April 30 , 1848 Dear Williams , I have not seen in the papers and evidence of a movement to send a delegate from your circuit to the June convention - I wish to say that I think it all important that a delegate should be sent - Mr. Clay 's chance for election is just no chance at all . He might get New York , and that would have elected in 1844 but it will not now ; because he must now at the least , have Tennessee , which he had then and , in addition , the fifteen new votes of Florida , Texas , Iowa , and Wisconsin . I know that our good friend Browning is a great admirer of Mr. Clay , and I therefore fear he is favoring his nomination . If he is , ask him to discard feeling , and try if he can possibly , as a matter of judgement , count the votes necessary to elect him . In my judgment , we can elect nobody but Gen. Taylor , and we can not elect him without a nomination - Therefore do n't fail to send a delegation - Your friend as ever , A. Lincoln This letter demonstrates the close friendship and easygoing familiarity between Abraham Lincoln and Archibald Williams . It also reveals Lincoln 's developing skills as an up and coming Illinois politician . It is not known whether Archibald Williams prevailed on Orville Browning to support Zachary Taylor for the Whig nomination for president in 1848 . What is known is that Zachary Taylor not only gained the Whig Party nomination but also won the presidency . Named U.S. District Attorney for Illinois Once in the White House in Washington , D.C. , newly elected President Zachary Taylor appointed Archibald Williams the United States District Attorney for the state of Illinois . Abraham Lincoln had sent the following letter in support of Williams 's nomination : Washington , March 8 , 1849 Hon : John M. Clayton Secretary of State Dear Sir : We Recommend that Archibald Williams , of Quincy , Illinois , be appointed U.S. District Attorney for the District of Illinois , when that office shall become vacant . Your Obt . Servts . A. Lincoln As U.S. District Attorney for Illinois , it was Archibald Williams 's job to prosecute cases in the U.S. District Court . The job became more difficult for Williams in 1850 when Congress enacted the Compromise of 1850 , which included a new Fugitive Slave Law . This law required Williams , in his role as U.S. District Attorney , to oversee the capture of runaway slaves and their return to their owners in the South . Williams was opposed to slavery personally but , in the 1850 's , acknowledged the right of slave owners in the South to keep their slaves . He fully discharged his duties under the Fugitive Slave Act . Death of Nancy Kemp Williams Archibald Williams 's wife , Nancy Kemp Williams , died on March 16 , 1854 , giving birth to a daughter , Nancy Williams . The baby survived the birth and lived to be an adult . Archibald and Nancy Williams had been married for 22 years . Candidate for the U.S. House of Representatives in 1854 In the early 1850 's , U.S. Senator Stephen Douglas of Illinois sought the adoption of the Kansas and Nebraska acts . The bills provided for Kansas and Nebraska to become territories with provision for `` popular sovereignty , '' the idea that the citizens of each new territory would be allowed to vote on whether the territory should be slave or free . This produced a sharp reaction on the part of those opposed to slavery in the territories , because the Missouri Compromise of 1820 had stated that the lands that comprised Kansas and Nebraska should be free territory , not slave territory . The result was the anti-Nebraska movement , which opposed popular sovereignty for Nebraska on the grounds that the citizens of the territory might vote for slavery and thereby spread slavery further into the territories . Archibald Williams and Abraham Lincoln both became anti-Nebraska men . For his part , Archibald Williams ran for the U.S. House of Representatives in 1854 on a strong anti-Nebraska platform . Williams was running against incumbent Democratic Representative William A. Richardson , a formidable opponent . The U.S. House district that comprised Quincy , Illinois , was strongly Democratic . On the other hand , Richardson was a close political ally of Stephen Douglas and had strongly backed popular sovereignty for Nebraska in the U.S. House . Williams and his supporters hoped the wave of anti-Nebraska sentiment sweeping the northern states might just be strong enough to defeat Richardson , despite the strong Democratic voting tendency of the House district . On October 31 , 1854 , Abraham Lincoln arrived in Quincy , Illinois , to give a speech in support of Archibald Williams 's candidacy for the U.S. House of Representatives . It took two days for him to travel by railroad and stagecoach to Quincy . In a letter to a friend and political ally , Lincoln wrote : `` I am here now going to Quincy , to try to give Mr. -LSB- Archibald -RSB- Williams a little life . '' Even with Abraham Lincoln 's help , Archibald Williams lost the election to William Richardson . The overall election was a success for the anti-Nebraska movement , however , as the anti-Nebraska forces won enough seats to gain a majority in the U.S. House of Representatives . After 1854 , Archibald Williams and Abraham Lincoln and other anti-Nebraskans took the lead in forming the Republican Party in Illinois around the issue of `` no slavery in the territories . '' An Archibald Williams Committee Influences Lincoln Abraham Lincoln wrote a letter in which he said he was ready to `` fuse '' with other anti-slavery groups according to `` principles '' adopted at a public meeting in Quincy , Illinois . The purpose of fusion was to bring many disparate anti-slavery groups together to form the Republican Party . Lincoln 's letter noted that the principles had been drawn up by a three-person committee led `` by Mr. Archibald Williams . '' The principles centered on the idea that Southern slave owners could keep their slaves but that slavery would be forbidden in the territories . Archibald Williams and his committee either influenced Lincoln directly on `` fusion , '' or else they confirmed a position on `` fusion '' that Lincoln had already adopted . At the United States Supreme Court Archibald Williams argued a case before the United States Supreme Court on December 6 and 7 , 1855 . Orville Browning , Williams 's good friend from Quincy , Illinois , was the opposing lawyer . The issue in dispute dealt with rival claims for lands and centered on whether the question of `` bad faith '' in the matter should be decided by a judge or by a jury . The Court ruled in Wright v. Mattison that `` bad faith '' should not be decided by the judge but by the jury , which had been the precedent . The Court ordered the case to be retried in a lower court . The outcome was a victory for Browning and a loss for Williams . The Beginnings of the Republican Party in Illinois In 1856 , Archibald Williams was the temporary chairman at a major anti-Nebraska convention in Bloomington , Illinois . Williams led the convention until a permanent chairman had been elected . While attending the convention , Abraham Lincoln and Archibald Williams slept in the same bed at the Bloomington home of David Davis , a close friend of both men.A historian noted : `` At Bloomington , Lincoln , Archibald Williams , his old associate in the Legislature , -LSB- and -RSB- T. Lyle Dickey , of Ottawa -LSB- Illinois -RSB- , a good lawyer , went to -LSB- David -RSB- Davis 's house and lived there during the Convention . Lincoln and Williams slept in one bed and Dickey and Whitney in another ... The course of the historic Bloomfield Convention was decisively influenced by the counsels that came from the steady men in the Davis House . '' Although the name `` Republican '' was applied at a later date , the anti-Nebraska convention in Bloomington was considered the birthplace of the Republican Party in Illinois . The Election of 1858 In 1858 , at a state party convention in Springfield , Illinois , Abraham Lincoln was nominated to be the Republican candidate for U.S. Senator from Illinois . A resolution passed at the convention stated that Lincoln `` was the first and only choice of the Republicans of Illinois for the U.S. Senate . '' In the famous Lincoln-Douglas debates in the 1858 Illinois U.S. Senate race , Democratic candidate Stephen Douglas attacked Lincoln three times for having been described as `` the first and only choice '' of Illinois Republicans for the Senate seat . All three times , Douglas pointed to Archibald Williams as an Illinois Republican who would have been an acceptable alternate choice to Lincoln in that contest . Archibald Williams traveled and spoke throughout the state of Illinois in Lincoln 's behalf during the 1858 U.S. Senate race . A newspaper in Quincy , Illinois , allied with the Republican Party , printed : `` Old Archie Williams is doing good service for the Republican cause ... He has already spoken at Macomb , Oquawka , Monmouth , Cameron , Galesburg , and other points ... to large assemblages ; and everywhere , he has created enthusiasm and confidence among our friends and animated the lukewarm ... In the winter of his life ... Mr. Williams is found battling for the cause of Republicanism . '' The Illinois state legislature chose Stephen Douglas over Abraham Lincoln in the 1858 U.S. Senate race . A close friend of Lincoln 's wrote : `` In January , 1859 , while the Democrats were celebrating the election of Stephen A. Douglas to the United States Senate , Archibald Williams ... came into Lincoln 's office and finding him writing said : ` Well , the Democrats are making a great noise over their victory . ' Looking up Lincoln replied : ` Yes , Archie , Douglas has taken this trick , but the game is not played out . ' '' The Lincoln-Douglas debates became so well-known that Lincoln gave personally signed presentation copies of the debates to his best friends and political associates . The one given to Archibald Williams was inscribed in Lincoln 's handwriting : `` To Hon : Archibald Williams , with respects of A. Lincoln . '' It was one more sign of Lincoln 's close friendship and strong political alliance with Archibald Williams . The Presidential Election of 1860 On December 25 , 1859 , a number of leading Republicans in Quincy , Illinois , including Archibald Williams , met with Horace Greeley , a prominent national journalist and editor of the New York Tribune . Greeley had famously stated `` Go west , young man . Go west ! '' Williams and the other Quincy Republicans talked to Greeley about Abraham Lincoln possibly becoming the Republican candidate for President in 1860 . Archibald Williams spoke throughout Illinois in behalf of Abraham Lincoln during Lincoln 's successful 1860 campaign for the White House in Washington , D.C. Almost on the Supreme Court , Then U.S. District Judge in Kansas Following his election to the U.S. presidency in 1860 , Abraham Lincoln offered Archibald Williams a seat on the U.S. Supreme Court . Williams refused the offer due to ill health and advanced age . Williams recommended that Lincoln appoint a younger court nominee who could live for more years and thereby serve longer on the Court . Archibald Williams was then appointed by President Lincoln to be the Judge for the U.S. District Court of Kansas . Williams was the first person to hold the office of U.S. District Court Judge in Kansas , because Kansas had just been admitted to the Union as a state . Williams moved to Topeka , Kansas , the state capital , where he served more than two years as U.S. Judge . He moved back to Quincy , Illinois , shortly before his death on September 21 , 1863 . During his tenure as the U.S. District Court Judge for Kansas , Archibald Williams worked on such issues as building a branch of the transcontinental railroad across Kansas , fair treatment of Native Americans in railroad matters , and the loyalty to the Union cause of a U.S. Army officer stationed in Kansas . Also while in Kansas , Williams married his second wife , Ellen M. Parker , on September 24 , 1861 . The marriage lasted a little less than two years until Archibald Williams death . While serving as the U.S. Judge for Kansas , Archibald Williams traveled to Washington , D.C. , and , on May 29 , 1962 , paid a last visit to his old friend Abraham Lincoln in the White House . Death and Burial of Archibald Williams Archibald Williams was praised in obituaries as a leading attorney in Illinois in the mid-19th Century . His many political and governmental activities were noted , along with his deep friendship with Abraham Lincoln . The bar association in Quincy , Illinois , donated a large marble grave marker for Williams . The base of the marker was a stack of law books ; an obelisk was placed on top of the law books . He was buried in Woodland Cemetery in Quincy , Illinois , at a grave site that overlooks the Mississippi River .","title":""},{"docid":"Lincoln–Douglas_debates","text":"The Lincoln -- Douglas Debates ( also known as The Great Debates of 1858 ) were a series of seven debates between Abraham Lincoln , the Republican candidate for the United States Senate from Illinois , and incumbent Senator Stephen Douglas , the Democratic Party candidate . At the time , U.S. senators were elected by state legislatures ; thus Lincoln and Douglas were trying for their respective parties to win control of the Illinois legislature . The debates previewed the issues that Lincoln would face in the aftermath of his victory in the 1860 presidential election . Although Illinois was a free state , the main issue discussed in all seven debates was slavery in the United States . In agreeing to the official debates , Lincoln and Douglas decided to hold one debate in each of the nine congressional districts in Illinois . Because both had already spoken in two -- Springfield and Chicago -- within a day of each other , they decided that their `` joint appearances '' would be held only in the remaining seven districts . The debates were held in seven towns in the state of Illinois : Ottawa on August 21 Freeport on August 27 Jonesboro on September 15 Charleston on September 18 Galesburg on October 7 Quincy on October 13 Alton on October 15 The debates in Freeport , Quincy and Alton drew especially large numbers of people from neighboring states , as the issue of slavery was of monumental importance to citizens across the nation . Newspaper coverage of the debates was intense . Major papers from Chicago sent stenographers to create complete texts of each debate , which newspapers across the United States reprinted in full , with some partisan edits . Newspapers that supported Douglas edited his speeches to remove any errors made by the stenographers and to correct grammatical errors , while they left Lincoln 's speeches in the rough form in which they had been transcribed . In the same way , pro-Lincoln papers edited Lincoln 's speeches , but left the Douglas texts as reported . After losing the election for Senator in Illinois , Lincoln edited the texts of all the debates and had them published in a book . The widespread coverage of the original debates and the subsequent popularity of the book led eventually to Lincoln 's nomination for President of the United States by the 1860 Republican National Convention in Chicago . The format for each debate was : one candidate spoke for 60 minutes , then the other candidate spoke for 90 minutes , and then the first candidate was allowed a 30-minute `` rejoinder . '' The candidates alternated speaking first . As the incumbent , Douglas spoke first in four of the debates .","title":""},{"docid":"United_States_presidential_election_in_California,_1860","text":"In the 1860 United States presidential election , California narrowly voted for the Republican nominee , former Illinois representative Abraham Lincoln , over the Democratic nominee , Illinois Senator Stephen A. Douglas and the Southern Democratic nominee , Vice President John C. Breckinridge .","title":""},{"docid":"Northern_Democratic_Party","text":"The Northern Democratic Party was a leg of the Democratic Party during the 1860 presidential election . It was when the party split in two due to problems with slavery . Stephen A. Douglas was the nominee and lost to Abraham Lincoln . They held two conventions before the election , in Charleston and Baltimore , where they established their platform .","title":""},{"docid":"William_P._Fessenden","text":"William Pitt Fessenden ( October 16 , 1806September 8 , 1869 ) was an American politician from the U.S. state of Maine . Fessenden was a Whig ( later a Republican ) and member of the Fessenden political family . He served in the United States House of Representatives and Senate before becoming Secretary of the Treasury under President Abraham Lincoln during the American Civil War . A lawyer , he was a leading antislavery Whig in Maine ; in Congress , he fought the Slave Power ( the plantation owners who controlled southern states ) . He built an antislavery coalition in the state legislature that elected him to the U.S. Senate ; it became Maine 's Republican organization . In the Senate , Fessenden played a central role in the debates on Kansas , denouncing the expansion of slavery . He led Radical Republicans in attacking Democrats Stephen Douglas , Franklin Pierce , and James Buchanan . Fessenden 's speeches were read widely , influencing Republicans such as Abraham Lincoln and building support for Lincoln 's 1860 Republican presidential nomination . During the war , Senator Fessenden helped shape the Union 's taxation and financial policies . He moderated his earlier radicalism , and supported Lincoln against the Radicals , becoming Lincoln 's Treasury Secretary . After the war , Fessenden was back in the Senate , as chair of the Joint Committee on Reconstruction , which established terms for resuming congressional representation for the southern states , and which drafted the Fourteenth Amendment to the United States Constitution . Later , Fessenden provided critical support that prevented Senate conviction of President Andrew Johnson , who had been impeached by the House . He was the first Republican Senator to ring out '' ... not guilty '' followed by six other Republican Senators resulting in the acquittal of President Johnson . He is the only person to have three streets in Portland named for him : William , Pitt and Fessenden streets in the city 's Oakdale neighborhood .","title":""},{"docid":"James_A._McDougall","text":"James Alexander McDougall ( November 19 , 1817 -- September 3 , 1867 ) was an American attorney and politician elected to statewide office in two U.S. states , then to the United States House of Representatives and United States Senate . A gifted orator , McDougall began his career as a civil engineer in New York , then read law , rising quickly to heights in his profession in Illinois , where he became a friend of fellow prairie attorneys Abraham Lincoln , Edward D. Baker , and Stephen Douglas . Like many Americans , McDougall was drawn to Gold Rush California in 1849 ; he resumed his law practice and was elected second attorney general for the new state of California . In the election of 1860 , Lincoln won the presidency as a Republican , Baker was elected Republican senator from Oregon , and McDougall was elected senator from California , joining Douglas in the Senate as fellow War Democrats . All three of McDougall 's Prairie State friends would die in the six years before his term as senator expired . A noted drinker , McDougall once gave an address to the Senate disparaging a proposed rule to outlaw the sale of alcohol in the United States Capitol , but died shortly after leaving the Senate , '' ... hastened by his indulgence in the bowl . ''","title":""},{"docid":"Lincoln's_House_Divided_Speech","text":"The House Divided Speech was an address given by Abraham Lincoln ( who would later become President of the United States ) on June 16 , 1858 , at what was then the Illinois State Capitol in Springfield , upon accepting the Illinois Republican Party 's nomination as that state 's United States senator . The speech became the launching point for his unsuccessful campaign for the Senate seat held by Stephen A. Douglas ; this campaign would climax with the Lincoln-Douglas debates of 1858 . Lincoln 's remarks in Springfield created an image of the danger of slavery-based disunion , and it rallied Republicans across the North . Along with the Gettysburg Address and his second inaugural address , this became one of the best-known speeches of his career . The best-known passage of the speech is : Lincoln 's goals with this speech were , firstly , to differentiate himself from Douglas , the incumbent ; and secondly , to publicly voice a prophecy for the future . Douglas had long advocated popular sovereignty , under which the settlers in each new territory decided their own status as a slave or free state ; he had repeatedly asserted that the proper application of popular sovereignty would end slavery-induced conflict , and would allow northern and southern states to resume their peaceful coexistence . Lincoln , however , responded that the Dred Scott decision had closed the door on Douglas 's preferred option and left the Union with only two remaining outcomes : the United States would inevitably become either all slave , or all free . Now that the North and the South had come to hold distinct opinions in the question of slavery , and now that this issue had come to permeate every other political question , the time would soon come when the Union would no longer be able to function .","title":""},{"docid":"Miller–Davis_Law_Buildings","text":"The Miller -- Davis Law Buildings , known commonly as the Miller Davis Building , are located on Main and Front Street in the McLean County , Illinois city of Bloomington . The law offices served future Supreme Court Justice David Davis and future Illinois State Senator Asahel Gridley . The buildings became a gathering place for local lawyers such as Abraham Lincoln and Stephen A. Douglas .","title":""},{"docid":"Lincoln_Oak","text":"The Lincoln Oak was an oak tree in Bloomington , Illinois . Stephen A. Douglas and Abraham Lincoln both gave speeches at the tree during the 1850s . The original Lincoln Oak died in 1976 .","title":""},{"docid":"Lincoln–Douglas_debate","text":"Lincoln -- Douglas debate ( commonly abbreviated as LD Debate , or simply LD ) is a type of one-on-one debate practiced mainly in the United States at the high school level . It is sometimes also called values debate because the format traditionally places a heavy emphasis on logic , ethical values , and philosophy ( also called as logos , ethos and pathos ) . The Lincoln -- Douglas Debate format is named for the 1858 Lincoln -- Douglas Debates between Abraham Lincoln and Stephen A. Douglas , because their debates focused on slavery and the morals , values , and logic behind it . LD Debates are used by the National Speech and Debate Association , or NSDA ( formerly known as the National Forensics League , or NFL ) competitions , and also widely used in related debate leagues such as the National Christian Forensics and Communication Association , the National Catholic Forensic League , the National Educational Debate Association , the Texas University Interscholastic League , Texas Forensic Association , Stoa USA and their affiliated regional organizations . The vast majority of tournaments use the current NSDA resolution .","title":""},{"docid":"Joseph_Arnold_(Rhode_Island)","text":"Joseph Arnold ( 1710 -- 1776 ) was a pre-revolutionary resident of North Kingstown and Exeter in the Colony of Rhode Island and Providence Plantations . He is most noted for having a very large progeny , having had 16 children of whom 15 grew to maturity , married , and had children of their own , giving him at least 89 grandchildren . He was the great great grandfather of presidential hopeful Stephen Arnold Douglas who debated Abraham Lincoln in 1858 , and lost to him in the 1860 presidential election . He was an ancestral link between Douglas and many prominent early Rhode Islanders such as Governor Benedict Arnold and two founders of the Rhode Island colony , Samuel Wilbore and John Porter .","title":""},{"docid":"Stephen_A._Douglas_Tomb","text":"The Stephen A. Douglas Tomb and Memorial or Stephen Douglas Monument Park is located at 636 E. 35th Street in the Bronzeville neighborhood of Chicago , Illinois ( part of the city 's Douglas community ) , near the site of the Union Army and prisoner of war Camp Douglas . A ten-foot statue of the man best remembered for debating Abraham Lincoln over slavery stands atop a 46 ft column of white marble from his native state , Vermont . Douglas died from typhoid fever on June 3 , 1861 in Chicago , where he was buried on the shore of Lake Michigan . The site was afterwards bought by the state of Illinois , and the imposing monument by Leonard Volk was built over his grave . The cornerstone was laid in 1861 and the tomb was completed in 1881 . The site was designated a Chicago Landmark on September 28 , 1977 . The tomb is maintained by the Illinois Historic Preservation Agency as a state historic site .","title":""},{"docid":"United_States_elections,_1860","text":"The 1860 United States elections elected the members of the 37th United States Congress . The election took place during the Third Party System , shortly before the start of the Civil War . The Republican Party won control of the Presidency and both houses of Congress , making it the fifth party ( following the Federalist Party , Democratic-Republican Party , Democratic Party , and Whig Party ) to accomplish that feat . The election is widely considered to be a realigning election . In the Presidential election , Republican former Representative Abraham Lincoln of Illinois defeated Democratic Vice President John C. Breckinridge ( who became the first incumbent Vice President to lose a presidential election ) and Democratic Senator Stephen A. Douglas of Illinois , as well as the Constitutional Union candidate , former Senator John Bell of Tennessee . Lincoln swept the Northern states while Breckinridge carried much of the South , foreshadowing the political alignment of the country throughout the Third Party System . At the 1860 Republican National Convention , Lincoln won on third ballot , defeating Senator William H. Seward of New York and several other candidates . The Democratic Party split its votes after three chaotic conventions . Douglas was nominated at the second Democratic convention , while the Southern Democrats nominated Breckinridge as their own candidate in a third convention . Bell ran on a platform of preserving the union regardless of the status of slavery . Lincoln 's victory made him the first Republican President . Lincoln took just under 40 percent of the popular vote , a lower share of the popular vote than any other winning presidential candidate aside from John Quincy Adams 's 1824 campaign . In the House , Republicans retained control of the chamber and won a majority for the first time after several states seceded . Democrats remained the largest minority , but several Congressmen also identified as unionists . In the Senate , Republicans made moderate gains , but won a majority after several states seceded . The Democrats remained the largest minority party , though some Congressmen identified as unionists .","title":""},{"docid":"Abraham_Lincoln_National_Heritage_Area","text":"The Abraham Lincoln National Heritage Area is a National Heritage Area in central Illinois telling the story of Abraham Lincoln . A National Heritage Area is a federal-designated area intended to encourage historic preservation and an appreciation of the history and heritage of the site . While National Heritage Areas are not federally owned or managed , the National Park Service provides an advisory role and some technical , planning and financial assistance . The Abraham Lincoln National Heritage Area was created as part of the Consolidated Natural Resources Act of 2008 ( S. 2739 ) , an omnibus bill . It was originally introduced in the Senate by Dick Durbin and in the House of Representatives by Ray LaHood , both from Illinois . The legislation also provided $ 10 million over 10 years , with no more than $ 1 million awarded in any single year , to make federal grants available for preservation , education and economic development . Grants awarded for Lincoln National Heritage Area activities must be matched dollar-for-dollar in state , local or private funds . The management authority for the Abraham Lincoln National Heritage Area is the Looking for Lincoln Heritage Coalition and follows Lincoln 's life from his birth and childhood , to his early life and career , to the Lincoln -- Douglas debates of 1858 . The legislation protects private property rights and would not require any private citizen or entity to be affiliated with the Lincoln Heritage Area . The bill names the Looking for Lincoln Heritage Coalition as the management authority for the National Heritage Area , but does not grant any zoning or land use power to the Coalition . Up to $ 10 million in federal grants would be available under this legislation The Heritage Area includes the following sites : Lincoln Home National Historic Site Lincoln Tomb State Historic Site Lincoln 's New Salem State Historic Site at New Salem , Menard County , Illinois Abraham Lincoln Presidential Library and Museum Lincoln Log Cabin State Historic Site Mount Pulaski Courthouse State Historic Site , Postville Courthouse State Historic Site and Metamora Courthouse State Historic Site Lincoln-Herndon Law Offices State Historic Site David Davis Mansion State Historic Site Vandalia State House State Historic Site Lincoln Douglas Debate Museum Macon County Log Court House Richard James Oglesby Mansion Lincoln Trail Homestead State Memorial John Wood Mansion Beardstown Courthouse Old Main at Knox College Carl Sandburg State Historic Site Bryant Cottage State Historic Site Dr. William Fithian Home Vermilion County Museum","title":""},{"docid":"Abe_Lincoln_in_Illinois_(play)","text":"Abe Lincoln in Illinois is a play written by the American playwright Robert E. Sherwood in 1938 . The play , in three acts , covers the life of President Abraham Lincoln from his childhood through his final speech in Illinois before he left for Washington . The play also covers his romance with Mary Todd and his debates with Stephen A. Douglas , and uses Lincoln 's own words in some scenes . Sherwood received the Pulitzer Prize for Drama in 1939 for his work .","title":""},{"docid":"Freeport_Doctrine","text":"The Freeport Doctrine was articulated by Stephen A. Douglas at the second of the Lincoln-Douglas debates on August 27 , 1858 , in Freeport , Illinois . Former one-term U.S. Representative Abraham Lincoln was campaigning to take Douglas ' U.S. Senate seat by strongly opposing all attempts to expand the geographic area in which slavery was practiced . Lincoln tried to force Douglas to choose between the principle of popular sovereignty proposed by the Kansas-Nebraska Act ( which left the fate of slavery in a U.S. territory up to its inhabitants ) , and the majority decision of the United States Supreme Court in the case of Dred Scott v. Sandford , which stated that slavery could not legally be excluded from U.S. territories ( since Douglas professed great respect for Supreme Court decisions , and accused the Republicans of disrespecting the court , yet this aspect of the Dred Scott decision was contrary to Douglas ' views and politically unpopular in Illinois ) . Instead of making a direct choice , Douglas ' response stated that despite the court 's ruling , slavery could be prevented from any territory by the refusal of the people living in that territory to pass laws favorable to slavery . Likewise , if the people of the territory supported slavery , legislation would provide for its continued existence . Douglas 's actual words were : The next question propounded to me by Mr. Lincoln is , Can the people of a Territory in any lawful way , against the wishes of any citizen of the United States , exclude slavery from their limits prior to the formation of a State constitution ? I answer emphatically , as Mr. Lincoln has heard me answer a hundred times from every stump in Illinois , that in my opinion the people of a Territory can , by lawful means , exclude slavery from their limits prior to the formation of a State constitution . Mr Lincoln knew that I had answered that question over and over again . He heard me argue the Nebraska bill on that principle all over the State in 1854 , in 1855 , and in 1856 , and he has no excuse for pretending to be in doubt as to my position on that question . It matters not what way the Supreme Court may hereafter decide as to the abstract question whether slavery may or may not go into a Territory under the Constitution , the people have the lawful means to introduce it or exclude it as they please , for the reason that slavery can not exist a day or an hour anywhere , unless it is supported by local police regulations . Those police regulations can only be established by the local legislature ; and if the people are opposed to slavery , they will elect representatives to that body who will by unfriendly legislation effectually prevent the introduction of it into their midst . If , on the contrary , they are for it , their legislation will favor its extension . Hence , no matter what the decision of the Supreme Court may be on that abstract question , still the right of the people to make a Slave Territory or a Free Territory is perfect and complete under the Nebraska bill . I hope Mr. Lincoln deems my answer satisfactory on that point . By taking this position , Douglas was defending his Popular Sovereignty or `` Squatter Sovereignty '' principle of 1854 , which he considered to be a compromise between pro-slavery and anti-slavery positions . It was satisfactory to the legislature of Illinois , which reelected Douglas over Lincoln to the Senate ( this was before the addition of the Seventeenth Amendment to the Constitution ) . However , the Freeport Doctrine alienated many Southern Democrats . Douglas had actually stated the essence of the doctrine previous to the debate at Freeport , but its prominent public assertion at Freeport contributed ( along with other political disputes , such as over the Lecompton Constitution ) to antagonizing those in the Southern United States who were demanding ever-increasing protections for slavery , and who subsequently insisted on the repudiation of the Freeport Doctrine ( i.e. , the passage of a congressional Slave Code for the territories ) in order to block Douglas ' presidential bid in 1860 . This led to the split of the Democratic party in 1860 , and Douglas ' loss in the 1860 presidential election .","title":""},{"docid":"Archibald_Dixon","text":"Archibald Dixon ( April 2 , 1802 -- April 23 , 1876 ) was a U.S. Senator from Kentucky . He represented the Whig Party in both houses of the Kentucky General Assembly , and was elected the 12th Lieutenant Governor of Kentucky in 1844 , serving under Governor William Owsley . In 1851 , the Whigs nominated him for governor , but he lost to Lazarus W. Powell , his former law partner . Dixon represented Henderson County at the Kentucky constitutional convention of 1849 . In this capacity , he ensured that strong protections of slave property were included in the Kentucky Constitution of 1850 . Later , the General Assembly chose Dixon to fill the unexpired Senate term of Henry Clay . He served from September 1 , 1852 , to March 3 , 1855 , and did not stand for re-election . During his short tenure , Dixon 's major accomplishment was convincing Stephen Douglas to include language in the Kansas-Nebraska Act that explicitly repealed the Missouri Compromise 's prohibition on slavery north of latitude 36 ° 30 ' . Despite his pro-slavery views , Dixon was loyal to the Union during the Civil War . He represented his county and his state in a number of failed conventions that sought to resolve the upcoming conflict before it began . In 1864 , he joined Kentucky governor Thomas E. Bramlette in an audience with President Abraham Lincoln protesting the recruitment of former slaves as Union soldiers in Kentucky . Dixon died on April 23 , 1876 .","title":""},{"docid":"Abraham_Jonas_(politician)","text":"Abraham Jonas ( born September 12 , 1801 in Exeter , England ; died June 8 , 1864 ) was the first permanent Jewish resident in Quincy , Illinois . He was a former member of the Illinois and Kentucky State Legislature , a leading lawyer , and a valued friend of Abraham Lincoln . Jonas was born in Exeter , England to Annie Ezekiel and Benjamin Jonas . Abraham 's brother , Joseph Jonas , moved to Cincinnati , Ohio becoming the first Jew to settle west of the Allegheny Mountains . Abraham and his brother Edward joined Joseph in Cincinnati in 1819 . Abraham and his two brothers were original members of Congregation B'nai Israel ( Sons of Israel ) , the first Jewish congregation west of the Allegheny Mountains . Abraham also joined the Freemasons in Cincinnati . He and Joseph married Lucy and Rachel Seixas ; daughters of the first Rabbi born in America -- Gershom Mendes Seixas . Lucy suddenly died in 1825 , and Abraham moved to Williamstown , Kentucky . There he married Louisa Block from a pioneering Jewish American family and operated a general store . He was elected to the state legislature for four years . While in Kentucky , Abraham organized a Masonic Lodge and was eventually elected Master of the lodge in 1832 . During that time he and Louisa had five children . In 1836 he moved to Columbus in Adams County , Illinois to operate another general store . Within two years he moved to Quincy , IL opening a carriage business and studying law in Orville Browning 's office . He then organized the Grand Masonic Lodge of Illinois in 1840 and was elected Grand Master . In 1842 he was elected as a Whig to the state legislature . Lucy and Abraham had three more children around this time . He decided to establish a law partnership with Henry Asbury , turning over the family business to his brothers Edward and Samuel who had joined him in Quincy in 1840 or 1841 . It is suspected that it was during his years in legislation in Springfield that Abraham Jonas met Abraham Lincoln , as Lincoln was too a member of the state legislation at the time . Jonas ran for the Illinois Senate in 1844 but was defeated by the Democratic candidate . But his loyalty to the Whig party earned him the position as postmaster of Quincy in 1849 serving until 1853 . Lincoln and Jonas remained dear friends during this time . When the Whig party died , Jonas and Lincoln both joined the new Republican Party . On November 1 , 1854 Lincoln was accused of attending a Know-Nothing Party meeting , but was vouched by Jonas who he was actually with . Jonas arranged the 1858 Lincoln-Douglas debate in Quincy , and aided Lincoln to his candidacy . It was his law partner Henry Asbury who suggested Lincoln 's candidacy in front of a group of local Republicans . Asbury 's suggestion was greeted by silence until Jonas agreed that it would be a good idea . Abraham Jonas was noted as one of the greatest orators himself in the area . He was elected Grand Orator of the Grand Lodge of Illinois in 1843 . Lincoln appointed Jonas postmaster of Quincy in 1861 until his death in 1864 . Jonas had seven children , six sons and a daughter . Four of his sons , including future U.S. Senator Benjamin F. Jonas , fought for the Confederacy during the Civil War , being residents of Louisiana ; two others fought for the Union . Lincoln personally ordered the release of his son Charles Jonas from a prisoner of war camp to be at his father 's bedside before he died .","title":""},{"docid":"Old_State_Capitol_State_Historic_Site","text":"The Old State Capitol State Historic Site , in Springfield , Illinois , is the fifth capitol building built for the U.S. state of Illinois . It was built in the Greek Revival style in 1837 -- 1840 , and served as the state house from 1840 to 1876 . It is the site of candidacy announcements by Abraham Lincoln in 1858 and Barack Obama in 2007 . It was designated a National Historic Landmark in 1961 , primarily for its association with Lincoln and his political rival Stephen Douglas .","title":""},{"docid":"Jesse_B._Thomas,_Jr.","text":"Jesse Burgess Thomas , Jr. ( July 31 , 1806 -- February 21 , 1850 ) was born in Lebanon , Ohio and was an Illinois politician who served as the Illinois Attorney General from 1835 -- 1836 and later on the state Supreme Court . After studying law at Transylvania University in Lexington , Kentucky , Thomas settled in Edwardsville , Illinois . By 1830 , Thomas was serving as the secretary to the Illinois State Senate . Four years later , he served a partial term in the Illinois House of Representatives for Madison County before being appointed Attorney General , a post he held for a single year . From 1837 through 1839 , he was a circuit court judge based in Springfield . His circuit included New Salem , where Thomas heard cases argued by Abraham Lincoln . When Stephen A. Douglas gave up his seat on the Illinois Supreme Court in 1843 after being elected to Congress , Governor Thomas Ford appointed Thomas as Douglas 's successor . After retiring from the Supreme Court in 1848 , he moved first to Galena and then to Chicago , where he died in 1850 . Thomas 's uncle was Jesse B. Thomas , one of Illinois ' first Senators . Thomas was married to one of the daughters of Illinois Supreme Court Justice Theophilus W. Smith .","title":""},{"docid":"Jesse_W._Fell","text":"Jesse W. Fell ( 1808 -- 1887 ) was a Bloomington , Illinois businessman and land owner instrumental in the establishment of communities throughout Central Illinois and for the founding of Illinois State University . A close friend of Abraham Lincoln it was Fell who urged him to challenge his opponent , Stephen A. Douglas , to their famous series of debates .","title":""},{"docid":"The_Lincoln_Hunters","text":"The Lincoln Hunters is a 1958 novel by Wilson Tucker . The novel , set in the year 2578 , details the story of a historian from the oppressive society of that year , who travels back in time to record Abraham Lincoln 's Lost Speech of May 19 , 1856 in Bloomington , Illinois . It contains a vivid description of Lincoln in the early stages of his career , seen through the eyes of a future American who feels that Lincoln and his time compare very favorably with the traveler 's own . The book is mentioned in 11/22/63 , a novel by Stephen King that also centers around time travel and an assassinated president . Furthermore , the protagonist springboards to 1958-the year `` Hunters '' first ran-to alter the timeline by 1963 . Category :1958 American novels Category :1950 s science fiction novels Category : American science fiction novels Category : Time travel novels Category : Novels by Wilson Tucker Category :1856 in fiction Category : Novels set in Illinois Category :26 th century in fiction Category : Fictional depictions of Abraham Lincoln in literature","title":""},{"docid":"Hampton_Roads_Conference","text":"The Hampton Roads Conference was a peace conference held between the United States and the Confederate States on February 3 , 1865 , aboard the steamboat River Queen in Hampton Roads , Virginia , to discuss terms to end the American Civil War . President Abraham Lincoln and Secretary of State William H. Seward , representing the Union , met with three commissioners from the Confederacy : Vice President Alexander H. Stephens , Senator Robert M. T. Hunter , and Assistant Secretary of War John A. Campbell . The representatives discussed a possible alliance against France , the possible terms of surrender , the question of whether slavery might persist after the war , and the question of whether the South would be compensated for property lost through emancipation . Lincoln and Seward reportedly offered some possibilities for compromise on the issue of slavery . The only concrete agreement reached was over prisoner-of-war exchanges . The Confederate commissioners immediately returned to Richmond at the conclusion of the conference . Confederate President Jefferson Davis announced that the North would not compromise . Lincoln drafted an amnesty agreement based on terms discussed at the Conference , but met with opposition from his Cabinet . John Campbell continued to advocate for a peace agreement and met again with Lincoln after the fall of Richmond on April 2 .","title":""}],"string":"[\n {\n \"docid\": \"L/D\",\n \"text\": \"L/D may refer to : Learning and development , in human resource management Lift-to-drag ratio , in aerodynamics Lincoln -- Douglas debates , a series of seven debates in 1858 between Abraham Lincoln , the Republican candidate for the Senate in Illinois , and Senator Stephen Douglas , the Democratic Party candidate\",\n \"title\": \"\"\n },\n {\n \"docid\": \"United_States_Senate_elections,_1858_and_1859\",\n \"text\": \"The United States Senate elections of 1858 and 1859 were elections which had the Republican Party gain five additional seats in the United States Senate , but the Democrats retained their majority . That majority would erode in 1860 with the secession of the southern states leading up to the Civil War . In Illinois , incumbent Stephen A. Douglas ( D ) and challenger Abraham Lincoln held a series of seven debates , known as the `` Lincoln -- Douglas debates . '' As this election was prior to ratification of the seventeenth amendment , Senators were chosen by State legislatures .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Abraham_Lincoln's_Peoria_speech\",\n \"text\": \"Abraham Lincoln 's Peoria speech was made in Peoria , Illinois on October 16 , 1854 . The speech , with its specific arguments against slavery , was an important step in Abraham Lincoln 's political ascension . The 1854 Kansas-Nebraska Act , written to form the territories of Kansas and Nebraska , was designed by Stephen A. Douglas , then the chairman of the Senate Committee on Territories . The Act included language that allowed settlers to decide whether they would or would not accept slavery in their region . Lincoln saw this as a repeal of the 1820 Missouri Compromise which had outlawed slavery above the 36 ° 30 ' parallel .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Pardon_Tillinghast\",\n \"text\": \"Pardon Tillinghast ( 1625 -- 1718 ) was an early settler of Providence , Rhode Island , a public official there , and a pastor of the Baptist Church of Providence . A cooper by profession , he immigrated to New England about 1645 , and became a successful merchant . Later in life he became a clergyman , serving without compensation for nearly four decades . He died in 1718 aged about 96 , and was buried in a family cemetery on Benefit Street in Providence that remains extant . Among his thousands of descendants are many of great prominence , including Continental Congress delegate Samuel Ward ; Julia Ward Howe who wrote the Battle Hymn of the Republic ; and Stephen Arnold Douglas who was involved in a series of famed debates with Abraham Lincoln in 1858 , prior to a Senate race , and later lost to him in the 1860 presidential election .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"The_Lincoln–Douglas_Debates_(1994_reenactments)\",\n \"text\": \"The 1994 reenactments of the Lincoln -- Douglas Debates took place between August 20 and October 15 , 1994 and were facilitated and aired by C-SPAN . They featured historical reenactors presenting , in their entireties , the series of seven debates between Abraham Lincoln and Stephen A. Douglas that took place during the 1858 U.S. Senate campaign in Illinois . The debate reenactments were held in the same seven cities as were the 1858 debates , and were performed on dates very close to the anniversaries of the original debates . They were broadcast live on C-SPAN , and have been rebroadcast periodically ever since .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"1860_Republican_National_Convention\",\n \"text\": \"The 1860 Republican National Convention , also known as the 2nd Republican National Convention , was a nominating convention of the Republican Party of the United States , held in Chicago , Illinois , from May 16 to 18 , 1860 . The gathering nominated former U.S. Representative Abraham Lincoln of Illinois for President of the United States and Senator Hannibal Hamlin of Maine for Vice President . Lincoln 's nomination was a surprise , as the favorite before the convention had been former Governor of New York and U.S. Senator William H. Seward . Lincoln 's campaign manager , David Davis , is credited for Lincoln 's victory over Thurlow Weed , Seward 's campaign manager . Lincoln-Hamlin went on to defeat three other major tickets that year , including Democratic nominee Stephen A. Douglas , U.S. Senator from Illinois .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Stephen_A._Douglas\",\n \"text\": \"Stephen Arnold Douglas ( April 23 , 1813 -- June 3 , 1861 ) was an American politician from Illinois and the designer of the Kansas -- Nebraska Act . He was a U.S. representative , a U.S. senator , and the Democratic Party nominee for president in the 1860 election , losing to Republican Abraham Lincoln . Douglas had previously defeated Lincoln in a Senate contest , noted for the famous Lincoln-Douglas debates of 1858 . He was nicknamed the `` Little Giant '' because he was short in physical stature , but a forceful and dominant figure in politics . ( His height is given in various sources as being in the range of 5 ft to 5 ft ; five feet four is reported most often . ) Douglas was well known as a resourceful party leader , and an adroit , ready , skillful tactician in debate and passage of legislation . He was a champion of the Young America movement which sought to modernize politics and replace the agrarian and strict constructionist orthodoxies of the past . Douglas was a leading proponent of democracy , and believed in the principle of popular sovereignty : that the majority of citizens should decide contentious issues such as slavery and territorial expansion . As chairman of the Committee on Territories , Douglas dominated the Senate from 1850 to 1859 . He was largely responsible for the Compromise of 1850 that apparently settled slavery issues ; however , in 1854 he reopened the slavery question with the Kansas -- Nebraska Act , which opened some previously prohibited territories to slavery under popular sovereignty . Opposition to this led to the formation of the Republican Party . Douglas initially endorsed the Dred Scott decision of 1857 . But during the 1858 Senate campaign , he argued its effect could be negated by popular sovereignty . He also opposed the efforts of President James Buchanan and his Southern allies to enact a Federal slave code and impose the Lecompton Constitution on Kansas . In 1860 , the conflict over slavery led to the split in the Democratic Party in the 1860 Convention . Hardline pro-slavery Southerners rejected Douglas , and nominated their own candidate , Vice President John C. Breckinridge , while the Northern Democrats nominated Douglas . Douglas deeply believed in democracy , arguing the will of the people should always be decisive . When civil war came in April 1861 , he rallied his supporters to the Union cause with all his energies , but he died of typhoid fever a few weeks later .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Archibald_Williams_(judge)\",\n \"text\": \"Archibald Williams ( June 10 , 1801 -- September 21 , 1863 ) was a United States federal judge . Born in Montgomery County , Kentucky , Williams read law to enter the bar in 1828 . He was in private practice in Quincy , Illinois beginning in 1829 . He was the United States Attorney for the District of Illinois from 1849 to 1853 . He served in both the Illinois House of Representatives and the Illinois State Senate . On March 8 , 1861 , Williams was nominated by President Abraham Lincoln to a new seat on the United States District Court for the District of Kansas created by 12 Stat . 126 . He was confirmed by the United States Senate on March 12 , 1861 , and received his commission the same day . Williams served in that capacity until his death , in 1863 , in Quincy , Illinois . Archibald Williams 's historical significance was based on his close friendship with Abraham Lincoln , the 16th President of the United States , who issued the Emancipation Proclamation freeing the slaves . Lincoln was from Springfield , Illinois , and Williams was from Quincy , Illinois , a port city on the Mississippi River along the western border of the state . The two men were close political allies in the Whig Party and , later on , in the newly founded Republican Party . They first met when serving in the Illinois state legislature in the early 1830 's . They were compatriots for 29 years . Archibald Williams led the life of a political party workhorse , first for the Whig Party and then the Republicans . He served in the Illinois state legislature , made two unsuccessful runs for the U.S. Senate as a Whig , played a leading role at the Illinois state Constitutional Convention of 1847 , chaired many important political meetings in Quincy , Illinois , attended many state political party conventions , made an unsuccessful run for the U.S. House of Representatives , and in 1858 campaigned in Illinois for his friend Abraham Lincoln . In all recorded instances , Archibald Williams gave Abraham Lincoln his true and unwavering support . Archibald Williams died in 1863 . By that time , Abraham Lincoln was President of the United States and the leader of the Northern states during the American Civil War . Birth and Early Life Archibald Williams was born in Montgomery County , Kentucky , on June 10 , 1801 . He was the son of John Williams and Amelia Gill Williams . He grew up in Kentucky , qualified to be a lawyer in the neighboring state of Tennessee , and then moved west with some of his brothers and sisters to Quincy , Illinois . As a young attorney , he rode circuit , going from county court to county court arguing legal cases . He was particularly noted for taking cases on appeal , and he argued many cases before the Illinois state Supreme Court . He married Nancy Kemp , who also had come from Kentucky , on July 28 , 1831 . They had nine children , but only five grew up to be adults . For several months in early 1832 he served as a volunteer in the Black Hawk War against Native Americans . In the fall of 1832 he strongly supported Henry Clay for President of the United States . At the Illinois State Legislature Archibald Williams was elected to the Illinois state Senate in 1832 . He studied and reported on School Financing to the state Senate , arguing for local control of schools rather than establishing a statewide system . Later in his legislative career , he labeled the Illinois Internal Improvements program `` Infernal Improvements '' due to its financial difficulties leading to bankruptcy . Abraham Lincoln was elected to the state legislature in 1834 . Archibald Williams and Lincoln became good friends and both subsequently joined the Whig Party . Lincoln was said to have seen Archibald Williams as a great `` reasoner . '' The two men were described as `` sitting next to each other in the southeast corner of the statehouse . '' It was noted : `` Lincoln did not hesitate to consult Williams at all times , and the two men were often associated in legal work . '' Twice the Whig Candidate for U.S. Senator Archibald Williams ran for the United States Senate as a Whig in 1836 and in 1842 . At those times the selection of U.S. senators was made by both houses of the state legislature . Lincoln voted for Archibald Williams the first time he ran for U.S. Senator in 1836 . The second time Archibald Williams ran , in 1842 , Lincoln was no longer in the state legislature and thus could not vote for his friend . In both instances , Archibald Williams was not elected . Witnessed Abraham Lincoln 's Admission to U.S. Courts Abraham Lincoln was admitted to practice law in the United States Circuit Court on December 3 , 1839 . U.S Court Judge Nathaniel Pope presided over the ceremony . A Quincy , Illinois , newspaper noted that Archibald Williams was present at the ceremony . Presided Over Whig Party State Conventions in Illinois Archibald Williams presided over a Whig Party state convention meeting in Springfield , Illinois , in 1843 . Abraham Lincoln attended the convention and was elected a Whig Party presidential elector for the 1844 presidential election . Unfortunately for the Whigs , Democrat James K. Polk of Tennessee won the presidential election . In June of 1844 , Archibald Williams was elected president of an Illinois state Whig Party convention in Peoria , Illinois . Abraham Lincoln spoke to the convention in support of the United States charging higher tariffs on imported goods , a major Whig position at the time . Supported African Colonization of Freed Slaves Along with Abraham Lincoln , Archibald Williams in the 1840 's supported the African colonization of freed slaves by joining the Illinois colonization society . Although opposed to slavery , both men believed Southerners should be allowed to keep their slaves but also should be urged to free their slaves voluntarily and return them to Africa . This was thought to be a reasonable and non-coercive solution to the slavery problem . The Mormon Problem in Illinois Joining with his friend and fellow Quincy lawyer Orville Browning , Archibald Williams in 1840 helped to defend Mormon leader Joseph Smith from being extradited to Missouri to face possible execution for alleged crimes . Joseph Smith was the founder of the Church of Latter Day Saints ( Mormons ) , and he and his church were unpopular because of the voting power of his supporters and their belief in men having multiple wives . Thanks to Browning 's and Williams 's arguments in court , Smith was not extradited to Missouri but remained in Illinois and founded a Mormon colony at Nauvoo , Illinois . Four years later , in 1844 , Smith and his brother Hyrum were murdered by a mob while incarcerated in the jail at Carthage , Illinois . Williams and Browning switched sides and helped to defend in court the accused murderers of Joseph and Hyrum Smith . The murderers were all found not-guilty . Shortly afterward , Archibald Williams chaired a meeting in Quincy , Illinois , that sought to arrange for a peaceful departure of the Mormons from Illinois to the far western state of Utah . Archibald Williams appointed a delegation of Quincy citizens that traveled to Nauvoo and convinced the new Mormon leader , Brigham Young , to leave Illinois for Utah in an orderly manner . Brigham Young said the Mormons could not leave immediately , but when `` grass grows and water runs , '' both signs of spring . The following spring the Mormons peacefully left Illinois for Utah , traveling mainly by wagon train . The Illinois Constitutional Convention of 1847 Archibald Williams was elected to the Illinois state Constitutional Convention of 1847 as a Whig . The convention met in the state capitol in Springfield , Illinois , and proceeded to write an improved state constitution . Williams was elected in a Democratic district against a Democratic candidate . Although the Democrats had a majority of the delegates to the convention , the Whigs could break away Democratic votes when they needed them and ended up dominating the convention . A historian noted : `` James W. Singleton of Mount Sterling , Archibald Williams of Quincy , and David M. Woodson of Carrollton aggressively upheld the Whig cause against the attacks of various capable Democratic opponents . '' At the constitutional convention , Archibald Williams and the Whig Party supported the rights of property , strict voting requirements in state elections , and allowing the state legislature to override the governor 's veto by a majority vote rather than a two-thirds vote . Two issues were sent to the state 's voters - one calling for the creation of an Illinois state bank and the other limiting the immigration into Illinois of freed slaves from the slave states . The voters of Illinois rejected the idea of an Illinois state bank but approved limiting the immigration of freed slaves . Archibald Williams gave a major speech at the constitutional convention opposing the idea that the Illinois Supreme Court should meet at various locations throughout the state rather than only in the state capital of Springfield . After the constitutional convention adjourned , the voters of Illinois approved the new constitution by a ratio of almost 4 to 1 . The Constitutional Convention of 1847 was a landmark in the legal and political career of Archibald Williams . He succeeded in furthering the ideals and policies of the Whig Party against stiff Democratic Party opposition . He was three months in Springfield , the state capital , meeting and working with many of the leading politicians and government officials from throughout the state . It helped to make him a significant figure in Illinois political and governmental history . The `` Lincoln Letter '' to Archibald Williams In the 1848 presidential election , Abraham Lincoln was backing General Zachary Taylor , a Mexican War hero , for the Whig Party nomination . A problem developed when Orville H. Browning , a Whig Party leader in Quincy , Illinois , supported the nomination of past Whig Party favorite Henry Clay . On April 30 , 1848 , Abraham Lincoln wrote a letter to Archibald Williams urging him to support Zachary Taylor and , if possible , also enlist the support of Browning . The letter read : Washington , April 30 , 1848 Dear Williams , I have not seen in the papers and evidence of a movement to send a delegate from your circuit to the June convention - I wish to say that I think it all important that a delegate should be sent - Mr. Clay 's chance for election is just no chance at all . He might get New York , and that would have elected in 1844 but it will not now ; because he must now at the least , have Tennessee , which he had then and , in addition , the fifteen new votes of Florida , Texas , Iowa , and Wisconsin . I know that our good friend Browning is a great admirer of Mr. Clay , and I therefore fear he is favoring his nomination . If he is , ask him to discard feeling , and try if he can possibly , as a matter of judgement , count the votes necessary to elect him . In my judgment , we can elect nobody but Gen. Taylor , and we can not elect him without a nomination - Therefore do n't fail to send a delegation - Your friend as ever , A. Lincoln This letter demonstrates the close friendship and easygoing familiarity between Abraham Lincoln and Archibald Williams . It also reveals Lincoln 's developing skills as an up and coming Illinois politician . It is not known whether Archibald Williams prevailed on Orville Browning to support Zachary Taylor for the Whig nomination for president in 1848 . What is known is that Zachary Taylor not only gained the Whig Party nomination but also won the presidency . Named U.S. District Attorney for Illinois Once in the White House in Washington , D.C. , newly elected President Zachary Taylor appointed Archibald Williams the United States District Attorney for the state of Illinois . Abraham Lincoln had sent the following letter in support of Williams 's nomination : Washington , March 8 , 1849 Hon : John M. Clayton Secretary of State Dear Sir : We Recommend that Archibald Williams , of Quincy , Illinois , be appointed U.S. District Attorney for the District of Illinois , when that office shall become vacant . Your Obt . Servts . A. Lincoln As U.S. District Attorney for Illinois , it was Archibald Williams 's job to prosecute cases in the U.S. District Court . The job became more difficult for Williams in 1850 when Congress enacted the Compromise of 1850 , which included a new Fugitive Slave Law . This law required Williams , in his role as U.S. District Attorney , to oversee the capture of runaway slaves and their return to their owners in the South . Williams was opposed to slavery personally but , in the 1850 's , acknowledged the right of slave owners in the South to keep their slaves . He fully discharged his duties under the Fugitive Slave Act . Death of Nancy Kemp Williams Archibald Williams 's wife , Nancy Kemp Williams , died on March 16 , 1854 , giving birth to a daughter , Nancy Williams . The baby survived the birth and lived to be an adult . Archibald and Nancy Williams had been married for 22 years . Candidate for the U.S. House of Representatives in 1854 In the early 1850 's , U.S. Senator Stephen Douglas of Illinois sought the adoption of the Kansas and Nebraska acts . The bills provided for Kansas and Nebraska to become territories with provision for `` popular sovereignty , '' the idea that the citizens of each new territory would be allowed to vote on whether the territory should be slave or free . This produced a sharp reaction on the part of those opposed to slavery in the territories , because the Missouri Compromise of 1820 had stated that the lands that comprised Kansas and Nebraska should be free territory , not slave territory . The result was the anti-Nebraska movement , which opposed popular sovereignty for Nebraska on the grounds that the citizens of the territory might vote for slavery and thereby spread slavery further into the territories . Archibald Williams and Abraham Lincoln both became anti-Nebraska men . For his part , Archibald Williams ran for the U.S. House of Representatives in 1854 on a strong anti-Nebraska platform . Williams was running against incumbent Democratic Representative William A. Richardson , a formidable opponent . The U.S. House district that comprised Quincy , Illinois , was strongly Democratic . On the other hand , Richardson was a close political ally of Stephen Douglas and had strongly backed popular sovereignty for Nebraska in the U.S. House . Williams and his supporters hoped the wave of anti-Nebraska sentiment sweeping the northern states might just be strong enough to defeat Richardson , despite the strong Democratic voting tendency of the House district . On October 31 , 1854 , Abraham Lincoln arrived in Quincy , Illinois , to give a speech in support of Archibald Williams 's candidacy for the U.S. House of Representatives . It took two days for him to travel by railroad and stagecoach to Quincy . In a letter to a friend and political ally , Lincoln wrote : `` I am here now going to Quincy , to try to give Mr. -LSB- Archibald -RSB- Williams a little life . '' Even with Abraham Lincoln 's help , Archibald Williams lost the election to William Richardson . The overall election was a success for the anti-Nebraska movement , however , as the anti-Nebraska forces won enough seats to gain a majority in the U.S. House of Representatives . After 1854 , Archibald Williams and Abraham Lincoln and other anti-Nebraskans took the lead in forming the Republican Party in Illinois around the issue of `` no slavery in the territories . '' An Archibald Williams Committee Influences Lincoln Abraham Lincoln wrote a letter in which he said he was ready to `` fuse '' with other anti-slavery groups according to `` principles '' adopted at a public meeting in Quincy , Illinois . The purpose of fusion was to bring many disparate anti-slavery groups together to form the Republican Party . Lincoln 's letter noted that the principles had been drawn up by a three-person committee led `` by Mr. Archibald Williams . '' The principles centered on the idea that Southern slave owners could keep their slaves but that slavery would be forbidden in the territories . Archibald Williams and his committee either influenced Lincoln directly on `` fusion , '' or else they confirmed a position on `` fusion '' that Lincoln had already adopted . At the United States Supreme Court Archibald Williams argued a case before the United States Supreme Court on December 6 and 7 , 1855 . Orville Browning , Williams 's good friend from Quincy , Illinois , was the opposing lawyer . The issue in dispute dealt with rival claims for lands and centered on whether the question of `` bad faith '' in the matter should be decided by a judge or by a jury . The Court ruled in Wright v. Mattison that `` bad faith '' should not be decided by the judge but by the jury , which had been the precedent . The Court ordered the case to be retried in a lower court . The outcome was a victory for Browning and a loss for Williams . The Beginnings of the Republican Party in Illinois In 1856 , Archibald Williams was the temporary chairman at a major anti-Nebraska convention in Bloomington , Illinois . Williams led the convention until a permanent chairman had been elected . While attending the convention , Abraham Lincoln and Archibald Williams slept in the same bed at the Bloomington home of David Davis , a close friend of both men.A historian noted : `` At Bloomington , Lincoln , Archibald Williams , his old associate in the Legislature , -LSB- and -RSB- T. Lyle Dickey , of Ottawa -LSB- Illinois -RSB- , a good lawyer , went to -LSB- David -RSB- Davis 's house and lived there during the Convention . Lincoln and Williams slept in one bed and Dickey and Whitney in another ... The course of the historic Bloomfield Convention was decisively influenced by the counsels that came from the steady men in the Davis House . '' Although the name `` Republican '' was applied at a later date , the anti-Nebraska convention in Bloomington was considered the birthplace of the Republican Party in Illinois . The Election of 1858 In 1858 , at a state party convention in Springfield , Illinois , Abraham Lincoln was nominated to be the Republican candidate for U.S. Senator from Illinois . A resolution passed at the convention stated that Lincoln `` was the first and only choice of the Republicans of Illinois for the U.S. Senate . '' In the famous Lincoln-Douglas debates in the 1858 Illinois U.S. Senate race , Democratic candidate Stephen Douglas attacked Lincoln three times for having been described as `` the first and only choice '' of Illinois Republicans for the Senate seat . All three times , Douglas pointed to Archibald Williams as an Illinois Republican who would have been an acceptable alternate choice to Lincoln in that contest . Archibald Williams traveled and spoke throughout the state of Illinois in Lincoln 's behalf during the 1858 U.S. Senate race . A newspaper in Quincy , Illinois , allied with the Republican Party , printed : `` Old Archie Williams is doing good service for the Republican cause ... He has already spoken at Macomb , Oquawka , Monmouth , Cameron , Galesburg , and other points ... to large assemblages ; and everywhere , he has created enthusiasm and confidence among our friends and animated the lukewarm ... In the winter of his life ... Mr. Williams is found battling for the cause of Republicanism . '' The Illinois state legislature chose Stephen Douglas over Abraham Lincoln in the 1858 U.S. Senate race . A close friend of Lincoln 's wrote : `` In January , 1859 , while the Democrats were celebrating the election of Stephen A. Douglas to the United States Senate , Archibald Williams ... came into Lincoln 's office and finding him writing said : ` Well , the Democrats are making a great noise over their victory . ' Looking up Lincoln replied : ` Yes , Archie , Douglas has taken this trick , but the game is not played out . ' '' The Lincoln-Douglas debates became so well-known that Lincoln gave personally signed presentation copies of the debates to his best friends and political associates . The one given to Archibald Williams was inscribed in Lincoln 's handwriting : `` To Hon : Archibald Williams , with respects of A. Lincoln . '' It was one more sign of Lincoln 's close friendship and strong political alliance with Archibald Williams . The Presidential Election of 1860 On December 25 , 1859 , a number of leading Republicans in Quincy , Illinois , including Archibald Williams , met with Horace Greeley , a prominent national journalist and editor of the New York Tribune . Greeley had famously stated `` Go west , young man . Go west ! '' Williams and the other Quincy Republicans talked to Greeley about Abraham Lincoln possibly becoming the Republican candidate for President in 1860 . Archibald Williams spoke throughout Illinois in behalf of Abraham Lincoln during Lincoln 's successful 1860 campaign for the White House in Washington , D.C. Almost on the Supreme Court , Then U.S. District Judge in Kansas Following his election to the U.S. presidency in 1860 , Abraham Lincoln offered Archibald Williams a seat on the U.S. Supreme Court . Williams refused the offer due to ill health and advanced age . Williams recommended that Lincoln appoint a younger court nominee who could live for more years and thereby serve longer on the Court . Archibald Williams was then appointed by President Lincoln to be the Judge for the U.S. District Court of Kansas . Williams was the first person to hold the office of U.S. District Court Judge in Kansas , because Kansas had just been admitted to the Union as a state . Williams moved to Topeka , Kansas , the state capital , where he served more than two years as U.S. Judge . He moved back to Quincy , Illinois , shortly before his death on September 21 , 1863 . During his tenure as the U.S. District Court Judge for Kansas , Archibald Williams worked on such issues as building a branch of the transcontinental railroad across Kansas , fair treatment of Native Americans in railroad matters , and the loyalty to the Union cause of a U.S. Army officer stationed in Kansas . Also while in Kansas , Williams married his second wife , Ellen M. Parker , on September 24 , 1861 . The marriage lasted a little less than two years until Archibald Williams death . While serving as the U.S. Judge for Kansas , Archibald Williams traveled to Washington , D.C. , and , on May 29 , 1962 , paid a last visit to his old friend Abraham Lincoln in the White House . Death and Burial of Archibald Williams Archibald Williams was praised in obituaries as a leading attorney in Illinois in the mid-19th Century . His many political and governmental activities were noted , along with his deep friendship with Abraham Lincoln . The bar association in Quincy , Illinois , donated a large marble grave marker for Williams . The base of the marker was a stack of law books ; an obelisk was placed on top of the law books . He was buried in Woodland Cemetery in Quincy , Illinois , at a grave site that overlooks the Mississippi River .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Lincoln–Douglas_debates\",\n \"text\": \"The Lincoln -- Douglas Debates ( also known as The Great Debates of 1858 ) were a series of seven debates between Abraham Lincoln , the Republican candidate for the United States Senate from Illinois , and incumbent Senator Stephen Douglas , the Democratic Party candidate . At the time , U.S. senators were elected by state legislatures ; thus Lincoln and Douglas were trying for their respective parties to win control of the Illinois legislature . The debates previewed the issues that Lincoln would face in the aftermath of his victory in the 1860 presidential election . Although Illinois was a free state , the main issue discussed in all seven debates was slavery in the United States . In agreeing to the official debates , Lincoln and Douglas decided to hold one debate in each of the nine congressional districts in Illinois . Because both had already spoken in two -- Springfield and Chicago -- within a day of each other , they decided that their `` joint appearances '' would be held only in the remaining seven districts . The debates were held in seven towns in the state of Illinois : Ottawa on August 21 Freeport on August 27 Jonesboro on September 15 Charleston on September 18 Galesburg on October 7 Quincy on October 13 Alton on October 15 The debates in Freeport , Quincy and Alton drew especially large numbers of people from neighboring states , as the issue of slavery was of monumental importance to citizens across the nation . Newspaper coverage of the debates was intense . Major papers from Chicago sent stenographers to create complete texts of each debate , which newspapers across the United States reprinted in full , with some partisan edits . Newspapers that supported Douglas edited his speeches to remove any errors made by the stenographers and to correct grammatical errors , while they left Lincoln 's speeches in the rough form in which they had been transcribed . In the same way , pro-Lincoln papers edited Lincoln 's speeches , but left the Douglas texts as reported . After losing the election for Senator in Illinois , Lincoln edited the texts of all the debates and had them published in a book . The widespread coverage of the original debates and the subsequent popularity of the book led eventually to Lincoln 's nomination for President of the United States by the 1860 Republican National Convention in Chicago . The format for each debate was : one candidate spoke for 60 minutes , then the other candidate spoke for 90 minutes , and then the first candidate was allowed a 30-minute `` rejoinder . '' The candidates alternated speaking first . As the incumbent , Douglas spoke first in four of the debates .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"United_States_presidential_election_in_California,_1860\",\n \"text\": \"In the 1860 United States presidential election , California narrowly voted for the Republican nominee , former Illinois representative Abraham Lincoln , over the Democratic nominee , Illinois Senator Stephen A. Douglas and the Southern Democratic nominee , Vice President John C. Breckinridge .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Northern_Democratic_Party\",\n \"text\": \"The Northern Democratic Party was a leg of the Democratic Party during the 1860 presidential election . It was when the party split in two due to problems with slavery . Stephen A. Douglas was the nominee and lost to Abraham Lincoln . They held two conventions before the election , in Charleston and Baltimore , where they established their platform .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"William_P._Fessenden\",\n \"text\": \"William Pitt Fessenden ( October 16 , 1806September 8 , 1869 ) was an American politician from the U.S. state of Maine . Fessenden was a Whig ( later a Republican ) and member of the Fessenden political family . He served in the United States House of Representatives and Senate before becoming Secretary of the Treasury under President Abraham Lincoln during the American Civil War . A lawyer , he was a leading antislavery Whig in Maine ; in Congress , he fought the Slave Power ( the plantation owners who controlled southern states ) . He built an antislavery coalition in the state legislature that elected him to the U.S. Senate ; it became Maine 's Republican organization . In the Senate , Fessenden played a central role in the debates on Kansas , denouncing the expansion of slavery . He led Radical Republicans in attacking Democrats Stephen Douglas , Franklin Pierce , and James Buchanan . Fessenden 's speeches were read widely , influencing Republicans such as Abraham Lincoln and building support for Lincoln 's 1860 Republican presidential nomination . During the war , Senator Fessenden helped shape the Union 's taxation and financial policies . He moderated his earlier radicalism , and supported Lincoln against the Radicals , becoming Lincoln 's Treasury Secretary . After the war , Fessenden was back in the Senate , as chair of the Joint Committee on Reconstruction , which established terms for resuming congressional representation for the southern states , and which drafted the Fourteenth Amendment to the United States Constitution . Later , Fessenden provided critical support that prevented Senate conviction of President Andrew Johnson , who had been impeached by the House . He was the first Republican Senator to ring out '' ... not guilty '' followed by six other Republican Senators resulting in the acquittal of President Johnson . He is the only person to have three streets in Portland named for him : William , Pitt and Fessenden streets in the city 's Oakdale neighborhood .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"James_A._McDougall\",\n \"text\": \"James Alexander McDougall ( November 19 , 1817 -- September 3 , 1867 ) was an American attorney and politician elected to statewide office in two U.S. states , then to the United States House of Representatives and United States Senate . A gifted orator , McDougall began his career as a civil engineer in New York , then read law , rising quickly to heights in his profession in Illinois , where he became a friend of fellow prairie attorneys Abraham Lincoln , Edward D. Baker , and Stephen Douglas . Like many Americans , McDougall was drawn to Gold Rush California in 1849 ; he resumed his law practice and was elected second attorney general for the new state of California . In the election of 1860 , Lincoln won the presidency as a Republican , Baker was elected Republican senator from Oregon , and McDougall was elected senator from California , joining Douglas in the Senate as fellow War Democrats . All three of McDougall 's Prairie State friends would die in the six years before his term as senator expired . A noted drinker , McDougall once gave an address to the Senate disparaging a proposed rule to outlaw the sale of alcohol in the United States Capitol , but died shortly after leaving the Senate , '' ... hastened by his indulgence in the bowl . ''\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Lincoln's_House_Divided_Speech\",\n \"text\": \"The House Divided Speech was an address given by Abraham Lincoln ( who would later become President of the United States ) on June 16 , 1858 , at what was then the Illinois State Capitol in Springfield , upon accepting the Illinois Republican Party 's nomination as that state 's United States senator . The speech became the launching point for his unsuccessful campaign for the Senate seat held by Stephen A. Douglas ; this campaign would climax with the Lincoln-Douglas debates of 1858 . Lincoln 's remarks in Springfield created an image of the danger of slavery-based disunion , and it rallied Republicans across the North . Along with the Gettysburg Address and his second inaugural address , this became one of the best-known speeches of his career . The best-known passage of the speech is : Lincoln 's goals with this speech were , firstly , to differentiate himself from Douglas , the incumbent ; and secondly , to publicly voice a prophecy for the future . Douglas had long advocated popular sovereignty , under which the settlers in each new territory decided their own status as a slave or free state ; he had repeatedly asserted that the proper application of popular sovereignty would end slavery-induced conflict , and would allow northern and southern states to resume their peaceful coexistence . Lincoln , however , responded that the Dred Scott decision had closed the door on Douglas 's preferred option and left the Union with only two remaining outcomes : the United States would inevitably become either all slave , or all free . Now that the North and the South had come to hold distinct opinions in the question of slavery , and now that this issue had come to permeate every other political question , the time would soon come when the Union would no longer be able to function .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Miller–Davis_Law_Buildings\",\n \"text\": \"The Miller -- Davis Law Buildings , known commonly as the Miller Davis Building , are located on Main and Front Street in the McLean County , Illinois city of Bloomington . The law offices served future Supreme Court Justice David Davis and future Illinois State Senator Asahel Gridley . The buildings became a gathering place for local lawyers such as Abraham Lincoln and Stephen A. Douglas .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Lincoln_Oak\",\n \"text\": \"The Lincoln Oak was an oak tree in Bloomington , Illinois . Stephen A. Douglas and Abraham Lincoln both gave speeches at the tree during the 1850s . The original Lincoln Oak died in 1976 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Lincoln–Douglas_debate\",\n \"text\": \"Lincoln -- Douglas debate ( commonly abbreviated as LD Debate , or simply LD ) is a type of one-on-one debate practiced mainly in the United States at the high school level . It is sometimes also called values debate because the format traditionally places a heavy emphasis on logic , ethical values , and philosophy ( also called as logos , ethos and pathos ) . The Lincoln -- Douglas Debate format is named for the 1858 Lincoln -- Douglas Debates between Abraham Lincoln and Stephen A. Douglas , because their debates focused on slavery and the morals , values , and logic behind it . LD Debates are used by the National Speech and Debate Association , or NSDA ( formerly known as the National Forensics League , or NFL ) competitions , and also widely used in related debate leagues such as the National Christian Forensics and Communication Association , the National Catholic Forensic League , the National Educational Debate Association , the Texas University Interscholastic League , Texas Forensic Association , Stoa USA and their affiliated regional organizations . The vast majority of tournaments use the current NSDA resolution .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Joseph_Arnold_(Rhode_Island)\",\n \"text\": \"Joseph Arnold ( 1710 -- 1776 ) was a pre-revolutionary resident of North Kingstown and Exeter in the Colony of Rhode Island and Providence Plantations . He is most noted for having a very large progeny , having had 16 children of whom 15 grew to maturity , married , and had children of their own , giving him at least 89 grandchildren . He was the great great grandfather of presidential hopeful Stephen Arnold Douglas who debated Abraham Lincoln in 1858 , and lost to him in the 1860 presidential election . He was an ancestral link between Douglas and many prominent early Rhode Islanders such as Governor Benedict Arnold and two founders of the Rhode Island colony , Samuel Wilbore and John Porter .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Stephen_A._Douglas_Tomb\",\n \"text\": \"The Stephen A. Douglas Tomb and Memorial or Stephen Douglas Monument Park is located at 636 E. 35th Street in the Bronzeville neighborhood of Chicago , Illinois ( part of the city 's Douglas community ) , near the site of the Union Army and prisoner of war Camp Douglas . A ten-foot statue of the man best remembered for debating Abraham Lincoln over slavery stands atop a 46 ft column of white marble from his native state , Vermont . Douglas died from typhoid fever on June 3 , 1861 in Chicago , where he was buried on the shore of Lake Michigan . The site was afterwards bought by the state of Illinois , and the imposing monument by Leonard Volk was built over his grave . The cornerstone was laid in 1861 and the tomb was completed in 1881 . The site was designated a Chicago Landmark on September 28 , 1977 . The tomb is maintained by the Illinois Historic Preservation Agency as a state historic site .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"United_States_elections,_1860\",\n \"text\": \"The 1860 United States elections elected the members of the 37th United States Congress . The election took place during the Third Party System , shortly before the start of the Civil War . The Republican Party won control of the Presidency and both houses of Congress , making it the fifth party ( following the Federalist Party , Democratic-Republican Party , Democratic Party , and Whig Party ) to accomplish that feat . The election is widely considered to be a realigning election . In the Presidential election , Republican former Representative Abraham Lincoln of Illinois defeated Democratic Vice President John C. Breckinridge ( who became the first incumbent Vice President to lose a presidential election ) and Democratic Senator Stephen A. Douglas of Illinois , as well as the Constitutional Union candidate , former Senator John Bell of Tennessee . Lincoln swept the Northern states while Breckinridge carried much of the South , foreshadowing the political alignment of the country throughout the Third Party System . At the 1860 Republican National Convention , Lincoln won on third ballot , defeating Senator William H. Seward of New York and several other candidates . The Democratic Party split its votes after three chaotic conventions . Douglas was nominated at the second Democratic convention , while the Southern Democrats nominated Breckinridge as their own candidate in a third convention . Bell ran on a platform of preserving the union regardless of the status of slavery . Lincoln 's victory made him the first Republican President . Lincoln took just under 40 percent of the popular vote , a lower share of the popular vote than any other winning presidential candidate aside from John Quincy Adams 's 1824 campaign . In the House , Republicans retained control of the chamber and won a majority for the first time after several states seceded . Democrats remained the largest minority , but several Congressmen also identified as unionists . In the Senate , Republicans made moderate gains , but won a majority after several states seceded . The Democrats remained the largest minority party , though some Congressmen identified as unionists .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Abraham_Lincoln_National_Heritage_Area\",\n \"text\": \"The Abraham Lincoln National Heritage Area is a National Heritage Area in central Illinois telling the story of Abraham Lincoln . A National Heritage Area is a federal-designated area intended to encourage historic preservation and an appreciation of the history and heritage of the site . While National Heritage Areas are not federally owned or managed , the National Park Service provides an advisory role and some technical , planning and financial assistance . The Abraham Lincoln National Heritage Area was created as part of the Consolidated Natural Resources Act of 2008 ( S. 2739 ) , an omnibus bill . It was originally introduced in the Senate by Dick Durbin and in the House of Representatives by Ray LaHood , both from Illinois . The legislation also provided $ 10 million over 10 years , with no more than $ 1 million awarded in any single year , to make federal grants available for preservation , education and economic development . Grants awarded for Lincoln National Heritage Area activities must be matched dollar-for-dollar in state , local or private funds . The management authority for the Abraham Lincoln National Heritage Area is the Looking for Lincoln Heritage Coalition and follows Lincoln 's life from his birth and childhood , to his early life and career , to the Lincoln -- Douglas debates of 1858 . The legislation protects private property rights and would not require any private citizen or entity to be affiliated with the Lincoln Heritage Area . The bill names the Looking for Lincoln Heritage Coalition as the management authority for the National Heritage Area , but does not grant any zoning or land use power to the Coalition . Up to $ 10 million in federal grants would be available under this legislation The Heritage Area includes the following sites : Lincoln Home National Historic Site Lincoln Tomb State Historic Site Lincoln 's New Salem State Historic Site at New Salem , Menard County , Illinois Abraham Lincoln Presidential Library and Museum Lincoln Log Cabin State Historic Site Mount Pulaski Courthouse State Historic Site , Postville Courthouse State Historic Site and Metamora Courthouse State Historic Site Lincoln-Herndon Law Offices State Historic Site David Davis Mansion State Historic Site Vandalia State House State Historic Site Lincoln Douglas Debate Museum Macon County Log Court House Richard James Oglesby Mansion Lincoln Trail Homestead State Memorial John Wood Mansion Beardstown Courthouse Old Main at Knox College Carl Sandburg State Historic Site Bryant Cottage State Historic Site Dr. William Fithian Home Vermilion County Museum\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Abe_Lincoln_in_Illinois_(play)\",\n \"text\": \"Abe Lincoln in Illinois is a play written by the American playwright Robert E. Sherwood in 1938 . The play , in three acts , covers the life of President Abraham Lincoln from his childhood through his final speech in Illinois before he left for Washington . The play also covers his romance with Mary Todd and his debates with Stephen A. Douglas , and uses Lincoln 's own words in some scenes . Sherwood received the Pulitzer Prize for Drama in 1939 for his work .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Freeport_Doctrine\",\n \"text\": \"The Freeport Doctrine was articulated by Stephen A. Douglas at the second of the Lincoln-Douglas debates on August 27 , 1858 , in Freeport , Illinois . Former one-term U.S. Representative Abraham Lincoln was campaigning to take Douglas ' U.S. Senate seat by strongly opposing all attempts to expand the geographic area in which slavery was practiced . Lincoln tried to force Douglas to choose between the principle of popular sovereignty proposed by the Kansas-Nebraska Act ( which left the fate of slavery in a U.S. territory up to its inhabitants ) , and the majority decision of the United States Supreme Court in the case of Dred Scott v. Sandford , which stated that slavery could not legally be excluded from U.S. territories ( since Douglas professed great respect for Supreme Court decisions , and accused the Republicans of disrespecting the court , yet this aspect of the Dred Scott decision was contrary to Douglas ' views and politically unpopular in Illinois ) . Instead of making a direct choice , Douglas ' response stated that despite the court 's ruling , slavery could be prevented from any territory by the refusal of the people living in that territory to pass laws favorable to slavery . Likewise , if the people of the territory supported slavery , legislation would provide for its continued existence . Douglas 's actual words were : The next question propounded to me by Mr. Lincoln is , Can the people of a Territory in any lawful way , against the wishes of any citizen of the United States , exclude slavery from their limits prior to the formation of a State constitution ? I answer emphatically , as Mr. Lincoln has heard me answer a hundred times from every stump in Illinois , that in my opinion the people of a Territory can , by lawful means , exclude slavery from their limits prior to the formation of a State constitution . Mr Lincoln knew that I had answered that question over and over again . He heard me argue the Nebraska bill on that principle all over the State in 1854 , in 1855 , and in 1856 , and he has no excuse for pretending to be in doubt as to my position on that question . It matters not what way the Supreme Court may hereafter decide as to the abstract question whether slavery may or may not go into a Territory under the Constitution , the people have the lawful means to introduce it or exclude it as they please , for the reason that slavery can not exist a day or an hour anywhere , unless it is supported by local police regulations . Those police regulations can only be established by the local legislature ; and if the people are opposed to slavery , they will elect representatives to that body who will by unfriendly legislation effectually prevent the introduction of it into their midst . If , on the contrary , they are for it , their legislation will favor its extension . Hence , no matter what the decision of the Supreme Court may be on that abstract question , still the right of the people to make a Slave Territory or a Free Territory is perfect and complete under the Nebraska bill . I hope Mr. Lincoln deems my answer satisfactory on that point . By taking this position , Douglas was defending his Popular Sovereignty or `` Squatter Sovereignty '' principle of 1854 , which he considered to be a compromise between pro-slavery and anti-slavery positions . It was satisfactory to the legislature of Illinois , which reelected Douglas over Lincoln to the Senate ( this was before the addition of the Seventeenth Amendment to the Constitution ) . However , the Freeport Doctrine alienated many Southern Democrats . Douglas had actually stated the essence of the doctrine previous to the debate at Freeport , but its prominent public assertion at Freeport contributed ( along with other political disputes , such as over the Lecompton Constitution ) to antagonizing those in the Southern United States who were demanding ever-increasing protections for slavery , and who subsequently insisted on the repudiation of the Freeport Doctrine ( i.e. , the passage of a congressional Slave Code for the territories ) in order to block Douglas ' presidential bid in 1860 . This led to the split of the Democratic party in 1860 , and Douglas ' loss in the 1860 presidential election .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Archibald_Dixon\",\n \"text\": \"Archibald Dixon ( April 2 , 1802 -- April 23 , 1876 ) was a U.S. Senator from Kentucky . He represented the Whig Party in both houses of the Kentucky General Assembly , and was elected the 12th Lieutenant Governor of Kentucky in 1844 , serving under Governor William Owsley . In 1851 , the Whigs nominated him for governor , but he lost to Lazarus W. Powell , his former law partner . Dixon represented Henderson County at the Kentucky constitutional convention of 1849 . In this capacity , he ensured that strong protections of slave property were included in the Kentucky Constitution of 1850 . Later , the General Assembly chose Dixon to fill the unexpired Senate term of Henry Clay . He served from September 1 , 1852 , to March 3 , 1855 , and did not stand for re-election . During his short tenure , Dixon 's major accomplishment was convincing Stephen Douglas to include language in the Kansas-Nebraska Act that explicitly repealed the Missouri Compromise 's prohibition on slavery north of latitude 36 ° 30 ' . Despite his pro-slavery views , Dixon was loyal to the Union during the Civil War . He represented his county and his state in a number of failed conventions that sought to resolve the upcoming conflict before it began . In 1864 , he joined Kentucky governor Thomas E. Bramlette in an audience with President Abraham Lincoln protesting the recruitment of former slaves as Union soldiers in Kentucky . Dixon died on April 23 , 1876 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Abraham_Jonas_(politician)\",\n \"text\": \"Abraham Jonas ( born September 12 , 1801 in Exeter , England ; died June 8 , 1864 ) was the first permanent Jewish resident in Quincy , Illinois . He was a former member of the Illinois and Kentucky State Legislature , a leading lawyer , and a valued friend of Abraham Lincoln . Jonas was born in Exeter , England to Annie Ezekiel and Benjamin Jonas . Abraham 's brother , Joseph Jonas , moved to Cincinnati , Ohio becoming the first Jew to settle west of the Allegheny Mountains . Abraham and his brother Edward joined Joseph in Cincinnati in 1819 . Abraham and his two brothers were original members of Congregation B'nai Israel ( Sons of Israel ) , the first Jewish congregation west of the Allegheny Mountains . Abraham also joined the Freemasons in Cincinnati . He and Joseph married Lucy and Rachel Seixas ; daughters of the first Rabbi born in America -- Gershom Mendes Seixas . Lucy suddenly died in 1825 , and Abraham moved to Williamstown , Kentucky . There he married Louisa Block from a pioneering Jewish American family and operated a general store . He was elected to the state legislature for four years . While in Kentucky , Abraham organized a Masonic Lodge and was eventually elected Master of the lodge in 1832 . During that time he and Louisa had five children . In 1836 he moved to Columbus in Adams County , Illinois to operate another general store . Within two years he moved to Quincy , IL opening a carriage business and studying law in Orville Browning 's office . He then organized the Grand Masonic Lodge of Illinois in 1840 and was elected Grand Master . In 1842 he was elected as a Whig to the state legislature . Lucy and Abraham had three more children around this time . He decided to establish a law partnership with Henry Asbury , turning over the family business to his brothers Edward and Samuel who had joined him in Quincy in 1840 or 1841 . It is suspected that it was during his years in legislation in Springfield that Abraham Jonas met Abraham Lincoln , as Lincoln was too a member of the state legislation at the time . Jonas ran for the Illinois Senate in 1844 but was defeated by the Democratic candidate . But his loyalty to the Whig party earned him the position as postmaster of Quincy in 1849 serving until 1853 . Lincoln and Jonas remained dear friends during this time . When the Whig party died , Jonas and Lincoln both joined the new Republican Party . On November 1 , 1854 Lincoln was accused of attending a Know-Nothing Party meeting , but was vouched by Jonas who he was actually with . Jonas arranged the 1858 Lincoln-Douglas debate in Quincy , and aided Lincoln to his candidacy . It was his law partner Henry Asbury who suggested Lincoln 's candidacy in front of a group of local Republicans . Asbury 's suggestion was greeted by silence until Jonas agreed that it would be a good idea . Abraham Jonas was noted as one of the greatest orators himself in the area . He was elected Grand Orator of the Grand Lodge of Illinois in 1843 . Lincoln appointed Jonas postmaster of Quincy in 1861 until his death in 1864 . Jonas had seven children , six sons and a daughter . Four of his sons , including future U.S. Senator Benjamin F. Jonas , fought for the Confederacy during the Civil War , being residents of Louisiana ; two others fought for the Union . Lincoln personally ordered the release of his son Charles Jonas from a prisoner of war camp to be at his father 's bedside before he died .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Old_State_Capitol_State_Historic_Site\",\n \"text\": \"The Old State Capitol State Historic Site , in Springfield , Illinois , is the fifth capitol building built for the U.S. state of Illinois . It was built in the Greek Revival style in 1837 -- 1840 , and served as the state house from 1840 to 1876 . It is the site of candidacy announcements by Abraham Lincoln in 1858 and Barack Obama in 2007 . It was designated a National Historic Landmark in 1961 , primarily for its association with Lincoln and his political rival Stephen Douglas .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Jesse_B._Thomas,_Jr.\",\n \"text\": \"Jesse Burgess Thomas , Jr. ( July 31 , 1806 -- February 21 , 1850 ) was born in Lebanon , Ohio and was an Illinois politician who served as the Illinois Attorney General from 1835 -- 1836 and later on the state Supreme Court . After studying law at Transylvania University in Lexington , Kentucky , Thomas settled in Edwardsville , Illinois . By 1830 , Thomas was serving as the secretary to the Illinois State Senate . Four years later , he served a partial term in the Illinois House of Representatives for Madison County before being appointed Attorney General , a post he held for a single year . From 1837 through 1839 , he was a circuit court judge based in Springfield . His circuit included New Salem , where Thomas heard cases argued by Abraham Lincoln . When Stephen A. Douglas gave up his seat on the Illinois Supreme Court in 1843 after being elected to Congress , Governor Thomas Ford appointed Thomas as Douglas 's successor . After retiring from the Supreme Court in 1848 , he moved first to Galena and then to Chicago , where he died in 1850 . Thomas 's uncle was Jesse B. Thomas , one of Illinois ' first Senators . Thomas was married to one of the daughters of Illinois Supreme Court Justice Theophilus W. Smith .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Jesse_W._Fell\",\n \"text\": \"Jesse W. Fell ( 1808 -- 1887 ) was a Bloomington , Illinois businessman and land owner instrumental in the establishment of communities throughout Central Illinois and for the founding of Illinois State University . A close friend of Abraham Lincoln it was Fell who urged him to challenge his opponent , Stephen A. Douglas , to their famous series of debates .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"The_Lincoln_Hunters\",\n \"text\": \"The Lincoln Hunters is a 1958 novel by Wilson Tucker . The novel , set in the year 2578 , details the story of a historian from the oppressive society of that year , who travels back in time to record Abraham Lincoln 's Lost Speech of May 19 , 1856 in Bloomington , Illinois . It contains a vivid description of Lincoln in the early stages of his career , seen through the eyes of a future American who feels that Lincoln and his time compare very favorably with the traveler 's own . The book is mentioned in 11/22/63 , a novel by Stephen King that also centers around time travel and an assassinated president . Furthermore , the protagonist springboards to 1958-the year `` Hunters '' first ran-to alter the timeline by 1963 . Category :1958 American novels Category :1950 s science fiction novels Category : American science fiction novels Category : Time travel novels Category : Novels by Wilson Tucker Category :1856 in fiction Category : Novels set in Illinois Category :26 th century in fiction Category : Fictional depictions of Abraham Lincoln in literature\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Hampton_Roads_Conference\",\n \"text\": \"The Hampton Roads Conference was a peace conference held between the United States and the Confederate States on February 3 , 1865 , aboard the steamboat River Queen in Hampton Roads , Virginia , to discuss terms to end the American Civil War . President Abraham Lincoln and Secretary of State William H. Seward , representing the Union , met with three commissioners from the Confederacy : Vice President Alexander H. Stephens , Senator Robert M. T. Hunter , and Assistant Secretary of War John A. Campbell . The representatives discussed a possible alliance against France , the possible terms of surrender , the question of whether slavery might persist after the war , and the question of whether the South would be compensated for property lost through emancipation . Lincoln and Seward reportedly offered some possibilities for compromise on the issue of slavery . The only concrete agreement reached was over prisoner-of-war exchanges . The Confederate commissioners immediately returned to Richmond at the conclusion of the conference . Confederate President Jefferson Davis announced that the North would not compromise . Lincoln drafted an amnesty agreement based on terms discussed at the Conference , but met with opposition from his Cabinet . John Campbell continued to advocate for a peace agreement and met again with Lincoln after the fall of Richmond on April 2 .\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":390,"cells":{"query_id":{"kind":"string","value":"PLAIN-1973"},"query":{"kind":"string","value":"quinoa"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-5042","text":"The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.","title":"Flavanols, the Kuna, Cocoa Consumption, and Nitric Oxide"},{"docid":"MED-4875","text":"The repertoire of gastrointestinal (GI) symptoms is finite; however, the etiologies and mechanisms underlying symptom generation and perception are diverse and, in many cases, unknown. This review examines the clinical and experimental evidence exploring the putative relationship between gluten sensitivity (GS) and the generation of GI symptoms. It explores the hypothesis that, in a proportion of patients, GS causes functional bowel disorder (FBD)-like symptoms. We propose a model for investigating and understanding the induction of GI symptoms and dysfunction by gluten in FBD and organic disease. We hypothesize that, even in the absence of fully developed celiac disease, gluten can induce symptoms similar to FBD. We discuss the hypothesis that GS and post-infectious irritable bowel syndrome (IBS) provide two triggers that can explain at least part of the spectrum that constitutes IBS, further advancing an understanding of the role of mucosal responses to luminal factors in FBDs. We propose that the animal model of GS in human leukocyte antigen (HLA)-DQ8 mice allows investigation of mucosal pathophysiological changes that occur before the onset of full-blown inflammation in a GS host. A better understanding of how gluten can cause symptoms in sensitive individuals will illuminate the interaction between host genotype, diet, and intestinal microbiota in generating one of the most common GI conditions.","title":"Between Celiac Disease and Irritable Bowel Syndrome: The “No Man’s Land” of Gluten Sensitivity"},{"docid":"MED-5154","text":"OBJECTIVE: To measure whole-grain intake in college students and determine the association with body mass index (BMI). DESIGN: Cross-sectional convenience sample of college students enrolled in an introductory nutrition course. SETTING: Large state university. PARTICIPANTS: 159 college students, mean age: 19.9. MAIN OUTCOME MEASURES: Intake of whole grains, refined grains, calories, and fiber from food records; BMI determined from height and weight measurements. ANALYSIS: Analysis of variance with linear contrasts; participants grouped by BMI category (P<.05). RESULTS: Average intake of cereal grains was 5.4 servings per day, of which whole-grain intake accounted for an average of 0.7 servings per day. Whole-grain intake was significantly higher in normal weight students than in overweight and obese students (based on BMI). CONCLUSIONS AND IMPLICATIONS: The low intake of whole grains in this population of college students indicates the need for interventions aiming to increase whole-grain intake to the recommended minimum of 3 servings per day. College students who are concerned about their body weight may be motivated to increase their intake of whole-grain foods; however, their intake of whole grains is likely to be influenced by the availability of these food items in campus dining halls and other locations around the college campus.","title":"Whole-grain intake is associated with body mass index in college students."},{"docid":"MED-5041","text":"Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer – all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.","title":"Does Flavanol Intake Influence Mortality from Nitric Oxide-Dependent Processes? Ischemic Heart Disease, Stroke, Diabetes Mellitus, and Cancer in Panama"}],"string":"[\n {\n \"docid\": \"MED-5042\",\n \"text\": \"The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.\",\n \"title\": \"Flavanols, the Kuna, Cocoa Consumption, and Nitric Oxide\"\n },\n {\n \"docid\": \"MED-4875\",\n \"text\": \"The repertoire of gastrointestinal (GI) symptoms is finite; however, the etiologies and mechanisms underlying symptom generation and perception are diverse and, in many cases, unknown. This review examines the clinical and experimental evidence exploring the putative relationship between gluten sensitivity (GS) and the generation of GI symptoms. It explores the hypothesis that, in a proportion of patients, GS causes functional bowel disorder (FBD)-like symptoms. We propose a model for investigating and understanding the induction of GI symptoms and dysfunction by gluten in FBD and organic disease. We hypothesize that, even in the absence of fully developed celiac disease, gluten can induce symptoms similar to FBD. We discuss the hypothesis that GS and post-infectious irritable bowel syndrome (IBS) provide two triggers that can explain at least part of the spectrum that constitutes IBS, further advancing an understanding of the role of mucosal responses to luminal factors in FBDs. We propose that the animal model of GS in human leukocyte antigen (HLA)-DQ8 mice allows investigation of mucosal pathophysiological changes that occur before the onset of full-blown inflammation in a GS host. A better understanding of how gluten can cause symptoms in sensitive individuals will illuminate the interaction between host genotype, diet, and intestinal microbiota in generating one of the most common GI conditions.\",\n \"title\": \"Between Celiac Disease and Irritable Bowel Syndrome: The “No Man’s Land” of Gluten Sensitivity\"\n },\n {\n \"docid\": \"MED-5154\",\n \"text\": \"OBJECTIVE: To measure whole-grain intake in college students and determine the association with body mass index (BMI). DESIGN: Cross-sectional convenience sample of college students enrolled in an introductory nutrition course. SETTING: Large state university. PARTICIPANTS: 159 college students, mean age: 19.9. MAIN OUTCOME MEASURES: Intake of whole grains, refined grains, calories, and fiber from food records; BMI determined from height and weight measurements. ANALYSIS: Analysis of variance with linear contrasts; participants grouped by BMI category (P<.05). RESULTS: Average intake of cereal grains was 5.4 servings per day, of which whole-grain intake accounted for an average of 0.7 servings per day. Whole-grain intake was significantly higher in normal weight students than in overweight and obese students (based on BMI). CONCLUSIONS AND IMPLICATIONS: The low intake of whole grains in this population of college students indicates the need for interventions aiming to increase whole-grain intake to the recommended minimum of 3 servings per day. College students who are concerned about their body weight may be motivated to increase their intake of whole-grain foods; however, their intake of whole grains is likely to be influenced by the availability of these food items in campus dining halls and other locations around the college campus.\",\n \"title\": \"Whole-grain intake is associated with body mass index in college students.\"\n },\n {\n \"docid\": \"MED-5041\",\n \"text\": \"Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer – all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.\",\n \"title\": \"Does Flavanol Intake Influence Mortality from Nitric Oxide-Dependent Processes? Ischemic Heart Disease, Stroke, Diabetes Mellitus, and Cancer in Panama\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-3985","text":"Deficiency of vitamin D is usually caused by dietary deficiency and/or lack of exposure to sunlight in dark skinned individuals living at northern latitudes. Simple vitamin D deficiency is commonly treated by prescribing a vitamin D containing calcium supplement. This report presents a patient who rejected this approach and instead, after researching alternative treatment options independently, opted to self-treat by consuming UVB-irradiated mushrooms. The beneficial effect of this on the patient's plasma biochemical markers is shown. Further research into the beneficial effect of consuming UVB-irradiated mushrooms is required.","title":"Vitamin D deficiency treated by consuming UVB-irradiated mushrooms"},{"docid":"MED-2990","text":"ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. INTRODUCTION: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. MATERIALS AND METHODS: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. RESULTS AND CONCLUSIONS: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1-10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined.","title":"Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research."},{"docid":"MED-1861","text":"INTRODUCTION: Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. OBJECTIVES: The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. METHODS: We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies. RESULTS: Four trials, with a total of 390 patients, met our inclusion criteria. Two studies compared Hibiscus sabdariffa to black tea; one study compared it to captopril and one to lisinopril. The studies found that Hibiscus had greater blood pressure reduction than tea but less than the ACE-inhibitors. However, all studies, except one, were short term and of poor quality with a Jadad scoring of <3 and did not meet international standards. CONCLUSION: The four randomized controlled studies identified in this review do not provide reliable evidence to support recommending Hibiscus sabdariffa for the treatment of primary hypertension in adults. Copyright 2009 Elsevier GmbH. All rights reserved.","title":"The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review."},{"docid":"MED-1932","text":"There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.","title":"Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study"},{"docid":"MED-2673","text":"Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.","title":"Determination of microbial transglutaminase in meat and meat products."},{"docid":"MED-1071","text":"BACKGROUND: Elevated serum saturated fatty acid levels and hepatocyte lipoapoptosis are features of nonalcoholic fatty liver disease (NAFLD). AIM: The purpose of this study was to investigate saturated fatty acid induction of lipoapoptosis in human liver cells and the underlying mechanisms. METHODS: Human liver L02 and HepG2 cells were treated with sodium palmitate, a saturated fatty acid, for up to 48 h with or without lithium chloride, a glycogen synthase kinase-3β (GSK-3β) inhibitor, or GSK-3β shRNA transfection. Transmission electron microscopy was used to detect morphological changes, flow cytometry was used to detect apoptosis, a colorimetric assay was used to detect caspase-3 activity, and western blot analysis was used to detect protein expression. RESULTS: The data showed that sodium palmitate was able to induce lipoapoptosis in L02 and HepG2 cells. Western blot analysis showed that sodium palmitate activated GSK-3β protein, which was indicated by dephosphorylation of GSK-3β at Ser-9. However, inhibition of GSK-3β activity with lithium chloride treatment or knockdown of GSK-3β expression with shRNA suppressed sodium palmitate-induced lipoapoptosis in L02 and HepG2 cells. On a molecular level, inhibition of GSK-3β expression or activity suppressed sodium palmitate-induced c-Jun-N-terminal kinase (JNK) phosphorylation and Bax upregulation, whereas GSK-3β inhibition did not affect endoplasmic reticulum stress-induced activation of unfolded protein response. CONCLUSIONS: The present data demonstrated that saturated fatty acid sodium palmitate-induced lipoapoptosis in human liver L02 and HepG2 cells was regulated by GSK-3β activation, which led to JNK activation and Bax upregulation. This finding indicates that GSK-3β inhibition may be a potential therapeutic target to control NAFLD.","title":"Saturated free fatty acid sodium palmitate-induced lipoapoptosis by targeting glycogen synthase kinase-3β activation in human liver cells."},{"docid":"MED-4436","text":"The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies.","title":"Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition."},{"docid":"MED-3728","text":"On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.","title":"Strawberry fields forever?"},{"docid":"MED-1950","text":"Several studies have found associations between microbial infections during pregnancy and preterm delivery (PTD). We investigated the influence of food with antimicrobial and prebiotic components on the risk of spontaneous PTD. A literature search identified microbes associated with spontaneous PTD. Subsequently, 2 main food types (alliums and dried fruits) were identified to contain antimicrobial components that affect the microbes associated with spontaneous PTD; they also contained dietary fibers recognized as prebiotics. We investigated intake in 18,888 women in the Norwegian Mother and Child Cohort (MoBa), of whom 950 (5%) underwent spontaneous PTD (<37 gestational weeks). Alliums (garlic, onion, leek, and spring onion) [OR: 0.82 (95% CI: 0.72, 0.94), P = 0.005] and dried fruits (raisins, apricots, prunes, figs, and dates) [OR: 0.82 (95% CI: 0.72, 0.94); P = 0.005] were associated with a decreased risk of spontaneous PTD. Intake of alliums was related to a more pronounced risk reduction in early spontaneous PTD (gestational weeks 28–31) [OR: 0.39 (95% CI: 0.19, 0.80)]. The strongest association in this group was with garlic [OR: 0.47 (95% CI: 0.25–0.89)], followed by cooked onions. Intake of dried fruits showed an association with preterm prelabor rupture of membranes (PPROM) [OR: 0.74 (95% CI: 0.65, 0.95)]; the strongest association in this group was with raisins [OR: 0.71 (95% CI: 0.56, 0.92)]. The strongest association with PPROM in the allium group was with garlic [OR: 0.74 (95% CI: 0.56, 0.97)]. In conclusion, intake of food with antimicrobial and prebiotic compounds may be of importance to reduce the risk of spontaneous PTD. In particular, garlic was associated with overall lower risk of spontaneous PTD. Dried fruits, especially raisins, were associated with reduced risk of PPROM.","title":"Intakes of Garlic and Dried Fruits Are Associated with Lower Risk of Spontaneous Preterm Delivery"},{"docid":"MED-5038","text":"Interest in the biological activities of cocoa polyphenols is increasing steadily. In fact, the high polyphenol content of cocoa, coupled with its widespread presence in many food items, render this food of particular interest from the nutritional and \"pharmacological\" viewpoints. This paper summarizes the new findings and developments regarding the effects of cocoa and chocolate consumption on human health as presented at the International Conference \"Chocolate, Lifestyle, and Health\" (Milan, Italy, March 2, 2007) regarding the effects of cocoa and chocolate consumption on human health.","title":"Chocolate, lifestyle, and health."},{"docid":"MED-4924","text":"High-dose β-carotene supplementation in high-risk persons has been linked to increased lung cancer risk in clinical trials; whether effects are similar in the general population is unclear. The authors examined associations of supplemental β-carotene, retinol, vitamin A, lutein, and lycopene with lung cancer risk among participants, aged 50–76 years, in the VITamins And Lifestyle (VITAL) cohort Study in Washington State. In 2000–2002, eligible persons (n = 77,126) completed a 24-page baseline questionnaire, including detailed questions about supplement use (duration, frequency, dose) during the previous 10 years from multivitamins and individual supplements/mixtures. Incident lung cancers (n = 521) through December 2005 were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. Longer duration of use of individual β-carotene, retinol, and lutein supplements (but not total 10-year average dose) was associated with statistically significantly elevated risk of total lung cancer and histologic cell types; for example, hazard ratio = 2.02, 95% confidence interval: 1.28, 3.17 for individual supplemental lutein with total lung cancer and hazard ratio = 3.22, 95% confidence interval: 1.29, 8.07 for individual β-carotene with small-cell lung cancer for >4 years versus no use. There was little evidence for effect modification by gender or smoking status. Long-term use of individual β-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers.","title":"Long-term Use of β-Carotene, Retinol, Lycopene, and Lutein Supplements and Lung Cancer Risk: Results From the VITamins And Lifestyle (VITAL) Study"},{"docid":"MED-3853","text":"PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.","title":"Serum enterolactone and prognosis of postmenopausal breast cancer."},{"docid":"MED-1508","text":"The obesity epidemic is attributed in part to reduced physical activity. Evidence supports that reducing time spent sitting, regardless of activity, may improve the metabolic consequences of obesity. Analyses were conducted in a large prospective study of US adults enrolled by the American Cancer Society to examine leisure time spent sitting and physical activity in relation to mortality. Time spent sitting and physical activity were queried by questionnaire on 53,440 men and 69,776 women who were disease free at enrollment. The authors identified 11,307 deaths in men and 7,923 deaths in women during the 14-year follow-up. After adjustment for smoking, body mass index, and other factors, time spent sitting (≥6 vs. <3 hours/day) was associated with mortality in both women (relative risk = 1.34, 95% confidence interval (CI): 1.25, 1.44) and men (relative risk = 1.17, 95% CI: 1.11, 1.24). Relative risks for sitting (≥6 hours/day) and physical activity (<24.5 metabolic equivalent (MET)-hours/week) combined were 1.94 (95% CI: 1.70, 2.20) for women and 1.48 (95% CI: 1.33, 1.65) for men, compared with those with the least time sitting and most activity. Associations were strongest for cardiovascular disease mortality. The time spent sitting was independently associated with total mortality, regardless of physical activity level. Public health messages should include both being physically active and reducing time spent sitting.","title":"Leisure Time Spent Sitting in Relation to Total Mortality in a Prospective Cohort of US Adults"},{"docid":"MED-306","text":"Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.","title":"Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure"},{"docid":"MED-4227","text":"Epidemiologic and biological data strongly support the existence of a strict link between cancer and aging. In spite of the relevance of the problem, there were numerous pitfalls in epidemiologic investigation until a few years ago. An apparent decrease of cancer incidence in old age was revealed to be a misconception based on lack of sufficient appreciation for changing population size. But not all problems are solved by using age-specific cancer incidence, as recently stressed by some authors. At very advanced ages a slowing of the rate of increase of age-specific cancer incidence is clearly demonstrated. These findings apparently clash with the majority of biological data and suggest that some mechanism may develop at advanced ages capable of decreasing cancer susceptibility. In this paper, it will be shown that just a slowing-down kinetics is predicted for cancer incidence by using a mathematical model of mortality kinetics recently proposed in the gerontologic field. The slowing of the increasing rate or even a decreasing trend of cancer incidence of an aging population is compatible with a continuously accelerating pace of loss of physiological capacity of the single subjects, as with advancing age there is a selection of individuals with better physiological functions.","title":"Cancer and aging: from the kinetics of biological parameters to the kinetics of cancer incidence and mortality."},{"docid":"MED-3096","text":"Background and objectives: Uncooked meat and poultry products are commonly enhanced by food processors using phosphate salts. The addition of potassium and phosphorus to these foods has been recognized but not quantified. Design, setting, participants, & measurements: We measured the phosphorus, potassium, and protein content of 36 uncooked meat and poultry products: Phosphorus using the Association of Analytical Communities (AOAC) official method 984.27, potassium using AOAC official method 985.01, and protein using AOAC official method 990.03. Results: Products that reported the use of additives had an average phosphate-protein ratio 28% higher than additive free products; the content ranged up to almost 100% higher. Potassium content in foods with additives varied widely; additive free products all contained <387 mg/100 g, whereas five of the 25 products with additives contained at least 692 mg/100 g (maximum 930 mg/100 g). Most but not all foods with phosphate and potassium additives reported the additives (unquantified) on the labeling; eight of 25 enhanced products did not list the additives. The results cannot be applied to other products. The composition of the food additives used by food processors may change over time. Conclusions: Uncooked meat and poultry products that are enhanced may contain additives that increase phosphorus and potassium content by as much as almost two- and three-fold, respectively; this modification may not be discernible from inspection of the food label.","title":"Original Articles: Phosphorus and Potassium Content of Enhanced Meat and Poultry Products: Implications for Patients Who Receive Dialysis"},{"docid":"MED-1509","text":"AIMS/HYPOTHESIS: Sedentary (sitting) behaviours are ubiquitous in modern society. We conducted a systematic review and meta-analysis to examine the association of sedentary time with diabetes, cardiovascular disease and cardiovascular and all-cause mortality. METHODS: Medline, Embase and the Cochrane Library databases were searched for terms related to sedentary time and health outcomes. Cross-sectional and prospective studies were included. RR/HR and 95% CIs were extracted by two independent reviewers. Data were adjusted for baseline event rate and pooled using a random-effects model. Bayesian predictive effects and intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future. RESULTS: Eighteen studies (16 prospective, two cross-sectional) were included, with 794,577 participants. Fifteen of these studies were moderate to high quality. The greatest sedentary time compared with the lowest was associated with a 112% increase in the RR of diabetes (RR 2.12; 95% credible interval [CrI] 1.61, 2.78), a 147% increase in the RR of cardiovascular events (RR 2.47; 95% CI 1.44, 4.24), a 90% increase in the risk of cardiovascular mortality (HR 1.90; 95% CrI 1.36, 2.66) and a 49% increase in the risk of all-cause mortality (HR 1.49; 95% CrI 1.14, 2.03). The predictive effects and intervals were only significant for diabetes. CONCLUSIONS/INTERPRETATION: Sedentary time is associated with an increased risk of diabetes, cardiovascular disease and cardiovascular and all-cause mortality; the strength of the association is most consistent for diabetes.","title":"Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis."},{"docid":"MED-3514","text":"BACKGROUND & AIMS: Lowered visceral perception thresholds have been suggested as a biological marker of irritable bowel syndrome (IBS). The current study sought to determine the prevalence of altered rectal visceral perception in patients with IBS and the correlation of altered perception thresholds with subjective symptoms. METHODS: Anorectal manometry and rectal perception thresholds to balloon distention were determined in 100 patients with IBS and 15 control subjects. Gastrointestinal and psychological symptoms were assessed by questionnaire. Perception thresholds and symptoms were reassessed after 3 months in 15 patients with IBS. RESULTS: Ninety-four percent of patients showed altered rectal perception in the form of lowered thresholds for aversive sensations (discomfort), increased intensity of sensations, or altered viscerosomatic referral. Hypersensitivity was found only for aversive sensations in response to rapid phasic distention; stool thresholds and thresholds in response to slow ramp distention were normal. Cluster analysis by physiological parameters identified three IBS subgroups with predominant patterns of symptoms. Longitudinal evaluation indicated a correlation between changes in perception thresholds and symptom severity. CONCLUSIONS: Because altered rectal perception is present in almost all patients with IBS and perception thresholds correlate with temporal changes in retrospective symptom severity, altered rectal perception represents a reliable biological marker of IBS.","title":"Altered rectal perception is a biological marker of patients with irritable bowel syndrome."},{"docid":"MED-2336","text":"Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.","title":"Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense"},{"docid":"MED-2101","text":"The notion that a breast-gut connection might modulate the microenvironment of breast tissue was supported by the finding that breast cyst fluid contains bile acids that are characteristically found in the intestines. To establish that the gut, rather than circulating steroid precursors, is the source of bile acids in breast cyst fluid, we gave two patients deuterium-labelled chenodeoxycholic acid (three 200 mg doses by mouth), starting 9 days before aspiration of breast cysts. The chenodeoxycholic acid concentration of seven samples of aspirated cyst fluid ranged from 42 to 94 mumol/L. The corresponding serum concentrations of chenodeoxycholic acid on the same day were 0.8 and 2.9 mumol/L, of which the labelled compound comprised 13.0% (0.38 mumol/L) and 28.2% (0.23 mumol/L). The deuterated chenodeoxycholic acid concentrations in cyst fluid were 0.79 and 1.26 mumol/L in two samples from patient 1 and 3.22 mumol/L in patient 2; these values are equivalent to 11-17% of the serum concentrations [corrected]. This study shows that intestinal bile acids rapidly gain access to cyst fluid. Further studies should investigate the mechanisms that govern the exchange processes and the maintenance of the high cyst fluid to plasma concentration gradients, and the biological half-lives of individual constituents.","title":"Breast-gut connection: origin of chenodeoxycholic acid in breast cyst fluid."},{"docid":"MED-4411","text":"Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.","title":"Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial."},{"docid":"MED-3840","text":"The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.","title":"Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo"},{"docid":"MED-2815","text":"Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.","title":"Curcumin, a component of turmeric: from farm to pharmacy."},{"docid":"MED-4952","text":"A vegetarian diet may have beneficial effects on human health, however when it is not well-balanced may be deficient in some nutrients, as minerals for example. The aim of the present study was to assess the nutritional status of zinc and selenium in vegetarians in the city of São Paulo. A cross-sectional study was performed, and the inclusion criteria were age > or = 18 years, both gender, no use of food or pharmaceutical supplements. Thirty vegetarian, of both genders, mean age of 27 years and 4.5 years of vegetarianism had performed the study, and their mean BMI was 21.5. Zinc plasma concentration was 71 and 62.5 microg/dL for men and women and erythrocyte concentration was 37 microg/gHb for both genders. Selenium concentration was 73.5 and 77.3 microg/L in plasma and 51.4 and 66.9 microg/L in erythrocytes for men and women, respectively. These biochemical values show that, according to the references, selenium blood levels are adequate and zinc concentration in erythrocytes is deficient in the studied population. For this reason, vegetarians should be constantly assessed and receive nutritional support to reduce the effects of inadequate zinc status.","title":"Zinc and selenium nutritional status in vegetarians."},{"docid":"MED-4173","text":"OBJECTIVE: To assess the public health significance of premature weaning of infants from breast milk on later-life risk of chronic illness. DESIGN: A review and summary of recent meta-analyses of studies linking premature weaning from breast milk with later-life chronic disease risk is presented followed by an estimation of the approximate exposure in a developed Western country, based on historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion of chronic disease associated with current patterns of artificial feeding in infancy is estimated. RESULTS: After adjustment for major confounding variables, current research suggests that the risks of chronic disease are 30-200 % higher in those who were not breast-fed compared to those who were breast-fed in infancy. Exposure to premature weaning ranges from 20 % to 90 % in post-World War II age cohorts. Overall, the attributable proportion of chronic disease in the population is estimated at 6-24 % for a 30 % exposure to premature weaning. CONCLUSIONS: Breast-feeding is of public health significance in preventing chronic disease. There is a small but consistent effect of premature weaning from breast milk in increasing later-life chronic disease risk. Risk exposure in the Australian population is substantial. Approximately 90 % of current 35-45-year-olds were weaned from breast-feeding by 6 months of age. Encouraging greater duration and exclusivity of breast-feeding is a potential avenue for reducing future chronic disease burden and health system costs.","title":"Chronic disease and infant nutrition: is it significant to public health?"},{"docid":"MED-4027","text":"Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.","title":"Dietary behavior and knowledge of dental erosion among Chinese adults"},{"docid":"MED-3423","text":"INTRODUCTION: There are no reported studies assessing the relation between diet and sexual function in women with diabetes. AIM: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women. METHODS: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study. MAIN OUTCOME MEASURES: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function. RESULTS: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders. CONCLUSIONS: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.","title":"Adherence to Mediterranean diet and sexual function in women with type 2 diabetes."},{"docid":"MED-4760","text":"The human gut is a lush microbial ecosystem containing about 100 trillion microorganisms, whose collective genome, the microbiome, contains 100-fold more genes than the entire human genome. The symbiosis of our extended genome plays a role in host homeostasis and energy extraction from diet. In this article, we summarize some of the studies that have advanced the understanding of the microbiome and its effects on metabolism, obesity, and health. Metagenomic studies demonstrated that certain mixes of gut microbiota may protect or predispose the host to obesity. Furthermore, microbiota transplantation studies in germ-free murine models showed that the efficient energy extraction traits of obese-type gut flora are transmissible. The proposed methods by which the microbiome may contribute to obesity include increasing dietary energy harvest, promoting fat deposition, and triggering systemic inflammation. Future treatments for obesity may involve modulation of gut microbiota using probiotics or prebiotics.","title":"The microbiome and obesity: is obesity linked to our gut flora?"},{"docid":"MED-2229","text":"BACKGROUND/OBJECTIVES: In vitro and animal studies have reported that young broccoli sprouts improve oxidative stress status in diabetic condition. The objective of this double-blind, placebo-controlled, randomized clinical trial was to investigate the effects of broccoli sprouts powder (BSP) on some oxidative stress parameters in type 2 diabetes patients. SUBJECTS/METHODS: A total of 81 patients with type 2 diabetes were randomly assigned to one of three treatment groups for 4 weeks. The groups received either 10 g/d BSP (n=27), 5 g/d BSP (n=29) or placebo (n=25). Serum total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and oxidized low density lipoprotein (LDL) cholesterol were measured at baseline and at 4 weeks after treatment. RESULTS: In all, 63 patients in three groups were included in the analysis: 10 g/d BSP (n=21), 5 g/d (n=22) and placebo (n=20). After 4 weeks, consumption of BSP resulted in significant decrease in MDA (P=0.001 for treatment effect), oxidized low density lipoprotein cholesterol (P=0.03 for treatment effect), OSI (P=0.001 for treatment effect) and significant increase in TAC (P=0.001 for treatment effect). No effects were found on TOS. CONCLUSION: BSP had favorable effects on oxidative stress status in type 2 diabetes patients.","title":"Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind clinical trial."},{"docid":"MED-1054","text":"For a long time non communicable diseases (NCDs) were discussed as burden of the developed world. Recent alarming data show a reverse trend and a dramatic increase of NCDs in the developing world, in particular in highly populated transition countries. This is true for the main mortality triggering diseases such as CVD, cancer or diabetes. Almost 4 out of 5 NCD based deaths happen in low- and middle income countries. This development is multi-factorial and is based on some main trends such as globalization, supermarket growth, rapid urbanization and increasingly sedentary lifestyles. The latter leads to overweight or obesity, which again promotes NCDs similar as high blood pressure, high cholesterol and elevated blood glucose. A high quality diet including functional food or functional ingredients, accompanied by physical activity and a non-smoking policy, is one of the most promising factors in primary and secondary prevention of NCDs. Copyright © 2011 Elsevier Inc. All rights reserved.","title":"A global view on the development of non communicable diseases."}],"string":"[\n {\n \"docid\": \"MED-3985\",\n \"text\": \"Deficiency of vitamin D is usually caused by dietary deficiency and/or lack of exposure to sunlight in dark skinned individuals living at northern latitudes. Simple vitamin D deficiency is commonly treated by prescribing a vitamin D containing calcium supplement. This report presents a patient who rejected this approach and instead, after researching alternative treatment options independently, opted to self-treat by consuming UVB-irradiated mushrooms. The beneficial effect of this on the patient's plasma biochemical markers is shown. Further research into the beneficial effect of consuming UVB-irradiated mushrooms is required.\",\n \"title\": \"Vitamin D deficiency treated by consuming UVB-irradiated mushrooms\"\n },\n {\n \"docid\": \"MED-2990\",\n \"text\": \"ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. INTRODUCTION: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. MATERIALS AND METHODS: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. RESULTS AND CONCLUSIONS: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1-10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined.\",\n \"title\": \"Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research.\"\n },\n {\n \"docid\": \"MED-1861\",\n \"text\": \"INTRODUCTION: Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. OBJECTIVES: The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. METHODS: We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies. RESULTS: Four trials, with a total of 390 patients, met our inclusion criteria. Two studies compared Hibiscus sabdariffa to black tea; one study compared it to captopril and one to lisinopril. The studies found that Hibiscus had greater blood pressure reduction than tea but less than the ACE-inhibitors. However, all studies, except one, were short term and of poor quality with a Jadad scoring of <3 and did not meet international standards. CONCLUSION: The four randomized controlled studies identified in this review do not provide reliable evidence to support recommending Hibiscus sabdariffa for the treatment of primary hypertension in adults. Copyright 2009 Elsevier GmbH. All rights reserved.\",\n \"title\": \"The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review.\"\n },\n {\n \"docid\": \"MED-1932\",\n \"text\": \"There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.\",\n \"title\": \"Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study\"\n },\n {\n \"docid\": \"MED-2673\",\n \"text\": \"Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.\",\n \"title\": \"Determination of microbial transglutaminase in meat and meat products.\"\n },\n {\n \"docid\": \"MED-1071\",\n \"text\": \"BACKGROUND: Elevated serum saturated fatty acid levels and hepatocyte lipoapoptosis are features of nonalcoholic fatty liver disease (NAFLD). AIM: The purpose of this study was to investigate saturated fatty acid induction of lipoapoptosis in human liver cells and the underlying mechanisms. METHODS: Human liver L02 and HepG2 cells were treated with sodium palmitate, a saturated fatty acid, for up to 48 h with or without lithium chloride, a glycogen synthase kinase-3β (GSK-3β) inhibitor, or GSK-3β shRNA transfection. Transmission electron microscopy was used to detect morphological changes, flow cytometry was used to detect apoptosis, a colorimetric assay was used to detect caspase-3 activity, and western blot analysis was used to detect protein expression. RESULTS: The data showed that sodium palmitate was able to induce lipoapoptosis in L02 and HepG2 cells. Western blot analysis showed that sodium palmitate activated GSK-3β protein, which was indicated by dephosphorylation of GSK-3β at Ser-9. However, inhibition of GSK-3β activity with lithium chloride treatment or knockdown of GSK-3β expression with shRNA suppressed sodium palmitate-induced lipoapoptosis in L02 and HepG2 cells. On a molecular level, inhibition of GSK-3β expression or activity suppressed sodium palmitate-induced c-Jun-N-terminal kinase (JNK) phosphorylation and Bax upregulation, whereas GSK-3β inhibition did not affect endoplasmic reticulum stress-induced activation of unfolded protein response. CONCLUSIONS: The present data demonstrated that saturated fatty acid sodium palmitate-induced lipoapoptosis in human liver L02 and HepG2 cells was regulated by GSK-3β activation, which led to JNK activation and Bax upregulation. This finding indicates that GSK-3β inhibition may be a potential therapeutic target to control NAFLD.\",\n \"title\": \"Saturated free fatty acid sodium palmitate-induced lipoapoptosis by targeting glycogen synthase kinase-3β activation in human liver cells.\"\n },\n {\n \"docid\": \"MED-4436\",\n \"text\": \"The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies.\",\n \"title\": \"Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition.\"\n },\n {\n \"docid\": \"MED-3728\",\n \"text\": \"On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.\",\n \"title\": \"Strawberry fields forever?\"\n },\n {\n \"docid\": \"MED-1950\",\n \"text\": \"Several studies have found associations between microbial infections during pregnancy and preterm delivery (PTD). We investigated the influence of food with antimicrobial and prebiotic components on the risk of spontaneous PTD. A literature search identified microbes associated with spontaneous PTD. Subsequently, 2 main food types (alliums and dried fruits) were identified to contain antimicrobial components that affect the microbes associated with spontaneous PTD; they also contained dietary fibers recognized as prebiotics. We investigated intake in 18,888 women in the Norwegian Mother and Child Cohort (MoBa), of whom 950 (5%) underwent spontaneous PTD (<37 gestational weeks). Alliums (garlic, onion, leek, and spring onion) [OR: 0.82 (95% CI: 0.72, 0.94), P = 0.005] and dried fruits (raisins, apricots, prunes, figs, and dates) [OR: 0.82 (95% CI: 0.72, 0.94); P = 0.005] were associated with a decreased risk of spontaneous PTD. Intake of alliums was related to a more pronounced risk reduction in early spontaneous PTD (gestational weeks 28–31) [OR: 0.39 (95% CI: 0.19, 0.80)]. The strongest association in this group was with garlic [OR: 0.47 (95% CI: 0.25–0.89)], followed by cooked onions. Intake of dried fruits showed an association with preterm prelabor rupture of membranes (PPROM) [OR: 0.74 (95% CI: 0.65, 0.95)]; the strongest association in this group was with raisins [OR: 0.71 (95% CI: 0.56, 0.92)]. The strongest association with PPROM in the allium group was with garlic [OR: 0.74 (95% CI: 0.56, 0.97)]. In conclusion, intake of food with antimicrobial and prebiotic compounds may be of importance to reduce the risk of spontaneous PTD. In particular, garlic was associated with overall lower risk of spontaneous PTD. Dried fruits, especially raisins, were associated with reduced risk of PPROM.\",\n \"title\": \"Intakes of Garlic and Dried Fruits Are Associated with Lower Risk of Spontaneous Preterm Delivery\"\n },\n {\n \"docid\": \"MED-5038\",\n \"text\": \"Interest in the biological activities of cocoa polyphenols is increasing steadily. In fact, the high polyphenol content of cocoa, coupled with its widespread presence in many food items, render this food of particular interest from the nutritional and \\\"pharmacological\\\" viewpoints. This paper summarizes the new findings and developments regarding the effects of cocoa and chocolate consumption on human health as presented at the International Conference \\\"Chocolate, Lifestyle, and Health\\\" (Milan, Italy, March 2, 2007) regarding the effects of cocoa and chocolate consumption on human health.\",\n \"title\": \"Chocolate, lifestyle, and health.\"\n },\n {\n \"docid\": \"MED-4924\",\n \"text\": \"High-dose β-carotene supplementation in high-risk persons has been linked to increased lung cancer risk in clinical trials; whether effects are similar in the general population is unclear. The authors examined associations of supplemental β-carotene, retinol, vitamin A, lutein, and lycopene with lung cancer risk among participants, aged 50–76 years, in the VITamins And Lifestyle (VITAL) cohort Study in Washington State. In 2000–2002, eligible persons (n = 77,126) completed a 24-page baseline questionnaire, including detailed questions about supplement use (duration, frequency, dose) during the previous 10 years from multivitamins and individual supplements/mixtures. Incident lung cancers (n = 521) through December 2005 were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. Longer duration of use of individual β-carotene, retinol, and lutein supplements (but not total 10-year average dose) was associated with statistically significantly elevated risk of total lung cancer and histologic cell types; for example, hazard ratio = 2.02, 95% confidence interval: 1.28, 3.17 for individual supplemental lutein with total lung cancer and hazard ratio = 3.22, 95% confidence interval: 1.29, 8.07 for individual β-carotene with small-cell lung cancer for >4 years versus no use. There was little evidence for effect modification by gender or smoking status. Long-term use of individual β-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers.\",\n \"title\": \"Long-term Use of β-Carotene, Retinol, Lycopene, and Lutein Supplements and Lung Cancer Risk: Results From the VITamins And Lifestyle (VITAL) Study\"\n },\n {\n \"docid\": \"MED-3853\",\n \"text\": \"PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.\",\n \"title\": \"Serum enterolactone and prognosis of postmenopausal breast cancer.\"\n },\n {\n \"docid\": \"MED-1508\",\n \"text\": \"The obesity epidemic is attributed in part to reduced physical activity. Evidence supports that reducing time spent sitting, regardless of activity, may improve the metabolic consequences of obesity. Analyses were conducted in a large prospective study of US adults enrolled by the American Cancer Society to examine leisure time spent sitting and physical activity in relation to mortality. Time spent sitting and physical activity were queried by questionnaire on 53,440 men and 69,776 women who were disease free at enrollment. The authors identified 11,307 deaths in men and 7,923 deaths in women during the 14-year follow-up. After adjustment for smoking, body mass index, and other factors, time spent sitting (≥6 vs. <3 hours/day) was associated with mortality in both women (relative risk = 1.34, 95% confidence interval (CI): 1.25, 1.44) and men (relative risk = 1.17, 95% CI: 1.11, 1.24). Relative risks for sitting (≥6 hours/day) and physical activity (<24.5 metabolic equivalent (MET)-hours/week) combined were 1.94 (95% CI: 1.70, 2.20) for women and 1.48 (95% CI: 1.33, 1.65) for men, compared with those with the least time sitting and most activity. Associations were strongest for cardiovascular disease mortality. The time spent sitting was independently associated with total mortality, regardless of physical activity level. Public health messages should include both being physically active and reducing time spent sitting.\",\n \"title\": \"Leisure Time Spent Sitting in Relation to Total Mortality in a Prospective Cohort of US Adults\"\n },\n {\n \"docid\": \"MED-306\",\n \"text\": \"Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.\",\n \"title\": \"Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure\"\n },\n {\n \"docid\": \"MED-4227\",\n \"text\": \"Epidemiologic and biological data strongly support the existence of a strict link between cancer and aging. In spite of the relevance of the problem, there were numerous pitfalls in epidemiologic investigation until a few years ago. An apparent decrease of cancer incidence in old age was revealed to be a misconception based on lack of sufficient appreciation for changing population size. But not all problems are solved by using age-specific cancer incidence, as recently stressed by some authors. At very advanced ages a slowing of the rate of increase of age-specific cancer incidence is clearly demonstrated. These findings apparently clash with the majority of biological data and suggest that some mechanism may develop at advanced ages capable of decreasing cancer susceptibility. In this paper, it will be shown that just a slowing-down kinetics is predicted for cancer incidence by using a mathematical model of mortality kinetics recently proposed in the gerontologic field. The slowing of the increasing rate or even a decreasing trend of cancer incidence of an aging population is compatible with a continuously accelerating pace of loss of physiological capacity of the single subjects, as with advancing age there is a selection of individuals with better physiological functions.\",\n \"title\": \"Cancer and aging: from the kinetics of biological parameters to the kinetics of cancer incidence and mortality.\"\n },\n {\n \"docid\": \"MED-3096\",\n \"text\": \"Background and objectives: Uncooked meat and poultry products are commonly enhanced by food processors using phosphate salts. The addition of potassium and phosphorus to these foods has been recognized but not quantified. Design, setting, participants, & measurements: We measured the phosphorus, potassium, and protein content of 36 uncooked meat and poultry products: Phosphorus using the Association of Analytical Communities (AOAC) official method 984.27, potassium using AOAC official method 985.01, and protein using AOAC official method 990.03. Results: Products that reported the use of additives had an average phosphate-protein ratio 28% higher than additive free products; the content ranged up to almost 100% higher. Potassium content in foods with additives varied widely; additive free products all contained <387 mg/100 g, whereas five of the 25 products with additives contained at least 692 mg/100 g (maximum 930 mg/100 g). Most but not all foods with phosphate and potassium additives reported the additives (unquantified) on the labeling; eight of 25 enhanced products did not list the additives. The results cannot be applied to other products. The composition of the food additives used by food processors may change over time. Conclusions: Uncooked meat and poultry products that are enhanced may contain additives that increase phosphorus and potassium content by as much as almost two- and three-fold, respectively; this modification may not be discernible from inspection of the food label.\",\n \"title\": \"Original Articles: Phosphorus and Potassium Content of Enhanced Meat and Poultry Products: Implications for Patients Who Receive Dialysis\"\n },\n {\n \"docid\": \"MED-1509\",\n \"text\": \"AIMS/HYPOTHESIS: Sedentary (sitting) behaviours are ubiquitous in modern society. We conducted a systematic review and meta-analysis to examine the association of sedentary time with diabetes, cardiovascular disease and cardiovascular and all-cause mortality. METHODS: Medline, Embase and the Cochrane Library databases were searched for terms related to sedentary time and health outcomes. Cross-sectional and prospective studies were included. RR/HR and 95% CIs were extracted by two independent reviewers. Data were adjusted for baseline event rate and pooled using a random-effects model. Bayesian predictive effects and intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future. RESULTS: Eighteen studies (16 prospective, two cross-sectional) were included, with 794,577 participants. Fifteen of these studies were moderate to high quality. The greatest sedentary time compared with the lowest was associated with a 112% increase in the RR of diabetes (RR 2.12; 95% credible interval [CrI] 1.61, 2.78), a 147% increase in the RR of cardiovascular events (RR 2.47; 95% CI 1.44, 4.24), a 90% increase in the risk of cardiovascular mortality (HR 1.90; 95% CrI 1.36, 2.66) and a 49% increase in the risk of all-cause mortality (HR 1.49; 95% CrI 1.14, 2.03). The predictive effects and intervals were only significant for diabetes. CONCLUSIONS/INTERPRETATION: Sedentary time is associated with an increased risk of diabetes, cardiovascular disease and cardiovascular and all-cause mortality; the strength of the association is most consistent for diabetes.\",\n \"title\": \"Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis.\"\n },\n {\n \"docid\": \"MED-3514\",\n \"text\": \"BACKGROUND & AIMS: Lowered visceral perception thresholds have been suggested as a biological marker of irritable bowel syndrome (IBS). The current study sought to determine the prevalence of altered rectal visceral perception in patients with IBS and the correlation of altered perception thresholds with subjective symptoms. METHODS: Anorectal manometry and rectal perception thresholds to balloon distention were determined in 100 patients with IBS and 15 control subjects. Gastrointestinal and psychological symptoms were assessed by questionnaire. Perception thresholds and symptoms were reassessed after 3 months in 15 patients with IBS. RESULTS: Ninety-four percent of patients showed altered rectal perception in the form of lowered thresholds for aversive sensations (discomfort), increased intensity of sensations, or altered viscerosomatic referral. Hypersensitivity was found only for aversive sensations in response to rapid phasic distention; stool thresholds and thresholds in response to slow ramp distention were normal. Cluster analysis by physiological parameters identified three IBS subgroups with predominant patterns of symptoms. Longitudinal evaluation indicated a correlation between changes in perception thresholds and symptom severity. CONCLUSIONS: Because altered rectal perception is present in almost all patients with IBS and perception thresholds correlate with temporal changes in retrospective symptom severity, altered rectal perception represents a reliable biological marker of IBS.\",\n \"title\": \"Altered rectal perception is a biological marker of patients with irritable bowel syndrome.\"\n },\n {\n \"docid\": \"MED-2336\",\n \"text\": \"Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.\",\n \"title\": \"Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense\"\n },\n {\n \"docid\": \"MED-2101\",\n \"text\": \"The notion that a breast-gut connection might modulate the microenvironment of breast tissue was supported by the finding that breast cyst fluid contains bile acids that are characteristically found in the intestines. To establish that the gut, rather than circulating steroid precursors, is the source of bile acids in breast cyst fluid, we gave two patients deuterium-labelled chenodeoxycholic acid (three 200 mg doses by mouth), starting 9 days before aspiration of breast cysts. The chenodeoxycholic acid concentration of seven samples of aspirated cyst fluid ranged from 42 to 94 mumol/L. The corresponding serum concentrations of chenodeoxycholic acid on the same day were 0.8 and 2.9 mumol/L, of which the labelled compound comprised 13.0% (0.38 mumol/L) and 28.2% (0.23 mumol/L). The deuterated chenodeoxycholic acid concentrations in cyst fluid were 0.79 and 1.26 mumol/L in two samples from patient 1 and 3.22 mumol/L in patient 2; these values are equivalent to 11-17% of the serum concentrations [corrected]. This study shows that intestinal bile acids rapidly gain access to cyst fluid. Further studies should investigate the mechanisms that govern the exchange processes and the maintenance of the high cyst fluid to plasma concentration gradients, and the biological half-lives of individual constituents.\",\n \"title\": \"Breast-gut connection: origin of chenodeoxycholic acid in breast cyst fluid.\"\n },\n {\n \"docid\": \"MED-4411\",\n \"text\": \"Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.\",\n \"title\": \"Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial.\"\n },\n {\n \"docid\": \"MED-3840\",\n \"text\": \"The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.\",\n \"title\": \"Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo\"\n },\n {\n \"docid\": \"MED-2815\",\n \"text\": \"Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.\",\n \"title\": \"Curcumin, a component of turmeric: from farm to pharmacy.\"\n },\n {\n \"docid\": \"MED-4952\",\n \"text\": \"A vegetarian diet may have beneficial effects on human health, however when it is not well-balanced may be deficient in some nutrients, as minerals for example. The aim of the present study was to assess the nutritional status of zinc and selenium in vegetarians in the city of São Paulo. A cross-sectional study was performed, and the inclusion criteria were age > or = 18 years, both gender, no use of food or pharmaceutical supplements. Thirty vegetarian, of both genders, mean age of 27 years and 4.5 years of vegetarianism had performed the study, and their mean BMI was 21.5. Zinc plasma concentration was 71 and 62.5 microg/dL for men and women and erythrocyte concentration was 37 microg/gHb for both genders. Selenium concentration was 73.5 and 77.3 microg/L in plasma and 51.4 and 66.9 microg/L in erythrocytes for men and women, respectively. These biochemical values show that, according to the references, selenium blood levels are adequate and zinc concentration in erythrocytes is deficient in the studied population. For this reason, vegetarians should be constantly assessed and receive nutritional support to reduce the effects of inadequate zinc status.\",\n \"title\": \"Zinc and selenium nutritional status in vegetarians.\"\n },\n {\n \"docid\": \"MED-4173\",\n \"text\": \"OBJECTIVE: To assess the public health significance of premature weaning of infants from breast milk on later-life risk of chronic illness. DESIGN: A review and summary of recent meta-analyses of studies linking premature weaning from breast milk with later-life chronic disease risk is presented followed by an estimation of the approximate exposure in a developed Western country, based on historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion of chronic disease associated with current patterns of artificial feeding in infancy is estimated. RESULTS: After adjustment for major confounding variables, current research suggests that the risks of chronic disease are 30-200 % higher in those who were not breast-fed compared to those who were breast-fed in infancy. Exposure to premature weaning ranges from 20 % to 90 % in post-World War II age cohorts. Overall, the attributable proportion of chronic disease in the population is estimated at 6-24 % for a 30 % exposure to premature weaning. CONCLUSIONS: Breast-feeding is of public health significance in preventing chronic disease. There is a small but consistent effect of premature weaning from breast milk in increasing later-life chronic disease risk. Risk exposure in the Australian population is substantial. Approximately 90 % of current 35-45-year-olds were weaned from breast-feeding by 6 months of age. Encouraging greater duration and exclusivity of breast-feeding is a potential avenue for reducing future chronic disease burden and health system costs.\",\n \"title\": \"Chronic disease and infant nutrition: is it significant to public health?\"\n },\n {\n \"docid\": \"MED-4027\",\n \"text\": \"Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.\",\n \"title\": \"Dietary behavior and knowledge of dental erosion among Chinese adults\"\n },\n {\n \"docid\": \"MED-3423\",\n \"text\": \"INTRODUCTION: There are no reported studies assessing the relation between diet and sexual function in women with diabetes. AIM: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women. METHODS: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study. MAIN OUTCOME MEASURES: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function. RESULTS: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders. CONCLUSIONS: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.\",\n \"title\": \"Adherence to Mediterranean diet and sexual function in women with type 2 diabetes.\"\n },\n {\n \"docid\": \"MED-4760\",\n \"text\": \"The human gut is a lush microbial ecosystem containing about 100 trillion microorganisms, whose collective genome, the microbiome, contains 100-fold more genes than the entire human genome. The symbiosis of our extended genome plays a role in host homeostasis and energy extraction from diet. In this article, we summarize some of the studies that have advanced the understanding of the microbiome and its effects on metabolism, obesity, and health. Metagenomic studies demonstrated that certain mixes of gut microbiota may protect or predispose the host to obesity. Furthermore, microbiota transplantation studies in germ-free murine models showed that the efficient energy extraction traits of obese-type gut flora are transmissible. The proposed methods by which the microbiome may contribute to obesity include increasing dietary energy harvest, promoting fat deposition, and triggering systemic inflammation. Future treatments for obesity may involve modulation of gut microbiota using probiotics or prebiotics.\",\n \"title\": \"The microbiome and obesity: is obesity linked to our gut flora?\"\n },\n {\n \"docid\": \"MED-2229\",\n \"text\": \"BACKGROUND/OBJECTIVES: In vitro and animal studies have reported that young broccoli sprouts improve oxidative stress status in diabetic condition. The objective of this double-blind, placebo-controlled, randomized clinical trial was to investigate the effects of broccoli sprouts powder (BSP) on some oxidative stress parameters in type 2 diabetes patients. SUBJECTS/METHODS: A total of 81 patients with type 2 diabetes were randomly assigned to one of three treatment groups for 4 weeks. The groups received either 10 g/d BSP (n=27), 5 g/d BSP (n=29) or placebo (n=25). Serum total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and oxidized low density lipoprotein (LDL) cholesterol were measured at baseline and at 4 weeks after treatment. RESULTS: In all, 63 patients in three groups were included in the analysis: 10 g/d BSP (n=21), 5 g/d (n=22) and placebo (n=20). After 4 weeks, consumption of BSP resulted in significant decrease in MDA (P=0.001 for treatment effect), oxidized low density lipoprotein cholesterol (P=0.03 for treatment effect), OSI (P=0.001 for treatment effect) and significant increase in TAC (P=0.001 for treatment effect). No effects were found on TOS. CONCLUSION: BSP had favorable effects on oxidative stress status in type 2 diabetes patients.\",\n \"title\": \"Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind clinical trial.\"\n },\n {\n \"docid\": \"MED-1054\",\n \"text\": \"For a long time non communicable diseases (NCDs) were discussed as burden of the developed world. Recent alarming data show a reverse trend and a dramatic increase of NCDs in the developing world, in particular in highly populated transition countries. This is true for the main mortality triggering diseases such as CVD, cancer or diabetes. Almost 4 out of 5 NCD based deaths happen in low- and middle income countries. This development is multi-factorial and is based on some main trends such as globalization, supermarket growth, rapid urbanization and increasingly sedentary lifestyles. The latter leads to overweight or obesity, which again promotes NCDs similar as high blood pressure, high cholesterol and elevated blood glucose. A high quality diet including functional food or functional ingredients, accompanied by physical activity and a non-smoking policy, is one of the most promising factors in primary and secondary prevention of NCDs. Copyright © 2011 Elsevier Inc. All rights reserved.\",\n \"title\": \"A global view on the development of non communicable diseases.\"\n }\n]"}}},{"rowIdx":391,"cells":{"query_id":{"kind":"string","value":"43504"},"query":{"kind":"string","value":"Richmond, Virginia is home to the Federal Reserve Bank of Richmond."},"positive_passages":{"kind":"list like","value":[{"docid":"Richmond,_Virginia","text":"Richmond ( -LSB- ˈrɪtʃmənd -RSB- ) is the capital of the Commonwealth of Virginia in the Mid-Atlantic region of the United States . It is the center of the Richmond Metropolitan Statistical Area ( MSA ) and the Greater Richmond Region . It was incorporated in 1742 , and has been an independent city since 1871 . As of the 2010 census , the population was 204,214 ; in 2016 , the population was estimated to be 223,170 , the fourth-most populous city in Virginia . The Richmond Metropolitan Area has a population of 1,260,029 , the third-most populous metro in the state . Richmond is located at the fall line of the James River , 44 mi west of Williamsburg , 66 mi east of Charlottesville , and 98 mi south of Washington , D.C. Surrounded by Henrico and Chesterfield counties , the city is located at the intersections of Interstate 95 and Interstate 64 , and encircled by Interstate 295 and Virginia State Route 288 . Major suburbs include Midlothian to the southwest , Glen Allen to the north and west , Short Pump to the west and Mechanicsville to the northeast . The site of Richmond had been an important village of the Powhatan Confederacy , and was briefly settled by English colonists from Jamestown in 1609 , and in 1610 -- 1611 . The present city of Richmond was founded in 1737 . It became the capital of the Colony and Dominion of Virginia in 1780 . During the Revolutionary War period , several notable events occurred in the city , including Patrick Henry 's `` Give me liberty or give me death '' speech in 1775 at St. John 's Church , and the passage of the Virginia Statute for Religious Freedom written by Thomas Jefferson . During the American Civil War , Richmond served as the capital of the Confederate States of America . The city entered the 20th century with one of the world 's first successful electric streetcar systems . The Jackson Ward neighborhood is a national hub of African-American commerce and culture . Richmond 's economy is primarily driven by law , finance , and government , with federal , state , and local governmental agencies , as well as notable legal and banking firms , located in the downtown area . The city is home to both the United States Court of Appeals for the Fourth Circuit , one of 13 United States courts of appeals , and the Federal Reserve Bank of Richmond , one of 12 Federal Reserve Banks . Dominion Resources and MeadWestvaco , Fortune 500 companies , are headquartered in the city , with others in the metropolitan area .","title":""}],"string":"[\n {\n \"docid\": \"Richmond,_Virginia\",\n \"text\": \"Richmond ( -LSB- ˈrɪtʃmənd -RSB- ) is the capital of the Commonwealth of Virginia in the Mid-Atlantic region of the United States . It is the center of the Richmond Metropolitan Statistical Area ( MSA ) and the Greater Richmond Region . It was incorporated in 1742 , and has been an independent city since 1871 . As of the 2010 census , the population was 204,214 ; in 2016 , the population was estimated to be 223,170 , the fourth-most populous city in Virginia . The Richmond Metropolitan Area has a population of 1,260,029 , the third-most populous metro in the state . Richmond is located at the fall line of the James River , 44 mi west of Williamsburg , 66 mi east of Charlottesville , and 98 mi south of Washington , D.C. Surrounded by Henrico and Chesterfield counties , the city is located at the intersections of Interstate 95 and Interstate 64 , and encircled by Interstate 295 and Virginia State Route 288 . Major suburbs include Midlothian to the southwest , Glen Allen to the north and west , Short Pump to the west and Mechanicsville to the northeast . The site of Richmond had been an important village of the Powhatan Confederacy , and was briefly settled by English colonists from Jamestown in 1609 , and in 1610 -- 1611 . The present city of Richmond was founded in 1737 . It became the capital of the Colony and Dominion of Virginia in 1780 . During the Revolutionary War period , several notable events occurred in the city , including Patrick Henry 's `` Give me liberty or give me death '' speech in 1775 at St. John 's Church , and the passage of the Virginia Statute for Religious Freedom written by Thomas Jefferson . During the American Civil War , Richmond served as the capital of the Confederate States of America . The city entered the 20th century with one of the world 's first successful electric streetcar systems . The Jackson Ward neighborhood is a national hub of African-American commerce and culture . Richmond 's economy is primarily driven by law , finance , and government , with federal , state , and local governmental agencies , as well as notable legal and banking firms , located in the downtown area . The city is home to both the United States Court of Appeals for the Fourth Circuit , one of 13 United States courts of appeals , and the Federal Reserve Bank of Richmond , one of 12 Federal Reserve Banks . Dominion Resources and MeadWestvaco , Fortune 500 companies , are headquartered in the city , with others in the metropolitan area .\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"Federal_Reserve_Bank_of_Richmond_Baltimore_Branch","text":"The Federal Reserve Bank of Richmond Baltimore Branch Office is one of the two Federal Reserve Bank of Richmond branch offices . The Federal Reserve Bank of Richmond 's Baltimore Branch is an operational and regional center for Maryland , the metropolitan Washington D.C. area , Northern Virginia , and northeastern West Virginia . The Baltimore branch is part of the Fifth District and has the code E5 . It supports Check 21 operations , supplies coin and currency to financial institutions and works to maintain stability in the financial sector throughout the Fifth District and also works with local elected officials and non-profit organizations to support fair housing initiatives throughout the Fifth District . The Baltimore branch was founded in March 1918 and is currently headed by William R. Roberts . Each branch of the Federal Reserve Banks has a board of either seven or five directors , a majority of whom are appointed by the parent Federal Reserve Bank ; the others are appointed by the Board of Governors . Branch directors serve staggered three-year terms ( two-year terms if the Branch has five directors ) . One of the members appointed by the Federal Reserve Board is designated annually as chairman of the board of that Branch in a manner prescribed by the parent Federal Reserve Bank . The Baltimore branch currently allows private and educational tours of up to thirty people with reservations . Cell phones and cameras are not permitted inside the building . The Federal Reserve Bank of Richmond Baltimore Branch Office sponsors the annual Fed Challenge to encourage better understanding of the nation 's central bank and the forces influencing economic conditions in the United States and abroad . In 1997 , the Federal Reserve Bank of Richmond - Baltimore Branch won the silver U.S. Senate Productivity and Maryland Quality Award . In 2008 , Dorothy Voorhees received the Federal Reserve Bank of Richmond Baltimore Branch 2008 Excellence Award for outstanding achievement in the study of economics .","title":""},{"docid":"Federal_Reserve_Bank_of_Richmond","text":"The Federal Reserve Bank of Richmond is the headquarters of the Fifth District of the Federal Reserve located in Richmond , Virginia . It covers the District of Columbia , Maryland , North Carolina , South Carolina , Virginia , and most of West Virginia excluding the Northern Panhandle . Branch offices are located in Baltimore , Maryland and Charlotte , North Carolina . Currently , the position of president is vacant following the retirement of Jeffrey M. Lacker in April of 2017 . The previous president , J. Alfred Broaddus , retired in 2004 .","title":""},{"docid":"VCU_School_of_Business","text":"The Virginia Commonwealth University School of Business is located in Richmond , Virginia , home to one of the twelve Federal Reserve Banks . Because the school is located in downtown Richmond , Virginia , many students are able to receive internships and other opportunities within the city . Richmond , Virginia includes the third highest concentration of U.S. Fortune 1000 headquarters and is ranked as one of the nation 's 10 best places for business and careers .","title":""},{"docid":"J._Alfred_Broaddus","text":"J. Alfred Broaddus , Jr. ( born July 8 , 1939 in Richmond , Virginia ) was the sixth president of the Federal Reserve Bank of Richmond , headquarters of the Fifth District of the Federal Reserve System serving the District of Columbia , Maryland , North Carolina , South Carolina , Virginia , and most of West Virginia with the exception of the Northern Panhandle . Broaddus succeeded Robert P. Black and served as the Richmond Fed 's president from January 1 , 1993 until his retirement on July 31 , 2004 . He was succeeded as president by Jeffrey M. Lacker .","title":""},{"docid":"Federal_Reserve_Bank_of_Richmond_Charlotte_Branch","text":"The Federal Reserve Bank of Richmond Charlotte Branch Office is one of the two Federal Reserve Bank of Richmond branch offices . The Federal Reserve Bank of Richmond 's Charlotte Branch is an operational and regional center for the Carolinas , including the nation 's second largest financial center in Charlotte , NC.They promote the safety and soundness of large bank holding companies headquartered in Charlotte . They distribute currency and coin to financial institutions in our region and provide check adjustment services for the Federal Reserve System . Their public programs include forums and conferences , economic education outreach , tours and a speakers ' bureau.Clemson Dean Lilly has been serving as the director since 2007 .","title":""},{"docid":"List_of_Federal_Reserve_branches","text":"There are 24 Federal Reserve branches . As late as 2008 , there were 25 branches , but in October 2008 the Federal Reserve Bank of New York Buffalo Branch was closed . List of Federal Reserve branches Boston New York Federal Reserve Bank of New York Buffalo Branch ( closed ) Philadelphia Cleveland Federal Reserve Bank of Cleveland Cincinnati Branch Federal Reserve Bank of Cleveland Pittsburgh Branch Richmond Federal Reserve Bank of Richmond Baltimore Branch Federal Reserve Bank of Richmond Charlotte Branch Atlanta Federal Reserve Bank of Atlanta Birmingham Branch Federal Reserve Bank of Atlanta Jacksonville Branch Federal Reserve Bank of Atlanta Miami Branch Federal Reserve Bank of Atlanta Nashville Branch Federal Reserve Bank of Atlanta New Orleans Branch Chicago Federal Reserve Bank of Chicago Detroit Branch St Louis Federal Reserve Bank of St. Louis Little Rock Branch Federal Reserve Bank of St. Louis Louisville Branch Federal Reserve Bank of St. Louis Memphis Branch Minneapolis Federal Reserve Bank of Minneapolis Helena Branch Kansas City Federal Reserve Bank of Kansas City Denver Branch Federal Reserve Bank of Kansas City Oklahoma City Branch Federal Reserve Bank of Kansas City Omaha Branch Dallas Federal Reserve Bank of Dallas El Paso Branch Federal Reserve Bank of Dallas Houston Branch Federal Reserve Bank of Dallas San Antonio Branch San Francisco Federal Reserve Bank of San Francisco Los Angeles Branch Federal Reserve Bank of San Francisco Portland Branch Federal Reserve Bank of San Francisco Salt Lake City Branch Federal Reserve Bank of San Francisco Seattle Branch","title":""},{"docid":"List_of_tallest_buildings_in_Richmond,_Virginia","text":"This is a list of tallest buildings in Richmond , Virginia . Presently , the tallest building in Richmond is the 29-story James Monroe Building . It was the tallest building in Virginia from the time of its completion in 1981 until 2007 , when the 38-story Westin Tower in Virginia Beach opened in downtown Virginia Beach . The next three tallest skyscrapers in the city each have 26 stories within the structure , although they vary in height . The SunTrust Plaza stands at 400 ft ( 120 m ) , while the Federal Reserve Bank of Richmond , which also has 26 stories stands at 394 ft ( 119 m ) . The third tallest building is the Bank of America Center which stands at 331 ft ( 101 m ) . Typically , the first high-rise in Richmond history is often considered to be the 19-story BB&T Bank Building , which was completed in 1913 . The structure stands at 262 ft ( 80 m ) and is located in Downtown Richmond . The newest high rises in Richmond include Brandt Hall , a 17-story college dorm on the Monroe Park campus of Virginia Commonwealth University , which was completed in 2005 , along the Vistas on the James , which were completed that same year . Additionally , in downtown , the 12-story MWV Building was completed in 2010 . The 23-story Central National Bank Building , built in 1930 , is being converted into apartments after being left abandoned for over 20 years . Currently , a new 18-story office building , Gateway Plaza , is being constructed downtown for the McGuire Woods law firm . It is scheduled for completion in December , 2015 .","title":""},{"docid":"Central_Office_District","text":"The Central Office District is the central business district for Downtown Richmond , Virginia . The district contains a majority of the city core , with several high rises situated in this region of the city . The District houses the Richmond Federal Reserve Bank , Dominion Virginia Power 's corporate headquarters , Kanawha Plaza and the Virginia Tourism Corporation . U.S. Route 60 ( South 9th Street ) is the main street through the district .","title":""},{"docid":"Federal_banking","text":"Federal banking is the term for the way the Federal Reserve distributes its money . The Reserve ( often called the `` Fed '' ) operates twelve banking districts around the country which oversee money distribution within their respective districts . The twelve cities which are home to the Reserve Banks are Boston , New York City , Philadelphia , Richmond , Atlanta , Dallas , Saint Louis , Cleveland , Chicago , Minneapolis , Kansas City , and San Francisco .","title":""},{"docid":"Federal_Reserve_Bank_Building","text":"Federal Reserve Bank Building may refer to : Federal Reserve Bank of Atlanta Birmingham Branch , Birmingham , Alabama Federal Reserve Bank Building ( Little Rock , Arkansas ) Federal Reserve Bank of San Francisco , Los Angeles Branch , Los Angeles , California Federal Reserve Bank of San Francisco ( San Francisco , California ) Federal Reserve Bank Building ( Seattle ) Federal Reserve Bank of Richmond , Baltimore Branch , Baltimore , Maryland Federal Reserve Bank Building ( Boston , Massachusetts ) Federal Reserve Bank of Chicago Detroit Branch Building , Detroit , Michigan 925 Grand , the former Federal Reserve Building in Kansas City , Missouri Federal Reserve Bank of Kansas City , Kansas City , Missouri Federal Reserve Bank of New York , New York , New York Federal Reserve Bank of Cleveland , Cleveland , Ohio Old Federal Reserve Bank Building ( Philadelphia ) , Philadelphia , Pennsylvania Federal Reserve Bank of Atlanta , Nashville , Tennessee Eccles Building , Washington , D.C. , home to the board of governors of the Federal Reserve System","title":""},{"docid":"Crestar_Bank","text":"Crestar Bank was a regional bank headquartered in Richmond , Virginia with branches throughout Virginia and in Maryland . The bank was originally chartered as State Planters Bank Of Commerce And Trusts on December 8 , 1865 in Richmond . It was renamed United Virginia Bank/State Planters on February 15 , 1969 , and became United Virginia Bankshares , Inc. on December 15 , 1971 . With plans for expansion outside of the Commonwealth of Virginia , the Bank changed its name to Crestar Financial Corporation on September 1 , 1987 . In 1995 , Crestar acquired the assets of Loyola Federal Savings and Loan of Maryland , according to The New York Times . On March 14 , 1997 , Crestar acquired Citizens Bank of Maryland . On January 1 , 2000 , Crestar was acquired by Suntrust Bank . Now known as the SunTrust Plaza , Crestar 's former headquarters , a 26 story office tower , located a block from the Virginia State Capitol in the heart of downtown Richmond is one of Richmond 's premiere class `` A '' office buildings .","title":""},{"docid":"John_Brockenbrough","text":"John Brockenbrough ( 1775 -- 1852 ) was a business man and civic leader in Richmond , Virginia . He was president of the Bank of Virginia . His home in Richmond 's Court End District later served as the `` White House '' for the Confederate States of America .","title":""},{"docid":"Columbia_(Richmond,_Virginia)","text":"Columbia , also known as the Philip Haxall House , is a historic home located in Richmond , Virginia . It was built in 1817-1818 , and is a two-story , three bay Federal style brick dwelling on a high basement . The entrance features an elliptical fanlight opening sheltered by a one-story Doric porch . It was added when the entrance was moved from the Lombardy Street side to the Grace Street side in 1924 , when the building was expanded to house the T.C. Williams School of Law of the University of Richmond . It housed the School of Law from 1917 to 1954 . After 1834 , the house was the main academic building of Richmond College , which grew to become the present University of Richmond . It was listed on the National Register of Historic Places in 1982 .","title":""},{"docid":"Central_National_Bank_(Richmond,_Virginia)","text":"The Central National Bank building is a 23-story Art Deco skyscraper located in Richmond , Virginia . Completed in 1929 , it was one of the first skyscrapers in the city of Richmond not in the heart of the financial district . According to architectural historian Richard Guy Wilson , it and the West Hospital building , are the only two skyscrapers in Richmond to have used the fashionable Art Deco ziggurat-inspired setback , and only a few others exist elsewhere in Virginia . When the bank later changed hands , it was known as the Central Fidelity Bank . It was used as a branch bank for Wachovia Corp. until that closed in 2000 . After nearly fifteen years of vacancy , it was converted into apartments , and the first resident moved into the building in mid-2016 . The redevelopment is called to `` Deco at CNB , '' a 200-apartment development by Douglas Development Corp. . It was added to the National Register of Historic Places in 1979 . It is located in the Grace Street Commercial Historic District .","title":""},{"docid":"Mayor_of_Richmond,_Virginia","text":"The Mayor of the City of Richmond , Virginia is head of the executive branch of Richmond , Virginia 's city government . The mayor 's office administers all city services , public property , police and fire protection , most public agencies , and enforces all city , state and federal laws within Richmond , Virginia . The mayor looks over a city budget at roughly $ 765 million a year .","title":""},{"docid":"Call_Federal_Credit_Union","text":"Call Federal Credit Union is a federally insured , not-for-profit financial cooperative headquartered in Richmond , Virginia . It is regulated under the authority of the National Credit Union Administration ( NCUA ) of the U.S. federal government . Call Federal Credit Union is the second-largest Richmond-based credit union . As of December 31 , 2011 , Call Federal Credit Union had $ 350 million USD in assets and 31,000 members . In accordance with the Federal Credit Union Act of 1934 , Call Federal Credit Union is a tax-exempt , federally chartered , federally insured , not-for-profit financial cooperative . Call Federal Credit Union accounts are insured up to $ 250,000 through the NCUA , which is comparable to the insurance provided to accounts at traditional banks via the Federal Deposit Insurance Corporation .","title":""},{"docid":"Sports_in_Richmond,_Virginia","text":"Richmond , Virginia , United States , is home to three professional sports teams , though none of which compete in any major professional league . Virginia is the most populated state without a major sports team . In 2008 , the Richmond Braves minor league baseball team left for Gwinnett County , Georgia , and was replaced by the Richmond Flying Squirrels in 2010 . But now , the Flying Squirrels ' owner has threatened to leave Richmond if they do not replace their current stadium , The Diamond . The Richmond Kickers are a non-profit soccer team that plays at City Stadium . Richmond has also come into the national spotlight in recent years due to the success of the region 's two Division I college basketball teams , the VCU Rams and Richmond Spiders . The VCU Rams men 's basketball team reached the Final Four of the 2011 NCAA Men 's Division I Basketball Tournament , while the Richmond Spiders men 's basketball team reached the Sweet 16 of the same tournament . As of 2016 , Richmond is also home to its first women 's sports team , the Richmond Black Widows . They are in the Women 's Football Alliance and play at Hovey Field . The expansion team plays in Tier III of the Women 's Football Alliance and is the National Conference Champion .","title":""},{"docid":"Richmond_Metropolitan_Authority","text":"The Richmond Metropolitan Authority is an independent authority and political subdivision which serves the Richmond , Virginia metropolitan area . Created by an act of the Virginia General Assembly in 1966 , the RMA was originally tasked with building and maintaining a toll expressway system for the Richmond area . Since then , the role of the RMA has been expanded , and it currently owns and operates other facilities , including a number of parking decks and The Diamond , home stadium of the Richmond Braves minor league baseball team until 2008 , and the current home of the Richmond Flying Squirrels . The Authority also operates historic Main Street Station on behalf of the City of Richmond . Facilities operated by the RMA include : Downtown Expressway Powhite Parkway Boulevard Bridge The Diamond Main Street Station","title":""},{"docid":"First_National_Bank_Building_(Richmond,_Virginia)","text":"First National Bank Building , also known as the Old First and Merchants National Bank Building and BB&T Bank Building , is a historic bank and office building located in Richmond , Virginia . It was designed by noted architect Alfred Bossom and built in 1912-1913 . It is a 19-story , four bay by five bay , Classical Revival style steel frame building clad in brick , limestone , and granite . The building features rich architectural ornament that follows the Corinthian order both within and without . It was the first high-rise office tower to be built in Richmond . The First & Merchants Bank would eventually become Sovran Bank . It was listed on the National Register of Historic Places in 1982 . It is located in the Main Street Banking Historic District .","title":""},{"docid":"Richmond_WCT","text":"The Richmond WCT ( also known as United Virginia Bank Tennis Classic ) was a men 's tennis tournament played in Richmond , Virginia from 1971-1984 . The event was part of the WCT Tour and was held on indoor carpet courts .","title":""},{"docid":"East_Rutherford_Operations_Center","text":"The East Rutherford Operations Center ( EROC ) at 100 Orchard Street , East Rutherford , New Jersey , is the regional office for cash handling and processing of the Federal Reserve Bank of New York . The facility , which was constructed by Torcon , features a 400000 sqft three-story structure which sits on 13 acres . The structure is designed to house fail-safe operations in a secure environment . The facility also has a state-of-the art automated vault measuring one million cubic feet , used for storing United States currency . The vault can hold at least USD 60 billion . It was from this facility that the United States shipped some $ 12 billion to Iraq much of which money subsequently is unaccounted for . The center is one of three Federal Reserve Automation Services ( FRAS ) facilities in the Federal Reserve Banks system . They provide support for mission-critical payment systems . They are the survivors of the FedNet 5-year initiative started in 1990 to reengineer the Federal Reserve 's fund transfer system , and consolidate twelve data centers into 3 . If operations at East Rutherford fail , then the Federal Reserve Bank of Richmond serve as backup , with the Federal Reserve Bank of Dallas as secondary backup . In 2000 , the facility processed 1.39 billion checks , and USD$ 320 billion . The center 's bank check processing unit was shut down in 2006 as part of the Federal Reserve 's check restructuring process due to more checks being processed digitally . Check processing operations were moved to the Federal Reserve Bank of Philadelphia .","title":""},{"docid":"CSS_Richmond","text":"CSS Richmond , an ironclad ram , was built at Gosport ( Norfolk ) Navy Yard to the design of John L. Porter with money and scrap iron collected by the citizens of Virginia , whose imagination had been captured by the ironclad CSS Virginia . Consequently , she was sometimes referred to as Virginia II , Virginia No. 2 or Young Virginia in the South and as Merrimack No. 2 , New Merrimack or Young Merrimack by Union writers , months before the actual CSS Virginia II was ever laid down . Begun in March 1862 , Richmond was launched May 6 and towed up to the Confederate capital that very night to escape Federal forces again in possession of Norfolk Navy Yard and the lower James River . Richmond was thus finished at Richmond , Virginia in July 1862 and placed in commission by Commander Robert B. Pegram , CSN as part of the James River Squadron . Twenty-two inches of yellow pine and oak plus 4 inches of iron on her casemate protected her roof , and `` she is ironed 3 1/2 feet below her load lines , '' wrote Shipyard Superintendent John H. Burroughs . During 1863 and early 1864 the James front was quiet , but from May 1864 momentous events followed in quick succession . The Confederate Navy had three new ironclads in Captain French Forrest 's squadron there , and minor actions were frequent . During 1864 Richmond , under Lieutenant William Harwar Parker , CSN , took part in engagements at Dutch Gap on August 13 , Fort Harrison on September 29 -- October 1 , and Chaffin 's Bluff on October 22 . On January 23 -- 24 , 1865 , she was under heavy fire while aground with Virginia II above the obstructions at Trent 's Reach -- at an angle that caused Federal projectiles to ricochet harmlessly off their casemates . But Richmond '' 's unarmored tender , CSS Scorpion , being lashed alongside Richmond , was severely damaged by the explosion of CSS Drewry 's magazine . The ironclads were forced to withdrew under the Confederate batteries at Chaffin 's Bluff . A few weeks later , however , Richmond '' had to be destroyed to avoid capture by order of Rear Admiral Raphael Semmes , CSN squadron commander , prior to the evacuation of the Confederate capital on April 3 .","title":""},{"docid":"City_Stadium_(Richmond)","text":"City Stadium is a sports stadium in Richmond , Virginia . It is owned by the City of Richmond and is located south of the Carytown district off the Downtown Expressway . The stadium was built in 1929 and seats approximately 22,000 people . It is used by the Richmond Kickers of the United Soccer League since 1993 . The stadium was used by the University of Richmond for American football from 1929 to 2009 . The University of Richmond 's final home football game at the stadium was played on December 5 , 2009 against Appalachian State University in the quarterfinals of the Football Championship Subdivision playoffs . From 1964 through 1967 , the stadium was home to the Richmond Rebels of the Atlantic Coast Football League and the Continental Football League . The Rebels left the Continental Football League in 1967 to become the Richmond Mustangs of the United American Football League . University of Richmond Stadium served as the site of the NCAA Division I Men 's Soccer Championship from 1995-1998 . For a time in the mid-2000s , the stadium also hosted Virginia 's high school football state championship games .","title":""},{"docid":"Richmond,_Kentucky","text":"Richmond is a home rule-class city in and the county seat of Madison County , Kentucky , United States . It is named after Richmond , Virginia , and is the home of Eastern Kentucky University . The population was 33,533 in 2015 . Richmond is the third-largest city in the Bluegrass region ( after Louisville and Lexington ) and the state 's sixth-largest city . Richmond serves as the center for work and shopping for south-central Kentucky . Richmond is the principal city of the Richmond -- Berea Micropolitan Statistical Area , which includes all of Madison and Rockcastle counties .","title":""},{"docid":"Chickahominy_people","text":"The Chickahominy are a tribe of Virginian Indians who primarily live in Charles City County , located along the James River midway between Richmond and Williamsburg in the Commonwealth of Virginia . This area of the Tidewater is not far from where they lived in 1600 , prior to English colonization . They were officially recognized by the state in 1983 . The Eastern Chickahominy split from the main tribe in 1983 and were recognized separately by the state . They are based in New Kent County , about 25 mi east of Richmond . Neither tribe has an Indian reservation , having lost their land to English colonists in the 18th century , but they have purchased lands that they devote to communal purposes . Both tribes are among the 11 who have organized and been officially recognized by Virginia since 1983 . Neither has received recognition from the federal government . In 2009 , a bill was proposed in Congress to federally recognize six `` landless '' Virginia tribes already recognized by the state , including these two . Although passed by the House , it did not gain Senate approval .","title":""},{"docid":"Robert_P._Black","text":"Robert P. Black ( 1927 - ) , a native of Hickman , Kentucky , was the fifth president ( 1973 -- 1992 ) of the Federal Reserve Bank of Richmond , the headquarters of the Fifth District of the Federal Reserve System . He was preceded in that position by Aubrey N. Heflin and succeeded by J. Alfred Broaddus ( 1993 -- 2004 ) and Jeffrey Lacker ( August 1 , 2004 -- April 4 , 2017 ) .","title":""},{"docid":"2011_Richmond_Revolution_season","text":"The Richmond Revolution season was the team 's second season as a professional indoor football franchise and second in the Indoor Football League ( IFL ) . One of twenty-two teams competing in the IFL for the 2011 season , the Richmond , Virginia-based Richmond Revolution were members of the Atlantic Division of the United Conference . Under the leadership of head coach Tony Hawkins , the team played their home games at the Arthur Ashe Athletic Center in Richmond , Virginia .","title":""},{"docid":"Reveille_(Richmond,_Virginia)","text":"Reveille , also known as the Brick House , is a historic home located in Richmond , Virginia . The house consists of three sections . The main 2 1/2 - story house dates to about 1806 ; the 1 1/2 - story west wing dates to 1839 ; and a rear kitchen wing was added to the west wing in 1920 . The house is an example of an early 19th-century Federal style country residence . In 1950 the property and house were acquired by the Reveille United Methodist Church . It was listed on the National Register of Historic Places in 1979 .","title":""},{"docid":"Richmond_County_Bank_Ballpark","text":"The Richmond County Bank Ballpark at St. George ( RCB Ballpark ) is a baseball stadium located on the north-eastern tip of Staten Island . The ballpark is the home of the Staten Island Yankees , the NY-Penn League affiliate of the New York Yankees , and of Wagner College Seahawks Baseball . The ballpark was also home of the city 's Pro Cricket team the New York Storm in 2004 . In addition , local high schools have the chance to play at least one game at the Richmond County Bank Ballpark . The Ballpark at St. George is more commonly referred to as Staten Island Yankees Stadium instead of its much longer name , whose naming rights were given to Richmond County Savings Bank .","title":""},{"docid":"Richmond_Revolution","text":"The Richmond Revolution was a professional indoor football team based in Richmond , Virginia that played in the Indoor Football League from 2010 to 2011 . For the 2010 season , they played their home games at the Arthur Ashe Athletic Center . Because of space issues at that facility the owner decided to move onto the SportsQuest campus in nearby Chesterfield for the 2011 season and play all home games outdoors , since the proposed arena had not yet been built . However , in late August , Richmond BizSense 's writer Aaron Kremer ( 8/25/11 ) reported that Charlie Hildbold , the general manager , was laid off . He had moved to Virginia to help launch the indoor arena football team . According to Steve Burton , the owner of the team , Richmond Revolution will sit out the 2012 season and be reinstated in 2013 . Scott Bass a writer for Style Weekly reported ( 3/9/2011 ) nearly half of the 40 players on the Raiders ' training camp roster for 2011 defected from Richmond Revolution , as well as the Revolution 's head coach , Steve Criswell . On February 9 , 2012 the Virginia attorney general 's office filed a civil suit against SportsQuest , the company that owns the Revolution . This was Richmond 's third attempt at trying to build a long lasting indoor professional football team . The demise of Richmond Revolution left the Richmond Raiders the only team in the area . Previous teams were the Richmond Speed of the Af2 and the Richmond Bandits of the AIFL . When the team was first organized a name-the-team contest was held on the SportsQuest webpage . Nominations continued until August 11 , 2009 , with the five finalist names Blitz , Rush , Rivermen , Revolution , and Reign chosen the next day . Voting continued until August 21 with the Revolution name unveiled on August 24 . The Indoor Football League announced on June 23 , 2010 , that the Revolution had won the 2010 IFL Franchise of the Year award . In addition the team also took home the League 's Media Relations of the Year . Revolution QB Bryan Randall was named the 2010 IFL Most Valuable Player , and head coach Steve Criswell was named the IFL Coach of the Year . Later in the Steve Criswell left the team and on October 7 , 2010 , Richmond Revolution announced their new head coach would be former local standout Tony Hawkins . Hawkins is the all-time leading passer in Virginia State University history .","title":""}],"string":"[\n {\n \"docid\": \"Federal_Reserve_Bank_of_Richmond_Baltimore_Branch\",\n \"text\": \"The Federal Reserve Bank of Richmond Baltimore Branch Office is one of the two Federal Reserve Bank of Richmond branch offices . The Federal Reserve Bank of Richmond 's Baltimore Branch is an operational and regional center for Maryland , the metropolitan Washington D.C. area , Northern Virginia , and northeastern West Virginia . The Baltimore branch is part of the Fifth District and has the code E5 . It supports Check 21 operations , supplies coin and currency to financial institutions and works to maintain stability in the financial sector throughout the Fifth District and also works with local elected officials and non-profit organizations to support fair housing initiatives throughout the Fifth District . The Baltimore branch was founded in March 1918 and is currently headed by William R. Roberts . Each branch of the Federal Reserve Banks has a board of either seven or five directors , a majority of whom are appointed by the parent Federal Reserve Bank ; the others are appointed by the Board of Governors . Branch directors serve staggered three-year terms ( two-year terms if the Branch has five directors ) . One of the members appointed by the Federal Reserve Board is designated annually as chairman of the board of that Branch in a manner prescribed by the parent Federal Reserve Bank . The Baltimore branch currently allows private and educational tours of up to thirty people with reservations . Cell phones and cameras are not permitted inside the building . The Federal Reserve Bank of Richmond Baltimore Branch Office sponsors the annual Fed Challenge to encourage better understanding of the nation 's central bank and the forces influencing economic conditions in the United States and abroad . In 1997 , the Federal Reserve Bank of Richmond - Baltimore Branch won the silver U.S. Senate Productivity and Maryland Quality Award . In 2008 , Dorothy Voorhees received the Federal Reserve Bank of Richmond Baltimore Branch 2008 Excellence Award for outstanding achievement in the study of economics .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Federal_Reserve_Bank_of_Richmond\",\n \"text\": \"The Federal Reserve Bank of Richmond is the headquarters of the Fifth District of the Federal Reserve located in Richmond , Virginia . It covers the District of Columbia , Maryland , North Carolina , South Carolina , Virginia , and most of West Virginia excluding the Northern Panhandle . Branch offices are located in Baltimore , Maryland and Charlotte , North Carolina . Currently , the position of president is vacant following the retirement of Jeffrey M. Lacker in April of 2017 . The previous president , J. Alfred Broaddus , retired in 2004 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"VCU_School_of_Business\",\n \"text\": \"The Virginia Commonwealth University School of Business is located in Richmond , Virginia , home to one of the twelve Federal Reserve Banks . Because the school is located in downtown Richmond , Virginia , many students are able to receive internships and other opportunities within the city . Richmond , Virginia includes the third highest concentration of U.S. Fortune 1000 headquarters and is ranked as one of the nation 's 10 best places for business and careers .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"J._Alfred_Broaddus\",\n \"text\": \"J. Alfred Broaddus , Jr. ( born July 8 , 1939 in Richmond , Virginia ) was the sixth president of the Federal Reserve Bank of Richmond , headquarters of the Fifth District of the Federal Reserve System serving the District of Columbia , Maryland , North Carolina , South Carolina , Virginia , and most of West Virginia with the exception of the Northern Panhandle . Broaddus succeeded Robert P. Black and served as the Richmond Fed 's president from January 1 , 1993 until his retirement on July 31 , 2004 . He was succeeded as president by Jeffrey M. Lacker .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Federal_Reserve_Bank_of_Richmond_Charlotte_Branch\",\n \"text\": \"The Federal Reserve Bank of Richmond Charlotte Branch Office is one of the two Federal Reserve Bank of Richmond branch offices . The Federal Reserve Bank of Richmond 's Charlotte Branch is an operational and regional center for the Carolinas , including the nation 's second largest financial center in Charlotte , NC.They promote the safety and soundness of large bank holding companies headquartered in Charlotte . They distribute currency and coin to financial institutions in our region and provide check adjustment services for the Federal Reserve System . Their public programs include forums and conferences , economic education outreach , tours and a speakers ' bureau.Clemson Dean Lilly has been serving as the director since 2007 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"List_of_Federal_Reserve_branches\",\n \"text\": \"There are 24 Federal Reserve branches . As late as 2008 , there were 25 branches , but in October 2008 the Federal Reserve Bank of New York Buffalo Branch was closed . List of Federal Reserve branches Boston New York Federal Reserve Bank of New York Buffalo Branch ( closed ) Philadelphia Cleveland Federal Reserve Bank of Cleveland Cincinnati Branch Federal Reserve Bank of Cleveland Pittsburgh Branch Richmond Federal Reserve Bank of Richmond Baltimore Branch Federal Reserve Bank of Richmond Charlotte Branch Atlanta Federal Reserve Bank of Atlanta Birmingham Branch Federal Reserve Bank of Atlanta Jacksonville Branch Federal Reserve Bank of Atlanta Miami Branch Federal Reserve Bank of Atlanta Nashville Branch Federal Reserve Bank of Atlanta New Orleans Branch Chicago Federal Reserve Bank of Chicago Detroit Branch St Louis Federal Reserve Bank of St. Louis Little Rock Branch Federal Reserve Bank of St. Louis Louisville Branch Federal Reserve Bank of St. Louis Memphis Branch Minneapolis Federal Reserve Bank of Minneapolis Helena Branch Kansas City Federal Reserve Bank of Kansas City Denver Branch Federal Reserve Bank of Kansas City Oklahoma City Branch Federal Reserve Bank of Kansas City Omaha Branch Dallas Federal Reserve Bank of Dallas El Paso Branch Federal Reserve Bank of Dallas Houston Branch Federal Reserve Bank of Dallas San Antonio Branch San Francisco Federal Reserve Bank of San Francisco Los Angeles Branch Federal Reserve Bank of San Francisco Portland Branch Federal Reserve Bank of San Francisco Salt Lake City Branch Federal Reserve Bank of San Francisco Seattle Branch\",\n \"title\": \"\"\n },\n {\n \"docid\": \"List_of_tallest_buildings_in_Richmond,_Virginia\",\n \"text\": \"This is a list of tallest buildings in Richmond , Virginia . Presently , the tallest building in Richmond is the 29-story James Monroe Building . It was the tallest building in Virginia from the time of its completion in 1981 until 2007 , when the 38-story Westin Tower in Virginia Beach opened in downtown Virginia Beach . The next three tallest skyscrapers in the city each have 26 stories within the structure , although they vary in height . The SunTrust Plaza stands at 400 ft ( 120 m ) , while the Federal Reserve Bank of Richmond , which also has 26 stories stands at 394 ft ( 119 m ) . The third tallest building is the Bank of America Center which stands at 331 ft ( 101 m ) . Typically , the first high-rise in Richmond history is often considered to be the 19-story BB&T Bank Building , which was completed in 1913 . The structure stands at 262 ft ( 80 m ) and is located in Downtown Richmond . The newest high rises in Richmond include Brandt Hall , a 17-story college dorm on the Monroe Park campus of Virginia Commonwealth University , which was completed in 2005 , along the Vistas on the James , which were completed that same year . Additionally , in downtown , the 12-story MWV Building was completed in 2010 . The 23-story Central National Bank Building , built in 1930 , is being converted into apartments after being left abandoned for over 20 years . Currently , a new 18-story office building , Gateway Plaza , is being constructed downtown for the McGuire Woods law firm . It is scheduled for completion in December , 2015 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Central_Office_District\",\n \"text\": \"The Central Office District is the central business district for Downtown Richmond , Virginia . The district contains a majority of the city core , with several high rises situated in this region of the city . The District houses the Richmond Federal Reserve Bank , Dominion Virginia Power 's corporate headquarters , Kanawha Plaza and the Virginia Tourism Corporation . U.S. Route 60 ( South 9th Street ) is the main street through the district .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Federal_banking\",\n \"text\": \"Federal banking is the term for the way the Federal Reserve distributes its money . The Reserve ( often called the `` Fed '' ) operates twelve banking districts around the country which oversee money distribution within their respective districts . The twelve cities which are home to the Reserve Banks are Boston , New York City , Philadelphia , Richmond , Atlanta , Dallas , Saint Louis , Cleveland , Chicago , Minneapolis , Kansas City , and San Francisco .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Federal_Reserve_Bank_Building\",\n \"text\": \"Federal Reserve Bank Building may refer to : Federal Reserve Bank of Atlanta Birmingham Branch , Birmingham , Alabama Federal Reserve Bank Building ( Little Rock , Arkansas ) Federal Reserve Bank of San Francisco , Los Angeles Branch , Los Angeles , California Federal Reserve Bank of San Francisco ( San Francisco , California ) Federal Reserve Bank Building ( Seattle ) Federal Reserve Bank of Richmond , Baltimore Branch , Baltimore , Maryland Federal Reserve Bank Building ( Boston , Massachusetts ) Federal Reserve Bank of Chicago Detroit Branch Building , Detroit , Michigan 925 Grand , the former Federal Reserve Building in Kansas City , Missouri Federal Reserve Bank of Kansas City , Kansas City , Missouri Federal Reserve Bank of New York , New York , New York Federal Reserve Bank of Cleveland , Cleveland , Ohio Old Federal Reserve Bank Building ( Philadelphia ) , Philadelphia , Pennsylvania Federal Reserve Bank of Atlanta , Nashville , Tennessee Eccles Building , Washington , D.C. , home to the board of governors of the Federal Reserve System\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Crestar_Bank\",\n \"text\": \"Crestar Bank was a regional bank headquartered in Richmond , Virginia with branches throughout Virginia and in Maryland . The bank was originally chartered as State Planters Bank Of Commerce And Trusts on December 8 , 1865 in Richmond . It was renamed United Virginia Bank/State Planters on February 15 , 1969 , and became United Virginia Bankshares , Inc. on December 15 , 1971 . With plans for expansion outside of the Commonwealth of Virginia , the Bank changed its name to Crestar Financial Corporation on September 1 , 1987 . In 1995 , Crestar acquired the assets of Loyola Federal Savings and Loan of Maryland , according to The New York Times . On March 14 , 1997 , Crestar acquired Citizens Bank of Maryland . On January 1 , 2000 , Crestar was acquired by Suntrust Bank . Now known as the SunTrust Plaza , Crestar 's former headquarters , a 26 story office tower , located a block from the Virginia State Capitol in the heart of downtown Richmond is one of Richmond 's premiere class `` A '' office buildings .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"John_Brockenbrough\",\n \"text\": \"John Brockenbrough ( 1775 -- 1852 ) was a business man and civic leader in Richmond , Virginia . He was president of the Bank of Virginia . His home in Richmond 's Court End District later served as the `` White House '' for the Confederate States of America .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Columbia_(Richmond,_Virginia)\",\n \"text\": \"Columbia , also known as the Philip Haxall House , is a historic home located in Richmond , Virginia . It was built in 1817-1818 , and is a two-story , three bay Federal style brick dwelling on a high basement . The entrance features an elliptical fanlight opening sheltered by a one-story Doric porch . It was added when the entrance was moved from the Lombardy Street side to the Grace Street side in 1924 , when the building was expanded to house the T.C. Williams School of Law of the University of Richmond . It housed the School of Law from 1917 to 1954 . After 1834 , the house was the main academic building of Richmond College , which grew to become the present University of Richmond . It was listed on the National Register of Historic Places in 1982 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Central_National_Bank_(Richmond,_Virginia)\",\n \"text\": \"The Central National Bank building is a 23-story Art Deco skyscraper located in Richmond , Virginia . Completed in 1929 , it was one of the first skyscrapers in the city of Richmond not in the heart of the financial district . According to architectural historian Richard Guy Wilson , it and the West Hospital building , are the only two skyscrapers in Richmond to have used the fashionable Art Deco ziggurat-inspired setback , and only a few others exist elsewhere in Virginia . When the bank later changed hands , it was known as the Central Fidelity Bank . It was used as a branch bank for Wachovia Corp. until that closed in 2000 . After nearly fifteen years of vacancy , it was converted into apartments , and the first resident moved into the building in mid-2016 . The redevelopment is called to `` Deco at CNB , '' a 200-apartment development by Douglas Development Corp. . It was added to the National Register of Historic Places in 1979 . It is located in the Grace Street Commercial Historic District .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Mayor_of_Richmond,_Virginia\",\n \"text\": \"The Mayor of the City of Richmond , Virginia is head of the executive branch of Richmond , Virginia 's city government . The mayor 's office administers all city services , public property , police and fire protection , most public agencies , and enforces all city , state and federal laws within Richmond , Virginia . The mayor looks over a city budget at roughly $ 765 million a year .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Call_Federal_Credit_Union\",\n \"text\": \"Call Federal Credit Union is a federally insured , not-for-profit financial cooperative headquartered in Richmond , Virginia . It is regulated under the authority of the National Credit Union Administration ( NCUA ) of the U.S. federal government . Call Federal Credit Union is the second-largest Richmond-based credit union . As of December 31 , 2011 , Call Federal Credit Union had $ 350 million USD in assets and 31,000 members . In accordance with the Federal Credit Union Act of 1934 , Call Federal Credit Union is a tax-exempt , federally chartered , federally insured , not-for-profit financial cooperative . Call Federal Credit Union accounts are insured up to $ 250,000 through the NCUA , which is comparable to the insurance provided to accounts at traditional banks via the Federal Deposit Insurance Corporation .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Sports_in_Richmond,_Virginia\",\n \"text\": \"Richmond , Virginia , United States , is home to three professional sports teams , though none of which compete in any major professional league . Virginia is the most populated state without a major sports team . In 2008 , the Richmond Braves minor league baseball team left for Gwinnett County , Georgia , and was replaced by the Richmond Flying Squirrels in 2010 . But now , the Flying Squirrels ' owner has threatened to leave Richmond if they do not replace their current stadium , The Diamond . The Richmond Kickers are a non-profit soccer team that plays at City Stadium . Richmond has also come into the national spotlight in recent years due to the success of the region 's two Division I college basketball teams , the VCU Rams and Richmond Spiders . The VCU Rams men 's basketball team reached the Final Four of the 2011 NCAA Men 's Division I Basketball Tournament , while the Richmond Spiders men 's basketball team reached the Sweet 16 of the same tournament . As of 2016 , Richmond is also home to its first women 's sports team , the Richmond Black Widows . They are in the Women 's Football Alliance and play at Hovey Field . The expansion team plays in Tier III of the Women 's Football Alliance and is the National Conference Champion .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Richmond_Metropolitan_Authority\",\n \"text\": \"The Richmond Metropolitan Authority is an independent authority and political subdivision which serves the Richmond , Virginia metropolitan area . Created by an act of the Virginia General Assembly in 1966 , the RMA was originally tasked with building and maintaining a toll expressway system for the Richmond area . Since then , the role of the RMA has been expanded , and it currently owns and operates other facilities , including a number of parking decks and The Diamond , home stadium of the Richmond Braves minor league baseball team until 2008 , and the current home of the Richmond Flying Squirrels . The Authority also operates historic Main Street Station on behalf of the City of Richmond . Facilities operated by the RMA include : Downtown Expressway Powhite Parkway Boulevard Bridge The Diamond Main Street Station\",\n \"title\": \"\"\n },\n {\n \"docid\": \"First_National_Bank_Building_(Richmond,_Virginia)\",\n \"text\": \"First National Bank Building , also known as the Old First and Merchants National Bank Building and BB&T Bank Building , is a historic bank and office building located in Richmond , Virginia . It was designed by noted architect Alfred Bossom and built in 1912-1913 . It is a 19-story , four bay by five bay , Classical Revival style steel frame building clad in brick , limestone , and granite . The building features rich architectural ornament that follows the Corinthian order both within and without . It was the first high-rise office tower to be built in Richmond . The First & Merchants Bank would eventually become Sovran Bank . It was listed on the National Register of Historic Places in 1982 . It is located in the Main Street Banking Historic District .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Richmond_WCT\",\n \"text\": \"The Richmond WCT ( also known as United Virginia Bank Tennis Classic ) was a men 's tennis tournament played in Richmond , Virginia from 1971-1984 . The event was part of the WCT Tour and was held on indoor carpet courts .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"East_Rutherford_Operations_Center\",\n \"text\": \"The East Rutherford Operations Center ( EROC ) at 100 Orchard Street , East Rutherford , New Jersey , is the regional office for cash handling and processing of the Federal Reserve Bank of New York . The facility , which was constructed by Torcon , features a 400000 sqft three-story structure which sits on 13 acres . The structure is designed to house fail-safe operations in a secure environment . The facility also has a state-of-the art automated vault measuring one million cubic feet , used for storing United States currency . The vault can hold at least USD 60 billion . It was from this facility that the United States shipped some $ 12 billion to Iraq much of which money subsequently is unaccounted for . The center is one of three Federal Reserve Automation Services ( FRAS ) facilities in the Federal Reserve Banks system . They provide support for mission-critical payment systems . They are the survivors of the FedNet 5-year initiative started in 1990 to reengineer the Federal Reserve 's fund transfer system , and consolidate twelve data centers into 3 . If operations at East Rutherford fail , then the Federal Reserve Bank of Richmond serve as backup , with the Federal Reserve Bank of Dallas as secondary backup . In 2000 , the facility processed 1.39 billion checks , and USD$ 320 billion . The center 's bank check processing unit was shut down in 2006 as part of the Federal Reserve 's check restructuring process due to more checks being processed digitally . Check processing operations were moved to the Federal Reserve Bank of Philadelphia .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"CSS_Richmond\",\n \"text\": \"CSS Richmond , an ironclad ram , was built at Gosport ( Norfolk ) Navy Yard to the design of John L. Porter with money and scrap iron collected by the citizens of Virginia , whose imagination had been captured by the ironclad CSS Virginia . Consequently , she was sometimes referred to as Virginia II , Virginia No. 2 or Young Virginia in the South and as Merrimack No. 2 , New Merrimack or Young Merrimack by Union writers , months before the actual CSS Virginia II was ever laid down . Begun in March 1862 , Richmond was launched May 6 and towed up to the Confederate capital that very night to escape Federal forces again in possession of Norfolk Navy Yard and the lower James River . Richmond was thus finished at Richmond , Virginia in July 1862 and placed in commission by Commander Robert B. Pegram , CSN as part of the James River Squadron . Twenty-two inches of yellow pine and oak plus 4 inches of iron on her casemate protected her roof , and `` she is ironed 3 1/2 feet below her load lines , '' wrote Shipyard Superintendent John H. Burroughs . During 1863 and early 1864 the James front was quiet , but from May 1864 momentous events followed in quick succession . The Confederate Navy had three new ironclads in Captain French Forrest 's squadron there , and minor actions were frequent . During 1864 Richmond , under Lieutenant William Harwar Parker , CSN , took part in engagements at Dutch Gap on August 13 , Fort Harrison on September 29 -- October 1 , and Chaffin 's Bluff on October 22 . On January 23 -- 24 , 1865 , she was under heavy fire while aground with Virginia II above the obstructions at Trent 's Reach -- at an angle that caused Federal projectiles to ricochet harmlessly off their casemates . But Richmond '' 's unarmored tender , CSS Scorpion , being lashed alongside Richmond , was severely damaged by the explosion of CSS Drewry 's magazine . The ironclads were forced to withdrew under the Confederate batteries at Chaffin 's Bluff . A few weeks later , however , Richmond '' had to be destroyed to avoid capture by order of Rear Admiral Raphael Semmes , CSN squadron commander , prior to the evacuation of the Confederate capital on April 3 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"City_Stadium_(Richmond)\",\n \"text\": \"City Stadium is a sports stadium in Richmond , Virginia . It is owned by the City of Richmond and is located south of the Carytown district off the Downtown Expressway . The stadium was built in 1929 and seats approximately 22,000 people . It is used by the Richmond Kickers of the United Soccer League since 1993 . The stadium was used by the University of Richmond for American football from 1929 to 2009 . The University of Richmond 's final home football game at the stadium was played on December 5 , 2009 against Appalachian State University in the quarterfinals of the Football Championship Subdivision playoffs . From 1964 through 1967 , the stadium was home to the Richmond Rebels of the Atlantic Coast Football League and the Continental Football League . The Rebels left the Continental Football League in 1967 to become the Richmond Mustangs of the United American Football League . University of Richmond Stadium served as the site of the NCAA Division I Men 's Soccer Championship from 1995-1998 . For a time in the mid-2000s , the stadium also hosted Virginia 's high school football state championship games .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Richmond,_Kentucky\",\n \"text\": \"Richmond is a home rule-class city in and the county seat of Madison County , Kentucky , United States . It is named after Richmond , Virginia , and is the home of Eastern Kentucky University . The population was 33,533 in 2015 . Richmond is the third-largest city in the Bluegrass region ( after Louisville and Lexington ) and the state 's sixth-largest city . Richmond serves as the center for work and shopping for south-central Kentucky . Richmond is the principal city of the Richmond -- Berea Micropolitan Statistical Area , which includes all of Madison and Rockcastle counties .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Chickahominy_people\",\n \"text\": \"The Chickahominy are a tribe of Virginian Indians who primarily live in Charles City County , located along the James River midway between Richmond and Williamsburg in the Commonwealth of Virginia . This area of the Tidewater is not far from where they lived in 1600 , prior to English colonization . They were officially recognized by the state in 1983 . The Eastern Chickahominy split from the main tribe in 1983 and were recognized separately by the state . They are based in New Kent County , about 25 mi east of Richmond . Neither tribe has an Indian reservation , having lost their land to English colonists in the 18th century , but they have purchased lands that they devote to communal purposes . Both tribes are among the 11 who have organized and been officially recognized by Virginia since 1983 . Neither has received recognition from the federal government . In 2009 , a bill was proposed in Congress to federally recognize six `` landless '' Virginia tribes already recognized by the state , including these two . Although passed by the House , it did not gain Senate approval .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Robert_P._Black\",\n \"text\": \"Robert P. Black ( 1927 - ) , a native of Hickman , Kentucky , was the fifth president ( 1973 -- 1992 ) of the Federal Reserve Bank of Richmond , the headquarters of the Fifth District of the Federal Reserve System . He was preceded in that position by Aubrey N. Heflin and succeeded by J. Alfred Broaddus ( 1993 -- 2004 ) and Jeffrey Lacker ( August 1 , 2004 -- April 4 , 2017 ) .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"2011_Richmond_Revolution_season\",\n \"text\": \"The Richmond Revolution season was the team 's second season as a professional indoor football franchise and second in the Indoor Football League ( IFL ) . One of twenty-two teams competing in the IFL for the 2011 season , the Richmond , Virginia-based Richmond Revolution were members of the Atlantic Division of the United Conference . Under the leadership of head coach Tony Hawkins , the team played their home games at the Arthur Ashe Athletic Center in Richmond , Virginia .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Reveille_(Richmond,_Virginia)\",\n \"text\": \"Reveille , also known as the Brick House , is a historic home located in Richmond , Virginia . The house consists of three sections . The main 2 1/2 - story house dates to about 1806 ; the 1 1/2 - story west wing dates to 1839 ; and a rear kitchen wing was added to the west wing in 1920 . The house is an example of an early 19th-century Federal style country residence . In 1950 the property and house were acquired by the Reveille United Methodist Church . It was listed on the National Register of Historic Places in 1979 .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Richmond_County_Bank_Ballpark\",\n \"text\": \"The Richmond County Bank Ballpark at St. George ( RCB Ballpark ) is a baseball stadium located on the north-eastern tip of Staten Island . The ballpark is the home of the Staten Island Yankees , the NY-Penn League affiliate of the New York Yankees , and of Wagner College Seahawks Baseball . The ballpark was also home of the city 's Pro Cricket team the New York Storm in 2004 . In addition , local high schools have the chance to play at least one game at the Richmond County Bank Ballpark . The Ballpark at St. George is more commonly referred to as Staten Island Yankees Stadium instead of its much longer name , whose naming rights were given to Richmond County Savings Bank .\",\n \"title\": \"\"\n },\n {\n \"docid\": \"Richmond_Revolution\",\n \"text\": \"The Richmond Revolution was a professional indoor football team based in Richmond , Virginia that played in the Indoor Football League from 2010 to 2011 . For the 2010 season , they played their home games at the Arthur Ashe Athletic Center . Because of space issues at that facility the owner decided to move onto the SportsQuest campus in nearby Chesterfield for the 2011 season and play all home games outdoors , since the proposed arena had not yet been built . However , in late August , Richmond BizSense 's writer Aaron Kremer ( 8/25/11 ) reported that Charlie Hildbold , the general manager , was laid off . He had moved to Virginia to help launch the indoor arena football team . According to Steve Burton , the owner of the team , Richmond Revolution will sit out the 2012 season and be reinstated in 2013 . Scott Bass a writer for Style Weekly reported ( 3/9/2011 ) nearly half of the 40 players on the Raiders ' training camp roster for 2011 defected from Richmond Revolution , as well as the Revolution 's head coach , Steve Criswell . On February 9 , 2012 the Virginia attorney general 's office filed a civil suit against SportsQuest , the company that owns the Revolution . This was Richmond 's third attempt at trying to build a long lasting indoor professional football team . The demise of Richmond Revolution left the Richmond Raiders the only team in the area . Previous teams were the Richmond Speed of the Af2 and the Richmond Bandits of the AIFL . When the team was first organized a name-the-team contest was held on the SportsQuest webpage . Nominations continued until August 11 , 2009 , with the five finalist names Blitz , Rush , Rivermen , Revolution , and Reign chosen the next day . Voting continued until August 21 with the Revolution name unveiled on August 24 . The Indoor Football League announced on June 23 , 2010 , that the Revolution had won the 2010 IFL Franchise of the Year award . In addition the team also took home the League 's Media Relations of the Year . Revolution QB Bryan Randall was named the 2010 IFL Most Valuable Player , and head coach Steve Criswell was named the IFL Coach of the Year . Later in the Steve Criswell left the team and on October 7 , 2010 , Richmond Revolution announced their new head coach would be former local standout Tony Hawkins . Hawkins is the all-time leading passer in Virginia State University history .\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":392,"cells":{"query_id":{"kind":"string","value":"738"},"query":{"kind":"string","value":"How prudent would it be to invest (stocks/equity) in businesses that are based on Cash transactions?"},"positive_passages":{"kind":"list like","value":[{"docid":"341119","text":"If they're hiding their profits from the government, what makes you think they wouldn't hide their profits from their shareholders?","title":""},{"docid":"424439","text":"Every listed company needs to maintain book of accounts, when you are investing in companies you would have to look at what is stated in the books and along with other info decide to invest in it.","title":""}],"string":"[\n {\n \"docid\": \"341119\",\n \"text\": \"If they're hiding their profits from the government, what makes you think they wouldn't hide their profits from their shareholders?\",\n \"title\": \"\"\n },\n {\n \"docid\": \"424439\",\n \"text\": \"Every listed company needs to maintain book of accounts, when you are investing in companies you would have to look at what is stated in the books and along with other info decide to invest in it.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"177946","text":"\"I think the \"\"right\"\" way to approach this is for your personal books and your business's books to be completely separate. You would need to really think of them as separate things, such that rather than being disappointed that there's no \"\"cross transactions\"\" between files, you think of it as \"\"In my personal account I invested in a new business like any other investment\"\" with a transfer from your personal account to a Stock or other investment account in your company, and \"\"This business received some additional capital\"\" which one handles with a transfer (probably from Equity) to its checking account or the like. Yes, you don't get the built-in checks that you entered the same dollar amount in each, but (1) you need to reconcile your books against reality anyway occasionally, so errors should get caught, and (2) the transactions really are separate things from each entity's perspective. The main way to \"\"hack it\"\" would be to have separate top-level placeholder accounts for the business's Equity, Income, Expenses, and Assets/Liabilities. That is, your top-level accounts would be \"\"Personal Equity\"\", \"\"Business Equity\"\", \"\"Personal Income\"\", \"\"Business Income\"\", and so on. You can combine Assets and Liabilities within a single top-level account if you want, which may help you with that \"\"outlook of my business value\"\" you're looking for. (In fact, in my personal books, I have in the \"\"Current Assets\"\" account both normal things like my Checking account, but also my credit cards, because once I spend the money on my credit card I want to think of the money as being gone, since it is. Obviously this isn't \"\"standard accounting\"\" in any way, but it works well for what I use it for.) You could also just have within each \"\"normal\"\" top-level placeholder account, a placeholder account for both \"\"Personal\"\" and \"\"My Business\"\", to at least have a consistent structure. Depending on how your business is getting taxed in your jurisdiction, this may even be closer to how your taxing authorities treat things (if, for instance, the business income all goes on your personal tax return, but on a separate form). Regardless of how you set up the accounts, you can then create reports and filter them to include just that set of business accounts. I can see how just looking at the account list and transaction registers can be useful for many things, but the reporting does let you look at everything you need and handles much better when you want to look through a filter to just part of your financial picture. Once you set up the reporting (and you can report on lists of account balances, as well as transaction lists, and lots of other things), you can save them as Custom Reports, and then open them up whenever you want. You can even just leave a report tab (or several) open, and switch to it (refreshing it if needed) just like you might switch to the main Account List tab. I suspect once you got it set up and tried it for a while you'd find it quite satisfactory.\"","title":""},{"docid":"250530","text":"Canadian Couch Potato has an article which is somewhat related. Ask the Spud: Can You Time the Markets? The argument roughly boils down to the following: That said, I didn't follow the advice. I inherited a sum of money, more than I had dealt with before, and I did not feel I was emotionally capable of immediately dumping it into my portfolio (Canadian stocks, US stocks, world stocks, Canadian bonds, all passive indexed mutual funds), and so I decided to add the money into my portfolio over the course of a year, twice a month. The money that I had not yet invested, I put into a money market account. That worked for me because I was purchasing mutual funds with no transaction costs. If you are buying ETFs, this strategy makes less sense. In hindsight, this was not financially prudent; I'd have been financially better off to buy all the mutual funds right at the beginning. But I was satisfied with the tradeoff, knowing that I did not have hindsight and I would have been emotionally hurt had the stock market crashed. There must be research that would prove, based on past performance, the statistically optimal time frame for dollar-cost averaging. However, I strongly suppose that the time frame is rather small, and so I would advise that you either invest the money immediately, or dollar-cost average your investment over the course of the year. This answer is not an ideal answer to your question because it is lacking such a citation.","title":""},{"docid":"333755","text":"\"There are many different methods for a corporation to get money, but they mostly fall into three categories: earnings, debt and equity. Earnings would be just the corporation's accumulation of cash due to the operation of its business. Perhaps if cash was needed for a particular reason immediately, a business may consider selling a division or group of assets to another party, and using the proceeds for a different part of the business. Debt is money that (to put it simply) the corporation legally must repay to the lender, likely with periodic interest payments. Apart from the interest payments (if any) and the principal (original amount leant), the lender has no additional rights to the value of the company. There are, basically, 2 types of corporate debt: bank debt, and bonds. Bank debt is just the corporation taking on a loan from a bank. Bonds are offered to the public - ie: you could potentially buy a \"\"Tesla Bond\"\", where you give Tesla $1k, and they give you a stated interest rate over time, and principal repayments according to a schedule. Which type of debt a corporation uses will depend mostly on the high cost of offering a public bond, the relationships with current banks, and the interest rates the corporation thinks it can get from either method. Equity [or, shares] is money that the corporation (to put it simply) likely does not have a legal obligation to repay, until the corporation is liquidated (sold at the end of its life) and all debt has already been repaid. But when the corporation is liquidated, the shareholders have a legal right to the entire value of the company, after those debts have been paid. So equity holders have higher risk than debt holders, but they also can share in higher reward. That is why stock prices are so volatile - the value of each share fluctuates based on the perceived value of the entire company. Some equity may be offered with specific rules about dividend payments - maybe they are required [a 'preferred' share likely has a stated dividend rate almost like a bond, but also likely has a limited value it can ever receive back from the corporation], maybe they are at the discretion of the board of directors, maybe they will never happen. There are 2 broad ways for a corporation to get money from equity: a private offering, or a public offering. A private offering could be a small mom and pop store asking their neighbors to invest 5k so they can repair their business's roof, or it could be an 'Angel Investor' [think Shark Tank] contributing significant value and maybe even taking control of the company. Perhaps shares would be offered to all current shareholders first. A public offering would be one where shares would be offered up to the public on the stock exchange, so that anyone could subscribe to them. Why a corporation would use any of these different methods depends on the price it feels it could get from them, and also perhaps whether there are benefits to having different shareholders involved in the business [ie: an Angel investor would likely be involved in the business to protect his/her investment, and that leadership may be what the corporation actually needs, as much or more than money]. Whether a corporation chooses to gain cash from earnings, debt, or equity depends on many factors, including but not limited to: (1) what assets / earnings potential it currently has; (2) the cost of acquiring the cash [ie: the high cost of undergoing a public offering vs the lower cost of increasing a bank loan]; and (3) the ongoing costs of that cash to both the corporation and ultimately the other shareholders - ie: a 3% interest rate on debt vs a 6% dividend rate on preferred shares vs a 5% dividend rate on common shares [which would also share in the net value of the company with the other current shareholders]. In summary: Earnings would be generally preferred, but if the company needs cash immediately, that may not be suitable. Debt is generally cheap to acquire and interest rates are generally lower than required dividend rates. Equity is often expensive to acquire and maintain [either through dividend payments or by reduction of net value attributable to other current shareholders], but may be required if a new venture is risky. ie: a bank/bondholder may not want to lend money for a new tech idea because it is too risky to just get interest from - they want access to the potential earnings as well, through equity.\"","title":""},{"docid":"273947","text":"\"Exactly what accounts are affected by any given transaction is not a fixed thing. Just for example, in a simple accounting system you might have one account for \"\"stock on hand\"\". In a more complex system you might have this broken out into many accounts for different types of stock, stock in different locations, etc. So I can only suggest example specific accounts. But account type -- asset, liability, capital (or \"\"equity\"\"), income, expense -- should be universal. Debit and credit rules should be universal. 1: Sold product on account: You say it cost you $500 to produce. You don't say the selling price, but let's say it's, oh, $700. Credit (decrease) Asset \"\"Stock on hand\"\" by $500. Debit (increase) Asset \"\"Accounts receivable\"\" by $700. Credit (increase) Income \"\"Sales\"\" by $700. Debit (increase) Expense \"\"Cost of goods sold\"\" by $500. 2: $1000 spent on wedding party by friend I'm not sure how your friend's expenses affect your accounts. Are you asking how he would record this expense? Did you pay it for him? Are you expecting him to pay you back? Did he pay with cash, check, a credit card, bought on credit? I just don't know what's happening here. But just for example, if you're asking how your friend would record this in his own records, and if he paid by check: Credit (decrease) Asset \"\"checking account\"\" by $1000. Debit (increase) Expense \"\"wedding expenses\"\" by $1000. If he paid with a credit card: Credit (increase) Liability \"\"credit card\"\" by $1000. Debit (increase) Expense \"\"wedding expenses\"\" by $1000. When he pays off the credit card: Debit (decrease) Liability \"\"credit card\"\" by $1000. Credit (decrease) Asset \"\"cash\"\" by $1000. (Or more realistically, there are other expenses on the credit card and the amount would be higher.) 3: Issue $3000 in stock to partner company I'm a little shakier on this, I haven't worked with the stock side of accounting. But here's my best stab: Well, did you get anything in return? Like did they pay you for the stock? I wouldn't think you would just give someone stock as a present. If they paid you cash for the stock: Debit (increase) Asset \"\"cash\"\". Credit (decrease) Capital \"\"shareholder equity\"\". Anyone else want to chime in on that one, I'm a little shaky there. Here, let me give you the general rules. My boss years ago described it to me this way: You only need to know three things to understand double-entry accounting: 1: There are five types of accounts: Assets: anything you have that has value, like cash, buildings, equipment, and merchandise. Includes things you may not actually have in your hands but that are rightly yours, like money people owe you but haven't yet paid. Liabilities: Anything you owe to someone else. Debts, merchandise paid for but not yet delivered, and taxes due. Capital (some call it \"\"capital\"\", others call it \"\"equity\"\"): The difference between Assets and Liabilities. The owners investment in the company, retained earnings, etc. Income: Money coming in, the biggest being sales. Expenses: Money going out, like salaries to employees, cost of purchasing merchandise for resale, rent, electric bill, taxes, etc. Okay, that's a big \"\"one thing\"\". 2: Every transaction must update two or more accounts. Each update is either a \"\"debit\"\" or a \"\"credit\"\". The total of the debits must equal the total of the credits. 3: A dollar bill in your pocket is a debit. With a little thought (okay, sometimes a lot of thought) you can figure out everything else from there.\"","title":""},{"docid":"178303","text":"\"Some thoughts: 1) Do you have a significant emergency fund (3-6 months of after-tax living expenses)? If not, you stand to take a significant loss if you have an unexpected need for cash that is tied up in investments. What if you lose/hate your job or your car breaks down? What if a you want to spend some time with a relative or significant other who learns they only have a few months to live? Having a dedicated emergency fund is an important way to avoid downside risk. 2) Lagerbaer has a good suggestion. Given that if you'd reinvested your dividends, the S&P 500 has returned about 3.5% over the last 5 years, you may be able to get a very nice risk-free return. 3) Do you have access to employer matching funds, such as in a 401(k) at work? If you get a dollar-for-dollar match, that is a risk-free pre-tax 100% return and should be a high priority. 4) What do you mean by \"\"medium\"\" volatility? Given that you are considering a 2/3 equity allocation, it would not be at all out of the realm of possibility that your balance could fall by 15% or more in any given year and take several years to recover. If that would spook you, you may want to consider lowering your equity weights. A high quality bond fund may be a good fit. 5) Personally, I would avoid putting money into stocks that I didn't need back for 10 years. If you only want to tie your money up for 2-5 years, you are taking a significant risk that if prices fall, you won't have time to recover before you need your money back. The portfolio you described would be appropriate for someone with a long-term investment horizon and significant risk tolerance, which is usually the case for young people saving for retirement. However, if your goals are to invest for 2-5 years only, your situation would be significantly different. 6) You can often borrow from an investment account to purchase a primary residence, but you must pay that amount back in order to avoid significant taxes and fees, unless you plan to liquidate assets. If you plan to buy a house, saving enough to avoid PMI is a good risk-free return on your money. 7) In general, and ETF or index fund is a good idea, the key being to minimize the compound effect of expenses over the long term. There are many good choices a la Vanguard here to choose from. 8) Don't worry about \"\"Buy low, sell high\"\". Don't be a speculator, be an investor (that's my version of Anthony Bourdain's, \"\"don't be a tourist, be a traveler\"\"). A speculator wants to sell shares at a higher price than they were purchased at. An investor wants to share in the profits of a company as a part-owner. If you can consistently beat the market by trying to time your transactions, good for you - you can move to Wall Street and make millions. However, almost no one can do this consistently, and it doesn't seem worth it to me to try. I don't mean to discourage you from investing, just make sure you have your bases covered so that you don't have to cash out at a bad time. Best of luck! Edit Response to additional questions below. 1) Emergency fund. I would recommend not investing in anything other than cash equivalents (money market, short-term CDs, etc.) until you've built up an emergency fund. It makes sense to want to make the \"\"best\"\" use of your money, but you also have to account for risk. My concern is that if you were to experience one or more adverse life events, that you could lose a lot of money, or need to pay a lot in interest on credit card debt, and it would be prudent to self-insure against some of those risks. I would also recommend against using an investment account as an emergency fund account. Taking money out of investment accounts is inefficient because the commissions/taxes/fees can easily eat up a significant portion of your returns. Ideally, you would want to put money in and not touch it for a long time in order to take advantage of compounding returns. There are also high penalties for early disbursements from retirement funds. Just like you need enough money in your checking account to buy food and pay the rent every month, you need enough money in an emergency fund to pay for things that are a real possibility, even if they are less common. Using a credit card or an investment account is a relatively expensive way to do this. 2) Invest at all? I would recommend starting an emergency fund, and then beginning to invest for retirement. Once your retirement savings are on track, you can begin saving for whatever other goals you may have\"","title":""},{"docid":"526422","text":"\"The question is asking for a European equivalent of the so-called \"\"Couch Potato\"\" portfolio. \"\"Couch Potato\"\" portfolio is defined by the two URLs provided in question as, Criteria for fund composition Fixed-income: Regardless of country or supra-national market, the fixed-income fund should have holdings throughout the entire length of the yield curve (most available maturities), as well as being a mix of government, municipal (general obligation), corporate and high-yield bonds. Equity: The common equity position should be in one equity market index fund. It shouldn't be a DAX-30 or CAC-40 or DJIA type fund. Instead, you want a combination of growth and value companies. The fund should have as many holdings as possible, while avoiding too much expense due to transaction costs. You can determine how much is too much by comparing candidate funds with those that are only investing in highly liquid, large company stocks. Why it is easier for U.S. and Canadian couch potatoes It will be easier to find two good funds, at lower cost, if one is investing in a country with sizable markets and its own currency. That's why the Couch Potato strategy lends itself most naturally to the U.S.A, Canada, Japan and probably Australia, Brazil, South Korea and possibly Mexico too. In Europe, pre-EU, any of Germany, France, Spain, Italy or the Scandinavian countries would probably have worked well. The only concern would be (possibly) higher equity transactions costs and certainly larger fixed-income buy-sell spreads, due to smaller and less liquid markets other than Germany. These costs would be experienced by the portfolio manager, and passed on to you, as the investor. For the EU couch potato Remember the criteria, especially part 2, and the intent as described by the Couch Potato name, implying extremely passive investing. You want to choose two funds offered by very stable, reputable fund management companies. You will be re-balancing every six months or a year, only. That is four transactions per year, maximum. You don't need a lot of interaction with anyone, but you DO need to have the means to quickly exit both sides of the trade, should you decide, for any reason, that you need the money or that the strategy isn't right for you. I would not choose an ETF from iShares just because it is easy to do online transactions. For many investors, that is important! Here, you don't need that convenience. Instead, you need stability and an index fund with a good reputation. You should try to choose an EU based fund manager, or one in your home country, as you'll be more likely to know who is good and who isn't. Don't use Vanguard's FTSE ETF or the equivalent, as there will probably be currency and foreign tax concerns, and possibly forex risk. The couch potato strategy requires an emphasis on low fees with high quality funds and brokers (if not buying directly from the fund). As for type of fund, it would be best to choose a fund that is invested in mostly or only EU or EEU (European Economic Union) stocks, and the same for bonds. That will help minimize your transaction costs and tax liability, while allowing for the sort of broad diversity that helps buy and hold index fund investors.\"","title":""},{"docid":"378137","text":"Diversification is just one aspect in an investment portfolio. The other aspects in Investment are Risk Taking Ability, Liquidity, Local Regulations, Tax benefits, Ease & Convenience, Cost of carrying out transactions etc. Investing in other regions is prone FX risk and other risks depending on the region of investment. For example investing in Emerging markets there is a risk of Local Regulations being changed, additional tax being levied, or Political instability and host of such risks. Investing in local markets give you better understanding of such changes and the risk associated is less plus the Ease of carrying out transactions is great, less expensive compared to cost of transactions in other markets. Diversification in Investment should also be looked upon how much you invest in; Equities Debt Bullion Real Estate Once you have a sizeable amount of investment in Equities or Debt, it would then make more sense to diversify this portion more to include funds from other regions. Unless you are an Running your own business, it makes sense to invest in your line of business if that is performing well. The reason being that the benefit / returns from the equities is much greater than the salary rise / bonus. For example I am in Information Technology and yet invest in all leading IT companies because the returns from companies in these segments have been good.","title":""},{"docid":"123263","text":"\"If you are looking for numerical metrics I think the following are popular: Price/Earnings (P/E) - You mentioned this very popular one in your question. There are different P/E ratios - forward (essentially an estimate of future earnings by management), trailing, etc.. I think of the P/E as a quick way to grade a company's income statement (i.e: How much does the stock cost verusus the amount of earnings being generated on a per share basis?). Some caution must be taken when looking at the P/E ratio. Earnings can be \"\"massaged\"\" by the company. Revenue can be moved between quarters, assets can be depreciated at different rates, residual value of assets can be adjusted, etc.. Knowing this, the P/E ratio alone doesn't help me determine whether or not a stock is cheap. In general, I think an affordable stock is one whose P/E is under 15. Price/Book - I look at the Price/Book as a quick way to grade a company's balance sheet. The book value of a company is the amount of cash that would be left if everything the company owned was sold and all debts paid (i.e. the company's net worth). The cash is then divided amoung the outstanding shares and the Price/Book can be computed. If a company had a price/book under 1.0 then theoretically you could purchase the stock, the company could be liquidated, and you would end up with more money then what you paid for the stock. This ratio attempts to answer: \"\"How much does the stock cost based on the net worth of the company?\"\" Again, this ratio can be \"\"massaged\"\" by the company. Asset values have to be estimated based on current market values (think about trying to determine how much a company's building is worth) unless, of course, mark-to-market is suspended. This involves some estimating. Again, I don't use this value alone in determing whether or not a stock is cheap. I consider a price/book value under 10 a good number. Cash - I look at growth in the cash balance of a company as a way to grade a company's cash flow statement. Is the cash account growing or not? As they say, \"\"Cash is King\"\". This is one measurement that can not be \"\"massaged\"\" which is why I like it. The P/E and Price/Book can be \"\"tuned\"\" but in the end the company cannot hide a shrinking cash balance. Return Ratios - Return on Equity is a measure of the amount of earnings being generated for a given amount of equity (ROE = earnings/(assets - liabilities)). This attempts to measure how effective the company is at generating earnings with a given amount of equity. There is also Return on Assets which measures earnings returns based on the company's assets. I tend to think an ROE over 15% is a good number. These measurements rely on a company accurately reporting its financial condition. Remember, in the US companies are allowed to falsify accounting reports if approved by the government so be careful. There are others who simply don't follow the rules and report whatever numbers they like without penalty. There are many others. These are just a few of the more popular ones. There are many other considerations to take into account as other posters have pointed out.\"","title":""},{"docid":"329637","text":"You need to be clear about who gets your money: If you pay the existing owner $25K and (s)he gives you half the business, then you now own half of a $50K business an the original owner has an extra $25K in spending cash. The value of the business has not changed. If you contribute $25 to the company, new equity shares are created. Shares should be priced correctly, meaning you now own $25K worth of shares in a company worth $75k, so you should have 1/3 of the outstanding shares (counting both old and new shares). If you get more or less than this, then the transaction has happened in an unfair way. If this is a public company, that would most likely be illegal and the SEC may throw you in jail. If it was a private company and your friend created enough shares that you own half the company, then (s)he has given you a gift. If you are contributing to the company at a fair price, you would need to contribute $50K in order to end up with half the equity of the new and now more valuable firm. In that case the firm would be worth $100K after your contribution. Bottom line, this is a common and not complex transaction and should end up with a completely fair outcome. Any unfair situation you can imagine is probably based on false assumptions or a situation where a non-arms-length transaction is transferring wealth contrary to normal rules and procedures.","title":""},{"docid":"40966","text":"It took me a while to understand the concept, so I'll break it down as best as I can. There are three parts to the accounting equation: Assets = Liabilities + Owner's Equity We'll look at this in two ways 1. As a business owner you invest (say) 10,000 USD into your bank. The entry would be: Debit: Assets: Cash for 10,000 Credit: Owner's Equity: Contributions for 10,000 In this case, you have assets of 10,000 from your deposit, but it is due to owner contributions and not business transactions. Another example (say a sale): Debit: Assets: Cash for 10,000 Credit: Owner's Equity: Sales for 10,000 Debit: Assets: Cash for 10,000 Credit: Liabilities: Deposits for 10,000 Deposits are a banking term to reflect a bank's obligation to return the amount on demand (though the bank has free reign with it, see fractional banking) You will NEVER debit or credit your bank as it is assumed you will be storing your money there, note bank reconciliation. Hope this helps, comment with any more questions.","title":""},{"docid":"425888","text":"How you should record the mortgage payments depends on if you are trying to achieve correct accounting, according to the standards, or if you are just tracking everything for you and your friends. If you're just keeping track for personal reasons, I'd suggest that you set up your check (or journal entry, your preference) how you'd like it to be recorded. Then, memorize that transaction. This allows you to use it as many times as you need to, without having to set it up each time. (Also note: there is no way to record a transaction that decreases cash and increases equity.) If you're trying to keep track of everything according to accounting standards, which it should be if you've set up an official business, then you have a lot more tracking to do with each payment. Mortgage payments technically do not affect the equity accounts of the owners. Each mortgage payment should decrease the bank balance, increase interest expense and decrease the mortgage balance, not to mention tracking any escrow account you may have. The equity accounts would be affected if the owners are contributing funds to the bank account, but equity would increase at the time the funds are deposited, not when the mortgage payments are made. Hope this helps!","title":""},{"docid":"546313","text":"\"Training8m Corporate Technologies Pty Ltd, Australia Australia ABN 48133544297 UK Company Number: 7538482 Maiden Pre-IPO offer from Training8m Corporate Technologies Pty Ltd, Australia!! Unique opportunity for investors!!! Move to a most profitable and defensive investment!!! We offer Preferential Allotment / Private Placement of Debt / Equity. Most Profitable offer from The Global Leader!! www.training8m.com Subscription Offer Open: First ever pre-IPO offer from Training8m Australia Group!! Unique opportunity for investors!!! Move to a most profitable and defensive investment!!! Preferential Allotment / Private Placement of Debt / Equity to multiple business investors pre IPO from $ 50k to $ 25 Mn for start up venture set up and Capital market Listing on Frankfurt Stock Exchange. We offer Preferential Allotment / Private Placement of Equity to multiple business investors Pre- IPO from $ 50K to $ 25 Mn. Higher investment welcome for this International public issue. Equivalent Debt / Equity / Options / Preference Shares can be discussed. Minority Equity participation can be discussed. We at Training8m Australia are Going Public Soon on Frankfurt Stock Exchange. Status: Approved funding by major Global Private Equity Fund. We are pleased to write that our major funding, raising funds from the equity market listing on Frankfurt Stock Exchange, is approved by major and most reputed Private Equity Group. This is one of the largest upcoming IPO, highly profitable with high ROI. Subscription: Open to Institutional and Retail Investors Pre IPO offer in Debt / Equity / Preference Shares / Options Serious investors only please. We would like to conclude this current deal immediately. We at Training8m, Australia are willing to discuss on the Debt / Equity / Options / preference shares and will be liberal for this transaction, which will be issued to you directly from our fund managers. This is definitely a really profitable and high return investment. Payback period: 1 - 2 years (expected turnover at least $ 2 Bn in 3 years) Start up Stage of business. This investment has very attractive returns. Unique opportunity to associate prior to the IPO on Global Stock Exchanges Location: Head Quartered in Gold Coast, Australia with Global Operating Offices. Set up including Property Investment, Recruitment and Appointment of permanent personnel, Fees for Listing on major Global Stock Exchange, other expenses as needed for the business. Business Models: Training8m Corporate Technologies Pty Ltd, Australia Corporate Training, Marketing, Premium Recruitment Portal, Premium and Moderated Recruitment Social Networking, Training and Development for all industry Verticals, Global Business Solutions. Advanced Lighting Designers Pty Ltd, Australia We offer International Lighting Technologies, Design, Specifications, Software Solutions and High End Information Technology Services to Global Industry sectors. Please do note that we are officially registered in Australia and UK for our Global Business ventures. With appropriate funding for takeovers, mergers and Acquisitions, we will be listing the companies Training8m Corporate Technologies Pty Ltd, and Advanced Lighting Designers Pty Ltd, on major global stock exchanges. The punch line of Advanced Lighting Designers Pty Ltd is “Go Green with Force Green\"\" in which we will be focussing on Green Energy Worldwide. Please feel free to ask details privately. Offer for limited time and closes on receipt of funds. E- Mails: investors@training8m.com, business@training8m.com Shrikant G. Shete Chairman and Managing Director Training8m, Australia LinkedIn: http://au.linkedin.com/in/shrikantshete +61-400769125 ................................Australia Mobiles +61-434415521 ................................Australia Mobiles\"","title":""},{"docid":"414505","text":"\"The key difference I've found between a stock split and a stock dividend – of the exact same stock and class, as opposed to a spin-off – seems to be from the company's own accounting perspective. There doesn't appear to be any actual transfer of value to the shareholder with either kind of transaction; i.e. in theory, each transaction would be immaterial to the value of your holdings. With respect to the company's accounting, a stock split affects the par value of the shares, whereas a stock dividend reduces the retained earnings account in order to increase paid-in or contributed capital. I found a good online source which explains the history behind this accounting difference: McGraw-Hill - Intermediate Accounting eBook, 6/e - Chapter 18 - Stock Dividends and Splits. Small quote: [...] Besides being based on fallacious reasoning, accounting for stock dividends by artificially reclassifying “earned” capital as “invested” capital conflicts with the reporting objective of reporting shareholders' equity by source. Despite these limitations, this outdated accounting standard still applies. Since neither the corporation nor its shareholders apparently benefits from stock dividends, why do companies declare them?23 Occasionally, a company tries to give shareholders the illusion that they are receiving a real dividend. Another reason is merely to enable the corporation to take advantage of the accepted accounting practice of capitalizing retained earnings. Specifically, a company might wish to reduce an existing balance in retained earnings—otherwise available for cash dividends—so it can reinvest the earned assets represented by that balance without carrying a large balance in retained earnings. [...] There's a lot more on that page, before and after, worth reading. From another book: Google Books - Comparative Income Taxation, a Structural Analysis - page 314 - Stock Dividends. Small quote: The distribution of dividends in the form of stock or \"\"bonus\"\" shares to existing shareholders typically involves a transfer for corporate law purposes of retained earnings into stated capital. It can been [sic] viewed as a deemed distribution of a cash dividend to the shareholders followed by a corresponding contribution to capital or as solely as an event at the corporate level which has no effect on the shareholders whose economic interest in the corporation is unchanged by the receipt of additional shares. The systems have taken varied approaches to the stock dividend problem. The treatment is in part a function of the rules dealing with distributions of stated capital. [emphases above are mine] [... continues w/descriptions of different countries' tax treatments of the kinds of stock dividends. Includes U.S., Sweden, Japan, Netherlands, Canada, Australia, U.K., France, Germany. ...] As far as why a corporation might want to capitalize earnings and reduce the equity otherwise available for dividends, I can only imagine that, ignoring taxes for a moment, that it may have something to do with capital ratios that need to be maintained for financing or regulatory purposes? Yet, I remain curious. If I discover more on this then I'll update my answer. Additional resources:\"","title":""},{"docid":"5710","text":"\"As Michael Pryor answered, a bond fund is a mutual fund that invests in bonds. I'd also consider an ETF based on bonds to be a bond fund, but I'm not sure that all investors would consider these as \"\"bond funds\"\". Not all bond funds are the same -- just like stock funds. You can classify bond funds based on the issuer of the bonds: You can also classify funds based on the time to maturity: In general, bond funds have lower risk and lower expected return than stock funds. Sometimes bond funds have price movements that are not tightly correlated to the price movements in the equity markets. This can make them a decent hedge against declines in your equity investments. See Michal Pryor's answer for some info on how you can get tax free treatment for your bond fund investments.\"","title":""},{"docid":"190891","text":"\"The price of real estate reacts to both demand for property and the rate of inflation and rate of income growth. Mortgage rates generally move as treasury rates move. See this paragraph: As we mentioned, intermediate term bonds and long-term mortgages (more properly, Mortgage-Backed Securities, or MBS) compete for the same fixed-income investor dollar. Treasury issues are 100% guaranteed to be repaid, but mortgages are not; therefore mortgages carry more risk of default or early repayment, which could potentially disturb the return on the investment. Therefore, mortgage rates must be priced higher to compensate for that risk. But how much higher are mortgages priced? In a normal market, the average \"\"spread\"\" or markup above the 100% secured Treasury is about 170 basis points, or 1.7%. That markup -- the spread relationship -- widens and contracts with a range of market conditions, investor appetites and supply of available product -- as well as the presence of competing investment opportunities, like corporate bonds or domestic (or foreign) equity markets Source: What Moves Mortgage Rates? And when the stock market crashes, investors tend to run to bonds and treasuries, which causes prices to go up and treasury yields to drop. Theoretically, this would also cause mortgage rates to drop, although most mortgage rates have a base price below which they cannot fall. How easy is it to profit from recent stock market drops and at what frequency? Incredibly difficult. The issue with your strategy is that you cannot predict the bottom of the market (at least us mortals can't). Just take the month of August for example. Stocks fell something like 15%? After the first 5-10% drop, people felt that the bottom was there, so they rushed in, only to have the market fall even more. How will you know when to invest? Even if the market falls by 50%, and there's a huge buying opportunity, and you increase the mortgage on your house, odds are your rates will increase because of the equity you take out. What if the market stays low for a very long time? Will you be able to maintain mortgage payments? Japan's stock bubble popped in the early 90's, and they've had two lost decade's now. Furthermore, there are issues of liquidity. What if you need more capital? Can you just sell a property or can you buy now property to draw equity against? What if the market is moving too fast for you to take advantage of. Don't ignore transaction costs and taxes either. Overall, there are a lot of ways that your idea can go wrong, and not many ways it can go right.\"","title":""},{"docid":"474467","text":"You only got 75 shares, so your basis is the fair market value of the stock as of the grant date times the number of shares you got: $20*75. Functionally, it's the same thing as if your employer did this: As such, the basis in that stock is $1,500 ($20*75). The other 25 shares aren't yours and weren't ever yours, so they aren't part of your basis (for net issuance; if they were sell to cover, then the end result would be pretty similar, but there'd be another transaction involved, but we won't go there). To put it another way, suppose your employer paid you a $2000 bonus, leaving you with a $1500 check after tax withholding. Being a prudent person and not wishing to blow your bonus on luxury goods, you invest that $1500 in a well-researched investment. You wouldn't doubt that your cost basis in that investment at $1500.","title":""},{"docid":"161230","text":"This is a bit of an open-ended answer as certain assumptions must be covered. Hope it helps though. My concern is that you have 1 year of university left - is there a chance that this money will be needed to fund this year of uni? And might it be needed for the period between uni and starting your first job? If the answer is 'yes' to either of these, keep any money you have as liquid as possible - ie. cash in an instant access Cash ISA. If the answer is 'no', let's move on... Are you likely to touch this money in the next 5 years? I'm thinking house & flat deposits - whether you rent or buy, cars, etc, etc. If yes, again keep it liquid in a Cash ISA but this time, perhaps look to get a slightly better interest rate by fixing for a 1 year or 2 year at a time. Something like MoneySavingExpert will show you best buy Cash ISAs. If this money is not going to be touched for more than 5 years, then things like bonds and equities come into play. Ultimately your appetite for risk determines your options. If you are uncomfortable with swings in value, then fixed-income products with fixed-term (ie. buy a bond, hold the bond, when the bond finishes, you get your money back plus the yield [interest]) may suit you better than equity-based investments. Equity-based means alot of things - stocks in just one company, an index tracker of a well-known stock market (eg. FTSE100 tracker), actively managed growth funds, passive ETFs of high-dividend stocks... And each of these has different volatility (price swings) and long-term performance - as well as different charges and risks. The only way to understand this is to learn. So that's my ultimate advice. Learn about bonds. Learn about equities. Learn about gilts, corporate bonds, bond funds, index trackers, ETFs, dividends, active v passive management. In the meantime, keep the money in a Cash ISA - where £1 stays £1 plus interest. Once you want to lock the money away into a long-term investment, then you can look at Stocks ISAs to protect the investment against taxation. You may also put just enough into a pension get the company 'match' for contributions. It's not uncommon to split your long-term saving between the two routes. Then come back and ask where to go next... but chances are you'll know yourself by then - because you self-educated. If you want an alternative to the US-based generic advice, check out my Simple Steps concept here (sspf.co.uk/seven-simple-steps) and my free posts on this framework at sspf.co.uk/blog. I also host a free weekly podcast at sspf.co.uk/podcast (also on iTunes, Miro, Mixcloud, and others...) They were designed to offer exactly that kind of guidance to the UK for free.","title":""},{"docid":"250354","text":"\"Well, this sub is generally pretty darn good. Among us are investment bankers, private equity analysts, valuation analysts, portfolio managers, traders, brokers, bachelors, masters, and doctorate students, etc. We're helpful, though sometimes snarky, and have an exceedingly low tolerance for bullshit. I love it here. And while your logic is sound, we can actually explore private equity directly, as while private and public equity are related, they are different enough to study separately, in my opinion. Private equity deals with private companies. By definition, these investments are illiquid (they cannot be easily sold like public stocks), and unmarketable (there is no ready market to trade these investments, like stock). They are generally held for longer time periods. At its earliest stage, private equity is synonymous with \"\"initial investment\"\" or \"\"seed funding.\"\" This includes (if we are maybe slightly liberal with our definition), the initial investment an entrepreneur makes into his business. At this stage, friends and family, angel investors and venture capital are present. At different points of a company lifecycle, different financiers become interested/applicable (mezzanine investors, etc.). The investment made into a company allocates a certain percentage of the ownership of the company to the investor in exchange for cash (usually). This cash is used to cover expenses and take on capital projects. The goal of these investments is to directly make the company (and its value, and thus the investor's value) grow. At some points in time, a new investor will show up and either invest directly in the company (same as before) or buy another investor's holding in the company (in which case, cash goes to *that specific investor* and *not* the company). At every stage of investment leading up to IPO, the deals are negotiated between the parties. The results of a given negotiation determines the value of that company's equity. For example, if I pay you $100 for 50% of your company, the company's implied worth is $200. If two days later, Joe comes and offers to buy 33% of the company for $100, the Company is worth $300. (Special note: these percentages are assumed to be the allocation of equity **after** the deal. In this last case, the ownership of your company would be 33% you, 33% me, and 33% Joe. This illustrates something called *dilution,* which is very important to investors as it effects their eventual potential payoff later down the road, along with some other things). At this point, do you have any questions?\"","title":""},{"docid":"130631","text":"\"In the US you are not required to have a corporation to use business expenses to offset your income. The technical term you need is \"\"deducting business expenses\"\", and in matters of taxes it's usually best to go straight to the horse's mouth: the IRS's explanations Deducting Business Expenses Business expenses are the cost of carrying on a trade or business. These expenses are usually deductible if the business operates to make a profit. What Can I Deduct? Cost of Goods Sold, Capital Expenses, Personal versus Business Expenses, Business Use of Your Home, Business Use of Your Car, Other Types of Business Expenses None of this requires any special incorporation or tax arrangements, and are a normal part of operating a business. However, there is a bit of a problem with your scenario. You said you \"\"invested\"\" into a business, but you mentioned buying specific things for the business which is not generally how one accounts for investment. If you are not an owner/operator of the business, then the scenario is not so straight-forward, as you can't simply claim someone else's business expenses as your own because you invested in it. Investments are taxed differently than expenses, and based upon your word choices I'm concerned that you could be getting yourself into a bit of a pickle. I would strongly advise you to speak with a professional, such as a Certified Public Accountant (CPA), to go over your current arrangement and advise you on how you should be structuring your ongoing investment into this shared business. If you are investing you should be receiving equity to reflect your ownership (or stock in the company, etc), and investments of this sort generally cannot be deducted as an expense on your taxes - it's just an investment, the same as buying stock or CDs. If you are just buying things for someone else's benefit, it's possible that this could be looked upon as a personal gift, and you may be in a precarious legal position as well (where the money is, indeed, just a gift). And gifts of this sort aren't deductible, either. Depending on how this is all structured, it's possible that you should both consider a different form of legal organization, such as a formal corporation or at least an official business partnership. A CPA and an appropriate business attorney should be able to advise you for a nominal (few hundred dollars, at most) fee. If a new legal structure is advisable, you can potentially do the work yourself for a few hundred dollars, or pay to have it done (especially if the situation is more complex) for a few hundred to a few thousand. That's a lot less than you'd be on the hook for if this business is being accounted for improperly, or if either of your tax returns are being reported improperly!\"","title":""},{"docid":"517323","text":"The stock market is just like any other market, but stocks are bought and sold here. Just like you buy and sell your electronics at the electronics market, this is a place where buyers and sellers come together to buy and sell shares or stocks or equity, no matter what you call it. What are these shares? A share is nothing but a portion of ownership of a company. Suppose a company has 100 shares issued to it, and you were sold 10 out of those, it literally means you are a 10% owner of the company. Why do companies sell shares? Companies sell shares to grow or expand. Suppose a business is manufacturing or producing and selling goods or services that are high in demand, the owners would want to take advantage of it and increase the production of his goods or services. And in order to increase production he would need money to buy land or equipment or labor, etc. Now either he could go get a loan by pledging something, or he could partner with someone who could give him money in exchange for some portion of the ownership of the company. This way, the owner gets the money to expand his business and make more profit, and the lender gets a portion of profit every time the company makes some. Now if the owner decides to sell shares rather than getting a loan, that's when the stock market comes into the picture. Why would a person want to trade stocks? First of all, please remember that stocks were never meant to be traded. You always invest in stocks. What's the difference? Trading is short term and investing is long term, in very simple language. It's the greed of humans which led to this concept of trading stocks. A person should only buy stocks if he believes in the business the company is doing and sees the potential of growth. Back to the question: a person would want to buy stocks of the company because: How does a stock market help society? Look around you for the answer to this question. Let me give you a start and I wish everyone reading this post to add at least one point to the answer. Corporations in general allow many people come together and invest in a business without fear that their investment will cause them undue liability - because shareholders are ultimately not liable for the actions of a corporation. The cornerstone North American case of how corporations add value is by allowing many investors to have put money towards the railroads that were built across America and Canada. For The stock market in particular, by making it easier to trade shares of a company once the company sells them, the number of people able to conveniently invest grows exponentially. This means that someone can buy shares in a company without needing to knock door to door in 5 years trying to find someone to sell to. Participating in the stock market creates 'liquidity', which is essentially the ease with which stocks are converted into cash. High liquidity reduces risk overall, and it means that those who want risk [because high risk often creates high reward] can buy shares, and those who want low risk [because say they are retiring and don't have a risk appetite anymore] can sell shares.","title":""},{"docid":"574327","text":"\"First, what structure does your index fund have? If it is an open-end mutual fund, there are no bid/ask spread as the structure of this security is that it is priced once a day and transactions are done with that price. If it is an exchange-traded fund, then the question becomes how well are authorized participants taking advantage of the spread to make the fund track the index well? This is where you have to get into the Creation and Redemption unit construct of the exchange-traded fund where there are \"\"in-kind\"\" transactions done to either create new shares of the fund or redeem out shares of the fund. In either case, you are making some serious assumptions about the structure of the fund that don't make sense given how these are built. Index funds have lower expense ratios and are thus cheaper than other mutual funds that may take on more costs. If you want suggested reading on this, look at the investing books of John C. Bogle who studied some of this rather extensively, in addition to being one of the first to create an index fund that became known as \"\"Bogle's Folly,\"\" where a couple of key ones would be \"\"Common Sense on Mutual Funds: New Imperatives for the Intelligent Investor\"\" and \"\"Bogle on Mutual Funds: New Perspectives for the Intelligent Investor.\"\" In the case of an open-end fund, there has to be a portion of the fund in cash to handle transaction costs of running the fund as there are management fees to come from running the fund in addition to dividends from the stocks that have to be carefully re-invested and other matters that make this quite easy to note. Vanguard 500 Index Investor portfolio(VFINX) has .38% in cash as an example here where you could look at any open-end mutual fund's portfolio and notice that there may well be some in cash as part of how the fund is managed. It’s the Execution, Stupid would be one of a few articles that looks at the idea of \"\"tracking error\"\" or how well does an index fund actually track the index where it can be noted that in some cases, there can be a little bit of active management in the fund. Just as a minor side note, when I lived in the US I did invest in index funds and found them to be a good investment. I'd still recommend them though I'd argue that while some want to see these as really simple investments, there can be details that make them quite interesting to my mind. How is its price set then? The price is computed by taking the sum value of all the assets of the fund minus the liabilities and divided by the number of outstanding shares. The price of the assets would include the closing price on the stock rather than a bid or ask, similar pricing for bonds held by the fund, derivatives and cash equivalents. Similarly, the liabilities would be costs a fund has to pay that may not have been paid yet such as management fees, brokerage costs, etc. Is it a weighted average of all the underlying stock spreads, or does it stand on its own and stems from the usual supply & demand laws ? There isn't any spread used in determining the \"\"Net Asset Value\"\" for the fund. The fund prices are determined after the market is closed and so a closing price can be used for stocks. The liabilities could include the costs to run the fund as part of the accounting in the fund, that most items have to come down to either being an asset, something with a positive value, or a liability, something with a negative value. Something to consider also is the size of the fund. With over $7,000,000,000 in assets, a .01% amount is still $700,000 which is quite a large amount in some ways.\"","title":""},{"docid":"202355","text":"\"Is the mortgage debt too high? The rental property is in a hot RE market, so could be easily sold with significant equity. However, they would prefer to keep it. Given the current income, there is no stress. However in absence of any other liquid [cash/near cash] assets, having everything locked into Mortgage is quite high. Even if real estate builds assets, these are highly illiquid investments. Have debt on such investments is risky; if there are no other investments. Essentially everything looks fine now, but if there is an crisis, unwinding mortgage debt is time consuming and if it forces distress sale, it would wipe out any gains. Can they afford another mortgage, and in what amount? (e.g. they are considering $50K for a small cabin, which could be rented out). I guess they can. But should they? Or diversify into other assets like stocks etc. Other than setting cash aside, what would be some good uses of funds to make sure the money would appreciate and outpace inflation and add a nice bonus to retirement? Mutual Funds / Stocks / bullions / 401K or other such retirement plans. They are currently in mid-30's. If there is ONE key strategy or decision they could make today that would help them retire \"\"early\"\" (say, mid-50's), what should it be? This opinion based ... it depends on \"\"what their lifestyle is\"\" and what would they want their \"\"lifestyle\"\" to be when they retire. They should look at saving enough corpus that would give an year on year yield equivalent to the retirement expenses.\"","title":""},{"docid":"561997","text":"I think your premise is slightly flawed. Every investment can add or reduce risk, depending on how it's used. If your ordering above is intended to represent the probability you will lose your principal, then it's roughly right, with caveats. If you buy a long-term government bond and interest rates increase while you're holding it, its value will decrease on the secondary markets. If you need/want to sell it before maturity, you may not recover your principal, and if you hold it, you will probably be subject to erosion of value due to inflation (inflation and interest rates are correlated). Over the short-term, the stock market can be very volatile, and you can suffer large paper losses. But over the long-term (decades), the stock market has beaten inflation. But this is true in aggregate, so, if you want to decrease equity risk, you need to invest in a very diversified portfolio (index mutual funds) and hold the portfolio for a long time. With a strategy like this, the stock market is not that risky over time. Derivatives, if used for their original purpose, can actually reduce volatility (and therefore risk) by reducing both the upside and downside of your other investments. For example, if you sell covered calls on your equity investments, you get an income stream as long as the underlying equities have a value that stays below the strike price. The cost to you is that you are forced to sell the equity at the strike price if its value increases above that. The person on the other side of that transaction loses the price of the call if the equity price doesn't go up, but gets a benefit if it does. In the commodity markets, Southwest Airlines used derivatives (options to buy at a fixed price in the future) on fuel to hedge against increases in fuel prices for years. This way, they added predictability to their cost structure and were able to beat the competition when fuel prices rose. Even had fuel prices dropped to zero, their exposure was limited to the pre-negotiated price of the fuel, which they'd already planned for. On the other hand, if you start doing things like selling uncovered calls, you expose yourself to potentially infinite losses, since there are no caps on how high the price of a stock can go. So it's not possible to say that derivatives as a class of investment are risky per se, because they can be used to reduce risk. I would take hedge funds, as a class, out of your list. You can't generally invest in those unless you have quite a lot of money, and they use strategies that vary widely, many of which are quite risky.","title":""},{"docid":"156747","text":"\"Equity could mean stock options. If that's the case if the company makes it big, you'll have the option to buy stocks cheap (which can then be sold at a huge profit) How are you going to buy those without income? 5% equity is laughable. I'd be looking for 30-40% if not better without salary. Or even better, a salary. To elaborate, 5% is fine, and even normal for an early employee taking a mild pay cut in exchange for a chance at return. That chance of any return on the equity is only about 1/20 (94% of startups fail) There is no reason for an employee to work for no pay. An argument could be made for a cofounder, with direct control and influence in the company to work for equity only, but it would be a /lot/ more (that 30-40%), or an advisory role (5% is reasonable) I also just noticed you mentioned \"\"investing\"\" in the startup with cash. As an angel investor, I'd still expect far more than 5%, and preferred shares at that. More like 16-20%. Read this for more info on how equity is usually split.\"","title":""},{"docid":"371012","text":"I was merely trying to be helpful - Conceptually, you have dump this idea that something is skewed. It isn't. Firm A sold for $500 (equity value aka purchase price to shareholders) + debt (zero) - cash (50) for 450. Enterprise value is the cash free, debt free sale price. The implied ev multiple is 4.5x on A - that is the answer. The other business sold for a higher multiple of 5x. If you would pile on more cash onto A, the purchase price would increase, but the EV wouldn't. The idea is to think hard about the difference between equity value and enterprise value when examining a transaction.","title":""},{"docid":"282483","text":"In general, investors with a long period of time until they would need to withdraw the cash are best off holding mostly equities. While the dividends that equities would return are less than the interest you would get in peer-to-peer lending, over long periods of time not only do you get the dividends from equity investment but the value of the stock will grow faster than interest on loans. The higher returns from stocks, however, comes with more risk of big downturns. Many people pull their investments out of stocks right after crashes which really hurts their long term returns. So, in order to get the benefit of investing in stocks you need to be strong enough to continue to hold the stocks through the crash and into the recovery. As for which stocks to invest in, generally it is best to invest in low-fee index funds/etfs where you own a broad collection of stocks so that if (when) any one stock goes bust that your portfolio does not take much damage. Try to own both international and domestic stocks to get good diversification. The consensus recommends adding just a little bit of REITs and bonds to your investments, but for someone at 25 it might not be worth it yet. Warren Buffett had some good thoughts on index investing.","title":""},{"docid":"328745","text":"It lowers the cost of capital. Debt is generally a 'cheaper' form of financing, and in addition you have the benefit of interest being tax deductible. Assume you have no capital to expand an existing business. How do you fund it? You could sell/issue some stock to outside investors for cash (or inject your personal cash into the business if you have it), or you can borrow the money. General the borrowing is 'cheaper' as debt investors need a lower return than equity investors, because debt is less risky (has claims on the business assets before equity holders) than equity.","title":""},{"docid":"383682","text":"One other consideration is that by paying off your mortgage early versus, for example, investing that capital in a mutual fund is that you are reducing your net liquidity to some degree. That is, if you find yourself needing an emergency infusion of cash it is easier to sell a stock/fund than to sell your house or get a equity loan. I suppose if you were planning to need a lot of cash to start a business or invest in real estate, then maybe it would make sense to keep your cash more liquid. However, in your situation I agree with Joe. Pay it off. It feels REALLY good to write that last check!","title":""},{"docid":"275249","text":"\"There are three (or four) ways that a company can grow: (Crowdfunding is a relatively new (in mainstream businesses) alternative financing method where people will finance a company with the expectation that they will benefit from the product or service that they provide.) Obviously a startup has no prior income to use, so it must either raise money through equity or debt. People say that one must borrow contingent on their salary. Banks lend money based on the ability to pay the loan back plus interest. For individuals, their income is their primary source of cash flow, so, yes, it is usually the determining factor in getting a loan. For a business the key factor is future cash flows. So a business will borrow money, say, to buy a new asset (like a factory) that will be used to generate cash flows in the future so that they can pay down the debt. If the bank believes that the use of the money is going to be profitable enough that they will get their money back with interest, they'll loan the money. Equity investors are essentially the same, but since they don't get a guaranteed payback (they only get paid through non-guaranteed dividends or liquidation), their risk is higher and they are looking for higher expected returns. So the question I'd have as a bank or equity investor is \"\"what are you going to do with the money?\"\" What is your business strategy? What are you going to do that will make profits in the future? Do you have a special idea or skill that you can turn into a profitable business? (Crowdfunding would be similar - people are willing to give you money based on either the social or personal benefit of some product or service.) So any business either starts small and grows over time (which is how the vast majority of businesses grow), or has some special idea, asset, skill, or something that would make a bank willing to take a risk on a huge loan. I know, again, that people here tend to turn blind eyes on unfortunate realities, but people do make giant businesses without having giant incomes. The \"\"unfortunate reality\"\" is that most startups fail. Which may sound bad, but also keep in mind that most startups are created by people that are OK with failing. They are people that are willing to fail 9 times with the thought that the 10th one will take off and make up for the losses of the first 9. So I would say - if you have some great idea or skill and a viable strategy and plan to take it to market, then GO FOR IT. You don't need a huge salary to start off. You need something that you can take to market and make money. Most people (myself included) either do not have that idea or skill to go out on their own, or don't have the courage to take that kind of risk. But don't go in assuming all you need is a loan and you'll be an instant millionaire. You might, but the odds are very long.\"","title":""},{"docid":"89714","text":"With a long enough time horizon, no matter when you buy, equities almost always outperform cash and bonds. There's an article here with some info: http://www.fool.co.uk/investing-basics/how-when-and-where-to-invest/ Holding period where shares have beaten cash There was a similar study done which showed if you picked any day in the last 100 years, no matter if the market was at a high or low, after 1 year your probability of being in profit was only 0.5, but after 10-20 years it was almost certainly 1.0. Equities compound dividends too, and the best place to invest is in diversified stock indices such as the S&P500, FTSE100, DOW30 or indices/funds which pay dividends. The best way to capture returns is to dollar cost average (e.g. place a lump sum, then add $x every month), to re-invest dividends, and oh, to forget about it in an IRA or SIPP (Self invested pension) or other vehicle which discourages tampering with your investment. Yes, values rise and fall but we humans are so short sighted, if we had bought the S&P in 2007 and sold in 2009 in fear, we would have missed out on the 25% gain (excluding dividends) from 2007-2014. That's about 3% a year gain even if you bought the 2007 high -beating cash or bonds even after the financial crisis. Now imagine had you dollar cost averaged the entire period from 2007-2014 where your gain would be. Your equity curve would have the same shape as the S&P (with its drastic dip in 2009) but an accelerated growth after. There are studies if you dig that demonstrate the above. From experience I can tell you timing the market is nigh impossible and most fund managers are unable to beat the indices. Far better to DCA and re-invest dividends and not care about market gyrations! ..","title":""}],"string":"[\n {\n \"docid\": \"177946\",\n \"text\": \"\\\"I think the \\\"\\\"right\\\"\\\" way to approach this is for your personal books and your business's books to be completely separate. You would need to really think of them as separate things, such that rather than being disappointed that there's no \\\"\\\"cross transactions\\\"\\\" between files, you think of it as \\\"\\\"In my personal account I invested in a new business like any other investment\\\"\\\" with a transfer from your personal account to a Stock or other investment account in your company, and \\\"\\\"This business received some additional capital\\\"\\\" which one handles with a transfer (probably from Equity) to its checking account or the like. Yes, you don't get the built-in checks that you entered the same dollar amount in each, but (1) you need to reconcile your books against reality anyway occasionally, so errors should get caught, and (2) the transactions really are separate things from each entity's perspective. The main way to \\\"\\\"hack it\\\"\\\" would be to have separate top-level placeholder accounts for the business's Equity, Income, Expenses, and Assets/Liabilities. That is, your top-level accounts would be \\\"\\\"Personal Equity\\\"\\\", \\\"\\\"Business Equity\\\"\\\", \\\"\\\"Personal Income\\\"\\\", \\\"\\\"Business Income\\\"\\\", and so on. You can combine Assets and Liabilities within a single top-level account if you want, which may help you with that \\\"\\\"outlook of my business value\\\"\\\" you're looking for. (In fact, in my personal books, I have in the \\\"\\\"Current Assets\\\"\\\" account both normal things like my Checking account, but also my credit cards, because once I spend the money on my credit card I want to think of the money as being gone, since it is. Obviously this isn't \\\"\\\"standard accounting\\\"\\\" in any way, but it works well for what I use it for.) You could also just have within each \\\"\\\"normal\\\"\\\" top-level placeholder account, a placeholder account for both \\\"\\\"Personal\\\"\\\" and \\\"\\\"My Business\\\"\\\", to at least have a consistent structure. Depending on how your business is getting taxed in your jurisdiction, this may even be closer to how your taxing authorities treat things (if, for instance, the business income all goes on your personal tax return, but on a separate form). Regardless of how you set up the accounts, you can then create reports and filter them to include just that set of business accounts. I can see how just looking at the account list and transaction registers can be useful for many things, but the reporting does let you look at everything you need and handles much better when you want to look through a filter to just part of your financial picture. Once you set up the reporting (and you can report on lists of account balances, as well as transaction lists, and lots of other things), you can save them as Custom Reports, and then open them up whenever you want. You can even just leave a report tab (or several) open, and switch to it (refreshing it if needed) just like you might switch to the main Account List tab. I suspect once you got it set up and tried it for a while you'd find it quite satisfactory.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"250530\",\n \"text\": \"Canadian Couch Potato has an article which is somewhat related. Ask the Spud: Can You Time the Markets? The argument roughly boils down to the following: That said, I didn't follow the advice. I inherited a sum of money, more than I had dealt with before, and I did not feel I was emotionally capable of immediately dumping it into my portfolio (Canadian stocks, US stocks, world stocks, Canadian bonds, all passive indexed mutual funds), and so I decided to add the money into my portfolio over the course of a year, twice a month. The money that I had not yet invested, I put into a money market account. That worked for me because I was purchasing mutual funds with no transaction costs. If you are buying ETFs, this strategy makes less sense. In hindsight, this was not financially prudent; I'd have been financially better off to buy all the mutual funds right at the beginning. But I was satisfied with the tradeoff, knowing that I did not have hindsight and I would have been emotionally hurt had the stock market crashed. There must be research that would prove, based on past performance, the statistically optimal time frame for dollar-cost averaging. However, I strongly suppose that the time frame is rather small, and so I would advise that you either invest the money immediately, or dollar-cost average your investment over the course of the year. This answer is not an ideal answer to your question because it is lacking such a citation.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"333755\",\n \"text\": \"\\\"There are many different methods for a corporation to get money, but they mostly fall into three categories: earnings, debt and equity. Earnings would be just the corporation's accumulation of cash due to the operation of its business. Perhaps if cash was needed for a particular reason immediately, a business may consider selling a division or group of assets to another party, and using the proceeds for a different part of the business. Debt is money that (to put it simply) the corporation legally must repay to the lender, likely with periodic interest payments. Apart from the interest payments (if any) and the principal (original amount leant), the lender has no additional rights to the value of the company. There are, basically, 2 types of corporate debt: bank debt, and bonds. Bank debt is just the corporation taking on a loan from a bank. Bonds are offered to the public - ie: you could potentially buy a \\\"\\\"Tesla Bond\\\"\\\", where you give Tesla $1k, and they give you a stated interest rate over time, and principal repayments according to a schedule. Which type of debt a corporation uses will depend mostly on the high cost of offering a public bond, the relationships with current banks, and the interest rates the corporation thinks it can get from either method. Equity [or, shares] is money that the corporation (to put it simply) likely does not have a legal obligation to repay, until the corporation is liquidated (sold at the end of its life) and all debt has already been repaid. But when the corporation is liquidated, the shareholders have a legal right to the entire value of the company, after those debts have been paid. So equity holders have higher risk than debt holders, but they also can share in higher reward. That is why stock prices are so volatile - the value of each share fluctuates based on the perceived value of the entire company. Some equity may be offered with specific rules about dividend payments - maybe they are required [a 'preferred' share likely has a stated dividend rate almost like a bond, but also likely has a limited value it can ever receive back from the corporation], maybe they are at the discretion of the board of directors, maybe they will never happen. There are 2 broad ways for a corporation to get money from equity: a private offering, or a public offering. A private offering could be a small mom and pop store asking their neighbors to invest 5k so they can repair their business's roof, or it could be an 'Angel Investor' [think Shark Tank] contributing significant value and maybe even taking control of the company. Perhaps shares would be offered to all current shareholders first. A public offering would be one where shares would be offered up to the public on the stock exchange, so that anyone could subscribe to them. Why a corporation would use any of these different methods depends on the price it feels it could get from them, and also perhaps whether there are benefits to having different shareholders involved in the business [ie: an Angel investor would likely be involved in the business to protect his/her investment, and that leadership may be what the corporation actually needs, as much or more than money]. Whether a corporation chooses to gain cash from earnings, debt, or equity depends on many factors, including but not limited to: (1) what assets / earnings potential it currently has; (2) the cost of acquiring the cash [ie: the high cost of undergoing a public offering vs the lower cost of increasing a bank loan]; and (3) the ongoing costs of that cash to both the corporation and ultimately the other shareholders - ie: a 3% interest rate on debt vs a 6% dividend rate on preferred shares vs a 5% dividend rate on common shares [which would also share in the net value of the company with the other current shareholders]. In summary: Earnings would be generally preferred, but if the company needs cash immediately, that may not be suitable. Debt is generally cheap to acquire and interest rates are generally lower than required dividend rates. Equity is often expensive to acquire and maintain [either through dividend payments or by reduction of net value attributable to other current shareholders], but may be required if a new venture is risky. ie: a bank/bondholder may not want to lend money for a new tech idea because it is too risky to just get interest from - they want access to the potential earnings as well, through equity.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"273947\",\n \"text\": \"\\\"Exactly what accounts are affected by any given transaction is not a fixed thing. Just for example, in a simple accounting system you might have one account for \\\"\\\"stock on hand\\\"\\\". In a more complex system you might have this broken out into many accounts for different types of stock, stock in different locations, etc. So I can only suggest example specific accounts. But account type -- asset, liability, capital (or \\\"\\\"equity\\\"\\\"), income, expense -- should be universal. Debit and credit rules should be universal. 1: Sold product on account: You say it cost you $500 to produce. You don't say the selling price, but let's say it's, oh, $700. Credit (decrease) Asset \\\"\\\"Stock on hand\\\"\\\" by $500. Debit (increase) Asset \\\"\\\"Accounts receivable\\\"\\\" by $700. Credit (increase) Income \\\"\\\"Sales\\\"\\\" by $700. Debit (increase) Expense \\\"\\\"Cost of goods sold\\\"\\\" by $500. 2: $1000 spent on wedding party by friend I'm not sure how your friend's expenses affect your accounts. Are you asking how he would record this expense? Did you pay it for him? Are you expecting him to pay you back? Did he pay with cash, check, a credit card, bought on credit? I just don't know what's happening here. But just for example, if you're asking how your friend would record this in his own records, and if he paid by check: Credit (decrease) Asset \\\"\\\"checking account\\\"\\\" by $1000. Debit (increase) Expense \\\"\\\"wedding expenses\\\"\\\" by $1000. If he paid with a credit card: Credit (increase) Liability \\\"\\\"credit card\\\"\\\" by $1000. Debit (increase) Expense \\\"\\\"wedding expenses\\\"\\\" by $1000. When he pays off the credit card: Debit (decrease) Liability \\\"\\\"credit card\\\"\\\" by $1000. Credit (decrease) Asset \\\"\\\"cash\\\"\\\" by $1000. (Or more realistically, there are other expenses on the credit card and the amount would be higher.) 3: Issue $3000 in stock to partner company I'm a little shakier on this, I haven't worked with the stock side of accounting. But here's my best stab: Well, did you get anything in return? Like did they pay you for the stock? I wouldn't think you would just give someone stock as a present. If they paid you cash for the stock: Debit (increase) Asset \\\"\\\"cash\\\"\\\". Credit (decrease) Capital \\\"\\\"shareholder equity\\\"\\\". Anyone else want to chime in on that one, I'm a little shaky there. Here, let me give you the general rules. My boss years ago described it to me this way: You only need to know three things to understand double-entry accounting: 1: There are five types of accounts: Assets: anything you have that has value, like cash, buildings, equipment, and merchandise. Includes things you may not actually have in your hands but that are rightly yours, like money people owe you but haven't yet paid. Liabilities: Anything you owe to someone else. Debts, merchandise paid for but not yet delivered, and taxes due. Capital (some call it \\\"\\\"capital\\\"\\\", others call it \\\"\\\"equity\\\"\\\"): The difference between Assets and Liabilities. The owners investment in the company, retained earnings, etc. Income: Money coming in, the biggest being sales. Expenses: Money going out, like salaries to employees, cost of purchasing merchandise for resale, rent, electric bill, taxes, etc. Okay, that's a big \\\"\\\"one thing\\\"\\\". 2: Every transaction must update two or more accounts. Each update is either a \\\"\\\"debit\\\"\\\" or a \\\"\\\"credit\\\"\\\". The total of the debits must equal the total of the credits. 3: A dollar bill in your pocket is a debit. With a little thought (okay, sometimes a lot of thought) you can figure out everything else from there.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"178303\",\n \"text\": \"\\\"Some thoughts: 1) Do you have a significant emergency fund (3-6 months of after-tax living expenses)? If not, you stand to take a significant loss if you have an unexpected need for cash that is tied up in investments. What if you lose/hate your job or your car breaks down? What if a you want to spend some time with a relative or significant other who learns they only have a few months to live? Having a dedicated emergency fund is an important way to avoid downside risk. 2) Lagerbaer has a good suggestion. Given that if you'd reinvested your dividends, the S&P 500 has returned about 3.5% over the last 5 years, you may be able to get a very nice risk-free return. 3) Do you have access to employer matching funds, such as in a 401(k) at work? If you get a dollar-for-dollar match, that is a risk-free pre-tax 100% return and should be a high priority. 4) What do you mean by \\\"\\\"medium\\\"\\\" volatility? Given that you are considering a 2/3 equity allocation, it would not be at all out of the realm of possibility that your balance could fall by 15% or more in any given year and take several years to recover. If that would spook you, you may want to consider lowering your equity weights. A high quality bond fund may be a good fit. 5) Personally, I would avoid putting money into stocks that I didn't need back for 10 years. If you only want to tie your money up for 2-5 years, you are taking a significant risk that if prices fall, you won't have time to recover before you need your money back. The portfolio you described would be appropriate for someone with a long-term investment horizon and significant risk tolerance, which is usually the case for young people saving for retirement. However, if your goals are to invest for 2-5 years only, your situation would be significantly different. 6) You can often borrow from an investment account to purchase a primary residence, but you must pay that amount back in order to avoid significant taxes and fees, unless you plan to liquidate assets. If you plan to buy a house, saving enough to avoid PMI is a good risk-free return on your money. 7) In general, and ETF or index fund is a good idea, the key being to minimize the compound effect of expenses over the long term. There are many good choices a la Vanguard here to choose from. 8) Don't worry about \\\"\\\"Buy low, sell high\\\"\\\". Don't be a speculator, be an investor (that's my version of Anthony Bourdain's, \\\"\\\"don't be a tourist, be a traveler\\\"\\\"). A speculator wants to sell shares at a higher price than they were purchased at. An investor wants to share in the profits of a company as a part-owner. If you can consistently beat the market by trying to time your transactions, good for you - you can move to Wall Street and make millions. However, almost no one can do this consistently, and it doesn't seem worth it to me to try. I don't mean to discourage you from investing, just make sure you have your bases covered so that you don't have to cash out at a bad time. Best of luck! Edit Response to additional questions below. 1) Emergency fund. I would recommend not investing in anything other than cash equivalents (money market, short-term CDs, etc.) until you've built up an emergency fund. It makes sense to want to make the \\\"\\\"best\\\"\\\" use of your money, but you also have to account for risk. My concern is that if you were to experience one or more adverse life events, that you could lose a lot of money, or need to pay a lot in interest on credit card debt, and it would be prudent to self-insure against some of those risks. I would also recommend against using an investment account as an emergency fund account. Taking money out of investment accounts is inefficient because the commissions/taxes/fees can easily eat up a significant portion of your returns. Ideally, you would want to put money in and not touch it for a long time in order to take advantage of compounding returns. There are also high penalties for early disbursements from retirement funds. Just like you need enough money in your checking account to buy food and pay the rent every month, you need enough money in an emergency fund to pay for things that are a real possibility, even if they are less common. Using a credit card or an investment account is a relatively expensive way to do this. 2) Invest at all? I would recommend starting an emergency fund, and then beginning to invest for retirement. Once your retirement savings are on track, you can begin saving for whatever other goals you may have\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"526422\",\n \"text\": \"\\\"The question is asking for a European equivalent of the so-called \\\"\\\"Couch Potato\\\"\\\" portfolio. \\\"\\\"Couch Potato\\\"\\\" portfolio is defined by the two URLs provided in question as, Criteria for fund composition Fixed-income: Regardless of country or supra-national market, the fixed-income fund should have holdings throughout the entire length of the yield curve (most available maturities), as well as being a mix of government, municipal (general obligation), corporate and high-yield bonds. Equity: The common equity position should be in one equity market index fund. It shouldn't be a DAX-30 or CAC-40 or DJIA type fund. Instead, you want a combination of growth and value companies. The fund should have as many holdings as possible, while avoiding too much expense due to transaction costs. You can determine how much is too much by comparing candidate funds with those that are only investing in highly liquid, large company stocks. Why it is easier for U.S. and Canadian couch potatoes It will be easier to find two good funds, at lower cost, if one is investing in a country with sizable markets and its own currency. That's why the Couch Potato strategy lends itself most naturally to the U.S.A, Canada, Japan and probably Australia, Brazil, South Korea and possibly Mexico too. In Europe, pre-EU, any of Germany, France, Spain, Italy or the Scandinavian countries would probably have worked well. The only concern would be (possibly) higher equity transactions costs and certainly larger fixed-income buy-sell spreads, due to smaller and less liquid markets other than Germany. These costs would be experienced by the portfolio manager, and passed on to you, as the investor. For the EU couch potato Remember the criteria, especially part 2, and the intent as described by the Couch Potato name, implying extremely passive investing. You want to choose two funds offered by very stable, reputable fund management companies. You will be re-balancing every six months or a year, only. That is four transactions per year, maximum. You don't need a lot of interaction with anyone, but you DO need to have the means to quickly exit both sides of the trade, should you decide, for any reason, that you need the money or that the strategy isn't right for you. I would not choose an ETF from iShares just because it is easy to do online transactions. For many investors, that is important! Here, you don't need that convenience. Instead, you need stability and an index fund with a good reputation. You should try to choose an EU based fund manager, or one in your home country, as you'll be more likely to know who is good and who isn't. Don't use Vanguard's FTSE ETF or the equivalent, as there will probably be currency and foreign tax concerns, and possibly forex risk. The couch potato strategy requires an emphasis on low fees with high quality funds and brokers (if not buying directly from the fund). As for type of fund, it would be best to choose a fund that is invested in mostly or only EU or EEU (European Economic Union) stocks, and the same for bonds. That will help minimize your transaction costs and tax liability, while allowing for the sort of broad diversity that helps buy and hold index fund investors.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"378137\",\n \"text\": \"Diversification is just one aspect in an investment portfolio. The other aspects in Investment are Risk Taking Ability, Liquidity, Local Regulations, Tax benefits, Ease & Convenience, Cost of carrying out transactions etc. Investing in other regions is prone FX risk and other risks depending on the region of investment. For example investing in Emerging markets there is a risk of Local Regulations being changed, additional tax being levied, or Political instability and host of such risks. Investing in local markets give you better understanding of such changes and the risk associated is less plus the Ease of carrying out transactions is great, less expensive compared to cost of transactions in other markets. Diversification in Investment should also be looked upon how much you invest in; Equities Debt Bullion Real Estate Once you have a sizeable amount of investment in Equities or Debt, it would then make more sense to diversify this portion more to include funds from other regions. Unless you are an Running your own business, it makes sense to invest in your line of business if that is performing well. The reason being that the benefit / returns from the equities is much greater than the salary rise / bonus. For example I am in Information Technology and yet invest in all leading IT companies because the returns from companies in these segments have been good.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"123263\",\n \"text\": \"\\\"If you are looking for numerical metrics I think the following are popular: Price/Earnings (P/E) - You mentioned this very popular one in your question. There are different P/E ratios - forward (essentially an estimate of future earnings by management), trailing, etc.. I think of the P/E as a quick way to grade a company's income statement (i.e: How much does the stock cost verusus the amount of earnings being generated on a per share basis?). Some caution must be taken when looking at the P/E ratio. Earnings can be \\\"\\\"massaged\\\"\\\" by the company. Revenue can be moved between quarters, assets can be depreciated at different rates, residual value of assets can be adjusted, etc.. Knowing this, the P/E ratio alone doesn't help me determine whether or not a stock is cheap. In general, I think an affordable stock is one whose P/E is under 15. Price/Book - I look at the Price/Book as a quick way to grade a company's balance sheet. The book value of a company is the amount of cash that would be left if everything the company owned was sold and all debts paid (i.e. the company's net worth). The cash is then divided amoung the outstanding shares and the Price/Book can be computed. If a company had a price/book under 1.0 then theoretically you could purchase the stock, the company could be liquidated, and you would end up with more money then what you paid for the stock. This ratio attempts to answer: \\\"\\\"How much does the stock cost based on the net worth of the company?\\\"\\\" Again, this ratio can be \\\"\\\"massaged\\\"\\\" by the company. Asset values have to be estimated based on current market values (think about trying to determine how much a company's building is worth) unless, of course, mark-to-market is suspended. This involves some estimating. Again, I don't use this value alone in determing whether or not a stock is cheap. I consider a price/book value under 10 a good number. Cash - I look at growth in the cash balance of a company as a way to grade a company's cash flow statement. Is the cash account growing or not? As they say, \\\"\\\"Cash is King\\\"\\\". This is one measurement that can not be \\\"\\\"massaged\\\"\\\" which is why I like it. The P/E and Price/Book can be \\\"\\\"tuned\\\"\\\" but in the end the company cannot hide a shrinking cash balance. Return Ratios - Return on Equity is a measure of the amount of earnings being generated for a given amount of equity (ROE = earnings/(assets - liabilities)). This attempts to measure how effective the company is at generating earnings with a given amount of equity. There is also Return on Assets which measures earnings returns based on the company's assets. I tend to think an ROE over 15% is a good number. These measurements rely on a company accurately reporting its financial condition. Remember, in the US companies are allowed to falsify accounting reports if approved by the government so be careful. There are others who simply don't follow the rules and report whatever numbers they like without penalty. There are many others. These are just a few of the more popular ones. There are many other considerations to take into account as other posters have pointed out.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"329637\",\n \"text\": \"You need to be clear about who gets your money: If you pay the existing owner $25K and (s)he gives you half the business, then you now own half of a $50K business an the original owner has an extra $25K in spending cash. The value of the business has not changed. If you contribute $25 to the company, new equity shares are created. Shares should be priced correctly, meaning you now own $25K worth of shares in a company worth $75k, so you should have 1/3 of the outstanding shares (counting both old and new shares). If you get more or less than this, then the transaction has happened in an unfair way. If this is a public company, that would most likely be illegal and the SEC may throw you in jail. If it was a private company and your friend created enough shares that you own half the company, then (s)he has given you a gift. If you are contributing to the company at a fair price, you would need to contribute $50K in order to end up with half the equity of the new and now more valuable firm. In that case the firm would be worth $100K after your contribution. Bottom line, this is a common and not complex transaction and should end up with a completely fair outcome. Any unfair situation you can imagine is probably based on false assumptions or a situation where a non-arms-length transaction is transferring wealth contrary to normal rules and procedures.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"40966\",\n \"text\": \"It took me a while to understand the concept, so I'll break it down as best as I can. There are three parts to the accounting equation: Assets = Liabilities + Owner's Equity We'll look at this in two ways 1. As a business owner you invest (say) 10,000 USD into your bank. The entry would be: Debit: Assets: Cash for 10,000 Credit: Owner's Equity: Contributions for 10,000 In this case, you have assets of 10,000 from your deposit, but it is due to owner contributions and not business transactions. Another example (say a sale): Debit: Assets: Cash for 10,000 Credit: Owner's Equity: Sales for 10,000 Debit: Assets: Cash for 10,000 Credit: Liabilities: Deposits for 10,000 Deposits are a banking term to reflect a bank's obligation to return the amount on demand (though the bank has free reign with it, see fractional banking) You will NEVER debit or credit your bank as it is assumed you will be storing your money there, note bank reconciliation. Hope this helps, comment with any more questions.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"425888\",\n \"text\": \"How you should record the mortgage payments depends on if you are trying to achieve correct accounting, according to the standards, or if you are just tracking everything for you and your friends. If you're just keeping track for personal reasons, I'd suggest that you set up your check (or journal entry, your preference) how you'd like it to be recorded. Then, memorize that transaction. This allows you to use it as many times as you need to, without having to set it up each time. (Also note: there is no way to record a transaction that decreases cash and increases equity.) If you're trying to keep track of everything according to accounting standards, which it should be if you've set up an official business, then you have a lot more tracking to do with each payment. Mortgage payments technically do not affect the equity accounts of the owners. Each mortgage payment should decrease the bank balance, increase interest expense and decrease the mortgage balance, not to mention tracking any escrow account you may have. The equity accounts would be affected if the owners are contributing funds to the bank account, but equity would increase at the time the funds are deposited, not when the mortgage payments are made. Hope this helps!\",\n \"title\": \"\"\n },\n {\n \"docid\": \"546313\",\n \"text\": \"\\\"Training8m Corporate Technologies Pty Ltd, Australia Australia ABN 48133544297 UK Company Number: 7538482 Maiden Pre-IPO offer from Training8m Corporate Technologies Pty Ltd, Australia!! Unique opportunity for investors!!! Move to a most profitable and defensive investment!!! We offer Preferential Allotment / Private Placement of Debt / Equity. Most Profitable offer from The Global Leader!! www.training8m.com Subscription Offer Open: First ever pre-IPO offer from Training8m Australia Group!! Unique opportunity for investors!!! Move to a most profitable and defensive investment!!! Preferential Allotment / Private Placement of Debt / Equity to multiple business investors pre IPO from $ 50k to $ 25 Mn for start up venture set up and Capital market Listing on Frankfurt Stock Exchange. We offer Preferential Allotment / Private Placement of Equity to multiple business investors Pre- IPO from $ 50K to $ 25 Mn. Higher investment welcome for this International public issue. Equivalent Debt / Equity / Options / Preference Shares can be discussed. Minority Equity participation can be discussed. We at Training8m Australia are Going Public Soon on Frankfurt Stock Exchange. Status: Approved funding by major Global Private Equity Fund. We are pleased to write that our major funding, raising funds from the equity market listing on Frankfurt Stock Exchange, is approved by major and most reputed Private Equity Group. This is one of the largest upcoming IPO, highly profitable with high ROI. Subscription: Open to Institutional and Retail Investors Pre IPO offer in Debt / Equity / Preference Shares / Options Serious investors only please. We would like to conclude this current deal immediately. We at Training8m, Australia are willing to discuss on the Debt / Equity / Options / preference shares and will be liberal for this transaction, which will be issued to you directly from our fund managers. This is definitely a really profitable and high return investment. Payback period: 1 - 2 years (expected turnover at least $ 2 Bn in 3 years) Start up Stage of business. This investment has very attractive returns. Unique opportunity to associate prior to the IPO on Global Stock Exchanges Location: Head Quartered in Gold Coast, Australia with Global Operating Offices. Set up including Property Investment, Recruitment and Appointment of permanent personnel, Fees for Listing on major Global Stock Exchange, other expenses as needed for the business. Business Models: Training8m Corporate Technologies Pty Ltd, Australia Corporate Training, Marketing, Premium Recruitment Portal, Premium and Moderated Recruitment Social Networking, Training and Development for all industry Verticals, Global Business Solutions. Advanced Lighting Designers Pty Ltd, Australia We offer International Lighting Technologies, Design, Specifications, Software Solutions and High End Information Technology Services to Global Industry sectors. Please do note that we are officially registered in Australia and UK for our Global Business ventures. With appropriate funding for takeovers, mergers and Acquisitions, we will be listing the companies Training8m Corporate Technologies Pty Ltd, and Advanced Lighting Designers Pty Ltd, on major global stock exchanges. The punch line of Advanced Lighting Designers Pty Ltd is “Go Green with Force Green\\\"\\\" in which we will be focussing on Green Energy Worldwide. Please feel free to ask details privately. Offer for limited time and closes on receipt of funds. E- Mails: investors@training8m.com, business@training8m.com Shrikant G. Shete Chairman and Managing Director Training8m, Australia LinkedIn: http://au.linkedin.com/in/shrikantshete +61-400769125 ................................Australia Mobiles +61-434415521 ................................Australia Mobiles\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"414505\",\n \"text\": \"\\\"The key difference I've found between a stock split and a stock dividend – of the exact same stock and class, as opposed to a spin-off – seems to be from the company's own accounting perspective. There doesn't appear to be any actual transfer of value to the shareholder with either kind of transaction; i.e. in theory, each transaction would be immaterial to the value of your holdings. With respect to the company's accounting, a stock split affects the par value of the shares, whereas a stock dividend reduces the retained earnings account in order to increase paid-in or contributed capital. I found a good online source which explains the history behind this accounting difference: McGraw-Hill - Intermediate Accounting eBook, 6/e - Chapter 18 - Stock Dividends and Splits. Small quote: [...] Besides being based on fallacious reasoning, accounting for stock dividends by artificially reclassifying “earned” capital as “invested” capital conflicts with the reporting objective of reporting shareholders' equity by source. Despite these limitations, this outdated accounting standard still applies. Since neither the corporation nor its shareholders apparently benefits from stock dividends, why do companies declare them?23 Occasionally, a company tries to give shareholders the illusion that they are receiving a real dividend. Another reason is merely to enable the corporation to take advantage of the accepted accounting practice of capitalizing retained earnings. Specifically, a company might wish to reduce an existing balance in retained earnings—otherwise available for cash dividends—so it can reinvest the earned assets represented by that balance without carrying a large balance in retained earnings. [...] There's a lot more on that page, before and after, worth reading. From another book: Google Books - Comparative Income Taxation, a Structural Analysis - page 314 - Stock Dividends. Small quote: The distribution of dividends in the form of stock or \\\"\\\"bonus\\\"\\\" shares to existing shareholders typically involves a transfer for corporate law purposes of retained earnings into stated capital. It can been [sic] viewed as a deemed distribution of a cash dividend to the shareholders followed by a corresponding contribution to capital or as solely as an event at the corporate level which has no effect on the shareholders whose economic interest in the corporation is unchanged by the receipt of additional shares. The systems have taken varied approaches to the stock dividend problem. The treatment is in part a function of the rules dealing with distributions of stated capital. [emphases above are mine] [... continues w/descriptions of different countries' tax treatments of the kinds of stock dividends. Includes U.S., Sweden, Japan, Netherlands, Canada, Australia, U.K., France, Germany. ...] As far as why a corporation might want to capitalize earnings and reduce the equity otherwise available for dividends, I can only imagine that, ignoring taxes for a moment, that it may have something to do with capital ratios that need to be maintained for financing or regulatory purposes? Yet, I remain curious. If I discover more on this then I'll update my answer. Additional resources:\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"5710\",\n \"text\": \"\\\"As Michael Pryor answered, a bond fund is a mutual fund that invests in bonds. I'd also consider an ETF based on bonds to be a bond fund, but I'm not sure that all investors would consider these as \\\"\\\"bond funds\\\"\\\". Not all bond funds are the same -- just like stock funds. You can classify bond funds based on the issuer of the bonds: You can also classify funds based on the time to maturity: In general, bond funds have lower risk and lower expected return than stock funds. Sometimes bond funds have price movements that are not tightly correlated to the price movements in the equity markets. This can make them a decent hedge against declines in your equity investments. See Michal Pryor's answer for some info on how you can get tax free treatment for your bond fund investments.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"190891\",\n \"text\": \"\\\"The price of real estate reacts to both demand for property and the rate of inflation and rate of income growth. Mortgage rates generally move as treasury rates move. See this paragraph: As we mentioned, intermediate term bonds and long-term mortgages (more properly, Mortgage-Backed Securities, or MBS) compete for the same fixed-income investor dollar. Treasury issues are 100% guaranteed to be repaid, but mortgages are not; therefore mortgages carry more risk of default or early repayment, which could potentially disturb the return on the investment. Therefore, mortgage rates must be priced higher to compensate for that risk. But how much higher are mortgages priced? In a normal market, the average \\\"\\\"spread\\\"\\\" or markup above the 100% secured Treasury is about 170 basis points, or 1.7%. That markup -- the spread relationship -- widens and contracts with a range of market conditions, investor appetites and supply of available product -- as well as the presence of competing investment opportunities, like corporate bonds or domestic (or foreign) equity markets Source: What Moves Mortgage Rates? And when the stock market crashes, investors tend to run to bonds and treasuries, which causes prices to go up and treasury yields to drop. Theoretically, this would also cause mortgage rates to drop, although most mortgage rates have a base price below which they cannot fall. How easy is it to profit from recent stock market drops and at what frequency? Incredibly difficult. The issue with your strategy is that you cannot predict the bottom of the market (at least us mortals can't). Just take the month of August for example. Stocks fell something like 15%? After the first 5-10% drop, people felt that the bottom was there, so they rushed in, only to have the market fall even more. How will you know when to invest? Even if the market falls by 50%, and there's a huge buying opportunity, and you increase the mortgage on your house, odds are your rates will increase because of the equity you take out. What if the market stays low for a very long time? Will you be able to maintain mortgage payments? Japan's stock bubble popped in the early 90's, and they've had two lost decade's now. Furthermore, there are issues of liquidity. What if you need more capital? Can you just sell a property or can you buy now property to draw equity against? What if the market is moving too fast for you to take advantage of. Don't ignore transaction costs and taxes either. Overall, there are a lot of ways that your idea can go wrong, and not many ways it can go right.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"474467\",\n \"text\": \"You only got 75 shares, so your basis is the fair market value of the stock as of the grant date times the number of shares you got: $20*75. Functionally, it's the same thing as if your employer did this: As such, the basis in that stock is $1,500 ($20*75). The other 25 shares aren't yours and weren't ever yours, so they aren't part of your basis (for net issuance; if they were sell to cover, then the end result would be pretty similar, but there'd be another transaction involved, but we won't go there). To put it another way, suppose your employer paid you a $2000 bonus, leaving you with a $1500 check after tax withholding. Being a prudent person and not wishing to blow your bonus on luxury goods, you invest that $1500 in a well-researched investment. You wouldn't doubt that your cost basis in that investment at $1500.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"161230\",\n \"text\": \"This is a bit of an open-ended answer as certain assumptions must be covered. Hope it helps though. My concern is that you have 1 year of university left - is there a chance that this money will be needed to fund this year of uni? And might it be needed for the period between uni and starting your first job? If the answer is 'yes' to either of these, keep any money you have as liquid as possible - ie. cash in an instant access Cash ISA. If the answer is 'no', let's move on... Are you likely to touch this money in the next 5 years? I'm thinking house & flat deposits - whether you rent or buy, cars, etc, etc. If yes, again keep it liquid in a Cash ISA but this time, perhaps look to get a slightly better interest rate by fixing for a 1 year or 2 year at a time. Something like MoneySavingExpert will show you best buy Cash ISAs. If this money is not going to be touched for more than 5 years, then things like bonds and equities come into play. Ultimately your appetite for risk determines your options. If you are uncomfortable with swings in value, then fixed-income products with fixed-term (ie. buy a bond, hold the bond, when the bond finishes, you get your money back plus the yield [interest]) may suit you better than equity-based investments. Equity-based means alot of things - stocks in just one company, an index tracker of a well-known stock market (eg. FTSE100 tracker), actively managed growth funds, passive ETFs of high-dividend stocks... And each of these has different volatility (price swings) and long-term performance - as well as different charges and risks. The only way to understand this is to learn. So that's my ultimate advice. Learn about bonds. Learn about equities. Learn about gilts, corporate bonds, bond funds, index trackers, ETFs, dividends, active v passive management. In the meantime, keep the money in a Cash ISA - where £1 stays £1 plus interest. Once you want to lock the money away into a long-term investment, then you can look at Stocks ISAs to protect the investment against taxation. You may also put just enough into a pension get the company 'match' for contributions. It's not uncommon to split your long-term saving between the two routes. Then come back and ask where to go next... but chances are you'll know yourself by then - because you self-educated. If you want an alternative to the US-based generic advice, check out my Simple Steps concept here (sspf.co.uk/seven-simple-steps) and my free posts on this framework at sspf.co.uk/blog. I also host a free weekly podcast at sspf.co.uk/podcast (also on iTunes, Miro, Mixcloud, and others...) They were designed to offer exactly that kind of guidance to the UK for free.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"250354\",\n \"text\": \"\\\"Well, this sub is generally pretty darn good. Among us are investment bankers, private equity analysts, valuation analysts, portfolio managers, traders, brokers, bachelors, masters, and doctorate students, etc. We're helpful, though sometimes snarky, and have an exceedingly low tolerance for bullshit. I love it here. And while your logic is sound, we can actually explore private equity directly, as while private and public equity are related, they are different enough to study separately, in my opinion. Private equity deals with private companies. By definition, these investments are illiquid (they cannot be easily sold like public stocks), and unmarketable (there is no ready market to trade these investments, like stock). They are generally held for longer time periods. At its earliest stage, private equity is synonymous with \\\"\\\"initial investment\\\"\\\" or \\\"\\\"seed funding.\\\"\\\" This includes (if we are maybe slightly liberal with our definition), the initial investment an entrepreneur makes into his business. At this stage, friends and family, angel investors and venture capital are present. At different points of a company lifecycle, different financiers become interested/applicable (mezzanine investors, etc.). The investment made into a company allocates a certain percentage of the ownership of the company to the investor in exchange for cash (usually). This cash is used to cover expenses and take on capital projects. The goal of these investments is to directly make the company (and its value, and thus the investor's value) grow. At some points in time, a new investor will show up and either invest directly in the company (same as before) or buy another investor's holding in the company (in which case, cash goes to *that specific investor* and *not* the company). At every stage of investment leading up to IPO, the deals are negotiated between the parties. The results of a given negotiation determines the value of that company's equity. For example, if I pay you $100 for 50% of your company, the company's implied worth is $200. If two days later, Joe comes and offers to buy 33% of the company for $100, the Company is worth $300. (Special note: these percentages are assumed to be the allocation of equity **after** the deal. In this last case, the ownership of your company would be 33% you, 33% me, and 33% Joe. This illustrates something called *dilution,* which is very important to investors as it effects their eventual potential payoff later down the road, along with some other things). At this point, do you have any questions?\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"130631\",\n \"text\": \"\\\"In the US you are not required to have a corporation to use business expenses to offset your income. The technical term you need is \\\"\\\"deducting business expenses\\\"\\\", and in matters of taxes it's usually best to go straight to the horse's mouth: the IRS's explanations Deducting Business Expenses Business expenses are the cost of carrying on a trade or business. These expenses are usually deductible if the business operates to make a profit. What Can I Deduct? Cost of Goods Sold, Capital Expenses, Personal versus Business Expenses, Business Use of Your Home, Business Use of Your Car, Other Types of Business Expenses None of this requires any special incorporation or tax arrangements, and are a normal part of operating a business. However, there is a bit of a problem with your scenario. You said you \\\"\\\"invested\\\"\\\" into a business, but you mentioned buying specific things for the business which is not generally how one accounts for investment. If you are not an owner/operator of the business, then the scenario is not so straight-forward, as you can't simply claim someone else's business expenses as your own because you invested in it. Investments are taxed differently than expenses, and based upon your word choices I'm concerned that you could be getting yourself into a bit of a pickle. I would strongly advise you to speak with a professional, such as a Certified Public Accountant (CPA), to go over your current arrangement and advise you on how you should be structuring your ongoing investment into this shared business. If you are investing you should be receiving equity to reflect your ownership (or stock in the company, etc), and investments of this sort generally cannot be deducted as an expense on your taxes - it's just an investment, the same as buying stock or CDs. If you are just buying things for someone else's benefit, it's possible that this could be looked upon as a personal gift, and you may be in a precarious legal position as well (where the money is, indeed, just a gift). And gifts of this sort aren't deductible, either. Depending on how this is all structured, it's possible that you should both consider a different form of legal organization, such as a formal corporation or at least an official business partnership. A CPA and an appropriate business attorney should be able to advise you for a nominal (few hundred dollars, at most) fee. If a new legal structure is advisable, you can potentially do the work yourself for a few hundred dollars, or pay to have it done (especially if the situation is more complex) for a few hundred to a few thousand. That's a lot less than you'd be on the hook for if this business is being accounted for improperly, or if either of your tax returns are being reported improperly!\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"517323\",\n \"text\": \"The stock market is just like any other market, but stocks are bought and sold here. Just like you buy and sell your electronics at the electronics market, this is a place where buyers and sellers come together to buy and sell shares or stocks or equity, no matter what you call it. What are these shares? A share is nothing but a portion of ownership of a company. Suppose a company has 100 shares issued to it, and you were sold 10 out of those, it literally means you are a 10% owner of the company. Why do companies sell shares? Companies sell shares to grow or expand. Suppose a business is manufacturing or producing and selling goods or services that are high in demand, the owners would want to take advantage of it and increase the production of his goods or services. And in order to increase production he would need money to buy land or equipment or labor, etc. Now either he could go get a loan by pledging something, or he could partner with someone who could give him money in exchange for some portion of the ownership of the company. This way, the owner gets the money to expand his business and make more profit, and the lender gets a portion of profit every time the company makes some. Now if the owner decides to sell shares rather than getting a loan, that's when the stock market comes into the picture. Why would a person want to trade stocks? First of all, please remember that stocks were never meant to be traded. You always invest in stocks. What's the difference? Trading is short term and investing is long term, in very simple language. It's the greed of humans which led to this concept of trading stocks. A person should only buy stocks if he believes in the business the company is doing and sees the potential of growth. Back to the question: a person would want to buy stocks of the company because: How does a stock market help society? Look around you for the answer to this question. Let me give you a start and I wish everyone reading this post to add at least one point to the answer. Corporations in general allow many people come together and invest in a business without fear that their investment will cause them undue liability - because shareholders are ultimately not liable for the actions of a corporation. The cornerstone North American case of how corporations add value is by allowing many investors to have put money towards the railroads that were built across America and Canada. For The stock market in particular, by making it easier to trade shares of a company once the company sells them, the number of people able to conveniently invest grows exponentially. This means that someone can buy shares in a company without needing to knock door to door in 5 years trying to find someone to sell to. Participating in the stock market creates 'liquidity', which is essentially the ease with which stocks are converted into cash. High liquidity reduces risk overall, and it means that those who want risk [because high risk often creates high reward] can buy shares, and those who want low risk [because say they are retiring and don't have a risk appetite anymore] can sell shares.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"574327\",\n \"text\": \"\\\"First, what structure does your index fund have? If it is an open-end mutual fund, there are no bid/ask spread as the structure of this security is that it is priced once a day and transactions are done with that price. If it is an exchange-traded fund, then the question becomes how well are authorized participants taking advantage of the spread to make the fund track the index well? This is where you have to get into the Creation and Redemption unit construct of the exchange-traded fund where there are \\\"\\\"in-kind\\\"\\\" transactions done to either create new shares of the fund or redeem out shares of the fund. In either case, you are making some serious assumptions about the structure of the fund that don't make sense given how these are built. Index funds have lower expense ratios and are thus cheaper than other mutual funds that may take on more costs. If you want suggested reading on this, look at the investing books of John C. Bogle who studied some of this rather extensively, in addition to being one of the first to create an index fund that became known as \\\"\\\"Bogle's Folly,\\\"\\\" where a couple of key ones would be \\\"\\\"Common Sense on Mutual Funds: New Imperatives for the Intelligent Investor\\\"\\\" and \\\"\\\"Bogle on Mutual Funds: New Perspectives for the Intelligent Investor.\\\"\\\" In the case of an open-end fund, there has to be a portion of the fund in cash to handle transaction costs of running the fund as there are management fees to come from running the fund in addition to dividends from the stocks that have to be carefully re-invested and other matters that make this quite easy to note. Vanguard 500 Index Investor portfolio(VFINX) has .38% in cash as an example here where you could look at any open-end mutual fund's portfolio and notice that there may well be some in cash as part of how the fund is managed. It’s the Execution, Stupid would be one of a few articles that looks at the idea of \\\"\\\"tracking error\\\"\\\" or how well does an index fund actually track the index where it can be noted that in some cases, there can be a little bit of active management in the fund. Just as a minor side note, when I lived in the US I did invest in index funds and found them to be a good investment. I'd still recommend them though I'd argue that while some want to see these as really simple investments, there can be details that make them quite interesting to my mind. How is its price set then? The price is computed by taking the sum value of all the assets of the fund minus the liabilities and divided by the number of outstanding shares. The price of the assets would include the closing price on the stock rather than a bid or ask, similar pricing for bonds held by the fund, derivatives and cash equivalents. Similarly, the liabilities would be costs a fund has to pay that may not have been paid yet such as management fees, brokerage costs, etc. Is it a weighted average of all the underlying stock spreads, or does it stand on its own and stems from the usual supply & demand laws ? There isn't any spread used in determining the \\\"\\\"Net Asset Value\\\"\\\" for the fund. The fund prices are determined after the market is closed and so a closing price can be used for stocks. The liabilities could include the costs to run the fund as part of the accounting in the fund, that most items have to come down to either being an asset, something with a positive value, or a liability, something with a negative value. Something to consider also is the size of the fund. With over $7,000,000,000 in assets, a .01% amount is still $700,000 which is quite a large amount in some ways.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"202355\",\n \"text\": \"\\\"Is the mortgage debt too high? The rental property is in a hot RE market, so could be easily sold with significant equity. However, they would prefer to keep it. Given the current income, there is no stress. However in absence of any other liquid [cash/near cash] assets, having everything locked into Mortgage is quite high. Even if real estate builds assets, these are highly illiquid investments. Have debt on such investments is risky; if there are no other investments. Essentially everything looks fine now, but if there is an crisis, unwinding mortgage debt is time consuming and if it forces distress sale, it would wipe out any gains. Can they afford another mortgage, and in what amount? (e.g. they are considering $50K for a small cabin, which could be rented out). I guess they can. But should they? Or diversify into other assets like stocks etc. Other than setting cash aside, what would be some good uses of funds to make sure the money would appreciate and outpace inflation and add a nice bonus to retirement? Mutual Funds / Stocks / bullions / 401K or other such retirement plans. They are currently in mid-30's. If there is ONE key strategy or decision they could make today that would help them retire \\\"\\\"early\\\"\\\" (say, mid-50's), what should it be? This opinion based ... it depends on \\\"\\\"what their lifestyle is\\\"\\\" and what would they want their \\\"\\\"lifestyle\\\"\\\" to be when they retire. They should look at saving enough corpus that would give an year on year yield equivalent to the retirement expenses.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"561997\",\n \"text\": \"I think your premise is slightly flawed. Every investment can add or reduce risk, depending on how it's used. If your ordering above is intended to represent the probability you will lose your principal, then it's roughly right, with caveats. If you buy a long-term government bond and interest rates increase while you're holding it, its value will decrease on the secondary markets. If you need/want to sell it before maturity, you may not recover your principal, and if you hold it, you will probably be subject to erosion of value due to inflation (inflation and interest rates are correlated). Over the short-term, the stock market can be very volatile, and you can suffer large paper losses. But over the long-term (decades), the stock market has beaten inflation. But this is true in aggregate, so, if you want to decrease equity risk, you need to invest in a very diversified portfolio (index mutual funds) and hold the portfolio for a long time. With a strategy like this, the stock market is not that risky over time. Derivatives, if used for their original purpose, can actually reduce volatility (and therefore risk) by reducing both the upside and downside of your other investments. For example, if you sell covered calls on your equity investments, you get an income stream as long as the underlying equities have a value that stays below the strike price. The cost to you is that you are forced to sell the equity at the strike price if its value increases above that. The person on the other side of that transaction loses the price of the call if the equity price doesn't go up, but gets a benefit if it does. In the commodity markets, Southwest Airlines used derivatives (options to buy at a fixed price in the future) on fuel to hedge against increases in fuel prices for years. This way, they added predictability to their cost structure and were able to beat the competition when fuel prices rose. Even had fuel prices dropped to zero, their exposure was limited to the pre-negotiated price of the fuel, which they'd already planned for. On the other hand, if you start doing things like selling uncovered calls, you expose yourself to potentially infinite losses, since there are no caps on how high the price of a stock can go. So it's not possible to say that derivatives as a class of investment are risky per se, because they can be used to reduce risk. I would take hedge funds, as a class, out of your list. You can't generally invest in those unless you have quite a lot of money, and they use strategies that vary widely, many of which are quite risky.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"156747\",\n \"text\": \"\\\"Equity could mean stock options. If that's the case if the company makes it big, you'll have the option to buy stocks cheap (which can then be sold at a huge profit) How are you going to buy those without income? 5% equity is laughable. I'd be looking for 30-40% if not better without salary. Or even better, a salary. To elaborate, 5% is fine, and even normal for an early employee taking a mild pay cut in exchange for a chance at return. That chance of any return on the equity is only about 1/20 (94% of startups fail) There is no reason for an employee to work for no pay. An argument could be made for a cofounder, with direct control and influence in the company to work for equity only, but it would be a /lot/ more (that 30-40%), or an advisory role (5% is reasonable) I also just noticed you mentioned \\\"\\\"investing\\\"\\\" in the startup with cash. As an angel investor, I'd still expect far more than 5%, and preferred shares at that. More like 16-20%. Read this for more info on how equity is usually split.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"371012\",\n \"text\": \"I was merely trying to be helpful - Conceptually, you have dump this idea that something is skewed. It isn't. Firm A sold for $500 (equity value aka purchase price to shareholders) + debt (zero) - cash (50) for 450. Enterprise value is the cash free, debt free sale price. The implied ev multiple is 4.5x on A - that is the answer. The other business sold for a higher multiple of 5x. If you would pile on more cash onto A, the purchase price would increase, but the EV wouldn't. The idea is to think hard about the difference between equity value and enterprise value when examining a transaction.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"282483\",\n \"text\": \"In general, investors with a long period of time until they would need to withdraw the cash are best off holding mostly equities. While the dividends that equities would return are less than the interest you would get in peer-to-peer lending, over long periods of time not only do you get the dividends from equity investment but the value of the stock will grow faster than interest on loans. The higher returns from stocks, however, comes with more risk of big downturns. Many people pull their investments out of stocks right after crashes which really hurts their long term returns. So, in order to get the benefit of investing in stocks you need to be strong enough to continue to hold the stocks through the crash and into the recovery. As for which stocks to invest in, generally it is best to invest in low-fee index funds/etfs where you own a broad collection of stocks so that if (when) any one stock goes bust that your portfolio does not take much damage. Try to own both international and domestic stocks to get good diversification. The consensus recommends adding just a little bit of REITs and bonds to your investments, but for someone at 25 it might not be worth it yet. Warren Buffett had some good thoughts on index investing.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"328745\",\n \"text\": \"It lowers the cost of capital. Debt is generally a 'cheaper' form of financing, and in addition you have the benefit of interest being tax deductible. Assume you have no capital to expand an existing business. How do you fund it? You could sell/issue some stock to outside investors for cash (or inject your personal cash into the business if you have it), or you can borrow the money. General the borrowing is 'cheaper' as debt investors need a lower return than equity investors, because debt is less risky (has claims on the business assets before equity holders) than equity.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"383682\",\n \"text\": \"One other consideration is that by paying off your mortgage early versus, for example, investing that capital in a mutual fund is that you are reducing your net liquidity to some degree. That is, if you find yourself needing an emergency infusion of cash it is easier to sell a stock/fund than to sell your house or get a equity loan. I suppose if you were planning to need a lot of cash to start a business or invest in real estate, then maybe it would make sense to keep your cash more liquid. However, in your situation I agree with Joe. Pay it off. It feels REALLY good to write that last check!\",\n \"title\": \"\"\n },\n {\n \"docid\": \"275249\",\n \"text\": \"\\\"There are three (or four) ways that a company can grow: (Crowdfunding is a relatively new (in mainstream businesses) alternative financing method where people will finance a company with the expectation that they will benefit from the product or service that they provide.) Obviously a startup has no prior income to use, so it must either raise money through equity or debt. People say that one must borrow contingent on their salary. Banks lend money based on the ability to pay the loan back plus interest. For individuals, their income is their primary source of cash flow, so, yes, it is usually the determining factor in getting a loan. For a business the key factor is future cash flows. So a business will borrow money, say, to buy a new asset (like a factory) that will be used to generate cash flows in the future so that they can pay down the debt. If the bank believes that the use of the money is going to be profitable enough that they will get their money back with interest, they'll loan the money. Equity investors are essentially the same, but since they don't get a guaranteed payback (they only get paid through non-guaranteed dividends or liquidation), their risk is higher and they are looking for higher expected returns. So the question I'd have as a bank or equity investor is \\\"\\\"what are you going to do with the money?\\\"\\\" What is your business strategy? What are you going to do that will make profits in the future? Do you have a special idea or skill that you can turn into a profitable business? (Crowdfunding would be similar - people are willing to give you money based on either the social or personal benefit of some product or service.) So any business either starts small and grows over time (which is how the vast majority of businesses grow), or has some special idea, asset, skill, or something that would make a bank willing to take a risk on a huge loan. I know, again, that people here tend to turn blind eyes on unfortunate realities, but people do make giant businesses without having giant incomes. The \\\"\\\"unfortunate reality\\\"\\\" is that most startups fail. Which may sound bad, but also keep in mind that most startups are created by people that are OK with failing. They are people that are willing to fail 9 times with the thought that the 10th one will take off and make up for the losses of the first 9. So I would say - if you have some great idea or skill and a viable strategy and plan to take it to market, then GO FOR IT. You don't need a huge salary to start off. You need something that you can take to market and make money. Most people (myself included) either do not have that idea or skill to go out on their own, or don't have the courage to take that kind of risk. But don't go in assuming all you need is a loan and you'll be an instant millionaire. You might, but the odds are very long.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"89714\",\n \"text\": \"With a long enough time horizon, no matter when you buy, equities almost always outperform cash and bonds. There's an article here with some info: http://www.fool.co.uk/investing-basics/how-when-and-where-to-invest/ Holding period where shares have beaten cash There was a similar study done which showed if you picked any day in the last 100 years, no matter if the market was at a high or low, after 1 year your probability of being in profit was only 0.5, but after 10-20 years it was almost certainly 1.0. Equities compound dividends too, and the best place to invest is in diversified stock indices such as the S&P500, FTSE100, DOW30 or indices/funds which pay dividends. The best way to capture returns is to dollar cost average (e.g. place a lump sum, then add $x every month), to re-invest dividends, and oh, to forget about it in an IRA or SIPP (Self invested pension) or other vehicle which discourages tampering with your investment. Yes, values rise and fall but we humans are so short sighted, if we had bought the S&P in 2007 and sold in 2009 in fear, we would have missed out on the 25% gain (excluding dividends) from 2007-2014. That's about 3% a year gain even if you bought the 2007 high -beating cash or bonds even after the financial crisis. Now imagine had you dollar cost averaged the entire period from 2007-2014 where your gain would be. Your equity curve would have the same shape as the S&P (with its drastic dip in 2009) but an accelerated growth after. There are studies if you dig that demonstrate the above. From experience I can tell you timing the market is nigh impossible and most fund managers are unable to beat the indices. Far better to DCA and re-invest dividends and not care about market gyrations! ..\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":393,"cells":{"query_id":{"kind":"string","value":"482"},"query":{"kind":"string","value":"Guanine nucleotide exchange factors (GEFs) mediate RhoA activation in response to tensional forces on fibronectin-binding integrins."},"positive_passages":{"kind":"list like","value":[{"docid":"10991183","text":"How individual cells respond to mechanical forces is of considerable interest to biologists as force affects many aspects of cell behaviour. The application of force on integrins triggers cytoskeletal rearrangements and growth of the associated adhesion complex, resulting in increased cellular stiffness, also known as reinforcement. Although RhoA has been shown to play a role during reinforcement, the molecular mechanisms that regulate its activity are unknown. By combining biochemical and biophysical approaches, we identified two guanine nucleotide exchange factors (GEFs), LARG and GEF-H1, as key molecules that regulate the cellular adaptation to force. We show that stimulation of integrins with tensional force triggers activation of these two GEFs and their recruitment to adhesion complexes. Surprisingly, activation of LARG and GEF-H1 involves distinct signalling pathways. Our results reveal that LARG is activated by the Src family tyrosine kinase Fyn, whereas GEF-H1 catalytic activity is enhanced by ERK downstream of a signalling cascade that includes FAK and Ras.","title":"The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins"}],"string":"[\n {\n \"docid\": \"10991183\",\n \"text\": \"How individual cells respond to mechanical forces is of considerable interest to biologists as force affects many aspects of cell behaviour. The application of force on integrins triggers cytoskeletal rearrangements and growth of the associated adhesion complex, resulting in increased cellular stiffness, also known as reinforcement. Although RhoA has been shown to play a role during reinforcement, the molecular mechanisms that regulate its activity are unknown. By combining biochemical and biophysical approaches, we identified two guanine nucleotide exchange factors (GEFs), LARG and GEF-H1, as key molecules that regulate the cellular adaptation to force. We show that stimulation of integrins with tensional force triggers activation of these two GEFs and their recruitment to adhesion complexes. Surprisingly, activation of LARG and GEF-H1 involves distinct signalling pathways. Our results reveal that LARG is activated by the Src family tyrosine kinase Fyn, whereas GEF-H1 catalytic activity is enhanced by ERK downstream of a signalling cascade that includes FAK and Ras.\",\n \"title\": \"The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"33076846","text":"Polyploidization can precede the development of aneuploidy in cancer. Polyploidization in megakaryocytes (Mks), in contrast, is a highly controlled developmental process critical for efficient platelet production via unknown mechanisms. Using primary cells, we demonstrate that the guanine exchange factors GEF-H1 and ECT2, which are often overexpressed in cancer and are essential for RhoA activation during cytokinesis, must be downregulated for Mk polyploidization. The first (2N-4N) endomitotic cycle requires GEF-H1 downregulation, whereas subsequent cycles (>4N) require ECT2 downregulation. Exogenous expression of both GEF-H1 and ECT2 prevents endomitosis, resulting in proliferation of 2N Mks. Furthermore, we have shown that the mechanism by which polyploidization is prevented in Mks lacking Mkl1, which is mutated in megakaryocytic leukemia, is via elevated GEF-H1 expression; shRNA-mediated GEF-H1 knockdown alone rescues this ploidy defect. These mechanistic insights enhance our understanding of normal versus malignant megakaryocytopoiesis, as well as aberrant mitosis in aneuploid cancers.","title":"Role of RhoA-specific guanine exchange factors in regulation of endomitosis in megakaryocytes."},{"docid":"24881307","text":"Synapses are specialized cell-cell contacts that mediate communication between neurons. Most excitatory synapses in the brain are housed on dendritic spines, small actin-rich protrusions extending from dendrites. During development and in response to environmental stimuli, spines undergo marked changes in shape and number thought to underlie processes like learning and memory. Improper spine development, in contrast, likely impedes information processing in the brain, since spine abnormalities are associated with numerous brain disorders. Elucidating the mechanisms that regulate the formation and plasticity of spines and their resident synapses is therefore crucial to our understanding of cognition and disease. Rho-family GTPases, key regulators of the actin cytoskeleton, play essential roles in orchestrating the development and remodeling of spines and synapses. Precise spatio-temporal regulation of Rho GTPase activity is critical for their function, since aberrant Rho GTPase signaling can cause spine and synapse defects as well as cognitive impairments. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and inhibited by GTPase-activating proteins (GAPs). We propose that Rho-family GEFs and GAPs provide the spatiotemporal regulation and signaling specificity necessary for proper Rho GTPase function based on the following features they possess: (i) existence of multiple GEFs and GAPs per Rho GTPase, (ii) developmentally regulated expression, (iii) discrete localization, (iv) ability to bind to and organize specific signaling networks, and (v) tightly regulated activity, perhaps involving GEF/GAP interactions. Recent studies describe several Rho-family GEFs and GAPs that uniquely contribute to spinogenesis and synaptogenesis. Here, we highlight several of these proteins and discuss how they occupy distinct biochemical niches critical for synaptic development.","title":"Control of synapse development and plasticity by Rho GTPase regulatory proteins"},{"docid":"8093935","text":"Sec7-related guanine nucleotide exchange factors (GEFs) initiate vesicle budding from the Golgi membrane surface by converting the GTPase ARF to a GTP-bound, membrane-associated form. Here we report the crystal structure of the catalytic Sec7 homology domain of Arno, a human GEF for ARF1, determined at 2.2 angstroms resolution. The Sec7 domain is an elongated, all-helical protein with a distinctive hydrophobic groove that is phylogenetically conserved. Structure-based mutagenesis identifies the groove and an adjacent conserved loop as the ARF-interacting surface. The sites of Sec7 domain interaction on ARF1 have subsequently been mapped, by protein footprinting experiments, to the switch 1 and switch 2 GTPase regions, leading to a model for the interaction between ARF GTPases and Sec7 domain exchange factors.","title":"Structure of the Guanine Nucleotide Exchange Factor Sec7 Domain of Human Arno and Analysis of the Interaction with ARF GTPase"},{"docid":"14461101","text":"Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp)-producing Neisseria gonorrhoeae (P(+)GC) induces an immediate recruitment of caveolin-1 (Cav1) in the host cell, which subsequently prevents bacterial internalization by triggering cytoskeletal rearrangements via downstream phosphotyrosine signaling. A broad and unbiased analysis of potential interaction partners for tyrosine-phosphorylated Cav1 revealed a direct interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role in the Cav1-mediated prevention of bacterial uptake. Our findings, which have been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing bacteria avoid host cell uptake. Further, our data establish a mechanistic link between Cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and advance our understanding of caveolin function.","title":"Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements"},{"docid":"10530014","text":"Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteopetrosis at an early age. These symptoms are consistent with but more severe than those reported for people with leukocyte adhesion deficiency III (LAD-III). Mechanistically, these symptoms arose from an inability to activate the integrins expressed on hematopoietic cells, including platelets and leukocytes. Immortalized lymphocyte cell lines isolated from the two individuals showed integrin activation defects. Several proteins previously implicated in integrin activation, including Ras-associated protein-1 (RAP1) and calcium and diacylglycerol-regulated guanine nucleotide exchange factor-1 (CALDAG-GEF1), were present and functional in these cell lines. The genetic basis for this disease was traced to a point mutation in the coding region of the KINDLIN3 (official gene symbol FERMT3) gene. When wild-type KINDLIN-3 was expressed in the immortalized lymphocytes, their integrins became responsive to activation signals. These results identify a genetic disease that severely compromises the health of the affected individuals and establish an essential role of KINDLIN-3 in integrin activation in humans. Furthermore, allogeneic bone marrow transplantation was shown to alleviate the symptoms of the disease.","title":"A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans"},{"docid":"10669582","text":"The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.","title":"Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin"},{"docid":"14119470","text":"Ran is an abundant nuclear GTPase with a clear role in nuclear transport during interphase but with roles in mitotic regulation that are less well understood. The nucleotide-binding state of Ran is regulated by a GTPase activating protein, RanGAP1, and by a guanine nucleotide exchange factor, RCC1. Ran also interacts with a guanine nucleotide dissociation inhibitor, RanBP1. RanBP1 has a high affinity for GTP-bound Ran, and it acts as a cofactor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on Ran approximately tenfold. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian cells and in Xenopus egg extracts (our unpublished observations). We investigated how increased concentrations of RanBP1 disturb mitosis. We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is added to M phase Xenopus egg extracts. We present evidence that the role of Ran in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.","title":"The Ran GTPase regulates mitotic spindle assembly"},{"docid":"32532238","text":"To understand how cells sense and adapt to mechanical stress, we applied tensional forces to magnetic microbeads bound to cell-surface integrin receptors and measured changes in bead displacement with sub-micrometer resolution using optical microscopy. Cells exhibited four types of mechanical responses: (1) an immediate viscoelastic response; (2) early adaptive behavior characterized by pulse-to-pulse attenuation in response to oscillatory forces; (3) later adaptive cell stiffening with sustained (>15 second) static stresses; and (4) a large-scale repositioning response with prolonged (>1 minute) stress. Importantly, these adaptation responses differed biochemically. The immediate and early responses were affected by chemically dissipating cytoskeletal prestress (isometric tension), whereas the later adaptive response was not. The repositioning response was prevented by inhibiting tension through interference with Rho signaling, similar to the case of the immediate and early responses, but it was also prevented by blocking mechanosensitive ion channels or by inhibiting Src tyrosine kinases. All adaptive responses were suppressed by cooling cells to 4 degrees C to slow biochemical remodeling. Thus, cells use multiple mechanisms to sense and respond to static and dynamic changes in the level of mechanical stress applied to integrins.","title":"Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels."},{"docid":"20943272","text":"ADAM13 is a member of the disintegrin and metalloprotease protein family that is expressed on cranial neural crest cells surface and is essential for their migration. ADAM13 is an active protease that can cleave fibronectin in vitro and remodel a fibronectin substrate in vivo. Using a recombinant secreted protein containing both disintegrin and cysteine-rich domains of ADAM13, we show that this \"adhesive\" region of the protein binds directly to fibronectin. Fibronectin fusion proteins corresponding to the various functional domains were used to define the second heparin-binding domain as the ADAM13 binding site. Mutation of the syndecan-binding site (PPRR --> PPTM) within this domain abolishes binding of the recombinant disintegrin and cysteine-rich domains of ADAM13. We further show that the adhesive disintegrin and cysteine-rich domain of ADAM13 can promote cell adhesion via beta(1) integrins. This adhesion requires integrin activation and can be prevented by antibodies to the cysteine-rich domain of ADAM13 and beta(1) integrin. Finally, wild type, but not the E/A mutant of ADAM13 metalloprotease domain, can be shed from the cell surface, releasing the metalloprotease domain associated with the disintegrin and cysteine-rich domains. This suggests that ADAM13 shedding may involve its own metalloprotease activity and that the released protease may interact with both integrins and extracellular matrix proteins.","title":"ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin."},{"docid":"9507605","text":"The transition of cell–matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II–driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein–tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136–143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force.","title":"Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCKindependent mechanism"},{"docid":"9185195","text":"AIMS The vascular endothelial growth factor (VEGF) stimulates angiogenesis by induction of vessel permeability, proliferation, and migration of endothelial cells, an important process in ischaemic diseases. ADP-ribosylation factor (ARF) nucleotide-binding site opener (ARNO) (cytohesin-2) is a guanine exchange factor important for cellular signalling through ARF GTPases. However, a role for ARNO in VEGF-dependent endothelial processes has so far not been documented. Therefore, we investigated whether ARNO has a role in VEGF-dependent activation of endothelial cells and thus vessel permeability. METHODS AND RESULTS ARNO expression was observed in endothelial cells in vitro by RT-PCR, western blotting, and immunofluorescence as well as ex vivo by immunohistochemical staining of mouse aorta. Treatment with the cytohesin inhibitor SecinH3 or with an ARNO siRNA prevented VEGF-dependent Akt activation, assessed by detection of phosphorylated Akt, and proliferation of endothelial cells in vitro, measured by methylthiazoletetrazolium (MTT) reduction. In addition, ARNO suppression reduced VEGF-induced permeability in vessels of the mouse (C57BL/6) cremaster muscle in vivo, as measured by extravasation of fluorescein isothiocyanate (FITC)-dextran. Moreover, ARNO knock-down accelerated ligand-induced reduction in vascular endothelial growth factor receptor-2 (VEGFR-2) surface expression, internalization, and degradation, as assessed by flow cytometry and western blotting, respectively. CONCLUSION Our findings indicate an important and novel role for endothelial ARNO in VEGF-dependent initiation of angiogenesis by regulation of VEGFR-2 internalization in endothelial cells, resulting in the activation of the Akt pathway, vessel permeability, and ultimately endothelial proliferation. Thus, ARNO may be a new essential player in endothelial signalling and angiogenesis.","title":"ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression."},{"docid":"23141360","text":"The morphogenesis of developing embryos and organs relies on the ability of cells to remodel their contacts with neighbouring cells. Using quantitative modelling and laser nano-dissection, we probed the mechanics of a morphogenetic process, the elongation of Drosophila melanogaster embryos, which results from polarized cell neighbour exchanges. We show that anisotropy of cortical tension at apical cell junctions is sufficient to drive tissue elongation. We estimated its value through comparisons between in silico and in vivo data using various tissue descriptors. Nano-dissection of the actomyosin network indicates that tension is anisotropically distributed and depends on myosin II accumulation. Junction relaxation after nano-dissection also suggests that cortical elastic forces are dominant in this process. Interestingly, fluctuations in vertex position (points where three or more cells meet) facilitate neighbour exchanges. We delineate the contribution of subcellular tensile activity polarizing junction remodelling, and the permissive role of vertex fluctuations during tissue elongation.","title":"Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis"},{"docid":"21164071","text":"Integrins are membrane receptors which mediate cell-cell or cell-matrix adhesion. Integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) acts as a fibrinogen receptor of platelets and mediates platelet aggregation. Platelet activation is required for alpha IIb beta 3 to shift from noncompetent to competent for binding soluble fibrinogen. The steps involved in this transition are poorly understood. We have studied a variant of Glanzmann thrombasthenia, a congenital bleeding disorder characterized by absence of platelet aggregation and fibrinogen binding. The patient's platelets did not bind fibrinogen after platelet activation by ADP or thrombin, though his platelets contained alpha IIb beta 3. However, isolated alpha IIb beta 3 was able to bind to an Arg-Gly-Asp-Ser affinity column, and binding of soluble fibrinogen to the patient's platelets could be triggered by modulators of alpha IIb beta 3 conformation such as the Arg-Gly-Asp-Ser peptide and alpha-chymotrypsin. These data suggested that a functional Arg-Gly-Asp binding site was present within alpha IIb beta 3 and that the patient's defect was not secondary to a blockade of alpha IIb beta 3 in a noncompetent conformational state. This was evocative of a defect in the coupling between platelet activation and alpha IIb beta 3 up-regulation. We therefore sequenced the cytoplasmic domain of beta 3, following polymerase chain reaction (PCR) on platelet RNA, and found a T-->C mutation at nucleotide 2259, corresponding to a Ser-752-->Pro substitution. This mutation is likely to be responsible for the uncoupling of alpha IIb beta 3 from cellular activation because (i) it is not a polymorphism, (ii) it is the only mutation in the entire alpha IIb beta 3 sequence, and (iii) genetic analysis of the family showed that absence of the Pro-752 beta 3 allele was associated with the normal phenotype. Our data thus identify the C-terminal portion of the cytoplasmic domain of beta 3 as an intrinsic element in the coupling between alpha IIb beta 3 and platelet activation.","title":"Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia."},{"docid":"20313748","text":"Adherens junctions (AJs), which are organized by adhesion proteins and the underlying actin cytoskeleton, probably sense pulling forces from adjacent cells and modulate opposing forces to maintain tissue integrity, but the regulatory mechanism remains unknown at the molecular level. Although the possibility that α-catenin acts as a direct linker between the membrane and the actin cytoskeleton for AJ formation and function has been minimized, here we show that α-catenin recruits vinculin, another main actin-binding protein of AJs, through force-dependent changes in α-catenin conformation. We identified regions in the α-catenin molecule that are required for its force-dependent binding of vinculin by introducing mutant α-catenin into cells and using in vitro binding assays. Fluorescence recovery after photobleaching analysis for α-catenin mobility and the existence of an antibody recognizing α-catenin in a force-dependent manner further supported the notion that α-catenin is a tension transducer that translates mechanical stimuli into a chemical response, resulting in AJ development.","title":"α-Catenin as a tension transducer that induces adherens junction development"},{"docid":"16511863","text":"BACKGROUND Although numerous signaling pathways are known to be activated in experimental cardiac hypertrophy, the molecular basis of the hypertrophic response inherent in human heart diseases remains largely unknown. Integrin-linked kinase (ILK) is a multifunctional protein kinase that physically links beta-integrins with the actin cytoskeleton, suggesting a potential mechanoreceptor role. METHODS AND RESULTS Here, we show a marked increase in ILK protein levels in hypertrophic ventricles of patients with congenital and acquired outflow tract obstruction. This increase in ILK was associated with activation of the Rho family guanine triphosphatases, Rac1 and Cdc42, and known hypertrophic signaling kinases, including extracellular signal-related kinases (ERK1/2) and p70 S6 kinase. Transgenic mice with cardiac-specific expression of a constitutively active ILK (ILK(S343D)) or wild-type ILK (ILK(WT)) exhibited a compensated ventricular hypertrophic phenotype and displayed an activation profile of guanine triphosphatases and downstream protein kinases concordant with that seen in human hypertrophy. In contrast, transgenic mice with cardiomyocyte-restricted expression of a kinase-inactive ILK (ILK(R211A)) were unable to mount a compensatory hypertrophic response to angiotensin II in vivo. CONCLUSIONS Taken together, these results identify ILK-regulated signaling as a broadly adaptive hypertrophic response mechanism relevant to a wide range of clinical heart disease.","title":"Integrin-linked kinase expression is elevated in human cardiac hypertrophy and induces hypertrophy in transgenic mice."},{"docid":"44640124","text":"SIGNIFICANCE The extracellular matrix (ECM) fulfills essential functions in multicellular organisms. It provides the mechanical scaffold and environmental cues to cells. Upon cell attachment, the ECM signals into the cells. In this process, reactive oxygen species (ROS) are physiologically used as signalizing molecules. RECENT ADVANCES ECM attachment influences the ROS-production of cells. In turn, ROS affect the production, assembly and turnover of the ECM during wound healing and matrix remodeling. Pathological changes of ROS levels lead to excess ECM production and increased tissue contraction in fibrotic disorders and desmoplastic tumors. Integrins are cell adhesion molecules which mediate cell adhesion and force transmission between cells and the ECM. They have been identified as a target of redox-regulation by ROS. Cysteine-based redox-modifications, together with structural data, highlighted particular regions within integrin heterodimers that may be subject to redox-dependent conformational changes along with an alteration of integrin binding activity. CRITICAL ISSUES In a molecular model, a long-range disulfide-bridge within the integrin β-subunit and disulfide bridges within the genu and calf-2 domains of the integrin α-subunit may control the transition between the bent/inactive and upright/active conformation of the integrin ectodomain. These thiol-based intramolecular cross-linkages occur in the stalk domain of both integrin subunits, whereas the ligand-binding integrin headpiece is apparently unaffected by redox-regulation. FUTURE DIRECTIONS Redox-regulation of the integrin activation state may explain the effect of ROS in physiological processes. A deeper understanding of the underlying mechanism may open new prospects for the treatment of fibrotic disorders.","title":"Redox-relevant aspects of the extracellular matrix and its cellular contacts via integrins."},{"docid":"4662264","text":"The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1). This Ser118 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro and in cells treated with epidermal growth factor (EGF) and insulin-like growth factor (IGF) in vivo. Overexpression of MAPK kinase (MAPKK) or of the guanine nucleotide binding protein Ras, both of which activate MAPK, enhanced estrogen-induced and antiestrogen (tamoxifen)-induced transcriptional activity of wild-type ER, but not that of a mutant ER with an alanine in place of Ser118. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.","title":"Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase."},{"docid":"23863576","text":"UNLABELLED Morphological characteristics of dendritic spines form the basis of cognitive ability. However, molecular mechanisms involved in fine-tuning of spine morphology during development are not fully understood. Moreover, it is unclear whether, and to what extent, these developmental mechanisms determine the normal adult spine morphological features. Here, we provide evidence that α2-isoform of Rac-specific GTPase-activating protein α-chimaerin (α2-chimaerin) is involved in spine morphological refinement during late postnatal period, and furthermore show that this developmental α2-chimaerin function affects adult spine morphologies. We used a series of mice with global and conditional knock-out of α-chimaerin isoforms (α1-chimaerin and α2-chimaerin). α2-Chimaerin disruption, but not α1-chimaerin disruption, in the mouse results in an increased size (and density) of spines in the hippocampus. In contrast, overexpression of α2-chimaerin in developing hippocampal neurons induces a decrease of spine size. Disruption of α2-chimaerin suppressed EphA-mediated spine morphogenesis in cultured developing hippocampal neurons. α2-Chimaerin disruption that begins during the juvenile stage results in an increased size of spines in the hippocampus. Meanwhile, spine morphologies are unaltered when α2-chimaerin is deleted only in adulthood. Consistent with these spine morphological results, disruption of α2-chimaerin beginning in the juvenile stage led to an increase in contextual fear learning in adulthood; whereas contextual learning was recently shown to be unaffected when α2-chimaerin was deleted only in adulthood. Together, these results suggest that α2-chimaerin signaling in developmental stages contributes to determination of the morphological features of adult spines and establishment of normal cognitive ability. SIGNIFICANCE STATEMENT Recent studies of neurodevelopmental disorders in humans and their animal models have led to an attractive hypothesis that spine morphogenesis during development forms the basis of adult cognition. In particular, the roles of Rac and its regulators, such as Rac-specific GTPase-activating proteins (RacGAPs) and Rac guanine nucleotide exchange factors, are a topic of focus in spine morphogenesis and cognitive ability. Using a series of mice with global and conditional knock-out (KO) of RacGAP α-chimaerin isoforms (α1-chimaerin and α2-chimaerin), we provide compelling evidence demonstrating that α2-chimaerin is involved in spine morphological refinement during late postnatal development and that this developmental α2-chimaerin function affects adult spine morphologies. Furthermore, our results clearly showed that α2-chimaerin signaling during late postnatal development contributes to normal cognitive ability in adult mice.","title":"Developmental RacGAP α2-Chimaerin Signaling Is a Determinant of the Morphological Features of Dendritic Spines in Adulthood."},{"docid":"2060137","text":"Cell-to-cell adhesions are crucial in maintaining the structural and functional integrity of cardiac cells. Little is known about the mechanosensitivity and mechanotransduction of cell-to-cell interactions. Most studies of cardiac mechanotransduction and myofibrillogenesis have focused on cell-extracellular matrix (ECM)-specific interactions. This study assesses the direct role of intercellular adhesion, specifically that of N-cadherin-mediated mechanotransduction, on the morphology and internal organization of neonatal ventricular cardiac myocytes. The results show that cadherin-mediated cell attachments are capable of eliciting a cytoskeletal network response similar to that of integrin-mediated force response and transmission, affecting myofibrillar organization, myocyte shape, and cortical stiffness. Traction forces mediated by N-cadherin were shown to be comparable to those sustained by ECM. The directional changes in predicted traction forces as a function of imposed loads (gel stiffness) provide the added evidence that N-cadherin is a mechanoresponsive adhesion receptor. Strikingly, the mechanical sensitivity response (gain) in terms of the measured cell-spread area as a function of imposed load (adhesive substrate rigidity) was consistently higher for N-cadherin-coated surfaces compared with ECM protein-coated surfaces. In addition, the cytoskeletal architecture of myocytes on an N-cadherin adhesive microenvironment was characteristically different from that on an ECM environment, suggesting that the two mechanotransductive cell adhesion systems may play both independent and complementary roles in myocyte cytoskeletal spatial organization. These results indicate that cell-to-cell-mediated force perception and transmission are involved in the organization and development of cardiac structure and function.","title":"Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing."},{"docid":"17997584","text":"Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear. Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation.","title":"Integrin αvβ8-Mediated TGF-β Activation by Effector Regulatory T Cells Is Essential for Suppression of T-Cell-Mediated Inflammation"},{"docid":"19912367","text":"Age-related changes in the niche have long been postulated to impair the function of somatic stem cells. Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs). Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers. By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen-activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche. Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration. Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism.","title":"Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice"},{"docid":"8698857","text":"TNF expression of macrophages is under stringent translational control that depends on the p38 MAPK/MK2 pathway and the AU-rich element (ARE) in the TNF mRNA. Here, we elucidate the molecular mechanism of phosphorylation-regulated translation of TNF. We demonstrate that translation of the TNF-precursor at the ER requires expression of the ARE-binding and -stabilizing factor human antigen R (HuR) together with either activity of the p38 MAPK/MK2 pathway or the absence of the ARE-binding and -destabilizing factor tristetraprolin (TTP). We show that phosphorylation of TTP by MK2 decreases its affinity to the ARE, inhibits its ability to replace HuR, and permits HuR-mediated initiation of translation of TNF mRNA. Since translation of TTP's own mRNA is also regulated by this mechanism, an intrinsic feedback control of the inflammatory response is ensured. The phosphorylation-regulated TTP/HuR exchange at target mRNAs provides a reversible switch between unstable/non-translatable and stable/efficiently translated mRNAs.","title":"The p38/MK2-Driven Exchange between Tristetraprolin and HuR Regulates AU–Rich Element–Dependent Translation"},{"docid":"12650610","text":"We have previously shown that the integrin beta6 is neo-expressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin beta6 promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin beta6 signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin beta6 signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it. The activation of Fyn recruited and activated focal adhesion kinase to this complex. This complex was necessary to activate Shc and to couple beta6 signaling to the Raf-ERK/MAPK pathway. This pathway transcriptionally activated the matrix metalloproteinase-3 gene and promoted oral SCC cell proliferation and experimental metastasis in vivo. These findings indicate that integrin beta6 signaling activates Fyn and thus promotes oral cancer progression.","title":"Alphavbeta6-Fyn signaling promotes oral cancer progression."},{"docid":"25191216","text":"Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gs alpha, leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin alpha v beta 3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during intramembranous but not endochondral ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos, which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for intramembranous ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gs alpha-cyclic adenosine monophosphate-c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease.","title":"Periostin, a novel marker of intramembranous ossification, is expressed in fibrous dysplasia and in c-Fos-overexpressing bone lesions."},{"docid":"19482914","text":"Integrin-mediated platelet adhesion and aggregation are essential for sealing injured blood vessels and preventing blood loss, and excessive platelet aggregation can initiate arterial thrombosis, causing heart attacks and stroke. To ensure that platelets aggregate only at injury sites, integrins on circulating platelets exist in a low-affinity state and shift to a high-affinity state (in a process known as integrin activation or priming) after contacting a wounded vessel. The shift is mediated through binding of the cytoskeletal protein Talin to the β subunit cytoplasmic tail. Here we show that platelets lacking the adhesion plaque protein Kindlin-3 cannot activate integrins despite normal Talin expression. As a direct consequence, Kindlin-3 deficiency results in severe bleeding and resistance to arterial thrombosis. Mechanistically, Kindlin-3 can directly bind to regions of β-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis.","title":"Kindlin-3 is essential for integrin activation and platelet aggregation"},{"docid":"13953762","text":"The Plk1-interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase bridges (UFBs) in mitosis alongside a complex of DNA repair proteins, including the Bloom's syndrome protein (BLM). However, very little is known about the function of PICH or how it is recruited to UFBs. Using a combination of microfluidics, fluorescence microscopy, and optical tweezers, we have defined the properties of PICH in an in vitro model of an anaphase bridge. We show that PICH binds with a remarkably high affinity to duplex DNA, resulting in ATP-dependent protein translocation and extension of the DNA. Most strikingly, the affinity of PICH for binding DNA increases with tension-induced DNA stretching, which mimics the effect of the mitotic spindle on a UFB. PICH binding also appears to diminish force-induced DNA melting. We propose a model in which PICH recognizes and stabilizes DNA under tension during anaphase, thereby facilitating the resolution of entangled sister chromatids.","title":"PICH: a DNA translocase specially adapted for processing anaphase bridge DNA."},{"docid":"24554740","text":"Cell cycle progression in mammalian cells is strictly regulated by both integrin-mediated adhesion to the extracellular matrix and by binding of growth factors to their receptors. This regulation is mediated by G1 phase cyclin-dependent kinases (CDKs), which are downstream of signaling pathways under the integrated control of both integrins and growth factor receptors. Recent advances demonstrate a surprisingly diverse array of integrin-dependent signals that are channeled into the regulation of the G1 phase CDKs. Regulation of cyclin D1 by the ERK pathway may provide a paradigm for understanding how cell adhesion can determine cell cycle progression.","title":"Integrins and cell proliferation: regulation of cyclin-dependent kinases via cytoplasmic signaling pathways."},{"docid":"18231257","text":"The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here, we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases.","title":"Dynamic control of excitatory synapse development by a Rac1 GEF/GAP regulatory complex."},{"docid":"17805221","text":"Sport fishermen keep tension on their lines to prevent hooked fish from releasing. A molecular version of this angler's trick, operating at kinetochores, ensures accuracy during mitosis: the mitotic spindle attaches randomly to chromosomes and then correctly bioriented attachments are stabilized due to the tension exerted on them by opposing microtubules. Incorrect attachments, which lack tension, are unstable and release quickly, allowing another chance for biorientation. Stabilization of molecular interactions by tension also occurs in other physiological contexts, such as cell adhesion, motility, hemostasis, and tissue morphogenesis. Here, we review models for the stabilization of kinetochore attachments with an eye toward emerging models for other force-activated systems. Although attention in the mitosis field has focused mainly on one kinase-based mechanism, multiple mechanisms may act together to stabilize properly bioriented kinetochores and some principles governing other tension-sensitive systems may also apply to kinetochores.","title":"Catch and release: how do kinetochores hook the right microtubules during mitosis?"},{"docid":"2988714","text":"Local translation mediates axonal responses to Semaphorin3A (Sema3A) and other guidance cues. However, only a subset of the axonal proteome is locally synthesized, whereas most proteins are trafficked from the soma. The reason why only specific proteins are locally synthesized is unknown. Here we show that local protein synthesis and degradation are linked events in growth cones. We find that growth cones exhibit high levels of ubiquitination and that local signalling pathways trigger the ubiquitination and degradation of RhoA, a mediator of Sema3A-induced growth cone collapse. Inhibition of RhoA degradation is sufficient to remove the protein-synthesis requirement for Sema3A-induced growth cone collapse. In addition to RhoA, we find that locally translated proteins are the main targets of the ubiquitin-proteasome system in growth cones. Thus, local protein degradation is a major feature of growth cones and creates a requirement for local translation to replenish proteins needed to maintain growth cone responses.","title":"Coupled local translation and degradation regulate growth cone collapse"}],"string":"[\n {\n \"docid\": \"33076846\",\n \"text\": \"Polyploidization can precede the development of aneuploidy in cancer. Polyploidization in megakaryocytes (Mks), in contrast, is a highly controlled developmental process critical for efficient platelet production via unknown mechanisms. Using primary cells, we demonstrate that the guanine exchange factors GEF-H1 and ECT2, which are often overexpressed in cancer and are essential for RhoA activation during cytokinesis, must be downregulated for Mk polyploidization. The first (2N-4N) endomitotic cycle requires GEF-H1 downregulation, whereas subsequent cycles (>4N) require ECT2 downregulation. Exogenous expression of both GEF-H1 and ECT2 prevents endomitosis, resulting in proliferation of 2N Mks. Furthermore, we have shown that the mechanism by which polyploidization is prevented in Mks lacking Mkl1, which is mutated in megakaryocytic leukemia, is via elevated GEF-H1 expression; shRNA-mediated GEF-H1 knockdown alone rescues this ploidy defect. These mechanistic insights enhance our understanding of normal versus malignant megakaryocytopoiesis, as well as aberrant mitosis in aneuploid cancers.\",\n \"title\": \"Role of RhoA-specific guanine exchange factors in regulation of endomitosis in megakaryocytes.\"\n },\n {\n \"docid\": \"24881307\",\n \"text\": \"Synapses are specialized cell-cell contacts that mediate communication between neurons. Most excitatory synapses in the brain are housed on dendritic spines, small actin-rich protrusions extending from dendrites. During development and in response to environmental stimuli, spines undergo marked changes in shape and number thought to underlie processes like learning and memory. Improper spine development, in contrast, likely impedes information processing in the brain, since spine abnormalities are associated with numerous brain disorders. Elucidating the mechanisms that regulate the formation and plasticity of spines and their resident synapses is therefore crucial to our understanding of cognition and disease. Rho-family GTPases, key regulators of the actin cytoskeleton, play essential roles in orchestrating the development and remodeling of spines and synapses. Precise spatio-temporal regulation of Rho GTPase activity is critical for their function, since aberrant Rho GTPase signaling can cause spine and synapse defects as well as cognitive impairments. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and inhibited by GTPase-activating proteins (GAPs). We propose that Rho-family GEFs and GAPs provide the spatiotemporal regulation and signaling specificity necessary for proper Rho GTPase function based on the following features they possess: (i) existence of multiple GEFs and GAPs per Rho GTPase, (ii) developmentally regulated expression, (iii) discrete localization, (iv) ability to bind to and organize specific signaling networks, and (v) tightly regulated activity, perhaps involving GEF/GAP interactions. Recent studies describe several Rho-family GEFs and GAPs that uniquely contribute to spinogenesis and synaptogenesis. Here, we highlight several of these proteins and discuss how they occupy distinct biochemical niches critical for synaptic development.\",\n \"title\": \"Control of synapse development and plasticity by Rho GTPase regulatory proteins\"\n },\n {\n \"docid\": \"8093935\",\n \"text\": \"Sec7-related guanine nucleotide exchange factors (GEFs) initiate vesicle budding from the Golgi membrane surface by converting the GTPase ARF to a GTP-bound, membrane-associated form. Here we report the crystal structure of the catalytic Sec7 homology domain of Arno, a human GEF for ARF1, determined at 2.2 angstroms resolution. The Sec7 domain is an elongated, all-helical protein with a distinctive hydrophobic groove that is phylogenetically conserved. Structure-based mutagenesis identifies the groove and an adjacent conserved loop as the ARF-interacting surface. The sites of Sec7 domain interaction on ARF1 have subsequently been mapped, by protein footprinting experiments, to the switch 1 and switch 2 GTPase regions, leading to a model for the interaction between ARF GTPases and Sec7 domain exchange factors.\",\n \"title\": \"Structure of the Guanine Nucleotide Exchange Factor Sec7 Domain of Human Arno and Analysis of the Interaction with ARF GTPase\"\n },\n {\n \"docid\": \"14461101\",\n \"text\": \"Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp)-producing Neisseria gonorrhoeae (P(+)GC) induces an immediate recruitment of caveolin-1 (Cav1) in the host cell, which subsequently prevents bacterial internalization by triggering cytoskeletal rearrangements via downstream phosphotyrosine signaling. A broad and unbiased analysis of potential interaction partners for tyrosine-phosphorylated Cav1 revealed a direct interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role in the Cav1-mediated prevention of bacterial uptake. Our findings, which have been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing bacteria avoid host cell uptake. Further, our data establish a mechanistic link between Cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and advance our understanding of caveolin function.\",\n \"title\": \"Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements\"\n },\n {\n \"docid\": \"10530014\",\n \"text\": \"Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteopetrosis at an early age. These symptoms are consistent with but more severe than those reported for people with leukocyte adhesion deficiency III (LAD-III). Mechanistically, these symptoms arose from an inability to activate the integrins expressed on hematopoietic cells, including platelets and leukocytes. Immortalized lymphocyte cell lines isolated from the two individuals showed integrin activation defects. Several proteins previously implicated in integrin activation, including Ras-associated protein-1 (RAP1) and calcium and diacylglycerol-regulated guanine nucleotide exchange factor-1 (CALDAG-GEF1), were present and functional in these cell lines. The genetic basis for this disease was traced to a point mutation in the coding region of the KINDLIN3 (official gene symbol FERMT3) gene. When wild-type KINDLIN-3 was expressed in the immortalized lymphocytes, their integrins became responsive to activation signals. These results identify a genetic disease that severely compromises the health of the affected individuals and establish an essential role of KINDLIN-3 in integrin activation in humans. Furthermore, allogeneic bone marrow transplantation was shown to alleviate the symptoms of the disease.\",\n \"title\": \"A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans\"\n },\n {\n \"docid\": \"10669582\",\n \"text\": \"The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.\",\n \"title\": \"Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin\"\n },\n {\n \"docid\": \"14119470\",\n \"text\": \"Ran is an abundant nuclear GTPase with a clear role in nuclear transport during interphase but with roles in mitotic regulation that are less well understood. The nucleotide-binding state of Ran is regulated by a GTPase activating protein, RanGAP1, and by a guanine nucleotide exchange factor, RCC1. Ran also interacts with a guanine nucleotide dissociation inhibitor, RanBP1. RanBP1 has a high affinity for GTP-bound Ran, and it acts as a cofactor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on Ran approximately tenfold. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian cells and in Xenopus egg extracts (our unpublished observations). We investigated how increased concentrations of RanBP1 disturb mitosis. We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is added to M phase Xenopus egg extracts. We present evidence that the role of Ran in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.\",\n \"title\": \"The Ran GTPase regulates mitotic spindle assembly\"\n },\n {\n \"docid\": \"32532238\",\n \"text\": \"To understand how cells sense and adapt to mechanical stress, we applied tensional forces to magnetic microbeads bound to cell-surface integrin receptors and measured changes in bead displacement with sub-micrometer resolution using optical microscopy. Cells exhibited four types of mechanical responses: (1) an immediate viscoelastic response; (2) early adaptive behavior characterized by pulse-to-pulse attenuation in response to oscillatory forces; (3) later adaptive cell stiffening with sustained (>15 second) static stresses; and (4) a large-scale repositioning response with prolonged (>1 minute) stress. Importantly, these adaptation responses differed biochemically. The immediate and early responses were affected by chemically dissipating cytoskeletal prestress (isometric tension), whereas the later adaptive response was not. The repositioning response was prevented by inhibiting tension through interference with Rho signaling, similar to the case of the immediate and early responses, but it was also prevented by blocking mechanosensitive ion channels or by inhibiting Src tyrosine kinases. All adaptive responses were suppressed by cooling cells to 4 degrees C to slow biochemical remodeling. Thus, cells use multiple mechanisms to sense and respond to static and dynamic changes in the level of mechanical stress applied to integrins.\",\n \"title\": \"Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels.\"\n },\n {\n \"docid\": \"20943272\",\n \"text\": \"ADAM13 is a member of the disintegrin and metalloprotease protein family that is expressed on cranial neural crest cells surface and is essential for their migration. ADAM13 is an active protease that can cleave fibronectin in vitro and remodel a fibronectin substrate in vivo. Using a recombinant secreted protein containing both disintegrin and cysteine-rich domains of ADAM13, we show that this \\\"adhesive\\\" region of the protein binds directly to fibronectin. Fibronectin fusion proteins corresponding to the various functional domains were used to define the second heparin-binding domain as the ADAM13 binding site. Mutation of the syndecan-binding site (PPRR --> PPTM) within this domain abolishes binding of the recombinant disintegrin and cysteine-rich domains of ADAM13. We further show that the adhesive disintegrin and cysteine-rich domain of ADAM13 can promote cell adhesion via beta(1) integrins. This adhesion requires integrin activation and can be prevented by antibodies to the cysteine-rich domain of ADAM13 and beta(1) integrin. Finally, wild type, but not the E/A mutant of ADAM13 metalloprotease domain, can be shed from the cell surface, releasing the metalloprotease domain associated with the disintegrin and cysteine-rich domains. This suggests that ADAM13 shedding may involve its own metalloprotease activity and that the released protease may interact with both integrins and extracellular matrix proteins.\",\n \"title\": \"ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin.\"\n },\n {\n \"docid\": \"9507605\",\n \"text\": \"The transition of cell–matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II–driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein–tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136–143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force.\",\n \"title\": \"Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCKindependent mechanism\"\n },\n {\n \"docid\": \"9185195\",\n \"text\": \"AIMS The vascular endothelial growth factor (VEGF) stimulates angiogenesis by induction of vessel permeability, proliferation, and migration of endothelial cells, an important process in ischaemic diseases. ADP-ribosylation factor (ARF) nucleotide-binding site opener (ARNO) (cytohesin-2) is a guanine exchange factor important for cellular signalling through ARF GTPases. However, a role for ARNO in VEGF-dependent endothelial processes has so far not been documented. Therefore, we investigated whether ARNO has a role in VEGF-dependent activation of endothelial cells and thus vessel permeability. METHODS AND RESULTS ARNO expression was observed in endothelial cells in vitro by RT-PCR, western blotting, and immunofluorescence as well as ex vivo by immunohistochemical staining of mouse aorta. Treatment with the cytohesin inhibitor SecinH3 or with an ARNO siRNA prevented VEGF-dependent Akt activation, assessed by detection of phosphorylated Akt, and proliferation of endothelial cells in vitro, measured by methylthiazoletetrazolium (MTT) reduction. In addition, ARNO suppression reduced VEGF-induced permeability in vessels of the mouse (C57BL/6) cremaster muscle in vivo, as measured by extravasation of fluorescein isothiocyanate (FITC)-dextran. Moreover, ARNO knock-down accelerated ligand-induced reduction in vascular endothelial growth factor receptor-2 (VEGFR-2) surface expression, internalization, and degradation, as assessed by flow cytometry and western blotting, respectively. CONCLUSION Our findings indicate an important and novel role for endothelial ARNO in VEGF-dependent initiation of angiogenesis by regulation of VEGFR-2 internalization in endothelial cells, resulting in the activation of the Akt pathway, vessel permeability, and ultimately endothelial proliferation. Thus, ARNO may be a new essential player in endothelial signalling and angiogenesis.\",\n \"title\": \"ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression.\"\n },\n {\n \"docid\": \"23141360\",\n \"text\": \"The morphogenesis of developing embryos and organs relies on the ability of cells to remodel their contacts with neighbouring cells. Using quantitative modelling and laser nano-dissection, we probed the mechanics of a morphogenetic process, the elongation of Drosophila melanogaster embryos, which results from polarized cell neighbour exchanges. We show that anisotropy of cortical tension at apical cell junctions is sufficient to drive tissue elongation. We estimated its value through comparisons between in silico and in vivo data using various tissue descriptors. Nano-dissection of the actomyosin network indicates that tension is anisotropically distributed and depends on myosin II accumulation. Junction relaxation after nano-dissection also suggests that cortical elastic forces are dominant in this process. Interestingly, fluctuations in vertex position (points where three or more cells meet) facilitate neighbour exchanges. We delineate the contribution of subcellular tensile activity polarizing junction remodelling, and the permissive role of vertex fluctuations during tissue elongation.\",\n \"title\": \"Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis\"\n },\n {\n \"docid\": \"21164071\",\n \"text\": \"Integrins are membrane receptors which mediate cell-cell or cell-matrix adhesion. Integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) acts as a fibrinogen receptor of platelets and mediates platelet aggregation. Platelet activation is required for alpha IIb beta 3 to shift from noncompetent to competent for binding soluble fibrinogen. The steps involved in this transition are poorly understood. We have studied a variant of Glanzmann thrombasthenia, a congenital bleeding disorder characterized by absence of platelet aggregation and fibrinogen binding. The patient's platelets did not bind fibrinogen after platelet activation by ADP or thrombin, though his platelets contained alpha IIb beta 3. However, isolated alpha IIb beta 3 was able to bind to an Arg-Gly-Asp-Ser affinity column, and binding of soluble fibrinogen to the patient's platelets could be triggered by modulators of alpha IIb beta 3 conformation such as the Arg-Gly-Asp-Ser peptide and alpha-chymotrypsin. These data suggested that a functional Arg-Gly-Asp binding site was present within alpha IIb beta 3 and that the patient's defect was not secondary to a blockade of alpha IIb beta 3 in a noncompetent conformational state. This was evocative of a defect in the coupling between platelet activation and alpha IIb beta 3 up-regulation. We therefore sequenced the cytoplasmic domain of beta 3, following polymerase chain reaction (PCR) on platelet RNA, and found a T-->C mutation at nucleotide 2259, corresponding to a Ser-752-->Pro substitution. This mutation is likely to be responsible for the uncoupling of alpha IIb beta 3 from cellular activation because (i) it is not a polymorphism, (ii) it is the only mutation in the entire alpha IIb beta 3 sequence, and (iii) genetic analysis of the family showed that absence of the Pro-752 beta 3 allele was associated with the normal phenotype. Our data thus identify the C-terminal portion of the cytoplasmic domain of beta 3 as an intrinsic element in the coupling between alpha IIb beta 3 and platelet activation.\",\n \"title\": \"Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia.\"\n },\n {\n \"docid\": \"20313748\",\n \"text\": \"Adherens junctions (AJs), which are organized by adhesion proteins and the underlying actin cytoskeleton, probably sense pulling forces from adjacent cells and modulate opposing forces to maintain tissue integrity, but the regulatory mechanism remains unknown at the molecular level. Although the possibility that α-catenin acts as a direct linker between the membrane and the actin cytoskeleton for AJ formation and function has been minimized, here we show that α-catenin recruits vinculin, another main actin-binding protein of AJs, through force-dependent changes in α-catenin conformation. We identified regions in the α-catenin molecule that are required for its force-dependent binding of vinculin by introducing mutant α-catenin into cells and using in vitro binding assays. Fluorescence recovery after photobleaching analysis for α-catenin mobility and the existence of an antibody recognizing α-catenin in a force-dependent manner further supported the notion that α-catenin is a tension transducer that translates mechanical stimuli into a chemical response, resulting in AJ development.\",\n \"title\": \"α-Catenin as a tension transducer that induces adherens junction development\"\n },\n {\n \"docid\": \"16511863\",\n \"text\": \"BACKGROUND Although numerous signaling pathways are known to be activated in experimental cardiac hypertrophy, the molecular basis of the hypertrophic response inherent in human heart diseases remains largely unknown. Integrin-linked kinase (ILK) is a multifunctional protein kinase that physically links beta-integrins with the actin cytoskeleton, suggesting a potential mechanoreceptor role. METHODS AND RESULTS Here, we show a marked increase in ILK protein levels in hypertrophic ventricles of patients with congenital and acquired outflow tract obstruction. This increase in ILK was associated with activation of the Rho family guanine triphosphatases, Rac1 and Cdc42, and known hypertrophic signaling kinases, including extracellular signal-related kinases (ERK1/2) and p70 S6 kinase. Transgenic mice with cardiac-specific expression of a constitutively active ILK (ILK(S343D)) or wild-type ILK (ILK(WT)) exhibited a compensated ventricular hypertrophic phenotype and displayed an activation profile of guanine triphosphatases and downstream protein kinases concordant with that seen in human hypertrophy. In contrast, transgenic mice with cardiomyocyte-restricted expression of a kinase-inactive ILK (ILK(R211A)) were unable to mount a compensatory hypertrophic response to angiotensin II in vivo. CONCLUSIONS Taken together, these results identify ILK-regulated signaling as a broadly adaptive hypertrophic response mechanism relevant to a wide range of clinical heart disease.\",\n \"title\": \"Integrin-linked kinase expression is elevated in human cardiac hypertrophy and induces hypertrophy in transgenic mice.\"\n },\n {\n \"docid\": \"44640124\",\n \"text\": \"SIGNIFICANCE The extracellular matrix (ECM) fulfills essential functions in multicellular organisms. It provides the mechanical scaffold and environmental cues to cells. Upon cell attachment, the ECM signals into the cells. In this process, reactive oxygen species (ROS) are physiologically used as signalizing molecules. RECENT ADVANCES ECM attachment influences the ROS-production of cells. In turn, ROS affect the production, assembly and turnover of the ECM during wound healing and matrix remodeling. Pathological changes of ROS levels lead to excess ECM production and increased tissue contraction in fibrotic disorders and desmoplastic tumors. Integrins are cell adhesion molecules which mediate cell adhesion and force transmission between cells and the ECM. They have been identified as a target of redox-regulation by ROS. Cysteine-based redox-modifications, together with structural data, highlighted particular regions within integrin heterodimers that may be subject to redox-dependent conformational changes along with an alteration of integrin binding activity. CRITICAL ISSUES In a molecular model, a long-range disulfide-bridge within the integrin β-subunit and disulfide bridges within the genu and calf-2 domains of the integrin α-subunit may control the transition between the bent/inactive and upright/active conformation of the integrin ectodomain. These thiol-based intramolecular cross-linkages occur in the stalk domain of both integrin subunits, whereas the ligand-binding integrin headpiece is apparently unaffected by redox-regulation. FUTURE DIRECTIONS Redox-regulation of the integrin activation state may explain the effect of ROS in physiological processes. A deeper understanding of the underlying mechanism may open new prospects for the treatment of fibrotic disorders.\",\n \"title\": \"Redox-relevant aspects of the extracellular matrix and its cellular contacts via integrins.\"\n },\n {\n \"docid\": \"4662264\",\n \"text\": \"The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1). This Ser118 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro and in cells treated with epidermal growth factor (EGF) and insulin-like growth factor (IGF) in vivo. Overexpression of MAPK kinase (MAPKK) or of the guanine nucleotide binding protein Ras, both of which activate MAPK, enhanced estrogen-induced and antiestrogen (tamoxifen)-induced transcriptional activity of wild-type ER, but not that of a mutant ER with an alanine in place of Ser118. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.\",\n \"title\": \"Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase.\"\n },\n {\n \"docid\": \"23863576\",\n \"text\": \"UNLABELLED Morphological characteristics of dendritic spines form the basis of cognitive ability. However, molecular mechanisms involved in fine-tuning of spine morphology during development are not fully understood. Moreover, it is unclear whether, and to what extent, these developmental mechanisms determine the normal adult spine morphological features. Here, we provide evidence that α2-isoform of Rac-specific GTPase-activating protein α-chimaerin (α2-chimaerin) is involved in spine morphological refinement during late postnatal period, and furthermore show that this developmental α2-chimaerin function affects adult spine morphologies. We used a series of mice with global and conditional knock-out of α-chimaerin isoforms (α1-chimaerin and α2-chimaerin). α2-Chimaerin disruption, but not α1-chimaerin disruption, in the mouse results in an increased size (and density) of spines in the hippocampus. In contrast, overexpression of α2-chimaerin in developing hippocampal neurons induces a decrease of spine size. Disruption of α2-chimaerin suppressed EphA-mediated spine morphogenesis in cultured developing hippocampal neurons. α2-Chimaerin disruption that begins during the juvenile stage results in an increased size of spines in the hippocampus. Meanwhile, spine morphologies are unaltered when α2-chimaerin is deleted only in adulthood. Consistent with these spine morphological results, disruption of α2-chimaerin beginning in the juvenile stage led to an increase in contextual fear learning in adulthood; whereas contextual learning was recently shown to be unaffected when α2-chimaerin was deleted only in adulthood. Together, these results suggest that α2-chimaerin signaling in developmental stages contributes to determination of the morphological features of adult spines and establishment of normal cognitive ability. SIGNIFICANCE STATEMENT Recent studies of neurodevelopmental disorders in humans and their animal models have led to an attractive hypothesis that spine morphogenesis during development forms the basis of adult cognition. In particular, the roles of Rac and its regulators, such as Rac-specific GTPase-activating proteins (RacGAPs) and Rac guanine nucleotide exchange factors, are a topic of focus in spine morphogenesis and cognitive ability. Using a series of mice with global and conditional knock-out (KO) of RacGAP α-chimaerin isoforms (α1-chimaerin and α2-chimaerin), we provide compelling evidence demonstrating that α2-chimaerin is involved in spine morphological refinement during late postnatal development and that this developmental α2-chimaerin function affects adult spine morphologies. Furthermore, our results clearly showed that α2-chimaerin signaling during late postnatal development contributes to normal cognitive ability in adult mice.\",\n \"title\": \"Developmental RacGAP α2-Chimaerin Signaling Is a Determinant of the Morphological Features of Dendritic Spines in Adulthood.\"\n },\n {\n \"docid\": \"2060137\",\n \"text\": \"Cell-to-cell adhesions are crucial in maintaining the structural and functional integrity of cardiac cells. Little is known about the mechanosensitivity and mechanotransduction of cell-to-cell interactions. Most studies of cardiac mechanotransduction and myofibrillogenesis have focused on cell-extracellular matrix (ECM)-specific interactions. This study assesses the direct role of intercellular adhesion, specifically that of N-cadherin-mediated mechanotransduction, on the morphology and internal organization of neonatal ventricular cardiac myocytes. The results show that cadherin-mediated cell attachments are capable of eliciting a cytoskeletal network response similar to that of integrin-mediated force response and transmission, affecting myofibrillar organization, myocyte shape, and cortical stiffness. Traction forces mediated by N-cadherin were shown to be comparable to those sustained by ECM. The directional changes in predicted traction forces as a function of imposed loads (gel stiffness) provide the added evidence that N-cadherin is a mechanoresponsive adhesion receptor. Strikingly, the mechanical sensitivity response (gain) in terms of the measured cell-spread area as a function of imposed load (adhesive substrate rigidity) was consistently higher for N-cadherin-coated surfaces compared with ECM protein-coated surfaces. In addition, the cytoskeletal architecture of myocytes on an N-cadherin adhesive microenvironment was characteristically different from that on an ECM environment, suggesting that the two mechanotransductive cell adhesion systems may play both independent and complementary roles in myocyte cytoskeletal spatial organization. These results indicate that cell-to-cell-mediated force perception and transmission are involved in the organization and development of cardiac structure and function.\",\n \"title\": \"Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing.\"\n },\n {\n \"docid\": \"17997584\",\n \"text\": \"Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear. Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation.\",\n \"title\": \"Integrin αvβ8-Mediated TGF-β Activation by Effector Regulatory T Cells Is Essential for Suppression of T-Cell-Mediated Inflammation\"\n },\n {\n \"docid\": \"19912367\",\n \"text\": \"Age-related changes in the niche have long been postulated to impair the function of somatic stem cells. Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs). Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers. By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen-activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche. Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration. Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism.\",\n \"title\": \"Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice\"\n },\n {\n \"docid\": \"8698857\",\n \"text\": \"TNF expression of macrophages is under stringent translational control that depends on the p38 MAPK/MK2 pathway and the AU-rich element (ARE) in the TNF mRNA. Here, we elucidate the molecular mechanism of phosphorylation-regulated translation of TNF. We demonstrate that translation of the TNF-precursor at the ER requires expression of the ARE-binding and -stabilizing factor human antigen R (HuR) together with either activity of the p38 MAPK/MK2 pathway or the absence of the ARE-binding and -destabilizing factor tristetraprolin (TTP). We show that phosphorylation of TTP by MK2 decreases its affinity to the ARE, inhibits its ability to replace HuR, and permits HuR-mediated initiation of translation of TNF mRNA. Since translation of TTP's own mRNA is also regulated by this mechanism, an intrinsic feedback control of the inflammatory response is ensured. The phosphorylation-regulated TTP/HuR exchange at target mRNAs provides a reversible switch between unstable/non-translatable and stable/efficiently translated mRNAs.\",\n \"title\": \"The p38/MK2-Driven Exchange between Tristetraprolin and HuR Regulates AU–Rich Element–Dependent Translation\"\n },\n {\n \"docid\": \"12650610\",\n \"text\": \"We have previously shown that the integrin beta6 is neo-expressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin beta6 promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin beta6 signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin beta6 signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it. The activation of Fyn recruited and activated focal adhesion kinase to this complex. This complex was necessary to activate Shc and to couple beta6 signaling to the Raf-ERK/MAPK pathway. This pathway transcriptionally activated the matrix metalloproteinase-3 gene and promoted oral SCC cell proliferation and experimental metastasis in vivo. These findings indicate that integrin beta6 signaling activates Fyn and thus promotes oral cancer progression.\",\n \"title\": \"Alphavbeta6-Fyn signaling promotes oral cancer progression.\"\n },\n {\n \"docid\": \"25191216\",\n \"text\": \"Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gs alpha, leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin alpha v beta 3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during intramembranous but not endochondral ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos, which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for intramembranous ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gs alpha-cyclic adenosine monophosphate-c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease.\",\n \"title\": \"Periostin, a novel marker of intramembranous ossification, is expressed in fibrous dysplasia and in c-Fos-overexpressing bone lesions.\"\n },\n {\n \"docid\": \"19482914\",\n \"text\": \"Integrin-mediated platelet adhesion and aggregation are essential for sealing injured blood vessels and preventing blood loss, and excessive platelet aggregation can initiate arterial thrombosis, causing heart attacks and stroke. To ensure that platelets aggregate only at injury sites, integrins on circulating platelets exist in a low-affinity state and shift to a high-affinity state (in a process known as integrin activation or priming) after contacting a wounded vessel. The shift is mediated through binding of the cytoskeletal protein Talin to the β subunit cytoplasmic tail. Here we show that platelets lacking the adhesion plaque protein Kindlin-3 cannot activate integrins despite normal Talin expression. As a direct consequence, Kindlin-3 deficiency results in severe bleeding and resistance to arterial thrombosis. Mechanistically, Kindlin-3 can directly bind to regions of β-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis.\",\n \"title\": \"Kindlin-3 is essential for integrin activation and platelet aggregation\"\n },\n {\n \"docid\": \"13953762\",\n \"text\": \"The Plk1-interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase bridges (UFBs) in mitosis alongside a complex of DNA repair proteins, including the Bloom's syndrome protein (BLM). However, very little is known about the function of PICH or how it is recruited to UFBs. Using a combination of microfluidics, fluorescence microscopy, and optical tweezers, we have defined the properties of PICH in an in vitro model of an anaphase bridge. We show that PICH binds with a remarkably high affinity to duplex DNA, resulting in ATP-dependent protein translocation and extension of the DNA. Most strikingly, the affinity of PICH for binding DNA increases with tension-induced DNA stretching, which mimics the effect of the mitotic spindle on a UFB. PICH binding also appears to diminish force-induced DNA melting. We propose a model in which PICH recognizes and stabilizes DNA under tension during anaphase, thereby facilitating the resolution of entangled sister chromatids.\",\n \"title\": \"PICH: a DNA translocase specially adapted for processing anaphase bridge DNA.\"\n },\n {\n \"docid\": \"24554740\",\n \"text\": \"Cell cycle progression in mammalian cells is strictly regulated by both integrin-mediated adhesion to the extracellular matrix and by binding of growth factors to their receptors. This regulation is mediated by G1 phase cyclin-dependent kinases (CDKs), which are downstream of signaling pathways under the integrated control of both integrins and growth factor receptors. Recent advances demonstrate a surprisingly diverse array of integrin-dependent signals that are channeled into the regulation of the G1 phase CDKs. Regulation of cyclin D1 by the ERK pathway may provide a paradigm for understanding how cell adhesion can determine cell cycle progression.\",\n \"title\": \"Integrins and cell proliferation: regulation of cyclin-dependent kinases via cytoplasmic signaling pathways.\"\n },\n {\n \"docid\": \"18231257\",\n \"text\": \"The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here, we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases.\",\n \"title\": \"Dynamic control of excitatory synapse development by a Rac1 GEF/GAP regulatory complex.\"\n },\n {\n \"docid\": \"17805221\",\n \"text\": \"Sport fishermen keep tension on their lines to prevent hooked fish from releasing. A molecular version of this angler's trick, operating at kinetochores, ensures accuracy during mitosis: the mitotic spindle attaches randomly to chromosomes and then correctly bioriented attachments are stabilized due to the tension exerted on them by opposing microtubules. Incorrect attachments, which lack tension, are unstable and release quickly, allowing another chance for biorientation. Stabilization of molecular interactions by tension also occurs in other physiological contexts, such as cell adhesion, motility, hemostasis, and tissue morphogenesis. Here, we review models for the stabilization of kinetochore attachments with an eye toward emerging models for other force-activated systems. Although attention in the mitosis field has focused mainly on one kinase-based mechanism, multiple mechanisms may act together to stabilize properly bioriented kinetochores and some principles governing other tension-sensitive systems may also apply to kinetochores.\",\n \"title\": \"Catch and release: how do kinetochores hook the right microtubules during mitosis?\"\n },\n {\n \"docid\": \"2988714\",\n \"text\": \"Local translation mediates axonal responses to Semaphorin3A (Sema3A) and other guidance cues. However, only a subset of the axonal proteome is locally synthesized, whereas most proteins are trafficked from the soma. The reason why only specific proteins are locally synthesized is unknown. Here we show that local protein synthesis and degradation are linked events in growth cones. We find that growth cones exhibit high levels of ubiquitination and that local signalling pathways trigger the ubiquitination and degradation of RhoA, a mediator of Sema3A-induced growth cone collapse. Inhibition of RhoA degradation is sufficient to remove the protein-synthesis requirement for Sema3A-induced growth cone collapse. In addition to RhoA, we find that locally translated proteins are the main targets of the ubiquitin-proteasome system in growth cones. Thus, local protein degradation is a major feature of growth cones and creates a requirement for local translation to replenish proteins needed to maintain growth cone responses.\",\n \"title\": \"Coupled local translation and degradation regulate growth cone collapse\"\n }\n]"}}},{"rowIdx":394,"cells":{"query_id":{"kind":"string","value":"263"},"query":{"kind":"string","value":"Citrullinated proteins externalized in neutrophil extracellular traps act indirectly to disrupt the inflammatory cycle."},"positive_passages":{"kind":"list like","value":[{"docid":"11328820","text":"The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.","title":"NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis."},{"docid":"30041340","text":"BACKGROUND Histone deimination regulates gene function and contributes to antimicrobial response, allowing the formation of neutrophil extracellular traps (NETs). Deiminated proteins are target of anti-citrullinated peptides antibodies (ACPA) in rheumatoid arthritis (RA). OBJECTIVE The objective of this paper is to test the hypothesis that RA sera react with deiminated histones contained in NETs. METHODS Neutrophils from peripheral blood were stimulated with A23187 and acid treated; NETosis was induced by phorbol myristate acetate, and NET proteins were isolated. Sera were tested by immunoblot on acid extracted proteins from neutrophils and from NETs, and by ELISA on deiminated histone H4 or H4-derived peptides. Bands reactive with RA sera were excised from gels, digested with trypsin and subjected to matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) analysis, before and after derivatisation to detect citrullinated peptides. RESULTS RA sera reacted with a deiminated antigen of 11 KDa from activated neutrophils, recognised also by anti-H4 and antideiminated H4 antibodies. A similar reactivity was observed with NET proteins. The antigen from neutrophils or NETs was identified as citrullinated H4 by MALDI-TOF analysis. By ELISA, RA sera bound in vitro citrullinated H4. Citrullinated H4 14-34 and 31-50 peptides detected antibodies in 67% and 63% of RA sera and in less than 5% of controls; antibody titre was correlated with anti-CCP2. CONCLUSIONS Citrullinated H4 from activated neutrophils and NETs is a target of antibodies in RA, and synthetic citrullinated H4-derived peptides are a new substrate for ACPA detection. As NETosis can generate antigens for ACPA, these data suggest a novel connection between innate and adaptive immunity in RA.","title":"Antibodies from patients with rheumatoid arthritis target citrullinated histone 4 contained in neutrophils extracellular traps."},{"docid":"14853989","text":"Autoantibodies to DNA and histones (chromatin) are the defining antigen specificity in systemic lupus erythematosus (SLE) and related musculoskeletal disorders but the mechanisms responsible for their induction remain mysterious. That situation rapidly changed once neutrophil extracellular chromatin traps (NETs) were discovered and observed to play a conserved role in innate immune responses to a broad variety of microbial pathogens. At the center of an infectious process, neutrophils exert various antimicrobial defenses, including the release of nuclear chromatin into the extracellular space. The externalized NETs, a complex meshwork of nuclear chromatin and antimicrobial proteins, serve to immobilize and degrade microbial pathogens. Here, we critically evaluate the evidence supporting NETs versus apoptotic bodies as a source for nuclear antigens in autoimmunity. We also discuss the possibility that NET chromatin forms an essential component of immune deposits in the pathogenesis of glomerulonephritis in SLE and other autoimmune immune complex diseases.","title":"Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity"}],"string":"[\n {\n \"docid\": \"11328820\",\n \"text\": \"The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.\",\n \"title\": \"NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis.\"\n },\n {\n \"docid\": \"30041340\",\n \"text\": \"BACKGROUND Histone deimination regulates gene function and contributes to antimicrobial response, allowing the formation of neutrophil extracellular traps (NETs). Deiminated proteins are target of anti-citrullinated peptides antibodies (ACPA) in rheumatoid arthritis (RA). OBJECTIVE The objective of this paper is to test the hypothesis that RA sera react with deiminated histones contained in NETs. METHODS Neutrophils from peripheral blood were stimulated with A23187 and acid treated; NETosis was induced by phorbol myristate acetate, and NET proteins were isolated. Sera were tested by immunoblot on acid extracted proteins from neutrophils and from NETs, and by ELISA on deiminated histone H4 or H4-derived peptides. Bands reactive with RA sera were excised from gels, digested with trypsin and subjected to matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) analysis, before and after derivatisation to detect citrullinated peptides. RESULTS RA sera reacted with a deiminated antigen of 11 KDa from activated neutrophils, recognised also by anti-H4 and antideiminated H4 antibodies. A similar reactivity was observed with NET proteins. The antigen from neutrophils or NETs was identified as citrullinated H4 by MALDI-TOF analysis. By ELISA, RA sera bound in vitro citrullinated H4. Citrullinated H4 14-34 and 31-50 peptides detected antibodies in 67% and 63% of RA sera and in less than 5% of controls; antibody titre was correlated with anti-CCP2. CONCLUSIONS Citrullinated H4 from activated neutrophils and NETs is a target of antibodies in RA, and synthetic citrullinated H4-derived peptides are a new substrate for ACPA detection. As NETosis can generate antigens for ACPA, these data suggest a novel connection between innate and adaptive immunity in RA.\",\n \"title\": \"Antibodies from patients with rheumatoid arthritis target citrullinated histone 4 contained in neutrophils extracellular traps.\"\n },\n {\n \"docid\": \"14853989\",\n \"text\": \"Autoantibodies to DNA and histones (chromatin) are the defining antigen specificity in systemic lupus erythematosus (SLE) and related musculoskeletal disorders but the mechanisms responsible for their induction remain mysterious. That situation rapidly changed once neutrophil extracellular chromatin traps (NETs) were discovered and observed to play a conserved role in innate immune responses to a broad variety of microbial pathogens. At the center of an infectious process, neutrophils exert various antimicrobial defenses, including the release of nuclear chromatin into the extracellular space. The externalized NETs, a complex meshwork of nuclear chromatin and antimicrobial proteins, serve to immobilize and degrade microbial pathogens. Here, we critically evaluate the evidence supporting NETs versus apoptotic bodies as a source for nuclear antigens in autoimmunity. We also discuss the possibility that NET chromatin forms an essential component of immune deposits in the pathogenesis of glomerulonephritis in SLE and other autoimmune immune complex diseases.\",\n \"title\": \"Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"17967608","text":"Neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs). We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation. However, the role of PAD4 in NET-mediated bacterial trapping and killing has not been tested. Here, we use PAD4 knockout mice to show that PAD4 is essential for NET-mediated antibacterial function. Unlike PAD4(+/+) neutrophils, PAD4(-/-) neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. In a mouse infectious disease model of necrotizing fasciitis, PAD4(-/-) mice are more susceptible to bacterial infection than PAD4(+/+) mice due to a lack of NET formation. Moreover, we found that citrullination decreased the bacterial killing activity of histones and nucleosomes, which suggests that PAD4 mainly plays a role in chromatin decondensation to form NETs instead of increasing histone-mediated bacterial killing. Our results define a role for histone hypercitrullination in innate immunity during bacterial infection.","title":"PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps"},{"docid":"28149602","text":"PURPOSE OF REVIEW Recent discoveries implicate neutrophils as important regulators of innate and adaptive immunity and in the development of organ damage in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). RECENT FINDINGS Various putative SLE biomarkers are neutrophil-related, including neutrophil granular proteins and histones undergoing post-translational modifications during neutrophil extracellular trap (NET) formation. In the bone marrow, lupus neutrophils can drive B and T cell abnormalities, at least in part, by their enhanced production of type-I interferons, tumor necrosis factor-alpha (TNFα) and the B-cell stimulating factors B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Lupus neutrophils and, in particular, lupus low-density granulocytes (a distinct pathogenic subset) display epigenetic modifications and genomic alterations that may be relevant to their deleterious roles in SLE. Proteins and enzymes externalized by lupus NETs can affect vascular health by inducing endothelial apoptosis and oxidizing lipoproteins. Hampering NET formation through peptidylarginine deiminase inhibitors abrogates lupus phenotype and atherosclerosis in murine studies. SUMMARY Recent discoveries support the notion that neutrophils, low-density granulocytes and aberrant NET formation and clearance play important roles in lupus pathogenesis. Future studies should focus on how to selectively target these immunostimulatory pathways in this disease.","title":"The role of neutrophils in the pathogenesis of systemic lupus erythematosus."},{"docid":"36089763","text":"Neutrophils phagocytose and kill microbes upon phagolysosomal fusion. Recently we found that activated neutrophils form extracellular fibres that consist of granule proteins and chromatin. These neutrophil extracellular traps (NETs) degrade virulence factors and kill Gram positive and negative bacteria. Here we show for the first time that Candida albicans, a eukaryotic pathogen, induces NET-formation and is susceptible to NET-mediated killing. C. albicans is the predominant aetiologic agent of fungal infections in humans, particularly in immunocompromised hosts. One major virulence trait of C. albicans is its ability to reversibly switch from singular budding cells to filamentous hyphae. We demonstrate that NETs kill both yeast-form and hyphal cells, and that granule components mediate fungal killing. Taken together our data indicate that neutrophils trap and kill ascomycetous yeasts by forming NETs.","title":"Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms."},{"docid":"1049501","text":"Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.","title":"Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease"},{"docid":"3330111","text":"Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, more recent evidence has extended the functions of these cells. The newly discovered repertoire of effector molecules in the neutrophil armamentarium includes a broad array of cytokines, extracellular traps and effector molecules of the humoral arm of the innate immune system. In addition, neutrophils are involved in the activation, regulation and effector functions of innate and adaptive immune cells. Accordingly, neutrophils have a crucial role in the pathogenesis of a broad range of diseases, including infections caused by intracellular pathogens, autoimmunity, chronic inflammation and cancer.","title":"Neutrophils in the activation and regulation of innate and adaptive immunity"},{"docid":"29399239","text":"Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed \"NETosis. \" Here we review our understanding of how NETs are made, their function in infections and as danger signals, and their emerging importance in autoimmunity and coagulation.","title":"Neutrophil extracellular traps: Is immunity the second function of chromatin?"},{"docid":"1800734","text":"Upon activation, neutrophils release DNA fibers decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). Although NETs are bactericidal and contribute to innate host defense, excessive NET formation has been linked to the pathogenesis of autoinflammatory diseases. However, the mechanisms regulating NET formation, particularly during chronic inflammation, are poorly understood. Here we show that the G protein–coupled receptor (GPCR) CXCR2 mediates NET formation. Downstream analyses showed that CXCR2-mediated NET formation was independent of NADPH oxidase and involved Src family kinases. We show the pathophysiological relevance of this mechanism in cystic fibrosis lung disease, characterized by chronic neutrophilic inflammation. We found abundant NETs in airway fluids of individuals with cystic fibrosis and mouse cystic fibrosis lung disease, and NET amounts correlated with impaired obstructive lung function. Pulmonary blockade of CXCR2 by intra-airway delivery of small-molecule antagonists inhibited NET formation and improved lung function in vivo without affecting neutrophil recruitment, proteolytic activity or antibacterial host defense. These studies establish CXCR2 as a receptor mediating NADPH oxidase–independent NET formation and provide evidence that this GPCR pathway is operative and druggable in cystic fibrosis lung disease.","title":"CXCR2 mediates NADPH oxidase–independent neutrophil extracellular trap formation in cystic fibrosis airway inflammation"},{"docid":"9878167","text":"Neutrophil extracellular traps (NETs) represent extracellular structures able to bind and kill microorganisms. It is believed that they are generated by neutrophils undergoing cell death, allowing these dying or dead cells to kill microbes. We show that, following priming with granulocyte/macrophage colony-stimulating factor (GM-CSF) and subsequent short-term toll-like receptor 4 (TLR4) or complement factor 5a (C5a) receptor stimulation, viable neutrophils are able to generate NETs. Strikingly, NETs formed by living cells contain mitochondrial, but no nuclear, DNA. Pharmacological or genetic approaches to block reactive oxygen species (ROS) production suggested that NET formation is ROS dependent. Moreover, neutrophil populations stimulated with GM-CSF and C5a showed increased survival compared with resting neutrophils, which did not generate NETs. In conclusion, mitochondrial DNA release by neutrophils and NET formation do not require neutrophil death and do also not limit the lifespan of these cells.","title":"Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps"},{"docid":"43054703","text":"Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.","title":"A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus."},{"docid":"24928817","text":"The initiation and progression of adult-onset periodontitis has been associated with infection of the gingival sulcus by Porphyromonas gingivalis. This organism utilizes a multitude of virulence factors to evade host defenses as it establishes itself as one of the predominant pathogens in periodontal pockets. A feature common to many other oral pathogens is the production of ammonia due to its protective effect during acidic cleansing cycles in the mouth. Additionally, ammonia production by P. gingivalis has been proposed as a virulence factor due to its negative effects on neutrophil function. In this study, we describe the first purification of a peptidylarginine deiminase (PAD) from a prokaryote. PAD exhibits biochemical characteristics and properties that suggest that it may be a virulence agent. PAD deiminates the guanidino group of carboxyl-terminal arginine residues on a variety of peptides, including the vasoregulatory peptide-hormone bradykinin, to yield ammonia and a citrulline residue. The soluble protein has an apparent mass of 46 kDa, while the DNA sequence predicts a full-length protein of 61.7 kDa. PAD is optimally active at 55 degrees C, stable at low pH, and shows the greatest activity above pH 9.0. Interestingly, in the presence of stabilizing factors, PAD is resistant to limited proteolysis and retains significant activity after short-term boiling. We propose that PAD, acting in concert with arginine-specific proteinases from P. gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses.","title":"Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase."},{"docid":"28015516","text":"Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a breakdown of tolerance to nuclear antigens and the development of immune complexes. Genomic approaches have shown that human SLE leukocytes homogeneously express type I interferon (IFN)-induced and neutrophil-related transcripts. Increased production and/or bioavailability of IFN-α and associated alterations in dendritic cell (DC) homeostasis have been linked to lupus pathogenesis. Although neutrophils have long been shown to be associated with lupus, their potential role in disease pathogenesis remains elusive. Here, we show that mature SLE neutrophils are primed in vivo by type I IFN and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). SLE NETs contain DNA as well as large amounts of LL37 and HMGB1, neutrophil proteins that facilitate the uptake and recognition of mammalian DNA by plasmacytoid DCs (pDCs). Indeed, SLE NETs activate pDCs to produce high levels of IFN-α in a DNA- and TLR9 (Toll-like receptor 9)-dependent manner. Our results reveal an unsuspected role for neutrophils in SLE pathogenesis and identify a novel link between nucleic acid-recognizing antibodies and type I IFN production in this disease.","title":"Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus."},{"docid":"20459964","text":"Neutrophil is a key cell in pathophysiology of granulomatosis with polyangiitis. Recently, neutrophil extracellular traps were described in this disease. Mitochondrial DNA is also released during traps formation. We measured circulating cell-free mitochondrial and genomic DNA in serum of patients with granulomatosis with polyangiitis. Subjects with the disease (14 active and 11 in remission stage) and 10 healthy controls were enrolled. Quantitative real-time polymerase chain reaction (PCR) was used to measure 79 base pairs (bp) and 230 bp mtDNA fragments. Alu repeats were quantified to evaluate abundance of nuclear DNA in serum at the presence of plasmid control. Both fragments of mtDNA (79 bp and 230 bp) and genomic DNA were elevated significantly in granulomatosis with polyangiitis compared to controls. Only the shorter 79 bp mtDNA correlated with active stage of granulomatosis with polyangiitis and clinical symptoms. A mechanism of extracellular release of mitochondrial DNA accompanies the active stage of the disease. Circulating mtDNA is extremely high in untreated patients. This suggests that biomarker properties of mtDNA are useful for monitoring of treatment.","title":"Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis."},{"docid":"52925737","text":"BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.","title":"Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration"},{"docid":"17741440","text":"Small-vessel vasculitis (SVV) is a chronic autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). Here we show that chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). Deposition of NETs in inflamed kidneys and circulating MPO-DNA complexes suggest that NET formation triggers vasculitis and promotes the autoimmune response against neutrophil components in individuals with SVV.","title":"Netting neutrophils in autoimmune small-vessel vasculitis"},{"docid":"2236768","text":"Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask.","title":"Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo"},{"docid":"46517055","text":"Uncontrolled proteolysis by neutrophil serine proteases (NSPs) in lung secretions is a hallmark of cystic fibrosis (CF). We have shown that the active neutrophil elastase, protease 3, and cathepsin G in CF sputum resist inhibition in part by exogenous protease inhibitors. This resistance may be due to their binding to neutrophil extracellular traps (NETs) secreted by the activated neutrophils in CF sputum and to genomic DNA released from senescent and dead neutrophils. Treating CF sputum with DNase dramatically increases its elastase activity, which can then be stoichiometrically inhibited by exogenous elastase inhibitors. However, DNase treatment does not increase the activities of protease 3 and cathepsin G, indicating their different distribution and/or binding in CF sputum. Purified blood neutrophils secrete NETs when stimulated by the opportunistic CF bacteria Pseudomonas aeruginosa and Staphylococcus aureus. The activities of the three proteases were unchanged in these conditions, but subsequent DNase treatment produced a dramatic increase in all three proteolytic activities. Neutrophils activated with a calcium ionophore did not secrete NETs but released huge amounts of active proteases whose activities were not modified by DNase. We conclude that NETs are reservoirs of active proteases that protect them from inhibition and maintain them in a rapidly mobilizable status. Combining the effects of protease inhibitors with that of DNA-degrading agents could counter the deleterious proteolytic effects of NSPs in CF lung secretions.","title":"Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum."},{"docid":"28712203","text":"Elastases of both the neutrophil and macrophage have been implicated in lung disease initiation and progression. Although it is unlikely that these proteases evolved for the purpose of injuring lung tissue, the elastin-rich connective tissue framework of the lungs appears to be particularly susceptible to the action of elastolytic proteases. Assuming that neutrophil elastase most likely plays a role in the migration of neutrophils toward a site of inflammation and degradation of proteins from invading organisms or other products of the inflammatory response, it is the role of inhibitors of this protease to protect normal tissues from its effects. In alpha-1 antitrypsin deficiency we find an experiment of nature that disrupts this protease-anti-protease balance, resulting in an increased risk of destructive lung disease.","title":"Neutrophil elastase-mediated lung disease."},{"docid":"13106686","text":"Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3' repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.","title":"Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing."},{"docid":"21487212","text":"Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.","title":"Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting."},{"docid":"13578199","text":"Human transglutaminase 2 (TG2), a member of a large family of enzymes that catalyze protein crosslinking, plays an important role in the extracellular matrix biology of many tissues and is implicated in the gluten-induced pathogenesis of celiac sprue. Although vertebrate transglutaminases have been studied extensively, thus far all structurally characterized members of this family have been crystallized in conformations with inaccessible active sites. We have trapped human TG2 in complex with an inhibitor that mimics inflammatory gluten peptide substrates and have solved, at 2-A resolution, its x-ray crystal structure. The inhibitor stabilizes TG2 in an extended conformation that is dramatically different from earlier transglutaminase structures. The active site is exposed, revealing that catalysis takes place in a tunnel, bridged by two tryptophan residues that separate acyl-donor from acyl-acceptor and stabilize the tetrahedral reaction intermediates. Site-directed mutagenesis was used to investigate the acyl-acceptor side of the tunnel, yielding mutants with a marked increase in preference for hydrolysis over transamidation. By providing the ability to visualize this activated conformer, our results create a foundation for understanding the catalytic as well as the non-catalytic roles of TG2 in biology, and for dissecting the process by which the autoantibody response to TG2 is induced in celiac sprue patients.","title":"Transglutaminase 2 Undergoes a Large Conformational Change upon Activation "},{"docid":"5172048","text":"Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood. One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK). Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading. Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation. We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders. Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis. Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment. These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.","title":"Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling"},{"docid":"5273056","text":"Eukaryotes have numerous checkpoint pathways to protect genome fidelity during normal cell division and in response to DNA damage. Through a screen for G2/M checkpoint regulators in zebrafish, we identified ticrr (for TopBP1-interacting, checkpoint, and replication regulator), a previously uncharacterized gene that is required to prevent mitotic entry after treatment with ionizing radiation. Ticrr deficiency is embryonic-lethal in the absence of exogenous DNA damage because it is essential for normal cell cycle progression. Specifically, the loss of ticrr impairs DNA replication and disrupts the S/M checkpoint, leading to premature mitotic entry and mitotic catastrophe. We show that the human TICRR ortholog associates with TopBP1, a known checkpoint protein and a core component of the DNA replication preinitiation complex (pre-IC), and that the TICRR-TopBP1 interaction is stable without chromatin and requires BRCT motifs essential for TopBP1's replication and checkpoint functions. Most importantly, we find that ticrr deficiency disrupts chromatin binding of pre-IC, but not prereplication complex, components. Taken together, our data show that TICRR acts in association with TopBP1 and plays an essential role in pre-IC formation. It remains to be determined whether Ticrr represents the vertebrate ortholog of the yeast pre-IC component Sld3, or a hitherto unknown metazoan replication and checkpoint regulator.","title":"A vertebrate gene, ticrr, is an essential checkpoint and replication regulator."},{"docid":"195683603","text":"Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses.","title":"Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A."},{"docid":"15248287","text":"Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.","title":"Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival"},{"docid":"20608982","text":"PURPOSE OF REVIEW As the migration of neutrophils from blood to inflamed tissues is an essential component of innate immunity and a key contributing factor to the pathogenesis of inflammatory disorders, this aspect of leukocyte biology continues to be a highly dynamic field of research. This review summarizes recent findings in this area, focusing on the mechanisms that mediate neutrophil transmigration, an area where significant progress has been made. RECENT FINDINGS The topics to be covered will include responses that are prerequisite to neutrophil migration through venular walls, such as leukocyte luminal crawling and cellular and molecular changes in leukocytes and endothelial cells (e.g. formation of protrusions) that collectively support leukocyte transendothelial cell migration. Advances in both paracellular and transcellular neutrophil migration through endothelial cells will be discussed, addressing the associated roles and regulation of expression of endothelial cell luminal and junctional adhesion molecules. Beyond the endothelium, migration through the vascular pericyte coverage and basement membrane will be reviewed. SUMMARY The unquestionable role of neutrophils in the development and progression of inflammatory conditions suggests that a better understanding of the tissue-specific and stimulus-specific mechanisms that mediate this response may identify novel pathways that could be exploited for the development of more specific anti-inflammatory interventions.","title":"Recent developments and complexities in neutrophil transmigration."},{"docid":"6417632","text":"BACKGROUND COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. METHODS To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. RESULTS Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). CONCLUSIONS Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation.","title":"Neutrophilic infiltration within the airway smooth muscle in patients with COPD."},{"docid":"10443642","text":"RNAIII is the intracellular effector of the quorum-sensing system in Staphylococcus aureus. It is one of the largest regulatory RNAs (514 nucleotides long) that are known to control the expression of a large number of virulence genes. Here, we show that the 3' domain of RNAIII coordinately represses at the post-transcriptional level, the expression of mRNAs that encode a class of virulence factors that act early in the infection process. We demonstrate that the 3' domain acts primarily as an antisense RNA and rapidly anneals to these mRNAs, forming long RNA duplexes. The interaction between RNAIII and the mRNAs results in repression of translation initiation and triggers endoribonuclease III hydrolysis. These processes are followed by rapid depletion of the mRNA pool. In addition, we show that RNAIII and its 3' domain mediate translational repression of rot mRNA through a limited number of base pairings involving two loop-loop interactions. Since Rot is a transcriptional regulatory protein, we proposed that RNAIII indirectly acts on many downstream genes, resulting in the activation of the synthesis of several exoproteins. These data emphasize the multitude of regulatory steps affected by RNAIII and its 3' domain in establishing a network of S. aureus virulence factors.","title":"Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism."},{"docid":"12058271","text":"The bone marrow is the primary site for neutrophil production and release into the circulation. Because the CXC chemokine receptor-4/stromal derived factor-1 (CXCR4/SDF-1) axis plays a central role in the interactions of hematopoietic stem cells, lymphocytes, and developing neutrophils in the marrow, we investigated whether reciprocal CXCR4-dependent mechanisms might be involved in neutrophil release and subsequent return to the marrow following circulation. Neutralizing antibody to CXCR4 reduced marrow retention of infused neutrophils (45.7% +/- 0.5% to 6.9% +/- 0.5%) and was found to mobilize neutrophils from marrow (34.4% +/- 4.4%). Neutrophil CXCR4 expression and SDF-1-induced calcium flux decreased with maturation and activation of the cells, corresponding to the decreased marrow homing associated with these characteristics in vivo. Infusion of the inflammatory mediator and CXCR2 ligand KC led to mobilization of neutrophils from marrow by itself and was augmented 3-fold by low doses of CXCR4-blocking antibody that otherwise had no mobilizing effect. Examination of KC and SDF-1 calcium signaling demonstrated that the effect of KC may, in part, be due to heterologous desensitization to SDF-1. These results suggest that the CXCR4/SDF-1 axis is critical in circulating neutrophil homeostasis and that it may participate in the rapid release of neutrophils from the marrow during inflammation through a novel interaction with inflammatory CXC chemokines.","title":"Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis."},{"docid":"14119470","text":"Ran is an abundant nuclear GTPase with a clear role in nuclear transport during interphase but with roles in mitotic regulation that are less well understood. The nucleotide-binding state of Ran is regulated by a GTPase activating protein, RanGAP1, and by a guanine nucleotide exchange factor, RCC1. Ran also interacts with a guanine nucleotide dissociation inhibitor, RanBP1. RanBP1 has a high affinity for GTP-bound Ran, and it acts as a cofactor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on Ran approximately tenfold. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian cells and in Xenopus egg extracts (our unpublished observations). We investigated how increased concentrations of RanBP1 disturb mitosis. We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is added to M phase Xenopus egg extracts. We present evidence that the role of Ran in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.","title":"The Ran GTPase regulates mitotic spindle assembly"},{"docid":"21395936","text":"Chronic obstructive pulmonary disease (COPD) is a chronic airway disorder characterized by obstructive airflow limitation which is not completely reversible with treatment. Inflammatory changes in the peripheral airways, especially those with the diameter less than 2mm (so-called small airway disease) have been speculated to be initial steps of COPD. And so it must be quite clear that neutrophils and macrophages play an essential role in the pathogenesis of these lesions. Studies with bronchoalveolar lavage demonstrated an increase in neutrophil numbers and the neutrophil chemoattractant interleukin-8. Recent studies demonstrated that neutrophils and macrophages are increased and contain a variety of proteases, which are involved in cell infiltration and activation. Studies with gene-engineered animals and anti-cytokine treatment will facilitate better understanding the role of neutrophils and macrophages, and eventual novel therapy.","title":"[Neutrophils and macrophages related to the pathogenesis and disease development of chronic obstructive pulmonary disease by the inflammatory reaction]."}],"string":"[\n {\n \"docid\": \"17967608\",\n \"text\": \"Neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs). We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation. However, the role of PAD4 in NET-mediated bacterial trapping and killing has not been tested. Here, we use PAD4 knockout mice to show that PAD4 is essential for NET-mediated antibacterial function. Unlike PAD4(+/+) neutrophils, PAD4(-/-) neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. In a mouse infectious disease model of necrotizing fasciitis, PAD4(-/-) mice are more susceptible to bacterial infection than PAD4(+/+) mice due to a lack of NET formation. Moreover, we found that citrullination decreased the bacterial killing activity of histones and nucleosomes, which suggests that PAD4 mainly plays a role in chromatin decondensation to form NETs instead of increasing histone-mediated bacterial killing. Our results define a role for histone hypercitrullination in innate immunity during bacterial infection.\",\n \"title\": \"PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps\"\n },\n {\n \"docid\": \"28149602\",\n \"text\": \"PURPOSE OF REVIEW Recent discoveries implicate neutrophils as important regulators of innate and adaptive immunity and in the development of organ damage in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). RECENT FINDINGS Various putative SLE biomarkers are neutrophil-related, including neutrophil granular proteins and histones undergoing post-translational modifications during neutrophil extracellular trap (NET) formation. In the bone marrow, lupus neutrophils can drive B and T cell abnormalities, at least in part, by their enhanced production of type-I interferons, tumor necrosis factor-alpha (TNFα) and the B-cell stimulating factors B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Lupus neutrophils and, in particular, lupus low-density granulocytes (a distinct pathogenic subset) display epigenetic modifications and genomic alterations that may be relevant to their deleterious roles in SLE. Proteins and enzymes externalized by lupus NETs can affect vascular health by inducing endothelial apoptosis and oxidizing lipoproteins. Hampering NET formation through peptidylarginine deiminase inhibitors abrogates lupus phenotype and atherosclerosis in murine studies. SUMMARY Recent discoveries support the notion that neutrophils, low-density granulocytes and aberrant NET formation and clearance play important roles in lupus pathogenesis. Future studies should focus on how to selectively target these immunostimulatory pathways in this disease.\",\n \"title\": \"The role of neutrophils in the pathogenesis of systemic lupus erythematosus.\"\n },\n {\n \"docid\": \"36089763\",\n \"text\": \"Neutrophils phagocytose and kill microbes upon phagolysosomal fusion. Recently we found that activated neutrophils form extracellular fibres that consist of granule proteins and chromatin. These neutrophil extracellular traps (NETs) degrade virulence factors and kill Gram positive and negative bacteria. Here we show for the first time that Candida albicans, a eukaryotic pathogen, induces NET-formation and is susceptible to NET-mediated killing. C. albicans is the predominant aetiologic agent of fungal infections in humans, particularly in immunocompromised hosts. One major virulence trait of C. albicans is its ability to reversibly switch from singular budding cells to filamentous hyphae. We demonstrate that NETs kill both yeast-form and hyphal cells, and that granule components mediate fungal killing. Taken together our data indicate that neutrophils trap and kill ascomycetous yeasts by forming NETs.\",\n \"title\": \"Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms.\"\n },\n {\n \"docid\": \"1049501\",\n \"text\": \"Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.\",\n \"title\": \"Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease\"\n },\n {\n \"docid\": \"3330111\",\n \"text\": \"Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, more recent evidence has extended the functions of these cells. The newly discovered repertoire of effector molecules in the neutrophil armamentarium includes a broad array of cytokines, extracellular traps and effector molecules of the humoral arm of the innate immune system. In addition, neutrophils are involved in the activation, regulation and effector functions of innate and adaptive immune cells. Accordingly, neutrophils have a crucial role in the pathogenesis of a broad range of diseases, including infections caused by intracellular pathogens, autoimmunity, chronic inflammation and cancer.\",\n \"title\": \"Neutrophils in the activation and regulation of innate and adaptive immunity\"\n },\n {\n \"docid\": \"29399239\",\n \"text\": \"Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed \\\"NETosis. \\\" Here we review our understanding of how NETs are made, their function in infections and as danger signals, and their emerging importance in autoimmunity and coagulation.\",\n \"title\": \"Neutrophil extracellular traps: Is immunity the second function of chromatin?\"\n },\n {\n \"docid\": \"1800734\",\n \"text\": \"Upon activation, neutrophils release DNA fibers decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). Although NETs are bactericidal and contribute to innate host defense, excessive NET formation has been linked to the pathogenesis of autoinflammatory diseases. However, the mechanisms regulating NET formation, particularly during chronic inflammation, are poorly understood. Here we show that the G protein–coupled receptor (GPCR) CXCR2 mediates NET formation. Downstream analyses showed that CXCR2-mediated NET formation was independent of NADPH oxidase and involved Src family kinases. We show the pathophysiological relevance of this mechanism in cystic fibrosis lung disease, characterized by chronic neutrophilic inflammation. We found abundant NETs in airway fluids of individuals with cystic fibrosis and mouse cystic fibrosis lung disease, and NET amounts correlated with impaired obstructive lung function. Pulmonary blockade of CXCR2 by intra-airway delivery of small-molecule antagonists inhibited NET formation and improved lung function in vivo without affecting neutrophil recruitment, proteolytic activity or antibacterial host defense. These studies establish CXCR2 as a receptor mediating NADPH oxidase–independent NET formation and provide evidence that this GPCR pathway is operative and druggable in cystic fibrosis lung disease.\",\n \"title\": \"CXCR2 mediates NADPH oxidase–independent neutrophil extracellular trap formation in cystic fibrosis airway inflammation\"\n },\n {\n \"docid\": \"9878167\",\n \"text\": \"Neutrophil extracellular traps (NETs) represent extracellular structures able to bind and kill microorganisms. It is believed that they are generated by neutrophils undergoing cell death, allowing these dying or dead cells to kill microbes. We show that, following priming with granulocyte/macrophage colony-stimulating factor (GM-CSF) and subsequent short-term toll-like receptor 4 (TLR4) or complement factor 5a (C5a) receptor stimulation, viable neutrophils are able to generate NETs. Strikingly, NETs formed by living cells contain mitochondrial, but no nuclear, DNA. Pharmacological or genetic approaches to block reactive oxygen species (ROS) production suggested that NET formation is ROS dependent. Moreover, neutrophil populations stimulated with GM-CSF and C5a showed increased survival compared with resting neutrophils, which did not generate NETs. In conclusion, mitochondrial DNA release by neutrophils and NET formation do not require neutrophil death and do also not limit the lifespan of these cells.\",\n \"title\": \"Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps\"\n },\n {\n \"docid\": \"43054703\",\n \"text\": \"Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.\",\n \"title\": \"A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus.\"\n },\n {\n \"docid\": \"24928817\",\n \"text\": \"The initiation and progression of adult-onset periodontitis has been associated with infection of the gingival sulcus by Porphyromonas gingivalis. This organism utilizes a multitude of virulence factors to evade host defenses as it establishes itself as one of the predominant pathogens in periodontal pockets. A feature common to many other oral pathogens is the production of ammonia due to its protective effect during acidic cleansing cycles in the mouth. Additionally, ammonia production by P. gingivalis has been proposed as a virulence factor due to its negative effects on neutrophil function. In this study, we describe the first purification of a peptidylarginine deiminase (PAD) from a prokaryote. PAD exhibits biochemical characteristics and properties that suggest that it may be a virulence agent. PAD deiminates the guanidino group of carboxyl-terminal arginine residues on a variety of peptides, including the vasoregulatory peptide-hormone bradykinin, to yield ammonia and a citrulline residue. The soluble protein has an apparent mass of 46 kDa, while the DNA sequence predicts a full-length protein of 61.7 kDa. PAD is optimally active at 55 degrees C, stable at low pH, and shows the greatest activity above pH 9.0. Interestingly, in the presence of stabilizing factors, PAD is resistant to limited proteolysis and retains significant activity after short-term boiling. We propose that PAD, acting in concert with arginine-specific proteinases from P. gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses.\",\n \"title\": \"Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase.\"\n },\n {\n \"docid\": \"28015516\",\n \"text\": \"Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a breakdown of tolerance to nuclear antigens and the development of immune complexes. Genomic approaches have shown that human SLE leukocytes homogeneously express type I interferon (IFN)-induced and neutrophil-related transcripts. Increased production and/or bioavailability of IFN-α and associated alterations in dendritic cell (DC) homeostasis have been linked to lupus pathogenesis. Although neutrophils have long been shown to be associated with lupus, their potential role in disease pathogenesis remains elusive. Here, we show that mature SLE neutrophils are primed in vivo by type I IFN and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). SLE NETs contain DNA as well as large amounts of LL37 and HMGB1, neutrophil proteins that facilitate the uptake and recognition of mammalian DNA by plasmacytoid DCs (pDCs). Indeed, SLE NETs activate pDCs to produce high levels of IFN-α in a DNA- and TLR9 (Toll-like receptor 9)-dependent manner. Our results reveal an unsuspected role for neutrophils in SLE pathogenesis and identify a novel link between nucleic acid-recognizing antibodies and type I IFN production in this disease.\",\n \"title\": \"Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus.\"\n },\n {\n \"docid\": \"20459964\",\n \"text\": \"Neutrophil is a key cell in pathophysiology of granulomatosis with polyangiitis. Recently, neutrophil extracellular traps were described in this disease. Mitochondrial DNA is also released during traps formation. We measured circulating cell-free mitochondrial and genomic DNA in serum of patients with granulomatosis with polyangiitis. Subjects with the disease (14 active and 11 in remission stage) and 10 healthy controls were enrolled. Quantitative real-time polymerase chain reaction (PCR) was used to measure 79 base pairs (bp) and 230 bp mtDNA fragments. Alu repeats were quantified to evaluate abundance of nuclear DNA in serum at the presence of plasmid control. Both fragments of mtDNA (79 bp and 230 bp) and genomic DNA were elevated significantly in granulomatosis with polyangiitis compared to controls. Only the shorter 79 bp mtDNA correlated with active stage of granulomatosis with polyangiitis and clinical symptoms. A mechanism of extracellular release of mitochondrial DNA accompanies the active stage of the disease. Circulating mtDNA is extremely high in untreated patients. This suggests that biomarker properties of mtDNA are useful for monitoring of treatment.\",\n \"title\": \"Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis.\"\n },\n {\n \"docid\": \"52925737\",\n \"text\": \"BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.\",\n \"title\": \"Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration\"\n },\n {\n \"docid\": \"17741440\",\n \"text\": \"Small-vessel vasculitis (SVV) is a chronic autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). Here we show that chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). Deposition of NETs in inflamed kidneys and circulating MPO-DNA complexes suggest that NET formation triggers vasculitis and promotes the autoimmune response against neutrophil components in individuals with SVV.\",\n \"title\": \"Netting neutrophils in autoimmune small-vessel vasculitis\"\n },\n {\n \"docid\": \"2236768\",\n \"text\": \"Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask.\",\n \"title\": \"Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo\"\n },\n {\n \"docid\": \"46517055\",\n \"text\": \"Uncontrolled proteolysis by neutrophil serine proteases (NSPs) in lung secretions is a hallmark of cystic fibrosis (CF). We have shown that the active neutrophil elastase, protease 3, and cathepsin G in CF sputum resist inhibition in part by exogenous protease inhibitors. This resistance may be due to their binding to neutrophil extracellular traps (NETs) secreted by the activated neutrophils in CF sputum and to genomic DNA released from senescent and dead neutrophils. Treating CF sputum with DNase dramatically increases its elastase activity, which can then be stoichiometrically inhibited by exogenous elastase inhibitors. However, DNase treatment does not increase the activities of protease 3 and cathepsin G, indicating their different distribution and/or binding in CF sputum. Purified blood neutrophils secrete NETs when stimulated by the opportunistic CF bacteria Pseudomonas aeruginosa and Staphylococcus aureus. The activities of the three proteases were unchanged in these conditions, but subsequent DNase treatment produced a dramatic increase in all three proteolytic activities. Neutrophils activated with a calcium ionophore did not secrete NETs but released huge amounts of active proteases whose activities were not modified by DNase. We conclude that NETs are reservoirs of active proteases that protect them from inhibition and maintain them in a rapidly mobilizable status. Combining the effects of protease inhibitors with that of DNA-degrading agents could counter the deleterious proteolytic effects of NSPs in CF lung secretions.\",\n \"title\": \"Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum.\"\n },\n {\n \"docid\": \"28712203\",\n \"text\": \"Elastases of both the neutrophil and macrophage have been implicated in lung disease initiation and progression. Although it is unlikely that these proteases evolved for the purpose of injuring lung tissue, the elastin-rich connective tissue framework of the lungs appears to be particularly susceptible to the action of elastolytic proteases. Assuming that neutrophil elastase most likely plays a role in the migration of neutrophils toward a site of inflammation and degradation of proteins from invading organisms or other products of the inflammatory response, it is the role of inhibitors of this protease to protect normal tissues from its effects. In alpha-1 antitrypsin deficiency we find an experiment of nature that disrupts this protease-anti-protease balance, resulting in an increased risk of destructive lung disease.\",\n \"title\": \"Neutrophil elastase-mediated lung disease.\"\n },\n {\n \"docid\": \"13106686\",\n \"text\": \"Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3' repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.\",\n \"title\": \"Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing.\"\n },\n {\n \"docid\": \"21487212\",\n \"text\": \"Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.\",\n \"title\": \"Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting.\"\n },\n {\n \"docid\": \"13578199\",\n \"text\": \"Human transglutaminase 2 (TG2), a member of a large family of enzymes that catalyze protein crosslinking, plays an important role in the extracellular matrix biology of many tissues and is implicated in the gluten-induced pathogenesis of celiac sprue. Although vertebrate transglutaminases have been studied extensively, thus far all structurally characterized members of this family have been crystallized in conformations with inaccessible active sites. We have trapped human TG2 in complex with an inhibitor that mimics inflammatory gluten peptide substrates and have solved, at 2-A resolution, its x-ray crystal structure. The inhibitor stabilizes TG2 in an extended conformation that is dramatically different from earlier transglutaminase structures. The active site is exposed, revealing that catalysis takes place in a tunnel, bridged by two tryptophan residues that separate acyl-donor from acyl-acceptor and stabilize the tetrahedral reaction intermediates. Site-directed mutagenesis was used to investigate the acyl-acceptor side of the tunnel, yielding mutants with a marked increase in preference for hydrolysis over transamidation. By providing the ability to visualize this activated conformer, our results create a foundation for understanding the catalytic as well as the non-catalytic roles of TG2 in biology, and for dissecting the process by which the autoantibody response to TG2 is induced in celiac sprue patients.\",\n \"title\": \"Transglutaminase 2 Undergoes a Large Conformational Change upon Activation \"\n },\n {\n \"docid\": \"5172048\",\n \"text\": \"Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood. One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK). Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading. Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation. We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders. Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis. Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment. These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.\",\n \"title\": \"Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling\"\n },\n {\n \"docid\": \"5273056\",\n \"text\": \"Eukaryotes have numerous checkpoint pathways to protect genome fidelity during normal cell division and in response to DNA damage. Through a screen for G2/M checkpoint regulators in zebrafish, we identified ticrr (for TopBP1-interacting, checkpoint, and replication regulator), a previously uncharacterized gene that is required to prevent mitotic entry after treatment with ionizing radiation. Ticrr deficiency is embryonic-lethal in the absence of exogenous DNA damage because it is essential for normal cell cycle progression. Specifically, the loss of ticrr impairs DNA replication and disrupts the S/M checkpoint, leading to premature mitotic entry and mitotic catastrophe. We show that the human TICRR ortholog associates with TopBP1, a known checkpoint protein and a core component of the DNA replication preinitiation complex (pre-IC), and that the TICRR-TopBP1 interaction is stable without chromatin and requires BRCT motifs essential for TopBP1's replication and checkpoint functions. Most importantly, we find that ticrr deficiency disrupts chromatin binding of pre-IC, but not prereplication complex, components. Taken together, our data show that TICRR acts in association with TopBP1 and plays an essential role in pre-IC formation. It remains to be determined whether Ticrr represents the vertebrate ortholog of the yeast pre-IC component Sld3, or a hitherto unknown metazoan replication and checkpoint regulator.\",\n \"title\": \"A vertebrate gene, ticrr, is an essential checkpoint and replication regulator.\"\n },\n {\n \"docid\": \"195683603\",\n \"text\": \"Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses.\",\n \"title\": \"Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A.\"\n },\n {\n \"docid\": \"15248287\",\n \"text\": \"Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.\",\n \"title\": \"Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival\"\n },\n {\n \"docid\": \"20608982\",\n \"text\": \"PURPOSE OF REVIEW As the migration of neutrophils from blood to inflamed tissues is an essential component of innate immunity and a key contributing factor to the pathogenesis of inflammatory disorders, this aspect of leukocyte biology continues to be a highly dynamic field of research. This review summarizes recent findings in this area, focusing on the mechanisms that mediate neutrophil transmigration, an area where significant progress has been made. RECENT FINDINGS The topics to be covered will include responses that are prerequisite to neutrophil migration through venular walls, such as leukocyte luminal crawling and cellular and molecular changes in leukocytes and endothelial cells (e.g. formation of protrusions) that collectively support leukocyte transendothelial cell migration. Advances in both paracellular and transcellular neutrophil migration through endothelial cells will be discussed, addressing the associated roles and regulation of expression of endothelial cell luminal and junctional adhesion molecules. Beyond the endothelium, migration through the vascular pericyte coverage and basement membrane will be reviewed. SUMMARY The unquestionable role of neutrophils in the development and progression of inflammatory conditions suggests that a better understanding of the tissue-specific and stimulus-specific mechanisms that mediate this response may identify novel pathways that could be exploited for the development of more specific anti-inflammatory interventions.\",\n \"title\": \"Recent developments and complexities in neutrophil transmigration.\"\n },\n {\n \"docid\": \"6417632\",\n \"text\": \"BACKGROUND COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. METHODS To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. RESULTS Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). CONCLUSIONS Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation.\",\n \"title\": \"Neutrophilic infiltration within the airway smooth muscle in patients with COPD.\"\n },\n {\n \"docid\": \"10443642\",\n \"text\": \"RNAIII is the intracellular effector of the quorum-sensing system in Staphylococcus aureus. It is one of the largest regulatory RNAs (514 nucleotides long) that are known to control the expression of a large number of virulence genes. Here, we show that the 3' domain of RNAIII coordinately represses at the post-transcriptional level, the expression of mRNAs that encode a class of virulence factors that act early in the infection process. We demonstrate that the 3' domain acts primarily as an antisense RNA and rapidly anneals to these mRNAs, forming long RNA duplexes. The interaction between RNAIII and the mRNAs results in repression of translation initiation and triggers endoribonuclease III hydrolysis. These processes are followed by rapid depletion of the mRNA pool. In addition, we show that RNAIII and its 3' domain mediate translational repression of rot mRNA through a limited number of base pairings involving two loop-loop interactions. Since Rot is a transcriptional regulatory protein, we proposed that RNAIII indirectly acts on many downstream genes, resulting in the activation of the synthesis of several exoproteins. These data emphasize the multitude of regulatory steps affected by RNAIII and its 3' domain in establishing a network of S. aureus virulence factors.\",\n \"title\": \"Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism.\"\n },\n {\n \"docid\": \"12058271\",\n \"text\": \"The bone marrow is the primary site for neutrophil production and release into the circulation. Because the CXC chemokine receptor-4/stromal derived factor-1 (CXCR4/SDF-1) axis plays a central role in the interactions of hematopoietic stem cells, lymphocytes, and developing neutrophils in the marrow, we investigated whether reciprocal CXCR4-dependent mechanisms might be involved in neutrophil release and subsequent return to the marrow following circulation. Neutralizing antibody to CXCR4 reduced marrow retention of infused neutrophils (45.7% +/- 0.5% to 6.9% +/- 0.5%) and was found to mobilize neutrophils from marrow (34.4% +/- 4.4%). Neutrophil CXCR4 expression and SDF-1-induced calcium flux decreased with maturation and activation of the cells, corresponding to the decreased marrow homing associated with these characteristics in vivo. Infusion of the inflammatory mediator and CXCR2 ligand KC led to mobilization of neutrophils from marrow by itself and was augmented 3-fold by low doses of CXCR4-blocking antibody that otherwise had no mobilizing effect. Examination of KC and SDF-1 calcium signaling demonstrated that the effect of KC may, in part, be due to heterologous desensitization to SDF-1. These results suggest that the CXCR4/SDF-1 axis is critical in circulating neutrophil homeostasis and that it may participate in the rapid release of neutrophils from the marrow during inflammation through a novel interaction with inflammatory CXC chemokines.\",\n \"title\": \"Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis.\"\n },\n {\n \"docid\": \"14119470\",\n \"text\": \"Ran is an abundant nuclear GTPase with a clear role in nuclear transport during interphase but with roles in mitotic regulation that are less well understood. The nucleotide-binding state of Ran is regulated by a GTPase activating protein, RanGAP1, and by a guanine nucleotide exchange factor, RCC1. Ran also interacts with a guanine nucleotide dissociation inhibitor, RanBP1. RanBP1 has a high affinity for GTP-bound Ran, and it acts as a cofactor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on Ran approximately tenfold. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian cells and in Xenopus egg extracts (our unpublished observations). We investigated how increased concentrations of RanBP1 disturb mitosis. We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is added to M phase Xenopus egg extracts. We present evidence that the role of Ran in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.\",\n \"title\": \"The Ran GTPase regulates mitotic spindle assembly\"\n },\n {\n \"docid\": \"21395936\",\n \"text\": \"Chronic obstructive pulmonary disease (COPD) is a chronic airway disorder characterized by obstructive airflow limitation which is not completely reversible with treatment. Inflammatory changes in the peripheral airways, especially those with the diameter less than 2mm (so-called small airway disease) have been speculated to be initial steps of COPD. And so it must be quite clear that neutrophils and macrophages play an essential role in the pathogenesis of these lesions. Studies with bronchoalveolar lavage demonstrated an increase in neutrophil numbers and the neutrophil chemoattractant interleukin-8. Recent studies demonstrated that neutrophils and macrophages are increased and contain a variety of proteases, which are involved in cell infiltration and activation. Studies with gene-engineered animals and anti-cytokine treatment will facilitate better understanding the role of neutrophils and macrophages, and eventual novel therapy.\",\n \"title\": \"[Neutrophils and macrophages related to the pathogenesis and disease development of chronic obstructive pulmonary disease by the inflammatory reaction].\"\n }\n]"}}},{"rowIdx":395,"cells":{"query_id":{"kind":"string","value":"1118"},"query":{"kind":"string","value":"Sweet taste receptors on the tongue are deactivated by between 1 and 10 mM glucose."},"positive_passages":{"kind":"list like","value":[{"docid":"23351136","text":"The tastes of sugars (sweet) and glutamate (umami) are thought to be detected by T1r receptors expressed in taste cells. Molecular genetics and heterologous expression implicate T1r2 plus T1r3 as a sweet-responsive receptor,and T1r1 plus T1r3,as well as a truncated form of the type 4 metabotropic glutamate receptor (taste-mGluR4),as umami-responsive receptors. Here,we show that mice lacking T1r3 showed no preference for artificial sweeteners and had diminished but not abolished behavioral and nerve responses to sugars and umami compounds. These results indicate that T1r3-independent sweet- and umami-responsive receptors and/or pathways exist in taste cells.","title":"Detection of sweet and umami taste in the absence of taste receptor T1r3."}],"string":"[\n {\n \"docid\": \"23351136\",\n \"text\": \"The tastes of sugars (sweet) and glutamate (umami) are thought to be detected by T1r receptors expressed in taste cells. Molecular genetics and heterologous expression implicate T1r2 plus T1r3 as a sweet-responsive receptor,and T1r1 plus T1r3,as well as a truncated form of the type 4 metabotropic glutamate receptor (taste-mGluR4),as umami-responsive receptors. Here,we show that mice lacking T1r3 showed no preference for artificial sweeteners and had diminished but not abolished behavioral and nerve responses to sugars and umami compounds. These results indicate that T1r3-independent sweet- and umami-responsive receptors and/or pathways exist in taste cells.\",\n \"title\": \"Detection of sweet and umami taste in the absence of taste receptor T1r3.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"20829129","text":"Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut \"taste\" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut \"taste cells\" may provide an important treatment for obesity, diabetes and abnormal gut motility.","title":"Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1."},{"docid":"718601","text":"Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities.","title":"Coding of Sweet, Bitter, and Umami Tastes Different Receptor Cells Sharing Similar Signaling Pathways"},{"docid":"5293024","text":"Our attitude towards candy—“if it tastes that good, it can't be healthy”—betrays society's puritanical stance towards pleasure. Candy has been blamed for various ills, including hyperactivity in children; however, clinical trials have not supported this.1 Candy—sugar confectionery and chocolate—is not a recent invention: the ancient Arabs, Chinese, and Egyptians candied fruits and nuts in honey, and the Aztecs made a chocolate drink from the bean of the cacao tree. Today, Americans gratify themselves with, on average, 5.4 kg of sugar candy and 6.5 kg of chocolate per person annually.2 Since candy has existed for centuries, we surmised that it cannot be totally unhealthy. We decided to investigate whether candy consumption was associated with longevity. Subjects were from the Harvard alumni health study, an ongoing study of men entering Harvard University as undergraduates between 1916 and 1950. We included 7841 men, free of cardiovascular disease and cancer, who responded to a health survey …","title":"Life is sweet: candy consumption and longevity."},{"docid":"12943966","text":"Ghrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (i) ghrelin release via α-gustducin and (ii) food intake and gastric emptying via the release of ghrelin. The mouse stomach contains two ghrelin cell populations: cells containing octanoyl and desoctanoyl ghrelin, which were colocalized with α-gustducin and α-transducin, and cells staining for desoctanoyl ghrelin. Gavage of T2R-agonists increased plasma octanoyl ghrelin levels in WT mice but the effect was partially blunted in gust(-/-) mice. Intragastric administration of T2R-agonists increased food intake during the first 30 min in WT but not in gust(-/-) and ghrelin receptor knockout mice. This increase was accompanied by an increase in the mRNA expression of agouti-related peptide in the hypothalamus of WT but not of gust(-/-) mice. The temporary increase in food intake was followed by a prolonged decrease (next 4 h), which correlated with an inhibition of gastric emptying. The delay in emptying, which was partially counteracted by ghrelin, was not mediated by cholecystokinin and GLP-1 but involved a direct inhibitory effect of T2R-agonists on gastric contractility. This study is unique in providing functional evidence that activation of bitter taste receptors stimulates ghrelin secretion. Modulation of endogenous ghrelin levels by tastants may provide novel therapeutic applications for the treatment of weight -and gastrointestinal motility disorders.","title":"Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying."},{"docid":"10247282","text":"In the rat isolated perfused kidney, arachidonic acid elicits cyclooxygenase-dependent vasoconstriction through activation of PGH2/TxA2 receptors; responses are enhanced in kidneys from diabetic rats. This study examined the roles of cyclooxygenase-1/cyclooxygenase-2 in the enhanced renal vasoconstrictor effect of arachidonic acid in streptozotocin-diabetic rats. Release of 20-HETE was also determined, as this eicosanoid has been reported to elicit cyclooxygenase-dependent vasoconstriction. We confirmed that vasoconstrictor responses to arachidonic acid were enhanced in the diabetic rat kidney associated with a 2-fold-greater increase in the release of 6-ketoPGF1alpha, which was used as an index of cyclooxygenase activity. One and three micrograms of arachidonic acid increased perfusion pressure by 85+/-37 and 186+/-6 mm Hg, respectively, in diabetic rat kidneys compared with 3+/-1 and 17+/-8 mm Hg, respectively, in control rat kidneys. Inhibition of both cyclooxygenase isoforms with indomethacin (10 micromol/L) abolished the vasoconstrictor response to arachidonic acid in both diabetic and control rat kidneys, whereas inhibition of cyclooxygenase-2 with nimesulide (5 micromol/L) reduced perfusion pressure responses to 1 and 3 microg arachidonic acid only in the diabetic rat kidney to 15+/-8 and 108+/-26 mm Hg, respectively, consistent with a 3-fold increase in the renal cortical expression of cyclooxygenase-2. 20-HETE release from the diabetic rat kidney was reduced almost 6-fold and was not increased in response to arachidonic acid. These results demonstrate that the renal vasoconstrictor effect of arachidonic acid is solely dependent on cyclooxygenase activity, with no evidence for a contribution from 20-HETE; in the diabetic rat, cyclooxygenase-2 activity contributes to the renal vasoconstrictor effect of arachidonic acid.","title":"Arachidonic Acid in the Diabetic Rat Kidney"},{"docid":"4857093","text":"Objective:To assess the relative validity and acceptability of the computerised 24-h recall ‘Young Adolescent's Nutrition Assessment on Computer (YANA-C)’.Design:Food and nutrient intakes assessed with YANA-C were compared with food records (study 1) and 24-h dietary recall interviews (study 2).Main outcome measures:Intakes of food groups (fruit, fruit juice, vegetables, potatoes, bread, cereals, milk, cheese, other milk products, soft drinks, diet soft drinks, sugar/sweets, pastry/cookies, savoury snacks, butter/sauces, eggs, fish, meat) and nutrients (energy, carbohydrates, protein, fat, fiber, calcium, vitamin C and iron).Subjects and setting:A total of 237 pupils (11–14 y) from two primary and four secondary schools (study 1: n=136; study 2: n=101) in Belgium-Flanders. Results:YANA-C proved to agree well with both standard methods in categorizing subjects in consumers and nonconsumers (κstudy 1=0.48–0.92; κstudy 2=0.38–0.90). Spearman's correlations for energy and nutrient intakes ranged between 0.44 and 0.79 for study 1 and between 0.44 and 0.86 for study 2. Nutrient and energy intakes were in general (excluding calcium) significantly higher in YANA-C in comparison with the food record, but not in comparison with the interview (only fiber). Statistics used to investigate whether YANA-C agreed with the other methods in ranking portions/amounts in consumers only were fair to moderate for most of the food groups (weighted κ study 1=0.11–0.55; study 2=0.04–0.73); amounts in consumers only, were significantly lower in YANA-C against both standards for cereals; amounts were significantly higher in YANA-C against the food record for milk, soft drinks, sugar/sweets and savoury snacks and against the interview for potatoes. Only a few pupils evaluated the program negatively. Conclusion:YANA-C is a promising method to collect detailed dietary information from young adolescents with relatively low staff resources, useful in many nutrition research applications.","title":"Young adolescents' nutrition assessment on computer (YANA-C)"},{"docid":"26058927","text":"Thiazolidinediones (TZDs) improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). There is growing evidence from in vivo and in vitro studies that TZDs improve pancreatic beta-cell function. The aim of this study was to determine whether TZD-induced improvement in glycemic control is associated with improved beta-cell function. We studied 11 normal glucose-tolerant and 53 T2DM subjects [age 53+/-2 yr; BMI 29.4+/-0.8 kg/m2; fasting plasma glucose (FPG) 10.3+/-0.4 mM; Hb A1c 8.2+/-0.3%]. Diabetic patients were randomized to receive placebo or TZD for 4 mo. Subjects received 1) 2-h OGTT with determination of plasma glucose, insulin, and C-peptide concentrations and 2) two-step euglycemic insulin (40 and 160 mU.m-2.min-1) clamp with [3-(3)H]glucose. T2DM patients were then randomized to receive 4 mo of treatment with pioglitazone (45 mg/day), rosiglitazone (8 mg/day), or placebo. Pioglitazone and rosiglitazone similarly improved FPG, mean plasma glucose during OGTT, Hb A1c, and insulin-mediated total body glucose disposal (Rd) and decreased mean plasma FFA during OGTT (all P<0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [DeltaISR(AUC)/Deltaglucose(AUC)/IR] was significantly improved in all TZD-treated groups: +1.8+/-0.7 (PIO+drug-naïve diabetics), +0.7+/-0.3 (PIO+sulfonylurea-treated diabetics), and 0.7+/-0.2 (ROSI+sulfonylurea-withdrawn diabetics) vs. -0.2+/-0.3 in the two placebo groups (P<0.01, all TZDs vs. placebo, ANOVA). Improved insulin secretion correlated positively with increased body weight, fat mass, and Rd and inversely with decreased plasma glucose and FFA during the OGTT. In T2DM patients, TZD treatment leads to improved beta-cell function, which correlates strongly with improved glycemic control.","title":"Thiazolidinediones improve beta-cell function in type 2 diabetic patients."},{"docid":"18346333","text":"Glutamate receptors mediate the majority of excitatory synaptic transmission in the CNS. The AMPA-subtype has rapid kinetics, with activation, deactivation and desensitization proceeding on the millisecond timescale or faster. Crystallographic, biochemical, and functional studies suggest that GluR2 Cys mutants which form intermolecular disulfide cross-links between the lower D2 lobes of the ligand binding cores can be trapped in a conformation that represents the desensitized state. We used multi-channel rapid perfusion techniques to examine the state dependence of cross-linking in these mutants. Under reducing conditions, both wild-type GluR2 and the G725C and S729C mutants have normal activation and desensitization kinetics, but the Cys mutants can be efficiently trapped in nonconducting states when oxidized. In contrast the I664C mutant is only partially inactivated under oxidizing conditions. For S729C, disulfide cross-links form rapidly when receptors are desensitized in the presence of glutamate, but receptors also become trapped at rest, in the absence of agonist. We assessed such spontaneous trapping in various conditions, including CNQX, a competitive antagonist; kainate, a weak partial agonist; or when desensitization was blocked by the L483Y mutation that stabilizes the D1 dimer interface. These experiments suggest that trapping in the absence of glutamate is due to two motions: Spontaneous breaking of the D1 dimer interface and hyperextension of the lower lobes of the ligand binding core. These data show that the glutamate binding domains are surprisingly mobile in the absence of ligand, which could influence receptor activity in the brain.","title":"AMPA receptor ligand binding domain mobility revealed by functional cross linking."},{"docid":"28633594","text":"BACKGROUND In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. METHODS The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. FINDINGS We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. INTERPRETATION We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. FUNDING Bill & Melinda Gates Foundation.","title":"International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project."},{"docid":"11090688","text":"The weight lowering potential of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP-1R on body weight response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has not yet been evaluated. Fifty-seven obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m2) were assigned to liraglutide 1.2 mg QD s.c. for 12 weeks and classified as strong responders regarding weight loss if they lost 5 % or more of their initial body weight. They were genotyped for common GLP-1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of measures of obesity were measured before and at the end of the treatment. Twenty out of 57 subjects were strong responders and lost 7.38 ± 1.74 compared to 2.11 ± 2.17 kg lost in poor responders. Carriers of at least one polymorphic rs10305420 allele had poor treatment response compared to carriers of two wild type alleles (OR = 0.27, 95 % CI = 0.09–0.85, P = 0.025). Carriers of at least one polymorphic rs6923761 allele tended to have stronger treatment response compared to carriers of two wild type alleles (OR = 3.06, 95 % CI = 0.96–9.74, P = 0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT) comparably decreased in both groups when compared to baseline, whereas no within treatment differences were found in androgen profile. Gastrointestinal adverse events were transit and balanced between strong and poor responders. GLP-1R rs10305420 polymorphism explained some of the inter-individual differences in response to liraglutide regarding weight loss in obese PCOS women.","title":"Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study"},{"docid":"16361581","text":"Notch receptors expressed on hematopoietic stem cells interact with their ligands on bone marrow stromal cells and thereby control cell fate decisions and survival. We recently demonstrated that Notch signaling is involved in proliferation and survival of B cell-derived tumor cells of classic Hodgkin disease and described a novel mechanism for the oncogenic capacity of Notch. In this study we investigated whether Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment, which are essential for tumor cell growth in multiple myeloma (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are highly expressed in cultured and primary MM cells, whereas nonneoplastic counterparts show low to undetectable levels of Notch. Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo.","title":"Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells."},{"docid":"15563864","text":"Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts. Treatment with EGCG also led to significant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-kappaB activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18). Expression of related genes at the protein level were also confirmed by Western blot analysis. These data demonstrate potent and specific antimyeloma activity of EGCG and provide the rationale for its clinical evaluation.","title":"Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications."},{"docid":"4506414","text":"BACKGROUND The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. METHODS We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. FINDINGS During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. INTERPRETATION The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. FUNDING Medical Research Council, National Institute for Health Research, and Wellcome Trust.","title":"Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people"},{"docid":"3981033","text":"The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical trials for their ability to induce tumor necrosis factor (TNF)-mediated apoptosis of cancer cells. However, cIAP1 and cIAP2 are recurrently homozygously deleted in multiple myeloma (MM), resulting in constitutive activation of the noncanonical nuclear factor (NF)-κB pathway. To our surprise, we observed robust in vivo anti-myeloma activity of LCL161 in a transgenic myeloma mouse model and in patients with relapsed-refractory MM, where the addition of cyclophosphamide resulted in a median progression-free-survival of 10 months. This effect was not a result of direct induction of tumor cell death, but rather of upregulation of tumor-cell-autonomous type I interferon (IFN) signaling and a strong inflammatory response that resulted in the activation of macrophages and dendritic cells, leading to phagocytosis of tumor cells. Treatment of a MM mouse model with LCL161 established long-term anti-tumor protection and induced regression in a fraction of the mice. Notably, combination of LCL161 with the immune-checkpoint inhibitor anti-PD1 was curative in all of the treated mice.","title":"IAP antagonists induce anti-tumor immunity in multiple myeloma"},{"docid":"10648422","text":"Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.","title":"Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection"},{"docid":"29387024","text":"BACKGROUND Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.","title":"Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial"},{"docid":"20767776","text":"Objective:A number of case reports describe multiple family members with gastroesophageal reflux disease and Barrett's esophagus. The wider importance of familial factors in gastroesophageal reflux disease has not been established. Therefore, we have studied the prevalence of reflux symptoms and medication use among relatives of patients with documented gastroesophageal reflux disease. Methods:A postal questionnaire study of the first degree relatives of six groups of matched patients. The groups comprised patients with 1) no dyspeptic symptoms; 2) reflux symptoms and a normal pH study; 3) reflux symptoms, an abnormal pH study, and a lower esophageal sphincter (LOS) pressure more than 10 mm Hg; 4) reflux symptoms, an abnormal pH study, and a LOS pressure less than 10 mm Hg; 5) Barrett's esophagus; and 6) peptic stricture. Results:Four hundred eighteen subjects replied (78% response). Infrequent reflux symptoms were equally common in all groups of relatives. Frequent reflux symptoms, however, were more common among relatives of patients with an abnormal pH study and normal (26%, p= 0.007) or low LOS pressure (27%, p= 0.01) or Barrett's esophagus (30%, p= 0.003), compared with relatives of nondyspeptic patients (9%). Frequent reflux symptoms were no more common among relatives of patients with a normal pH study (16%) or peptic stricture (18%). Reflux medication use showed a similar pattern. Conclusions:Familial clustering of reflux symptoms is seen in relatives of patients with reflux symptoms and increased esophageal acid exposure and in relatives of patients with Barrett's esophagus.","title":"Familial clustering of reflux symptoms"},{"docid":"14300799","text":"A key feature of speech is its stereotypical 5 Hz rhythm. One theory posits that this rhythm evolved through the modification of rhythmic facial movements in ancestral primates. If the hypothesis has any validity, then a comparative approach may shed some light. We tested this idea by using cineradiography (X-ray movies) to characterize and quantify the internal dynamics of the macaque monkey vocal tract during lip-smacking (a rhythmic facial expression) versus chewing. Previous human studies showed that speech movements are faster than chewing movements, and the functional coordination between vocal tract structures is different between the two behaviors. If rhythmic speech evolved through a rhythmic ancestral facial movement, then one hypothesis is that monkey lip-smacking versus chewing should also exhibit these differences. We found that the lips, tongue, and hyoid move with a speech-like 5 Hz rhythm during lip-smacking, but not during chewing. Most importantly, the functional coordination between these structures was distinct for each behavior. These data provide empirical support for the idea that the human speech rhythm evolved from the rhythmic facial expressions of ancestral primates.","title":"Cineradiography of Monkey Lip-Smacking Reveals Putative Precursors of Speech Dynamics"},{"docid":"145416918","text":"The effects of product information on responses to frankfurter sausages and chocolate bars were studied by comparing sensory and hedonic ratings in two conditions: blind tasting and tasting with information present. Furthermore, the effect of information alone was investigated by having the subjects rate the expected sensory and hedonic intensities of the products on the basis of packages with different claims. Three groups of subjects were tested by giving them different information: The basic group (no added claims, n = 31), the reduced-fat group (products claimed to have reduced-fat, n=29) and the flavorful group (products claimed to have full meat/chocolate flavor, n = 31). Product information increased the rated pleasantness of the frankfurter in all three information groups compared to the blind ratings. The information did not affect the pleasantness of the chocolate bars. The expected attribute intensities of the frankfurters and chocolates were rated lower by the reduced-fat group than by the other groups. Overall, the effect of product information was more clearly seen in ratings of sensory attributes than in pleasantness ratings.","title":"The effect of information related to fat content and taste on consumer responses to a reduced-fat frankfurter and a reduced-fat chocolate bar"},{"docid":"33554389","text":"Abstract The effect of increased levels of cAMP upon the differentiation of primary cultures of chick myo blasts has been investigated. 0.1 mM But 2 cAMP or 1 mM 3-isobutyl-1-methylxanthine was added to the cultures 24 h after plating and maintained throughout the 70 h period of culture examined. Both reagents were found to markedly delay the time of fusion of the myoblasts but had no observable effect upon the increase in activity of creatine phosphokinase. Morphological examination of the cells revealed no difference in the relative numbers of myoblasts and fibroblasts between the control, But 2 cAMP and 3-isobutyl-1-methylxanthine cultures, but the latter reagent appeared to cause some inhibition of cell proliferation.","title":"The relationship of the level of cyclic amp to differentiation in primary cultures of chick muscle cells."},{"docid":"12280462","text":"Bile acids are recognized as metabolic modulators. The present study was aimed at evaluating the effects of a potent Asbt inhibitor (264W94), which blocks intestinal absorption of bile acids, on glucose homeostasis in Zucker Diabetic Fatty (ZDF) rats. Oral administration of 264W94 for two wk increased fecal bile acid concentrations and elevated non-fasting plasma total Glp-1. Treatment of 264W94 significantly decreased HbA1c and glucose, and prevented the drop of insulin levels typical of ZDF rats in a dose-dependent manner. An oral glucose tolerance test revealed up to two-fold increase in plasma total Glp-1 and three-fold increase in insulin in 264W94 treated ZDF rats at doses sufficient to achieve glycemic control. Tissue mRNA analysis indicated a decrease in farnesoid X receptor (Fxr) activation in small intestines and the liver but co-administration of a Fxr agonist (GW4064) did not attenuate 264W94 induced glucose lowering effects. In summary, our results demonstrate that inhibition of Asbt increases bile acids in the distal intestine, promotes Glp-1 release and may offer a new therapeutic strategy for type 2 diabetes mellitus.","title":"Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes."},{"docid":"19205437","text":"Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca2+ cycling by sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein. Conversely, enhanced Ca2+ cycling by activation of α1- and/or β3-adrenergic receptors or the SERCA2b-RyR2 pathway stimulates UCP1-independent thermogenesis in beige adipocytes. In the absence of UCP1, beige fat dynamically expends glucose through enhanced glycolysis, tricarboxylic acid metabolism and pyruvate dehydrogenase activity for ATP-dependent thermogenesis through the SERCA2b pathway; beige fat thereby functions as a 'glucose sink' and improves glucose tolerance independently of body weight loss. Our study uncovers a noncanonical thermogenic mechanism through which beige fat controls whole-body energy homeostasis via Ca2+ cycling.","title":"UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis"},{"docid":"11201004","text":"Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P < 0.01). No associations were observed with consumption of added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.","title":"Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity."},{"docid":"13445579","text":"BACKGROUND AND PURPOSE IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.","title":"Results of screening for intracranial aneurysms in patients with coarctation of the aorta."},{"docid":"42800527","text":"BACKGROUND Adverse effects of metformin are primarily related to gastrointestinal (GI) intolerance that could limit titration to an efficacious dose or cause discontinuation of the medication. Because some metformin side effects may be attributable to shifts in the GI microbiome, we tested whether a GI microbiome modulator (GIMM) used in combination with metformin would ameliorate the GI symptoms. METHODS A 2-period crossover study design was used with 2 treatment sequences, either placebo in period 1 followed by GIMM in period 2 or vice versa. Study periods lasted for 2 weeks, with a 2-week washout period between. During the first week, type 2 diabetes patients (T2D) who experienced metformin GI intolerance took 500 mg metformin along with their assigned NM504 (GIMM) or placebo treatment with breakfast and with dinner. In the second week, the 10 subjects took 500 mg metformin (t.i.d.), with GIMM or placebo consumed with the first and third daily metformin doses. Subjects were permitted to discontinue metformin dosing if it became intolerable. RESULTS The combination of metformin and GIMM treatment produced a significantly better tolerance score to metformin than the placebo combination (6.78 ± 0.65 [mean ± SEM] versus 4.45 ± 0.69, P = .0006). Mean fasting glucose levels were significantly (P < .02) lower with the metformin-GIMM combination (121.3 ± 7.8 mg/dl) than with metformin-placebo (151.9 ± 7.8 mg/dl). CONCLUSION Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.","title":"Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels."},{"docid":"1171121","text":"A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤ 214.8 microvesells/mm(2)) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P = 0.000) and in estrogen (P = 0.046) or progesterone receptors (P = 0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P = 0.000), steroid receptors negativity (P = 0.000), cytokeratin5/6 positivity (P = 0.026), topoisomerase IIα overexpression (P = 0.005) and higher proliferation rate (P = 0.001). In univariate analysis, higher MVD (P = 0.016) and p53 negativity (P = 0.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.","title":"Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group"},{"docid":"21547032","text":"Objective:In mice and in humans, treatment with the second-generation antipsychotic drug olanzapine (OLZ) produces excessive weight gain, adiposity and secondary metabolic complications, including loss of glucose and insulin homeostasis. In mice consuming a high-fat (HF) diet, a similar phenotype develops, which is inhibited by the analgesic acetaminophen (APAP) and by the antioxidant tetrahydroindenoindole (THII). Therefore, we examined the ability of APAP and THII to prevent metabolic changes in mice receiving OLZ.Design and Measurement:C57BL/6J mice received either a normal diet or a HF diet, and were administered daily dosages of OLZ (3 mg kg−1 body weight), alone or with APAP (30 mg kg−1 body weight) or THII (4.5 mg kg−1 body weight), for 10 weeks. Parameters of body composition and metabolism, including glucose and insulin homeostasis and oxidative stress, were examined. Results:OLZ treatment doubled the HF diet-induced increases in body weight and percent body fat. These increases were partially prevented by both APAP and THII, although food consumption was constant in all groups. The THII protection was associated with an increase in whole body and mitochondrial respiration. OLZ also exacerbated, and both APAP and THII prevented, HF diet-induced loss of glucose tolerance and insulin resistance. As increased body fat promotes insulin resistance by a pathway involving oxidative stress, we evaluated production of reactive oxygen and lipid peroxidation in white adipose tissue (WAT). HF diet caused an increase in lipid peroxidation, NADPH-dependent O2 uptake and H2O2 production, which were further exacerbated by OLZ. APAP, THII and the NADPH oxidase inhibitor, diphenyleneiodonium chloride, each abolished oxidative stress in WAT.Conclusions:We conclude that both APAP and THII intervene in the development of obesity and metabolic complications associated with OLZ treatment.","title":"Protection from olanzapine-induced metabolic toxicity in mice by acetaminophen and tetrahydroindenoindole"},{"docid":"13492264","text":"Glomerular basement membrane (GBM) and podocalyxin are essential for podocyte morphology. We provide evidence of functional interconnections between basement membrane components (collagen IV and laminin), the expression of podocalyxin and the morphology of human glomerular epithelial cells (podocytes). We demonstrated that GBM and laminin, but not collagen IV, up-regulated the expression of podocalyxin. Scanning electron microscopy revealed that laminin induced a modified morphology of podocytes with process formation, which was more extensive in the presence of GBM. Under high magnification, podocytes appeared ruffled. Using transmission electron microscopy we observed that raised areas occurred in the basal cell surface. Furthermore, the presence of anti-podocalyxin antibody increased the extent of adhesion and spreading of podocytes to both collagen IV and laminin, thus podocalyxin apparently inhibits cell-matrix interactions. We also performed adhesion and spreading assays on podocytes grown under increased glucose concentration (25 mM). Under these conditions, the expression of podocalyxin was almost totally suppressed. The cells adhered and spread to basement membrane components but there was no increase in the extent of adhesion and spreading in the presence of anti-podocalyxin antibody, or ruffling of the cell edges. Additionally, in podocytes expressing podocalyxin, the presence of anti-podocalyxin antibody partially reversed the inhibition of adhesion to collagen IV provoked by anti-beta1 integrin antibody, thus podocalyxin should compete with beta1-related cell adhesion. We suggest that the observed podocalyxin-mediated inhibition of binding to the matrix could be in part responsible for the specialized conformation of the basal surface of podocytes.","title":"Summary"},{"docid":"21931005","text":"Permeabilized rat kidney cells rapidly released glucose 6-phosphate dehydrogenase (G6PD) following stimulation with peptide growth factors (Stanton, R.C., Seifter, J.L., Boxer, D.C., Zimmerman, E., and Cantley, L. C. (1991) J. Biol. Chem. 266, 12442-12448). To evaluate the signal transduction pathways mediating release of G6PD, two cell lines transfected with wild type or mutant platelet-derived growth factor (PDGF) receptors (PDGFR) were studied using two permeabilization protocols. G6PD release was evaluated by enzyme activity and Western blot analysis. PDGF caused a significant increase in G6PD release in 1 min in cells transfected with wild type PDGFR. PDGF did not stimulate G6PD release in cells transfected with tyrosine kinase-deficient PDGFR. PDGF did not stimulate G6PD release in cells transfected with partially autophosphorylation-deficient PDGFR in which four known signaling proteins do not associate with the PDGFR. The PDGF-stimulated release of G6PD was partially restored in PDGFR mutants in which either phosphatidylinositol-3-kinase or phospholipase C gamma 1 could associate with the PDGFR. Lastly, there was no basal or PDGF-stimulated phosphorylation of G6PD. We conclude that release of G6PD: 1) requires intrinsic PDGFR tyrosine kinase activity; 2) requires PDGFR autophosphorylation; 3) is mediated by signaling proteins that associate with the PDGFR; 4) is not mediated by direct phosphorylation of G6PD.","title":"Signal transduction proteins that associate with the platelet-derived growth factor (PDGF) receptor mediate the PDGF-induced release of glucose-6-phosphate dehydrogenase from permeabilized cells."},{"docid":"12438901","text":"BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.","title":"Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial"}],"string":"[\n {\n \"docid\": \"20829129\",\n \"text\": \"Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut \\\"taste\\\" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut \\\"taste cells\\\" may provide an important treatment for obesity, diabetes and abnormal gut motility.\",\n \"title\": \"Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1.\"\n },\n {\n \"docid\": \"718601\",\n \"text\": \"Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities.\",\n \"title\": \"Coding of Sweet, Bitter, and Umami Tastes Different Receptor Cells Sharing Similar Signaling Pathways\"\n },\n {\n \"docid\": \"5293024\",\n \"text\": \"Our attitude towards candy—“if it tastes that good, it can't be healthy”—betrays society's puritanical stance towards pleasure. Candy has been blamed for various ills, including hyperactivity in children; however, clinical trials have not supported this.1 Candy—sugar confectionery and chocolate—is not a recent invention: the ancient Arabs, Chinese, and Egyptians candied fruits and nuts in honey, and the Aztecs made a chocolate drink from the bean of the cacao tree. Today, Americans gratify themselves with, on average, 5.4 kg of sugar candy and 6.5 kg of chocolate per person annually.2 Since candy has existed for centuries, we surmised that it cannot be totally unhealthy. We decided to investigate whether candy consumption was associated with longevity. Subjects were from the Harvard alumni health study, an ongoing study of men entering Harvard University as undergraduates between 1916 and 1950. We included 7841 men, free of cardiovascular disease and cancer, who responded to a health survey …\",\n \"title\": \"Life is sweet: candy consumption and longevity.\"\n },\n {\n \"docid\": \"12943966\",\n \"text\": \"Ghrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (i) ghrelin release via α-gustducin and (ii) food intake and gastric emptying via the release of ghrelin. The mouse stomach contains two ghrelin cell populations: cells containing octanoyl and desoctanoyl ghrelin, which were colocalized with α-gustducin and α-transducin, and cells staining for desoctanoyl ghrelin. Gavage of T2R-agonists increased plasma octanoyl ghrelin levels in WT mice but the effect was partially blunted in gust(-/-) mice. Intragastric administration of T2R-agonists increased food intake during the first 30 min in WT but not in gust(-/-) and ghrelin receptor knockout mice. This increase was accompanied by an increase in the mRNA expression of agouti-related peptide in the hypothalamus of WT but not of gust(-/-) mice. The temporary increase in food intake was followed by a prolonged decrease (next 4 h), which correlated with an inhibition of gastric emptying. The delay in emptying, which was partially counteracted by ghrelin, was not mediated by cholecystokinin and GLP-1 but involved a direct inhibitory effect of T2R-agonists on gastric contractility. This study is unique in providing functional evidence that activation of bitter taste receptors stimulates ghrelin secretion. Modulation of endogenous ghrelin levels by tastants may provide novel therapeutic applications for the treatment of weight -and gastrointestinal motility disorders.\",\n \"title\": \"Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying.\"\n },\n {\n \"docid\": \"10247282\",\n \"text\": \"In the rat isolated perfused kidney, arachidonic acid elicits cyclooxygenase-dependent vasoconstriction through activation of PGH2/TxA2 receptors; responses are enhanced in kidneys from diabetic rats. This study examined the roles of cyclooxygenase-1/cyclooxygenase-2 in the enhanced renal vasoconstrictor effect of arachidonic acid in streptozotocin-diabetic rats. Release of 20-HETE was also determined, as this eicosanoid has been reported to elicit cyclooxygenase-dependent vasoconstriction. We confirmed that vasoconstrictor responses to arachidonic acid were enhanced in the diabetic rat kidney associated with a 2-fold-greater increase in the release of 6-ketoPGF1alpha, which was used as an index of cyclooxygenase activity. One and three micrograms of arachidonic acid increased perfusion pressure by 85+/-37 and 186+/-6 mm Hg, respectively, in diabetic rat kidneys compared with 3+/-1 and 17+/-8 mm Hg, respectively, in control rat kidneys. Inhibition of both cyclooxygenase isoforms with indomethacin (10 micromol/L) abolished the vasoconstrictor response to arachidonic acid in both diabetic and control rat kidneys, whereas inhibition of cyclooxygenase-2 with nimesulide (5 micromol/L) reduced perfusion pressure responses to 1 and 3 microg arachidonic acid only in the diabetic rat kidney to 15+/-8 and 108+/-26 mm Hg, respectively, consistent with a 3-fold increase in the renal cortical expression of cyclooxygenase-2. 20-HETE release from the diabetic rat kidney was reduced almost 6-fold and was not increased in response to arachidonic acid. These results demonstrate that the renal vasoconstrictor effect of arachidonic acid is solely dependent on cyclooxygenase activity, with no evidence for a contribution from 20-HETE; in the diabetic rat, cyclooxygenase-2 activity contributes to the renal vasoconstrictor effect of arachidonic acid.\",\n \"title\": \"Arachidonic Acid in the Diabetic Rat Kidney\"\n },\n {\n \"docid\": \"4857093\",\n \"text\": \"Objective:To assess the relative validity and acceptability of the computerised 24-h recall ‘Young Adolescent's Nutrition Assessment on Computer (YANA-C)’.Design:Food and nutrient intakes assessed with YANA-C were compared with food records (study 1) and 24-h dietary recall interviews (study 2).Main outcome measures:Intakes of food groups (fruit, fruit juice, vegetables, potatoes, bread, cereals, milk, cheese, other milk products, soft drinks, diet soft drinks, sugar/sweets, pastry/cookies, savoury snacks, butter/sauces, eggs, fish, meat) and nutrients (energy, carbohydrates, protein, fat, fiber, calcium, vitamin C and iron).Subjects and setting:A total of 237 pupils (11–14 y) from two primary and four secondary schools (study 1: n=136; study 2: n=101) in Belgium-Flanders. Results:YANA-C proved to agree well with both standard methods in categorizing subjects in consumers and nonconsumers (κstudy 1=0.48–0.92; κstudy 2=0.38–0.90). Spearman's correlations for energy and nutrient intakes ranged between 0.44 and 0.79 for study 1 and between 0.44 and 0.86 for study 2. Nutrient and energy intakes were in general (excluding calcium) significantly higher in YANA-C in comparison with the food record, but not in comparison with the interview (only fiber). Statistics used to investigate whether YANA-C agreed with the other methods in ranking portions/amounts in consumers only were fair to moderate for most of the food groups (weighted κ study 1=0.11–0.55; study 2=0.04–0.73); amounts in consumers only, were significantly lower in YANA-C against both standards for cereals; amounts were significantly higher in YANA-C against the food record for milk, soft drinks, sugar/sweets and savoury snacks and against the interview for potatoes. Only a few pupils evaluated the program negatively. Conclusion:YANA-C is a promising method to collect detailed dietary information from young adolescents with relatively low staff resources, useful in many nutrition research applications.\",\n \"title\": \"Young adolescents' nutrition assessment on computer (YANA-C)\"\n },\n {\n \"docid\": \"26058927\",\n \"text\": \"Thiazolidinediones (TZDs) improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). There is growing evidence from in vivo and in vitro studies that TZDs improve pancreatic beta-cell function. The aim of this study was to determine whether TZD-induced improvement in glycemic control is associated with improved beta-cell function. We studied 11 normal glucose-tolerant and 53 T2DM subjects [age 53+/-2 yr; BMI 29.4+/-0.8 kg/m2; fasting plasma glucose (FPG) 10.3+/-0.4 mM; Hb A1c 8.2+/-0.3%]. Diabetic patients were randomized to receive placebo or TZD for 4 mo. Subjects received 1) 2-h OGTT with determination of plasma glucose, insulin, and C-peptide concentrations and 2) two-step euglycemic insulin (40 and 160 mU.m-2.min-1) clamp with [3-(3)H]glucose. T2DM patients were then randomized to receive 4 mo of treatment with pioglitazone (45 mg/day), rosiglitazone (8 mg/day), or placebo. Pioglitazone and rosiglitazone similarly improved FPG, mean plasma glucose during OGTT, Hb A1c, and insulin-mediated total body glucose disposal (Rd) and decreased mean plasma FFA during OGTT (all P<0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [DeltaISR(AUC)/Deltaglucose(AUC)/IR] was significantly improved in all TZD-treated groups: +1.8+/-0.7 (PIO+drug-naïve diabetics), +0.7+/-0.3 (PIO+sulfonylurea-treated diabetics), and 0.7+/-0.2 (ROSI+sulfonylurea-withdrawn diabetics) vs. -0.2+/-0.3 in the two placebo groups (P<0.01, all TZDs vs. placebo, ANOVA). Improved insulin secretion correlated positively with increased body weight, fat mass, and Rd and inversely with decreased plasma glucose and FFA during the OGTT. In T2DM patients, TZD treatment leads to improved beta-cell function, which correlates strongly with improved glycemic control.\",\n \"title\": \"Thiazolidinediones improve beta-cell function in type 2 diabetic patients.\"\n },\n {\n \"docid\": \"18346333\",\n \"text\": \"Glutamate receptors mediate the majority of excitatory synaptic transmission in the CNS. The AMPA-subtype has rapid kinetics, with activation, deactivation and desensitization proceeding on the millisecond timescale or faster. Crystallographic, biochemical, and functional studies suggest that GluR2 Cys mutants which form intermolecular disulfide cross-links between the lower D2 lobes of the ligand binding cores can be trapped in a conformation that represents the desensitized state. We used multi-channel rapid perfusion techniques to examine the state dependence of cross-linking in these mutants. Under reducing conditions, both wild-type GluR2 and the G725C and S729C mutants have normal activation and desensitization kinetics, but the Cys mutants can be efficiently trapped in nonconducting states when oxidized. In contrast the I664C mutant is only partially inactivated under oxidizing conditions. For S729C, disulfide cross-links form rapidly when receptors are desensitized in the presence of glutamate, but receptors also become trapped at rest, in the absence of agonist. We assessed such spontaneous trapping in various conditions, including CNQX, a competitive antagonist; kainate, a weak partial agonist; or when desensitization was blocked by the L483Y mutation that stabilizes the D1 dimer interface. These experiments suggest that trapping in the absence of glutamate is due to two motions: Spontaneous breaking of the D1 dimer interface and hyperextension of the lower lobes of the ligand binding core. These data show that the glutamate binding domains are surprisingly mobile in the absence of ligand, which could influence receptor activity in the brain.\",\n \"title\": \"AMPA receptor ligand binding domain mobility revealed by functional cross linking.\"\n },\n {\n \"docid\": \"28633594\",\n \"text\": \"BACKGROUND In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. METHODS The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. FINDINGS We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. INTERPRETATION We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. FUNDING Bill & Melinda Gates Foundation.\",\n \"title\": \"International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.\"\n },\n {\n \"docid\": \"11090688\",\n \"text\": \"The weight lowering potential of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP-1R on body weight response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has not yet been evaluated. Fifty-seven obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m2) were assigned to liraglutide 1.2 mg QD s.c. for 12 weeks and classified as strong responders regarding weight loss if they lost 5 % or more of their initial body weight. They were genotyped for common GLP-1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of measures of obesity were measured before and at the end of the treatment. Twenty out of 57 subjects were strong responders and lost 7.38 ± 1.74 compared to 2.11 ± 2.17 kg lost in poor responders. Carriers of at least one polymorphic rs10305420 allele had poor treatment response compared to carriers of two wild type alleles (OR = 0.27, 95 % CI = 0.09–0.85, P = 0.025). Carriers of at least one polymorphic rs6923761 allele tended to have stronger treatment response compared to carriers of two wild type alleles (OR = 3.06, 95 % CI = 0.96–9.74, P = 0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT) comparably decreased in both groups when compared to baseline, whereas no within treatment differences were found in androgen profile. Gastrointestinal adverse events were transit and balanced between strong and poor responders. GLP-1R rs10305420 polymorphism explained some of the inter-individual differences in response to liraglutide regarding weight loss in obese PCOS women.\",\n \"title\": \"Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study\"\n },\n {\n \"docid\": \"16361581\",\n \"text\": \"Notch receptors expressed on hematopoietic stem cells interact with their ligands on bone marrow stromal cells and thereby control cell fate decisions and survival. We recently demonstrated that Notch signaling is involved in proliferation and survival of B cell-derived tumor cells of classic Hodgkin disease and described a novel mechanism for the oncogenic capacity of Notch. In this study we investigated whether Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment, which are essential for tumor cell growth in multiple myeloma (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are highly expressed in cultured and primary MM cells, whereas nonneoplastic counterparts show low to undetectable levels of Notch. Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo.\",\n \"title\": \"Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells.\"\n },\n {\n \"docid\": \"15563864\",\n \"text\": \"Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts. Treatment with EGCG also led to significant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-kappaB activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18). Expression of related genes at the protein level were also confirmed by Western blot analysis. These data demonstrate potent and specific antimyeloma activity of EGCG and provide the rationale for its clinical evaluation.\",\n \"title\": \"Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications.\"\n },\n {\n \"docid\": \"4506414\",\n \"text\": \"BACKGROUND The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. METHODS We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. FINDINGS During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. INTERPRETATION The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. FUNDING Medical Research Council, National Institute for Health Research, and Wellcome Trust.\",\n \"title\": \"Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people\"\n },\n {\n \"docid\": \"3981033\",\n \"text\": \"The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical trials for their ability to induce tumor necrosis factor (TNF)-mediated apoptosis of cancer cells. However, cIAP1 and cIAP2 are recurrently homozygously deleted in multiple myeloma (MM), resulting in constitutive activation of the noncanonical nuclear factor (NF)-κB pathway. To our surprise, we observed robust in vivo anti-myeloma activity of LCL161 in a transgenic myeloma mouse model and in patients with relapsed-refractory MM, where the addition of cyclophosphamide resulted in a median progression-free-survival of 10 months. This effect was not a result of direct induction of tumor cell death, but rather of upregulation of tumor-cell-autonomous type I interferon (IFN) signaling and a strong inflammatory response that resulted in the activation of macrophages and dendritic cells, leading to phagocytosis of tumor cells. Treatment of a MM mouse model with LCL161 established long-term anti-tumor protection and induced regression in a fraction of the mice. Notably, combination of LCL161 with the immune-checkpoint inhibitor anti-PD1 was curative in all of the treated mice.\",\n \"title\": \"IAP antagonists induce anti-tumor immunity in multiple myeloma\"\n },\n {\n \"docid\": \"10648422\",\n \"text\": \"Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.\",\n \"title\": \"Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection\"\n },\n {\n \"docid\": \"29387024\",\n \"text\": \"BACKGROUND Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.\",\n \"title\": \"Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial\"\n },\n {\n \"docid\": \"20767776\",\n \"text\": \"Objective:A number of case reports describe multiple family members with gastroesophageal reflux disease and Barrett's esophagus. The wider importance of familial factors in gastroesophageal reflux disease has not been established. Therefore, we have studied the prevalence of reflux symptoms and medication use among relatives of patients with documented gastroesophageal reflux disease. Methods:A postal questionnaire study of the first degree relatives of six groups of matched patients. The groups comprised patients with 1) no dyspeptic symptoms; 2) reflux symptoms and a normal pH study; 3) reflux symptoms, an abnormal pH study, and a lower esophageal sphincter (LOS) pressure more than 10 mm Hg; 4) reflux symptoms, an abnormal pH study, and a LOS pressure less than 10 mm Hg; 5) Barrett's esophagus; and 6) peptic stricture. Results:Four hundred eighteen subjects replied (78% response). Infrequent reflux symptoms were equally common in all groups of relatives. Frequent reflux symptoms, however, were more common among relatives of patients with an abnormal pH study and normal (26%, p= 0.007) or low LOS pressure (27%, p= 0.01) or Barrett's esophagus (30%, p= 0.003), compared with relatives of nondyspeptic patients (9%). Frequent reflux symptoms were no more common among relatives of patients with a normal pH study (16%) or peptic stricture (18%). Reflux medication use showed a similar pattern. Conclusions:Familial clustering of reflux symptoms is seen in relatives of patients with reflux symptoms and increased esophageal acid exposure and in relatives of patients with Barrett's esophagus.\",\n \"title\": \"Familial clustering of reflux symptoms\"\n },\n {\n \"docid\": \"14300799\",\n \"text\": \"A key feature of speech is its stereotypical 5 Hz rhythm. One theory posits that this rhythm evolved through the modification of rhythmic facial movements in ancestral primates. If the hypothesis has any validity, then a comparative approach may shed some light. We tested this idea by using cineradiography (X-ray movies) to characterize and quantify the internal dynamics of the macaque monkey vocal tract during lip-smacking (a rhythmic facial expression) versus chewing. Previous human studies showed that speech movements are faster than chewing movements, and the functional coordination between vocal tract structures is different between the two behaviors. If rhythmic speech evolved through a rhythmic ancestral facial movement, then one hypothesis is that monkey lip-smacking versus chewing should also exhibit these differences. We found that the lips, tongue, and hyoid move with a speech-like 5 Hz rhythm during lip-smacking, but not during chewing. Most importantly, the functional coordination between these structures was distinct for each behavior. These data provide empirical support for the idea that the human speech rhythm evolved from the rhythmic facial expressions of ancestral primates.\",\n \"title\": \"Cineradiography of Monkey Lip-Smacking Reveals Putative Precursors of Speech Dynamics\"\n },\n {\n \"docid\": \"145416918\",\n \"text\": \"The effects of product information on responses to frankfurter sausages and chocolate bars were studied by comparing sensory and hedonic ratings in two conditions: blind tasting and tasting with information present. Furthermore, the effect of information alone was investigated by having the subjects rate the expected sensory and hedonic intensities of the products on the basis of packages with different claims. Three groups of subjects were tested by giving them different information: The basic group (no added claims, n = 31), the reduced-fat group (products claimed to have reduced-fat, n=29) and the flavorful group (products claimed to have full meat/chocolate flavor, n = 31). Product information increased the rated pleasantness of the frankfurter in all three information groups compared to the blind ratings. The information did not affect the pleasantness of the chocolate bars. The expected attribute intensities of the frankfurters and chocolates were rated lower by the reduced-fat group than by the other groups. Overall, the effect of product information was more clearly seen in ratings of sensory attributes than in pleasantness ratings.\",\n \"title\": \"The effect of information related to fat content and taste on consumer responses to a reduced-fat frankfurter and a reduced-fat chocolate bar\"\n },\n {\n \"docid\": \"33554389\",\n \"text\": \"Abstract The effect of increased levels of cAMP upon the differentiation of primary cultures of chick myo blasts has been investigated. 0.1 mM But 2 cAMP or 1 mM 3-isobutyl-1-methylxanthine was added to the cultures 24 h after plating and maintained throughout the 70 h period of culture examined. Both reagents were found to markedly delay the time of fusion of the myoblasts but had no observable effect upon the increase in activity of creatine phosphokinase. Morphological examination of the cells revealed no difference in the relative numbers of myoblasts and fibroblasts between the control, But 2 cAMP and 3-isobutyl-1-methylxanthine cultures, but the latter reagent appeared to cause some inhibition of cell proliferation.\",\n \"title\": \"The relationship of the level of cyclic amp to differentiation in primary cultures of chick muscle cells.\"\n },\n {\n \"docid\": \"12280462\",\n \"text\": \"Bile acids are recognized as metabolic modulators. The present study was aimed at evaluating the effects of a potent Asbt inhibitor (264W94), which blocks intestinal absorption of bile acids, on glucose homeostasis in Zucker Diabetic Fatty (ZDF) rats. Oral administration of 264W94 for two wk increased fecal bile acid concentrations and elevated non-fasting plasma total Glp-1. Treatment of 264W94 significantly decreased HbA1c and glucose, and prevented the drop of insulin levels typical of ZDF rats in a dose-dependent manner. An oral glucose tolerance test revealed up to two-fold increase in plasma total Glp-1 and three-fold increase in insulin in 264W94 treated ZDF rats at doses sufficient to achieve glycemic control. Tissue mRNA analysis indicated a decrease in farnesoid X receptor (Fxr) activation in small intestines and the liver but co-administration of a Fxr agonist (GW4064) did not attenuate 264W94 induced glucose lowering effects. In summary, our results demonstrate that inhibition of Asbt increases bile acids in the distal intestine, promotes Glp-1 release and may offer a new therapeutic strategy for type 2 diabetes mellitus.\",\n \"title\": \"Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes.\"\n },\n {\n \"docid\": \"19205437\",\n \"text\": \"Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca2+ cycling by sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein. Conversely, enhanced Ca2+ cycling by activation of α1- and/or β3-adrenergic receptors or the SERCA2b-RyR2 pathway stimulates UCP1-independent thermogenesis in beige adipocytes. In the absence of UCP1, beige fat dynamically expends glucose through enhanced glycolysis, tricarboxylic acid metabolism and pyruvate dehydrogenase activity for ATP-dependent thermogenesis through the SERCA2b pathway; beige fat thereby functions as a 'glucose sink' and improves glucose tolerance independently of body weight loss. Our study uncovers a noncanonical thermogenic mechanism through which beige fat controls whole-body energy homeostasis via Ca2+ cycling.\",\n \"title\": \"UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis\"\n },\n {\n \"docid\": \"11201004\",\n \"text\": \"Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P < 0.01). No associations were observed with consumption of added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.\",\n \"title\": \"Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.\"\n },\n {\n \"docid\": \"13445579\",\n \"text\": \"BACKGROUND AND PURPOSE IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.\",\n \"title\": \"Results of screening for intracranial aneurysms in patients with coarctation of the aorta.\"\n },\n {\n \"docid\": \"42800527\",\n \"text\": \"BACKGROUND Adverse effects of metformin are primarily related to gastrointestinal (GI) intolerance that could limit titration to an efficacious dose or cause discontinuation of the medication. Because some metformin side effects may be attributable to shifts in the GI microbiome, we tested whether a GI microbiome modulator (GIMM) used in combination with metformin would ameliorate the GI symptoms. METHODS A 2-period crossover study design was used with 2 treatment sequences, either placebo in period 1 followed by GIMM in period 2 or vice versa. Study periods lasted for 2 weeks, with a 2-week washout period between. During the first week, type 2 diabetes patients (T2D) who experienced metformin GI intolerance took 500 mg metformin along with their assigned NM504 (GIMM) or placebo treatment with breakfast and with dinner. In the second week, the 10 subjects took 500 mg metformin (t.i.d.), with GIMM or placebo consumed with the first and third daily metformin doses. Subjects were permitted to discontinue metformin dosing if it became intolerable. RESULTS The combination of metformin and GIMM treatment produced a significantly better tolerance score to metformin than the placebo combination (6.78 ± 0.65 [mean ± SEM] versus 4.45 ± 0.69, P = .0006). Mean fasting glucose levels were significantly (P < .02) lower with the metformin-GIMM combination (121.3 ± 7.8 mg/dl) than with metformin-placebo (151.9 ± 7.8 mg/dl). CONCLUSION Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.\",\n \"title\": \"Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels.\"\n },\n {\n \"docid\": \"1171121\",\n \"text\": \"A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤ 214.8 microvesells/mm(2)) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P = 0.000) and in estrogen (P = 0.046) or progesterone receptors (P = 0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P = 0.000), steroid receptors negativity (P = 0.000), cytokeratin5/6 positivity (P = 0.026), topoisomerase IIα overexpression (P = 0.005) and higher proliferation rate (P = 0.001). In univariate analysis, higher MVD (P = 0.016) and p53 negativity (P = 0.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.\",\n \"title\": \"Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group\"\n },\n {\n \"docid\": \"21547032\",\n \"text\": \"Objective:In mice and in humans, treatment with the second-generation antipsychotic drug olanzapine (OLZ) produces excessive weight gain, adiposity and secondary metabolic complications, including loss of glucose and insulin homeostasis. In mice consuming a high-fat (HF) diet, a similar phenotype develops, which is inhibited by the analgesic acetaminophen (APAP) and by the antioxidant tetrahydroindenoindole (THII). Therefore, we examined the ability of APAP and THII to prevent metabolic changes in mice receiving OLZ.Design and Measurement:C57BL/6J mice received either a normal diet or a HF diet, and were administered daily dosages of OLZ (3 mg kg−1 body weight), alone or with APAP (30 mg kg−1 body weight) or THII (4.5 mg kg−1 body weight), for 10 weeks. Parameters of body composition and metabolism, including glucose and insulin homeostasis and oxidative stress, were examined. Results:OLZ treatment doubled the HF diet-induced increases in body weight and percent body fat. These increases were partially prevented by both APAP and THII, although food consumption was constant in all groups. The THII protection was associated with an increase in whole body and mitochondrial respiration. OLZ also exacerbated, and both APAP and THII prevented, HF diet-induced loss of glucose tolerance and insulin resistance. As increased body fat promotes insulin resistance by a pathway involving oxidative stress, we evaluated production of reactive oxygen and lipid peroxidation in white adipose tissue (WAT). HF diet caused an increase in lipid peroxidation, NADPH-dependent O2 uptake and H2O2 production, which were further exacerbated by OLZ. APAP, THII and the NADPH oxidase inhibitor, diphenyleneiodonium chloride, each abolished oxidative stress in WAT.Conclusions:We conclude that both APAP and THII intervene in the development of obesity and metabolic complications associated with OLZ treatment.\",\n \"title\": \"Protection from olanzapine-induced metabolic toxicity in mice by acetaminophen and tetrahydroindenoindole\"\n },\n {\n \"docid\": \"13492264\",\n \"text\": \"Glomerular basement membrane (GBM) and podocalyxin are essential for podocyte morphology. We provide evidence of functional interconnections between basement membrane components (collagen IV and laminin), the expression of podocalyxin and the morphology of human glomerular epithelial cells (podocytes). We demonstrated that GBM and laminin, but not collagen IV, up-regulated the expression of podocalyxin. Scanning electron microscopy revealed that laminin induced a modified morphology of podocytes with process formation, which was more extensive in the presence of GBM. Under high magnification, podocytes appeared ruffled. Using transmission electron microscopy we observed that raised areas occurred in the basal cell surface. Furthermore, the presence of anti-podocalyxin antibody increased the extent of adhesion and spreading of podocytes to both collagen IV and laminin, thus podocalyxin apparently inhibits cell-matrix interactions. We also performed adhesion and spreading assays on podocytes grown under increased glucose concentration (25 mM). Under these conditions, the expression of podocalyxin was almost totally suppressed. The cells adhered and spread to basement membrane components but there was no increase in the extent of adhesion and spreading in the presence of anti-podocalyxin antibody, or ruffling of the cell edges. Additionally, in podocytes expressing podocalyxin, the presence of anti-podocalyxin antibody partially reversed the inhibition of adhesion to collagen IV provoked by anti-beta1 integrin antibody, thus podocalyxin should compete with beta1-related cell adhesion. We suggest that the observed podocalyxin-mediated inhibition of binding to the matrix could be in part responsible for the specialized conformation of the basal surface of podocytes.\",\n \"title\": \"Summary\"\n },\n {\n \"docid\": \"21931005\",\n \"text\": \"Permeabilized rat kidney cells rapidly released glucose 6-phosphate dehydrogenase (G6PD) following stimulation with peptide growth factors (Stanton, R.C., Seifter, J.L., Boxer, D.C., Zimmerman, E., and Cantley, L. C. (1991) J. Biol. Chem. 266, 12442-12448). To evaluate the signal transduction pathways mediating release of G6PD, two cell lines transfected with wild type or mutant platelet-derived growth factor (PDGF) receptors (PDGFR) were studied using two permeabilization protocols. G6PD release was evaluated by enzyme activity and Western blot analysis. PDGF caused a significant increase in G6PD release in 1 min in cells transfected with wild type PDGFR. PDGF did not stimulate G6PD release in cells transfected with tyrosine kinase-deficient PDGFR. PDGF did not stimulate G6PD release in cells transfected with partially autophosphorylation-deficient PDGFR in which four known signaling proteins do not associate with the PDGFR. The PDGF-stimulated release of G6PD was partially restored in PDGFR mutants in which either phosphatidylinositol-3-kinase or phospholipase C gamma 1 could associate with the PDGFR. Lastly, there was no basal or PDGF-stimulated phosphorylation of G6PD. We conclude that release of G6PD: 1) requires intrinsic PDGFR tyrosine kinase activity; 2) requires PDGFR autophosphorylation; 3) is mediated by signaling proteins that associate with the PDGFR; 4) is not mediated by direct phosphorylation of G6PD.\",\n \"title\": \"Signal transduction proteins that associate with the platelet-derived growth factor (PDGF) receptor mediate the PDGF-induced release of glucose-6-phosphate dehydrogenase from permeabilized cells.\"\n },\n {\n \"docid\": \"12438901\",\n \"text\": \"BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.\",\n \"title\": \"Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial\"\n }\n]"}}},{"rowIdx":396,"cells":{"query_id":{"kind":"string","value":"4699"},"query":{"kind":"string","value":"Can one use Google Finance to backtest (i.e. simulate trades in the past)?"},"positive_passages":{"kind":"list like","value":[{"docid":"239683","text":"Yes, add the stocks/mutual funds that you want and then you would just need to add all the transactions that you theoretically would have made. Performing the look up on the price at each date that you would have sold or bought is quite tedious as well as adding each transaction.","title":""},{"docid":"239137","text":"If you use Google Finance, you will get incorrect results because Google Finance does not show the dividend history. Since your requirement is that dividends are re-invested, you should use Yahoo Finance instead, downloading the historical 'adjusted' price.","title":""},{"docid":"154559","text":"I've used yahoo to perform the exercise you're asking about. It allows you to download price data, month end if you wish, and by manipulating via a spreadsheet to add a column for purchases, you can easily see how your £100/mo would end after so long a time period.","title":""}],"string":"[\n {\n \"docid\": \"239683\",\n \"text\": \"Yes, add the stocks/mutual funds that you want and then you would just need to add all the transactions that you theoretically would have made. Performing the look up on the price at each date that you would have sold or bought is quite tedious as well as adding each transaction.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"239137\",\n \"text\": \"If you use Google Finance, you will get incorrect results because Google Finance does not show the dividend history. Since your requirement is that dividends are re-invested, you should use Yahoo Finance instead, downloading the historical 'adjusted' price.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"154559\",\n \"text\": \"I've used yahoo to perform the exercise you're asking about. It allows you to download price data, month end if you wish, and by manipulating via a spreadsheet to add a column for purchases, you can easily see how your £100/mo would end after so long a time period.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"78342","text":"\"What do I mean by infrastructure? Well, if you're doing algorithmic trading, you have to have something monitoring data and making decisions on its own, presumably. How do you set that up? There are many ways, and some are better than others. First is a problem of scale. If you're a newbie starting out with some small set of equity tick data, perhaps just trades for instance, you can whip together something that can handle that pretty easily. Check out http://www.marketdatapeaks.com/ though. That's your messaging rates you have to deal with once you go full data feeds direct from all the exchanges. 6.65 million messages/events per second. That's a lot. And if you fall behind, you lose your lunch. Building a robust system that allows you to easily backtest and deploy strategies is crucial as well. The speed at which you're able to conduct the backtest matters a lot. Doing that rapidly, and accurately is not easy. For a broad market-data handling algo design (and now, clearly, for very specific things you can design one that'll handle stuff better for that one corner case, but this is for general algo trading), optimally you have some sort of setup where you have a: [feed handlers] -> [tickerplant] -> [mkt data subscribers/CEP] -> [order management system] -> [broker] in this setup you have feed handlers that are taking the raw exchange feeds and pushing them to a consolidated tickerplant, where CEP subscribers can come through and sub to the data they want (perhaps I just want ES futures on one, and only want to arb CMCSA and CMCSK on another -- you dont want each CEP subscriber getting your full feed for all tickers all the time, its a waste). so more or less, each independent strategy is its own subscriber to the tickerplant, taking whatever data it wants and only that data (could be \"\"give me all the trades and quotes for all nasdaq stocks, but not book depth\"\" for instance). your CEP does whatever maths it has to do to figure out trading decisions, and when it does, it sends it to your order management system which does your risk checks, etc (\"\"do you have enough money to place this trade?\"\" \"\"do you already have a position in this?\"\" \"\"are you trading against yourself?\"\" ... million other things). your OMS knows how to talk to your broker/directly to the exchange depending on your setup. Assuming all your risk checks pass, off the order goes to the exchange, and it deals with the fill msgs, etc. Now, as far as speed is concerned - try to do all of this at 6.5 million events/second. It's hard. Some strats/cep subscribers will run faster than others, some are slower, some need to keep a full book to work while some work on just trades. Your OMS depending on if youre using only market data sources may need to keep its own book to place orders on behalf of your subscribers if they lack information about various markets (think all the twitter trading bots these days for instance), etc. If you look back at the above setup as well, you'll notice some interesting things. [tickerplant] -> [cep subscriber] portion can stay the same for live trading or backtesting. This is huge. The only thing that changes here for backtesting is that if you're trying to backtest, you can take historical data (query it out of your hopefully column-store database) and push it into your tickerplant rather than having it come from a live feed through the feed handler. Your tickerplant and cep subscriber will never know the difference, so you can use the same exact code for backtesting as you can for live. On the other end, you obviously cant send historical orders to your live broker, so you need to code a simulated OMS that does the backtest simulation (another huge piece of software to code that is hard to do well). But, for backtesting, your setup is staying largely the same except those two end pieces. This means that testing/deving/deploying strats can be pretty rapid, and uses the same code base for live and historical, which helps you eliminate bugs and have to code everything twice. Backtesting design: [historical mkt data db] -> [tickerplant] -> [mkt data subscribers/CEP] -> [order management system simulator/backtester] These are just a few of the many problems that you hit when trying to dev good infra. There are like a million more. Point was simply, it's complicated. And C++ is a good lang. I use a wide variety of languages depending on exactly whats going on and how fast the code needs to be. With a proper tickerplant design, youre using some ipc protocol so a subscriber can be coded in any language. Check out http://www.zeromq.org/ -- thats an excellent piece of software to use to make a tickerplant out of, think they even have a design for one in the docs if I recall. With that, your CEP subscribers can be in any language - perhaps pure C if you need the speed, perhaps .NET or Java if you dont (check out http://esper.codehaus.org/ for a Java implement of a CEP subscriber, nEsper for the C# port of that I believe). But I use C, C++, C#, python, R, x86 asm for a few very minor things, and a lang or two I can't mention here.\"","title":""},{"docid":"154525","text":"You would have to compare your backtesting to what you will be doing in real trading, and try to have the backtesting as close to your real trading as possible. Note: you may never get the backtesting to match your real trading exactly but you need to get as close as possible. The whole purpose of backtesting is to check if your trading strategies - your signals, entries and exits, and your stops - are profitable over various market conditions. As you would be using actual closes to do your real trading you should be using this to also do your backtesting. Rather than using adjusted data to get an idea of your total return from your backtesting, you can always add the value of the dividends and other corporate actions to the results from using the actual data. You may even find a way to add any dividends and other corporate action to your results automatically, i.e. any dividend amount added to your total return if the stock is held during the ex-dividend date. If you are using adjusted data in your backtesting this may affect any stops you have placed, i.e. it may cause your stop to be triggered earlier or later than in real trading. So you will need to determine how you will treat your stops in real trading. Will you adjust them when there is corporate action such as dividends? Or will you leave them constant until actual prices have gone up? If you will be leaving your stops constant then you should definitely be using actual data in your backtesting to better match your real trading.","title":""},{"docid":"49893","text":"About 10 years ago, I used to use MetaStock Trader which was a very sound tool, with a large number of indicators, but it has been a number of years since I have used it, so my comments on it will be out of date. At the time it relied upon me purchasing trading data myself, which is why I switched to Incredible Charts. I currently use Incredible Charts which I have done for a number of years, initially on the free adware service, now on the $10/year for EOD data access. There are quicker levels of data access, which might suit you, but I can't comment on these. It is web-based which is key for me. The data quality is very good and the number of inbuilt indicators is excellent. You can build search routines on the basis of specific indicators which is very effective. I'm looking at VectorVest, as a replacement for (or in addition to) Incredible Charts, as it has very powerful backtesting routines and the ability to run test portfolios with specific buy/sell criteria that can simulate and backtest a number of trading scenarios at the same time. The advantage of all of these is they are not tied to a particular broker.","title":""},{"docid":"396657","text":"The study of technical analysis is generally used (sometimes successfully) to time the markets. There are many aspects to technical analysis, but the simplest form is to look for uptrends and downtrends in the charts. Generally higher highs and higher lows is considered an uptrend. And lower lows and lower highs is considered a downtrend. A trend follower would go with the trend, for example see a dip to the trend-line and buy on the rebound. A simple strategy for this is shown in the chart below: I would be buying this stock when the price hits or gets very close to the trendline and then it bounces back above it. I would then have sold this stock once it has broken through below the trendline. This may also be an appropriate time if you were looking to short this stock. Other indicators could also be used in combination for additional confirmation of what is happening to the price. Another type of trader is called a bottom fisher. A bottom fisher would wait until a break above the downtrend line (second chart) and buy after confirmation of a higher high and possibly a higher low (as this could be the start of a new uptrend). There are many more strategies dealing with the study of technical analysis, and if you are interested you would need to find and learn about ones that suit your investment styles, whether you prefer short term trading or longer term investing, and your appetite for risk. You can develop strategies using various indicators and then paper trade or backtest these strategies. You can also manually backtest a strategy in most charting packages. You can go back in time on the chart so that the right side of the chart shows a date in the past (say one year ago or 10 years ago), then you can click forward one day at a time (or one week at a time if using weekly charts). With your indicators on the chart you can do virtual trades to buy or sell whenever a signal is given as you move forward in time. This way you may be able to check years of data in a day to see if your strategy works. Whatever you do, you need to document your strategies in writing in a written trading or investment plan together with a risk management strategy. You should always follow the rules in your written plan to avoid you making decisions based on emotions. By backtesting or paper trading your strategies it will give you confidence that they will work over the long term. There is a lot of work involved at the start, but once you have developed a documented strategy that has been thoroughly backtested, it will take you minimal time to successfully manage your investments. In my shorter term trading (positions held from a couple of days to a few weeks) I spend about half an hour per night to manage my trades and am up about 50% over the last 7 months. For my longer term investing (positions held from months to years) I spend about an hour per week and have been averaging over 25% over the last 4 years. Technical Analysis does work for those who have a documented plan, have approached it in a systematic way and use risk management to protect their existing and future capital. Most people who say that is doesn't work either have not used it themselves or have used it ad-hock without putting in the initial time and work to develop a documented and systematic approach to their trading or investing.","title":""},{"docid":"588481","text":"\"I think you're on the wrong track. Getting more and more samples from the real world does not make your backtest more accurate, it just confirms that your strategy can withstand one particular sample path of a stochastic process. The reason why you find it simple to incorporate fees, commissions, taxes, etc. is because they're a static and constant process -- well they might change over time but most definitely uncorrelated to the markets. Modelling overnight returns or the top levels of the order book the next day is serious work. First you have to select a suitable model (that's mostly theoretical work but experience can help a lot). Then, in order to do it data-driven, you'd have to plough through thousands of days of sample data on a set of thousands of instruments to get a \"\"feeling\"\" (aka significant model parameters). Apropos data mining, I think Excel might be the wrong tool for the job. Level-2 data (even just the first 10 levels) is a massive blob. For example, the NYSE OpenBook historical data weighs in at a massive 15 TB compressed (uncompressed 74 TB) for the last 10 years, and costs USD 200k. Anyway, as for other factors to take into account: So how to account for all this in a backtest? Personally, I would put in some penalty terms (as % on a return basis) for every factor you want to consider, don't hardcode them. You can then run a stress test by exploring these parameters (i.e. assign some values in the range of 0 to whatever fits). Explore them individually (only set one penalty term at a time) to get a feeling how the strategy might react to stress from that factor. Then you can run the backtest with typical (or observed) combinations of penalty factors and slowly stress them altogether. Edit Just to avoid confusion about terminology. A backtest in the strict sense (had I implemented this strategy X years ago, what would have happened?) won't benefit from any modelling simply because the real-world \"\"does the sampling\"\" for us. However, to evaluate a strategy's robustness you should account for the additional factors and run some stress tests. If the strategy performs well in the real-world or no-stress scenario but produces losses once a tiny slippage occurs every now and again, you could conclude that the strategy is very fragile. The key is to explore the maximum stress the strategy can handle (by whatever measure); if a lot you can call the strategy robust. The latter is what I personally call a backtest; the first procedure would go by the name \"\"extension towards the past\"\" or so. Some lightweight literature:\"","title":""},{"docid":"573708","text":"\"A couple options that I know of: Interactive Brokers offers a \"\"paper trading\"\" mode to its account holders that allows you to start with a pretend stack of money and place simulated trades to test trading ideas. They also provide an API that allows you to interface with their platform programmatically for retrieving quotes, placing orders, and the such. As you noted, however, it's not free; you must hold a funded brokerage account in order to qualify for access to their platform. In order to maintain an account, there are minimums for required equity and monthly activity (measured in dollars that you spend on commissions), so you won't get access to their platform without having a decent amount of skin in the game. IB's native API is Java-based; IbPy is an unofficial wrapper that makes the interface available in Python. I've not used IB at all myself, but I've heard good things about their API and its accessibility via IbPy. Edit: IB now supports Python natively via their published API, so using IbPy is no longer needed, unless you wish to use Python 2.x. The officially supported API is based on Python 3. TD Ameritrade also offers an API that is usable by its brokerage clients. They do not offer any such \"\"paper trading\"\" mode, so you would need to \"\"execute\"\" transactions based on quotes at the corresponding trade times and then keep track of your simulated account history yourself. The API supports quote retrieval, price history, and trade execution, among other functions. TDA might be more attractive than IB if you're looking for a low-cost link into market data, as I believe their minimum-equity levels are lower. To get access, you'll need to sign up for an API developer account, which I believe requires an NDA. I don't believe there is an official Python implementation of the API, but if you're a capable Python writer, you shouldn't have trouble hooking up to the published interfaces. Some caveats: as when doing any strategy backtesting, you'll want to be sure to be pessimistic when doing so, so your optimism doesn't make your trades look more successful than they would be in the real world. At a minimum, you'll want to ensure that your simulations transact at the posted bid/ask prices, not necessarily the last trade's price, as well as any commissions and fees associated with the trade. A more robust scheme would also take into account the depth of the order book (also known as level 2 quotes), which can cause additional slippage in the prices at which you buy/sell your security. An even more robust scheme would take into account the potential latency of trade execution, looking at all prices over some time period that covers the maximum expected latency and simulating the trade at the worst-possible price.\"","title":""},{"docid":"484730","text":"Sounds like you are a candidate for stock trading simulators. Or just pick stocks and use Yahoo! or Google finance tools to track and see how you do. I wouldn't suggest you put real money into it. You need to learn about research and timing and a bunch of other topics you can learn about here. I personally just stick to life cycle funds that are managed products that offer me a cruise control setting for investing.","title":""},{"docid":"146632","text":"\"Yes. There are several downsides to this strategy: You aren't taking into account commissions. If you pay $5 each time you buy or sell a stock, you may greatly reduce or even eliminate any possible gains you would make from trading such small amounts. This next point sounds obvious, but remember that you pay a commission on every trade regardless of profit, so every trade you make that you make at a loss also costs you commissions. Even if you make trades that are profitable more often than not, if you make quite a few trades with small amounts like this, your commissions may eat away all of your profits. Commissions represent a fixed cost, so their effect on your gains decreases proportionally with the amount of money you place at risk in each trade. Since you're in the US, you're required to follow the SEC rules on pattern day trading. From that link, \"\"FINRA rules define a “pattern day trader” as any customer who executes four or more “day trades” within five business days, provided that the number of day trades represents more than six percent of the customer’s total trades in the margin account for that same five business day period.\"\" If you trip this rule, you'll be required to maintain $25,000 in a margin brokerage account. If you can't maintain the balance, your account will be locked. Don't forget about capital gains taxes. Since you're holding these securities for less than a year, your gains will be taxed at your ordinary income tax rates. You can deduct your capital losses too (assuming you don't repurchase the same security within 30 days, because in that case, the wash sale rule prevents you from deducting the loss), but it's important to think about gains and losses in real terms, not nominal terms. The story is different if you make these trades in a tax-sheltered account like an IRA, but the other problems still apply. You're implicitly assuming that the stock's prices are skewed in the positive direction. Remember that you have limit orders placed at the upper and lower bounds of the range, so if the stock price decreases before it increases, your limit order at the lower bound will be triggered and you'll trade at a loss. If you're hoping to make a profit through buying low and selling high, you want a stock that hits its upper bound before hitting the lower bound the majority of the time. Unless you have data analysis (not just your intuition or a pattern you've talked yourself into from looking at a chart) to back this up, you're essentially gambling that more often than not, the stock price will increase before it decreases. It's dangerous to use any strategy that you haven't backtested extensively. Find several months or years of historical data, either intra-day or daily data, depending on the time frame you're using to trade, and simulate your strategy exactly. This helps you determine the potential profitability of your strategy, and it also forces you to decide on a plan for precisely when you want to invest. Do you invest as soon as the stock trades in a range (which algorithms can determine far better than intuition)? It also helps you figure out how to manage your risk and how much loss you're willing to accept. For risk management, using limit orders is a start, but see my point above about positively skewed prices. Limit orders aren't enough. In general, if an active investment strategy seems like a \"\"no-brainer\"\" or too good to be true, it's probably not viable. In general, as a retail investor, it's foolish to assume that no one else has thought of your simple active strategy to make easy money. I can promise you that someone has thought of it. Trading firms have quantitative researchers that are paid to think of and implement trading strategies all the time. If it's viable at any scale, they'll probably already have utilized it and arbitraged away the potential for small traders to make significant gains. Trust me, you're not the first person who thought of using limit orders to make \"\"easy money\"\" off volatile stocks. The fact that you're asking here and doing research before implementing this strategy, however, means that you're on the right track. It's always wise to research a strategy extensively before deploying it in the wild. To answer the question in your title, since it could be interpreted a little differently than the body of the question: No, there's nothing wrong with investing in volatile stocks, indexes, etc. I certainly do, and I'm sure many others on this site do as well. It's not the investing that gets you into trouble and costs you a lot of money; it's the rapid buying and selling and attempting to time the market that proves costly, which is what you're doing when you implicitly bet that the distribution of the stock's prices is positively skewed. To address the commission fee problem, assuming a fee of $8 per trade ... and a minimum of $100 profit per sale Commissions aren't your only problem, and counting on $100 profit per sale is a significant assumption. Look at point #4 above. Through your use of limit orders, you're making the implicit assumption that, more often than not, the price will trigger your upper limit order before your lower limit order. Here's a simple example; let's assume you have limit orders placed at +2 and -2 of your purchase price, and that triggering the limit order at +2 earns you $100 profit, while triggering the limit order at -2 incurs a loss of $100. Assume your commission is $5 on each trade. If your upper limit order is triggered, you earn a profit of 100 - 10 = 90, then set up the same set of limit orders again. If your lower limit order is triggered this time, you incur a loss of 100 + 10 = 110, so your net gain is 90 - 110 = -20. This is a perfect example of why, when taking into account transaction costs, even strategies that at first glance seem profitable mathematically can actually fail. If you set up the same situation again and incur a loss again (100 + 10 = 110), you're now down -20 - 110 = -130. To make a profit, you need to make two profitable trades, without incurring further losses. This is why point #4 is so important. Whenever you trade, it's critical to completely understand the risk you're taking and the bet you're actually making, not just the bet you think you're making. Also, according to my \"\"algorithm\"\" a sale only takes place once the stock rises by 1 or 2 points; otherwise the stock is held until it does. Does this mean you've removed the lower limit order? If yes, then you expose yourself to downside risk. What if the stock has traded within a range, then suddenly starts declining because of bad earnings reports or systemic risks (to name a few)? If you haven't removed the lower limit order, then point #4 still stands. However, I never specified that the trades have to be done within the same day. Let the investor open up 5 brokerage accounts at 5 different firms (for safeguarding against being labeled a \"\"Pattern Day Trader\"\"). Each account may only hold 1 security at any time, for the span of 1 business week. How do you control how long the security is held? You're using limit orders, which will be triggered when the stock price hits a certain level, regardless of when that happens. Maybe that will happen within a week, or maybe it will happen within the same day. Once again, the bet you're actually making is different from the bet you think you're making. Can you provide some algorithms or methods that do work for generating some extra cash on the side, aside from purchasing S&P 500 type index funds and waiting? When I purchase index funds, it's not to generate extra liquid cash on the side. I don't invest nearly enough to be able to purchase an index fund and earn substantial dividends. I don't want to get into any specific strategies because I'm not in the business of making investment recommendations, and I don't want to start. Furthermore, I don't think explicit investment recommendations are welcome here (unless it's describing why something is a bad idea), and I agree with that policy. I will make a couple of points, however. Understand your goals. Are you investing for retirement or a shorter horizon, e.g. some side income? You seem to know this already, but I include it for future readers. If a strategy seems too good to be true, it probably is. Educate yourself before designing a strategy. Research fundamental analysis, different types of orders (e.g., so you fully understand that you don't have control over when limit orders are executed), different sectors of the market if that's where your interests lie, etc. Personally, I find some sectors fascinating, so researching them thoroughly allows me to make informed investment decisions as well as learn about something that interests me. Understand your limits. How much money are you willing to risk and possibly lose? Do you have a risk management strategy in place to prevent unexpected losses? What are the costs of the risk management itself? Backtest, backtest, backtest. Ideally your backtesting and simulating should be identical to actual market conditions and incorporate all transaction costs and a wide range of historical data. Get other opinions. Evaluate those opinions with the same critical eye as I and others have evaluated your proposed strategy.\"","title":""},{"docid":"492503","text":"I will assume that you are not asking in the context of high frequency trading, as this is Personal Finance Stack Exchange. It is completely acceptable to trade odd lots for retail brokerage customers. The odd lot description that you provided in your link, from Interactive Brokers is correct. But even in that context, it says, regarding the acceptability of odd lots to stock exchanges: The exception is that odd lots can be routed to NYSE/ARCA/AMEX, but only as part of a basket order or as a market-on-close (MOC) order. Google GOOG is traded on the NASDAQ. Everything on the NASDAQ is electronic, and always has been. You will have no problem selling or buying less than 100 shares of Google. There is also an issue of higher commissions with odd lots: While trading commissions for odd lots may still be higher than for standard lots on a percentage basis, the popularity of online trading platforms and the consequent plunge in brokerage commissions means that it is no longer as difficult or expensive for investors to dispose of odd lots as it used to be in the past. Notice what it says about online trading making it easier, not more difficult, to trade odd lots.","title":""},{"docid":"471131","text":"Usually backtests for (long-term) strategies are evaluated on a end-of-day basis where you only consider close prices. If your strategy performs well in these backtests, hopes are that if you use a market-on-close (MOC) order your performance will not diverge too much from the backtest. The fact that it won't diverge much is important if you keep backtesting the strategy along with the real trading to see regime changes or similar. If you used end-of-day prices for the backtests but some arbitrary intraday market order, you'd have some difficulties to explain deviations between the two. What it is: MOC orders can be submitted during the day, but they won't be executed until shortly before the market (or more precise the current session) closes.","title":""},{"docid":"251893","text":"If you have a great technical trading system that gets you winning trading 80-85% of the time in backtesting, the question should be why are you not trading it? To get a better idea of how good your trading system is you should work out your expectancy per trade. This will tell you how much you should make on average for every trade you take. Expectancy not only considers your win rate but also you win size to loss size ratio. For example if you are getting winning trades 80% of the time but your average win size is $100, and your 20% of losses average $500, then you will still be losing money. You should be aiming for an average win size of at least 2.5 to 3 times you average loss size. This will provide you a profitable trading system even if your win rate is 50%. If your trading system is really that good and provides a win size of at least 2.5 times your loss size then you should be actively trading it. Also, if you put your trading system out there in the public domain together with your trading results you will actually find that, quite opposite to what the consensus above is, your results from your trading plan should actually improve further. The more people acting on the outcome of a signal in the same direction the higher the probability that the movement in the desired direction will actually occur. If you are looking to make money from your trading ideas, no one will pay anything unless you have real results to back it up. So if you are so confident about your system you should start trading it with real money. Of course you should start off small and build it up over time as your results eventuate as per your simulations.","title":""},{"docid":"381195","text":"i have been trading with dollarbird Trading firm for past 1 year there is absolutly no problem everything is fine you can google them to find anything about them.they have provided me with LASER trading platform which requires a bit of training as in to know the software but i can say one thing trading in US Equity market exp. is very diffrent from indian market they are very mature market and highly liqd and have good volatality to trade best equity market to trade with great trading platform you should have a exp. to trade on US equity it is diffrent","title":""},{"docid":"98532","text":"Our Finance organization does much of their reporting out of Excel being fed out of SSAS cubes, and beyond that, there's significant need for PowerPivot charts, forecasting, and Monte Carlo simulation, as well as significant use of various plugins and VBA code. We kept Office 365 ProPlus around for Finance and HR. For the rest of the organization, they don't need particularly advanced capabilities for slides, drawing, or word processing, or light spreadsheet capability and we're quite content to output to PDF, Google Sheets, and other things as needed, as well as using cost free alternatives to MS Exchange/Outlook, Visio, and Project. The collaboration is a particular plus, and Google Hangouts is really convenient working from multiple sites/screen sharing. We've done our best to keep our data centralized and universally accessible, in lieu of living in Excel spreadsheets and MS Access databases as tribal knowledge.","title":""},{"docid":"467373","text":"After looking at both S&P GSCI Crude Oil Index Excess Return (INDEXSP:SPGSCLP) and CS VS 3x LC ETN NYSEARCA: UWTI they seem to track well (using Google Finance). I'm not seeing where your statement this ETN loses whether oil is gaining or not holds true. Both have posted a year-over-year loss. In the past year the Crude Oil index has fallen from a high of 494 on October 6, 2014 to a low of 213 as of today October 5th, 2015. So of course the UWTI will lose as well. Please also notice that that, as stated in the prospectus for UWTI: The ETNs are intended to be daily trading tools for sophisticated investors to manage daily trading risks. They are designed t o achieve their stated investment objectives on a daily basis, but their performance over different periods of time can differ significantly fr om their stated daily objectives. The ETNs are riskier than securities that have intermediate or long-term investment objectives, and may not be sui table for investors who plan to hold them for a period other than one day. You might want to look into investing in an ETF for long term investment goals and objectives. Oil ETF List","title":""},{"docid":"97180","text":"Using any simulator will never be exactly the same as real trading. One reason is that a simulator will always execute your trades at the exact price you want, but that may not always happen in real life. For example, if you place a limit order to buy 1000 shares of a stock at 10.50, and the price drops down to exactly 10.50, then the simulator will execute your trade and you will have 1000 shares at 10.50. But in real life, the price of the stock may drop to 10.50, but other people may have buy orders ahead of you. If the price of the stock drops to 10.50 but then starts going up again, you may not get all the shares that you wanted (or you may not even get any shares at all) due to the fact that people were ahead of you. In real trading there is also slippage, which you don't see in a simulator. For example, if you have a stop order to sell 1000 shares of a stock if it drops to 7.50, then the simulator will sell all 1000 shares at 7.50 if the price drops to 7.50. But in real trading, if the price drops to 7.50, then you may not be able to sell all 1000 shares at 7.50 if there's not enough liquidity or the market is moving very fast. You may end up selling 100 shares at 7.50, 100 shares at 7.49, 100 shares at 7.48, 50 shares at 7.47, 50 shares at 7.46, 200 shares at 7.45, and 400 shares at 7.44. Another thing is that you don't experience the emotional aspect of trading with a simulator. If you buy a stock in a simulator and it goes down, it's not real money, so you may be more willing to hold it and wait for it to come back up. But if you are trading real money and the stock goes down, you may not be so willing to hold if it goes down. You may be more apt to sell the stock for a small loss before the loss gets too big.","title":""},{"docid":"181425","text":"\"Because an equity option can be constructed at essentially any price by two willing counterparties on an exchange, there are not enough ISINs to represent the entire (i.e. infinite) option chain for even a single stock on a single expiration date. As a result, ISINs are not generated for each individual possible options contract. Instead the ISIN is used only to refer to the \"\"underlying\"\" symbol, and a separate formula is used to refer to the specific option contract for that symbol: So that code you pasted is not an ISIN but rather the standard US equity option naming scheme that you need to provide in addition to the ISIN when talking to your broker. Note that ISINs and formulas for referring to option contracts in other countries can behave quite differently. Also, there are many countries and markets that don't need ISINs because the products in question only exist on a single exchange. In those cases the exchange is pretty much free to make up whatever ID scheme it wants. P.S. Now I'm curious how option chains are identified for strike prices above $99,999. I looked up the only stock I can think of that trades above that price (BRK.A), but it doesn't seem to have an option chain (or at least Google doesn't show it) ...\"","title":""},{"docid":"128281","text":"\"The professional financial advisors do have tools which will take a general description of a portfolio and run monte-carlo simulations based on the stock market's historical behavior. After about 100 simulation passes they can give a statistical statement about the probable returns, the risk involved in that strategy, and their confidence in these numbers. Note that they do not just use the historical data or individual stocks. There's no way to guarantee that the same historical accidents would have occurred that made one company more successful than another, or that they will again. \"\"Past performance is no guarantee of future results\"\"... but general trends and patterns can be roughly modelled. Which makes that a good fit for those of us buying index funds, less good for those who want to play at a greater level of detail in the hope of doing better. But that's sorta the point; to beat market rate of return with the same kind of statistical confidence takes a lot more work.\"","title":""},{"docid":"81865","text":"This is going to be a bit of a shameless plug, but I've build a portfolio tracking website to track your portfolio and be able to share it (in read-only mode) as well. It is at http://frano.carelessmusings.com and currently in beta. Most portfolio trackers are behind a login wall and thus will lack the sharing function you are looking for. Examples of these are: Yahoo Finance, Google Finance, Reuters Portfolios, MorningStart Portfolios, and many others. Another very quick and easy solution (if you are not trading too often) is a shared google docs spreadsheet. Gdocs has integration with google finance and can retrieve prices for stocks by symbol. A spreadsheet can contain the following: Symbol, Quantity, Avg. Buy Price, Price, P/L, P/L% and so on. The current price and P/L data can be functions that use the google finance API. Hope this helps, and if you check out my site please let me know what you think and what I could change.","title":""},{"docid":"241423","text":"\"See Solid reading/literature for investment/retirement/income taxes? – not exactly the same question, but a great reading list for you. You are putting the cart before the horse here, first, you learn, then you invest. There's a large danger in confusing intelligent investing with \"\"fooling around\"\". The idea that you think you'd like to use derivatives without knowing how or why is a tough one. I suggest you go to Yahoo! Finance and set yourself up with a portfolio (click on the \"\"My Portfolios\"\" tab), in effect, creating your own simulated account. Assume you are starting with some reasonable amount of money, say $10,000, but not $1M, as part of real investing is to learn how to asset allocate the funds you have. Learning that way for a time is the smarter way to start. That said, individual stocks are not for everyone. Most investors can lead a successful investing life by using ETFs or mutual funds of one type or another. Learning to pick individual stocks can be a life's work, and if you put too little time into it, are likely to be disappointed. But learning by 'paper trading' can be a good learning experience nonetheless.\"","title":""},{"docid":"371720","text":"Most of stock trading occurs on what is called a secondary market. For example, Microsoft is traded on NASDAQ, which is a stock exchange. An analogy that can be made is that of selling a used car. When you sell a used car to a third person, the maker of your car is unaffected by this transaction and the same goes for stock trading. Still within the same analogy, when the car is first sold, money goes directly to the maker (actually more complicated than that but good enough for our purposes). In the case of stock trading, this is called an Initial Public Offering (IPO) / Seasoned Public Offering (SPO), for most purposes. What this means is that a drop of value on a secondary market does not directly affect earning potential. Let me add some nuance to this. Say this drop from 20$ to 10$ is permanent and this company needs to finance itself through equity (stock) in the future. It is likely that it would not be able to obtain as much financing in this matter and would either 1) have to rely more on debt and raise its cost of capital or 2) obtain less financing overall. This could potentially affect earnings through less cash available from financing. One last note: in any case, financing does not affect earnings except through cost of capital (i.e. interest paid) because it is neither revenue nor expense. Financing obtained from debt increases assets (cash) and liabilities (debt) and financing obtained from stock issuance increases assets (cash) and shareholder equity.","title":""},{"docid":"445971","text":"\"Back-testing itself is flawed. \"\"Past performance is no guarantee of future results\"\" is an important lesson to understand. Market strategies of one kind or another work until they don't. Edited in -- AssetPlay.net provides a tool that's halfway to what you are looking for. It only goes back to 1972, however. Just to try it, I compared 100% S&P to a 60/40 blend of S&P with 5 yr t-bills (a misnamed asset, 5 yr treasuries are 'notes' not 'bills') I found the mix actually had a better return with lower volatility. Now, can I count on that to work moving forward? Rates fell during most of this entire period so bonds/notes both looked pretty good. This is my point regarding the backtest concept. GeniusTrader appears more sophisticated, but command line work on PCs is beyond me. It may be worth a look for you, JP. ETF Replay appears to be another backtest tool. It has its drawbacks, however, (ETFs only)\"","title":""},{"docid":"206756","text":"How would this trade behave IRL? I don't know how the simulation handles limit orders and bid/ask spreads to know it's feasible, but buying at 4.04 when the current ask is 8.00 seems unlikely. That would mean that all other sell orders between 8.00 and 4.04 were fulfilled, which means that there were very few sellers or that sell pressure spiked, both of which seem unlikely. In reality, it seems more likely that your order would have sat there until the ask dropped to $4.04 (if it ever did), and then you'd have to wait until the bid rose to $7.89 in order to sell them at that price. However, that kind of swing in option prices in not unrealistic. Options near at-the-money tend to move in price at about 50% of the change in the underlying, so if amazon suddenly dropped by $5, the option price could drop by $2.60 (from 6.66 to $4.04), and then rise back to $7.89 if the price rose $8 (which would be 1% swing and not unheard of intra-day). But it sounds like you got very lucky (or the simulation doesn't handle option trading realistically) - I've traded options in the past and have had some breaks similar to yours. I've also had bad breaks where I lost my entire investment (the options expire out-of-the money). So it should be a very limited part of your portfolio, and probably only used for risk management (e.g. buying put options to lock in some gains but keeping some upside potential).","title":""},{"docid":"88105","text":"Based on my experience with OpenQuant, which is a development platform for automated trading strategies (and therefore can be easily be used for backtesting your personal strategy), I can give a little insight into what you might look for in such a platform. OpenQuant is a coding environment, which reads data feeds from a variety of sources (more on that in the second point), and runs the code for your strategy on that data and gives you the results. The data could be imported from a live data feed or from historical data, either through numerous API's, CSV/Excel, etc. You can write your own strategies using the custom C# libraries included with the software, which spares you from implementing your own code for technical indicators, basic statistical functions, etc. Getting the data is another issue. You could use joe's strategy and calculate option prices yourself, although you need to exercise caution when doing this to test a strategy. However, there is no substitute for backtesting a strategy on real data. Markets change over time, and depending on how far back you're interested in testing your strategy, you may run into problems. The reason there is no substitute for using real data is that attempting to replicate the data may fail in some circumstances, and you need a method of verifying that the data you're generating is correct and realistic. Calculating a few values, comparing them to the real values, and calibrating accordingly is a good idea, but you have to decide for yourself how many checks you want to do. More is better, but it may not be enough to realistically test your strategy. Disclaimer: Lest you interpret my post as a shameless plug for the OpenQuant platform, I'll state that I found the interface awful (it looked vaguely like Office 2000 but ten years too late) and the documentation woefully incomplete. I last used the software in 2010, so it may have improved in the intervening years, but your mileage may vary. I only use it as an example to give some insight into what you might look for in a backtesting platform. When you actually begin trading, a different platform is likely in order. That being said, it responded fairly quickly and the learning curve wasn't too steep. The platform wasn't too expensive at the time (about $700 for a license with no data feeds, I think) but I was happy that the cost wasn't coming out of my pocket. It's only gotten more expensive and I'm not sure it's worth it.","title":""},{"docid":"577585","text":"Pivots Points are significant levels technical analysts can use to determine directional movement, support and resistance. Pivot Points use the prior period's high, low and close to formulate future support and resistance. In this regard, Pivot Points are predictive or leading indicators. There are at least five different versions of Pivot Points. I will focus on Standard Pivot Points here as they are the simplest. If you are looking to trade off daily charts you would work out your Pivot Points from the prior month's data. For example, Pivot Points for first trading day of February would be based on the high, low and close for January. They remain the same for the entire month of February. New Pivot Points would then be calculated on the first trading day of March using the high, low and close for February. To work out the Standard Pivot Points you use the High, Low and Close from the previous period (i.e. for daily charts it would be from the previous month) in the following formulas: You will now have 5 horizontal lines: P, R1, R2, S1 and S2 which will set the general tone for price action over the next month. A move above the Pivot Point P suggests strength with a target to the first resistance R1. A break above first resistance shows even more strength with a target to the second resistance level R2. The converse is true on the downside. A move below the Pivot Point P suggests weakness with a target to the first support level S1. A break below the first support level shows even more weakness with a target to the second support level S2. The second resistance and support levels (R2 & S2) can also be used to identify potentially overbought and oversold situations. A move above the second resistance level R2 would show strength, but it would also indicate an overbought situation that could give way to a pullback. Similarly, a move below the second support level S2 would show weakness, but would also suggest a short-term oversold condition that could give way to a bounce. This could be used together with a momentum indicator such as RSI or Stochastic to confirm overbought or oversold conditions. Pivot Points offer a methodology to determine price direction and then set support and resistance levels, however, it is important to confirm Pivot Point signals with other technical analysis indicators, such as candle stick reversal patterns, stochastic and general Support and Resistance Levels in the price action. These pivot points can be handy but I actually haven’t used them for trade setups and entries myself. I prefer to use candle sticks together with stochastic to determine potential turning points and then take out trades based on these. You can then use the Pivot Points Resistance and Support levels to help you estimate profit targets or areas to start becoming cautious and start tightening your stops. Say, for example, you have gone long from a signal you got a few days ago, you are now in profit and the price is now approaching R2 whilst the Stochastic is approaching overbought, you might want to start tightening your stop loss as you might expect some weakness in the price in the near future. If prices continue up you keep increasing your profits, if prices do reverse then you keep the majority of your existing profits. This would become part of your trade management. If you are after finding potential market turning points and take out trades based on these, then I would suggest using candlestick charting reversal patterns for your trade setups. The patterns I like to use most in my trading can be described as either the Hammer or One White Soldier for Bullish reversals and Shooting Star or One Black Crow for Bearish reversals. Below are diagrams of where to place your entries and exits on both Bullish and Bearish reversal patterns. Bullish Reversal Pattern So after some period of weakness in the price you would look for a bullish day where the price closes above the previous day’s high, you place your buy order here just before market close and place your initial stop just below the low of the day. You would apply this either for an uptrending stock where the price has retracted from or near the trendline or Moving Average, or a ranging stock where price is bouncing off the support line. The trade is reinforced if the Stochastic is in or near the oversold and crossing back upwards, volume on the up day is higher than volume on the down days, and the market as a whole is moving up as well. The benefit with this entry is that you are in early so you capture any bullish move up at the open of the next day, such as gaps. The drawbacks are that you need to be in front of your screen before market close to get your price close to the market close and you may get whipsawed if prices reverse at the open of the next day, thus being stopped out with a small loss. As the price moves up you would move your stop loss to just below the low of each day. Alternative Bullish Reversal Entry An alternative, entry would be to wait for after market close and then start your analysis (easier to do after market close than whilst the market is open and less emotions involved). Place a stop buy order to buy at the open of next trading day just above the high of the bullish green candle. Your stop is placed exactly the same, just below the low of the green bullish candle. The benefits of this alternative entry include you avoid the trade if the price reverses at the open of next day, thus avoiding a potential small loss (in other words you wait for further confirmation on the next trading day), and you avoid trading during market open hours where your emotions can get the better of you. I prefer to do my trading after market close so prefer this alternative. The drawback with this alternative is that you may miss out on bullish news prior to and at the next open, so miss out on some potential profits if prices do gap up at the open. This may also increase your loss on the trade if the prices gaps up then reverses and hits your stop on the same day. However, if you choose this method, then you will just need to incorporate this into your trading plan as potential slippage. Bearish Reversal Pattern So after some short period of strength in the price you would look for a bearish day where the price closes below the previous day’s low, you place your sell short order here just before market close and place your initial stop just above the high of the day. You would apply this either for an downtrending stock where the price has retracted from or near the trendline or Moving Average, or a ranging stock where price is bouncing off the resistance line. The trade is reinforced if the Stochastic is in or near the overbought and crossing back downwards, volume on the up day is higher than volume on the up days, and the market as a whole is moving down as well. The benefit with this entry is that you are in early so you capture any bearish move down at the open of the next day, such as gaps. The drawbacks are that you need to be in front of your screen before market close to get your price close to the market close and you may get whipsawed if prices reverse at the open of the next day, thus being stopped out with a small loss. As the price moves down you would move your stop loss to just above the high of each day. Alternative Bearish Reversal Entry An alternative, entry would be to wait for after market close and then start your analysis (easier to do after market close than whilst the market is open and less emotions involved). Place a stop sell short order to sell at the open of next trading day just below the low of the bearish red candle. Your stop is placed exactly the same, just above the high of the red bearish candle. The benefits of this alternative entry include you avoid the trade if the price reverses at the open of next day, thus avoiding a potential small loss (in other words you wait for further confirmation on the next trading day), and you avoid trading during market open hours where your emotions can get the better of you. I prefer to do my trading after market close so prefer this alternative. The drawback with this alternative is that you may miss out on bearish news prior to and at the next open, so miss out on some potential profits if prices do gap down at the open. This may also increase your loss on the trade if the prices gaps down then reverses and hits your stop on the same day. However, if you choose this method, then you will just need to incorporate this into your trading plan as potential slippage. You could also trade other candle stick patterns is similar ways. And with the long entries you can also use them to get into the market with longer term trend following strategies, you would usually just use a larger stop for longer term trading. To determine the size of your order you would use the price difference between your entry and your stop. You should not be risking more than 1% of your trading capital on any one trade. So if your trading capital is $20,000 your risk per trade should be $200. If you were looking to place your buy at 5.00 and had your initial stop at $4.60, you would divide $200 by $0.40 to get 500 stocks to buy. Using this form of money management you keep your losses down to a maximum of $200 (some trades may be a bit higher due to some slippage which you should allow for in your trading plan), which becomes your R-multiple. Your aim is to have your average win at 3R or higher (3 x your average loss), which will give you a positive expectancy even with a win ratio under 50%. Once you have written down your trading rules you can search stock charts for potential setups. When you find one you can backtest the chart for similar setup over the past few years. For each setup in the past jot down the prices you would have entered at, where you would have set your stop, work out your R, and go day by day, moving your stop as you go, and see where you would have been stopped out. Work out your profit or loss in terms of R for each setup and then add them up. If you get a positive R multiple, then this may be a good stock to trade on this setup. If you get a negative R multiple, then maybe give this stock a miss and look for the next setup. You can setup watch-lists of stocks that perform well for both long setups and short setups, and then trade these stocks when you get a new signal. It can take some time starting off, but once you have got your watch-lists for a particular setup, you just need to keep monitoring those stocks. You can create other watch-lists for other type of setups you have backtested as well.","title":""},{"docid":"234892","text":"Yes, exactly. VaR is just a single tailed confidence interval. To go from model to strategy, you need to design some kind of indicator (i.e. when to buy and when to short or stay out). In practice, this will look like a large matrix with values ranging from -1 to 1 (corresponding to shorting and holding respectively) for each security and each day (or hour, or minute, or tick, etc.), which you then just multiply with the matrix of the stock returns. The resulting matrix will be your daily returns for each stock, you can then just row sum for daily returns of a portfolio, or calculate a cumulative product for cumulative returns. A simple example of an indicator would be something like a value of 1 when the price of the stock is below the 30 day moving average, and 0 otherwise. You can use a battery of econometric models to design these indicators, but the rest of the strategy design is essentially the same, and it's *relatively* easy to build a one-size-fits-all back-testing code. I'll try to edit this post later and link a blog that goes through some of the code. Edit: [Here](http://www.signalplot.com/simple-machine-learning-model-trade-spy/) is a post that discusses implementing a simple ML strategy. You can ignore most of the content but if you go through the github, you'll see how the ML model is implemented as a strategy. An even easier example can be found from [the github connected to this post](http://www.signalplot.com/how-to-measure-the-performance-of-a-trading-strategy/), where the author is just using a totally arbitrary signal. As you can see, deriving a signal can be a ton of work, but once you have, actually simulating the strategy can be done in just a few lines of code. Hopefully the author won't mind me linking his page here, but I find his coding style to be very clean and good for educational purposes.","title":""},{"docid":"383399","text":"Algo traders/quants/market backtesters/coders/et al. I am looking to backtest basic things like the correlation of P/E, EV/EBITDA, etc. to market performance. I know a little R and Python. What is the easiest way to learn to backtest this sort of stuff? I want to eventually get into algo trading sort of stuff. I'd **greatly** appreciate it!","title":""},{"docid":"568043","text":"\"Though you're looking to repeat this review with multiple securities and events at different times, I've taken liberty in assuming you are not looking to conduct backtests with hundreds of events. I've answered below assuming it's an ad hoc review for a single event pertaining to one security. Had the event occurred more recently, your full-service broker could often get it for you for free. Even some discount brokers will offer it so. If the stock and its options were actively traded, you can request \"\"time and sales,\"\" or \"\"TNS,\"\" data for the dates you have in mind. If not active, then request \"\"time and quotes,\"\" or \"\"TNQ\"\" data. If the event happened long ago, as seems to be the case, then your choices become much more limited and possibly costly. Below are some suggestions: Wall Street Journal and Investors' Business Daily print copies have daily stock options trading data. They are best for trading data on actively traded options. Since the event sounds like it was a major one for the company, it may have been actively traded that day and hence reported in the papers' listings. Some of the print pages have been digitized; otherwise you'll need to review the archived printed copies. Bloomberg has these data and access to them will depend on whether the account you use has that particular subscription. I've used it to get detailed equity trading data on defunct and delisted companies on specific dates and times and for and futures trading data. If you don't have personal access to Bloomberg, as many do not, you can try to request access from a public, commercial or business school library. The stock options exchanges sell their data; some strictly to resellers and others to anyone willing to pay. If you know which exchange(s) the options traded on, you can contact the exchange's market data services department and request TNS and / or TNQ data and a list of resellers, as the resellers may be cheaper for single queries.\"","title":""},{"docid":"485757","text":"I stumbled on the same discrepancy, and was puzzled by a significant difference between the two prices on ETR and FRA. For example, today is Sunday, and google shows the following closing prices for DAI. FRA:DAI: ETR:DAI: So it looks like there are indeed two different exchanges trading at different prices. Now, the important value here, is the last column (Volume). According to Wikipedia, the trading on Frankfort Stock Exchange is done today exclusively via Xetra platform, thus the volume on ETR:DAI is much more important than on FRA:DAI. Obviously, they Wikipedia is not 100% accurate, i.e. not all trading is done electronically via Xetra. According to their web-page, Frankfort exchange has a Specialist Trading on Frankfurt Floor service which has slightly different trading hours. I suspect what Google and Yahoo show as Frankfort exchange is this manual trading via a Specialist (opposed to Xetra electronic trading). To answer your question, the stock you're having is exactly the same, meaning if you bought an ETR:BMW you can still sell it on FRA (by calling a FRA Trading Floor Specialist which will probably cost you a fee). On the other hand, for the portfolio valuation and performance assessments you should only use ETR:BMW prices, because it is way more liquid, and thus better reflect the current market valuation.","title":""},{"docid":"535470","text":"\"With my current, limited knowledge (see end), I understand it the following way: Are share prices really described as \"\"memoryless\"\"? Yes. Is there a technical meaning of the term? What does it really mean? The meaning comes from Markov Models: Think of the behavior of the stock market over time as a Markov Chain, i.e. a probabilistic model with states and probabilistic transitions. A state is the current price of all stocks of the market, a transition is a step in time. Memoryless means that transitions that the stock market might make can be modelled by a relation from one state to another, i.e. it only depends on the current state. The model is a Markov Chain, as opposed to a more general Stochastic Process where the next state depends on more than the current state. So in a Markov Chain, all the history of one stock is \"\"encoded\"\" already in its current price (more precisely in all stock's prices). The memorylessness of stocks is the main statement of the Efficient Market Theory (EMT). If a company's circumstances don't change, then a drop in its share price is going to be followed by a rise later. So if the EMT holds, your statement above is not necessarily true. I personally belief the EMT is a good approximation - only large corporations (e.g. Renaissance Technologies) have enough ressources (hundreds of mathematicians, billions of $) to be able to leverage tiny non-random movements that stem from a not completely random, mostly chaotic market. The prices can of course change when the company's circumstances change, but they aren't \"\"memoryless\"\" either. A company's future state is influenced by its past. In the EMT, a stock's future state is only influenced by its past as much as is encoded in its current price (more precisely, the complete market's current state). Whether that price was reached by a drop or a rise makes no difference. The above is my believe, but I'm by far no finance expert. I am working professionally with probabilistic models, but have only read one book on finance: Kommer's \"\"Souverän investieren mit Indexfonds und ETFs\"\". It's supposed to contain many statements of Malkiel's \"\"A Random Walk Down Wall Street\"\".\"","title":""},{"docid":"127263","text":"The article links to William Bernstein’s plan that he outlined for Business Insider, which says: Modelling this investment strategy Picking three funds from Google and running some numbers. The international stock index only goes back to April 29th 1996, so a run of 21 years was modelled. Based on 15% of a salary of $550 per month with various annual raises: Broadly speaking, this investment doubles the value of the contributions over two decades. Note: Rebalancing fees are not included in the simulation. Below is the code used to run the simulation. If you have Mathematica you can try with different funds. Notice above how the bond index (VBMFX) preserves value during the 2008 crash. This illustrates the rationale for diversifying across different fund types.","title":""}],"string":"[\n {\n \"docid\": \"78342\",\n \"text\": \"\\\"What do I mean by infrastructure? Well, if you're doing algorithmic trading, you have to have something monitoring data and making decisions on its own, presumably. How do you set that up? There are many ways, and some are better than others. First is a problem of scale. If you're a newbie starting out with some small set of equity tick data, perhaps just trades for instance, you can whip together something that can handle that pretty easily. Check out http://www.marketdatapeaks.com/ though. That's your messaging rates you have to deal with once you go full data feeds direct from all the exchanges. 6.65 million messages/events per second. That's a lot. And if you fall behind, you lose your lunch. Building a robust system that allows you to easily backtest and deploy strategies is crucial as well. The speed at which you're able to conduct the backtest matters a lot. Doing that rapidly, and accurately is not easy. For a broad market-data handling algo design (and now, clearly, for very specific things you can design one that'll handle stuff better for that one corner case, but this is for general algo trading), optimally you have some sort of setup where you have a: [feed handlers] -> [tickerplant] -> [mkt data subscribers/CEP] -> [order management system] -> [broker] in this setup you have feed handlers that are taking the raw exchange feeds and pushing them to a consolidated tickerplant, where CEP subscribers can come through and sub to the data they want (perhaps I just want ES futures on one, and only want to arb CMCSA and CMCSK on another -- you dont want each CEP subscriber getting your full feed for all tickers all the time, its a waste). so more or less, each independent strategy is its own subscriber to the tickerplant, taking whatever data it wants and only that data (could be \\\"\\\"give me all the trades and quotes for all nasdaq stocks, but not book depth\\\"\\\" for instance). your CEP does whatever maths it has to do to figure out trading decisions, and when it does, it sends it to your order management system which does your risk checks, etc (\\\"\\\"do you have enough money to place this trade?\\\"\\\" \\\"\\\"do you already have a position in this?\\\"\\\" \\\"\\\"are you trading against yourself?\\\"\\\" ... million other things). your OMS knows how to talk to your broker/directly to the exchange depending on your setup. Assuming all your risk checks pass, off the order goes to the exchange, and it deals with the fill msgs, etc. Now, as far as speed is concerned - try to do all of this at 6.5 million events/second. It's hard. Some strats/cep subscribers will run faster than others, some are slower, some need to keep a full book to work while some work on just trades. Your OMS depending on if youre using only market data sources may need to keep its own book to place orders on behalf of your subscribers if they lack information about various markets (think all the twitter trading bots these days for instance), etc. If you look back at the above setup as well, you'll notice some interesting things. [tickerplant] -> [cep subscriber] portion can stay the same for live trading or backtesting. This is huge. The only thing that changes here for backtesting is that if you're trying to backtest, you can take historical data (query it out of your hopefully column-store database) and push it into your tickerplant rather than having it come from a live feed through the feed handler. Your tickerplant and cep subscriber will never know the difference, so you can use the same exact code for backtesting as you can for live. On the other end, you obviously cant send historical orders to your live broker, so you need to code a simulated OMS that does the backtest simulation (another huge piece of software to code that is hard to do well). But, for backtesting, your setup is staying largely the same except those two end pieces. This means that testing/deving/deploying strats can be pretty rapid, and uses the same code base for live and historical, which helps you eliminate bugs and have to code everything twice. Backtesting design: [historical mkt data db] -> [tickerplant] -> [mkt data subscribers/CEP] -> [order management system simulator/backtester] These are just a few of the many problems that you hit when trying to dev good infra. There are like a million more. Point was simply, it's complicated. And C++ is a good lang. I use a wide variety of languages depending on exactly whats going on and how fast the code needs to be. With a proper tickerplant design, youre using some ipc protocol so a subscriber can be coded in any language. Check out http://www.zeromq.org/ -- thats an excellent piece of software to use to make a tickerplant out of, think they even have a design for one in the docs if I recall. With that, your CEP subscribers can be in any language - perhaps pure C if you need the speed, perhaps .NET or Java if you dont (check out http://esper.codehaus.org/ for a Java implement of a CEP subscriber, nEsper for the C# port of that I believe). But I use C, C++, C#, python, R, x86 asm for a few very minor things, and a lang or two I can't mention here.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"154525\",\n \"text\": \"You would have to compare your backtesting to what you will be doing in real trading, and try to have the backtesting as close to your real trading as possible. Note: you may never get the backtesting to match your real trading exactly but you need to get as close as possible. The whole purpose of backtesting is to check if your trading strategies - your signals, entries and exits, and your stops - are profitable over various market conditions. As you would be using actual closes to do your real trading you should be using this to also do your backtesting. Rather than using adjusted data to get an idea of your total return from your backtesting, you can always add the value of the dividends and other corporate actions to the results from using the actual data. You may even find a way to add any dividends and other corporate action to your results automatically, i.e. any dividend amount added to your total return if the stock is held during the ex-dividend date. If you are using adjusted data in your backtesting this may affect any stops you have placed, i.e. it may cause your stop to be triggered earlier or later than in real trading. So you will need to determine how you will treat your stops in real trading. Will you adjust them when there is corporate action such as dividends? Or will you leave them constant until actual prices have gone up? If you will be leaving your stops constant then you should definitely be using actual data in your backtesting to better match your real trading.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"49893\",\n \"text\": \"About 10 years ago, I used to use MetaStock Trader which was a very sound tool, with a large number of indicators, but it has been a number of years since I have used it, so my comments on it will be out of date. At the time it relied upon me purchasing trading data myself, which is why I switched to Incredible Charts. I currently use Incredible Charts which I have done for a number of years, initially on the free adware service, now on the $10/year for EOD data access. There are quicker levels of data access, which might suit you, but I can't comment on these. It is web-based which is key for me. The data quality is very good and the number of inbuilt indicators is excellent. You can build search routines on the basis of specific indicators which is very effective. I'm looking at VectorVest, as a replacement for (or in addition to) Incredible Charts, as it has very powerful backtesting routines and the ability to run test portfolios with specific buy/sell criteria that can simulate and backtest a number of trading scenarios at the same time. The advantage of all of these is they are not tied to a particular broker.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"396657\",\n \"text\": \"The study of technical analysis is generally used (sometimes successfully) to time the markets. There are many aspects to technical analysis, but the simplest form is to look for uptrends and downtrends in the charts. Generally higher highs and higher lows is considered an uptrend. And lower lows and lower highs is considered a downtrend. A trend follower would go with the trend, for example see a dip to the trend-line and buy on the rebound. A simple strategy for this is shown in the chart below: I would be buying this stock when the price hits or gets very close to the trendline and then it bounces back above it. I would then have sold this stock once it has broken through below the trendline. This may also be an appropriate time if you were looking to short this stock. Other indicators could also be used in combination for additional confirmation of what is happening to the price. Another type of trader is called a bottom fisher. A bottom fisher would wait until a break above the downtrend line (second chart) and buy after confirmation of a higher high and possibly a higher low (as this could be the start of a new uptrend). There are many more strategies dealing with the study of technical analysis, and if you are interested you would need to find and learn about ones that suit your investment styles, whether you prefer short term trading or longer term investing, and your appetite for risk. You can develop strategies using various indicators and then paper trade or backtest these strategies. You can also manually backtest a strategy in most charting packages. You can go back in time on the chart so that the right side of the chart shows a date in the past (say one year ago or 10 years ago), then you can click forward one day at a time (or one week at a time if using weekly charts). With your indicators on the chart you can do virtual trades to buy or sell whenever a signal is given as you move forward in time. This way you may be able to check years of data in a day to see if your strategy works. Whatever you do, you need to document your strategies in writing in a written trading or investment plan together with a risk management strategy. You should always follow the rules in your written plan to avoid you making decisions based on emotions. By backtesting or paper trading your strategies it will give you confidence that they will work over the long term. There is a lot of work involved at the start, but once you have developed a documented strategy that has been thoroughly backtested, it will take you minimal time to successfully manage your investments. In my shorter term trading (positions held from a couple of days to a few weeks) I spend about half an hour per night to manage my trades and am up about 50% over the last 7 months. For my longer term investing (positions held from months to years) I spend about an hour per week and have been averaging over 25% over the last 4 years. Technical Analysis does work for those who have a documented plan, have approached it in a systematic way and use risk management to protect their existing and future capital. Most people who say that is doesn't work either have not used it themselves or have used it ad-hock without putting in the initial time and work to develop a documented and systematic approach to their trading or investing.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"588481\",\n \"text\": \"\\\"I think you're on the wrong track. Getting more and more samples from the real world does not make your backtest more accurate, it just confirms that your strategy can withstand one particular sample path of a stochastic process. The reason why you find it simple to incorporate fees, commissions, taxes, etc. is because they're a static and constant process -- well they might change over time but most definitely uncorrelated to the markets. Modelling overnight returns or the top levels of the order book the next day is serious work. First you have to select a suitable model (that's mostly theoretical work but experience can help a lot). Then, in order to do it data-driven, you'd have to plough through thousands of days of sample data on a set of thousands of instruments to get a \\\"\\\"feeling\\\"\\\" (aka significant model parameters). Apropos data mining, I think Excel might be the wrong tool for the job. Level-2 data (even just the first 10 levels) is a massive blob. For example, the NYSE OpenBook historical data weighs in at a massive 15 TB compressed (uncompressed 74 TB) for the last 10 years, and costs USD 200k. Anyway, as for other factors to take into account: So how to account for all this in a backtest? Personally, I would put in some penalty terms (as % on a return basis) for every factor you want to consider, don't hardcode them. You can then run a stress test by exploring these parameters (i.e. assign some values in the range of 0 to whatever fits). Explore them individually (only set one penalty term at a time) to get a feeling how the strategy might react to stress from that factor. Then you can run the backtest with typical (or observed) combinations of penalty factors and slowly stress them altogether. Edit Just to avoid confusion about terminology. A backtest in the strict sense (had I implemented this strategy X years ago, what would have happened?) won't benefit from any modelling simply because the real-world \\\"\\\"does the sampling\\\"\\\" for us. However, to evaluate a strategy's robustness you should account for the additional factors and run some stress tests. If the strategy performs well in the real-world or no-stress scenario but produces losses once a tiny slippage occurs every now and again, you could conclude that the strategy is very fragile. The key is to explore the maximum stress the strategy can handle (by whatever measure); if a lot you can call the strategy robust. The latter is what I personally call a backtest; the first procedure would go by the name \\\"\\\"extension towards the past\\\"\\\" or so. Some lightweight literature:\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"573708\",\n \"text\": \"\\\"A couple options that I know of: Interactive Brokers offers a \\\"\\\"paper trading\\\"\\\" mode to its account holders that allows you to start with a pretend stack of money and place simulated trades to test trading ideas. They also provide an API that allows you to interface with their platform programmatically for retrieving quotes, placing orders, and the such. As you noted, however, it's not free; you must hold a funded brokerage account in order to qualify for access to their platform. In order to maintain an account, there are minimums for required equity and monthly activity (measured in dollars that you spend on commissions), so you won't get access to their platform without having a decent amount of skin in the game. IB's native API is Java-based; IbPy is an unofficial wrapper that makes the interface available in Python. I've not used IB at all myself, but I've heard good things about their API and its accessibility via IbPy. Edit: IB now supports Python natively via their published API, so using IbPy is no longer needed, unless you wish to use Python 2.x. The officially supported API is based on Python 3. TD Ameritrade also offers an API that is usable by its brokerage clients. They do not offer any such \\\"\\\"paper trading\\\"\\\" mode, so you would need to \\\"\\\"execute\\\"\\\" transactions based on quotes at the corresponding trade times and then keep track of your simulated account history yourself. The API supports quote retrieval, price history, and trade execution, among other functions. TDA might be more attractive than IB if you're looking for a low-cost link into market data, as I believe their minimum-equity levels are lower. To get access, you'll need to sign up for an API developer account, which I believe requires an NDA. I don't believe there is an official Python implementation of the API, but if you're a capable Python writer, you shouldn't have trouble hooking up to the published interfaces. Some caveats: as when doing any strategy backtesting, you'll want to be sure to be pessimistic when doing so, so your optimism doesn't make your trades look more successful than they would be in the real world. At a minimum, you'll want to ensure that your simulations transact at the posted bid/ask prices, not necessarily the last trade's price, as well as any commissions and fees associated with the trade. A more robust scheme would also take into account the depth of the order book (also known as level 2 quotes), which can cause additional slippage in the prices at which you buy/sell your security. An even more robust scheme would take into account the potential latency of trade execution, looking at all prices over some time period that covers the maximum expected latency and simulating the trade at the worst-possible price.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"484730\",\n \"text\": \"Sounds like you are a candidate for stock trading simulators. Or just pick stocks and use Yahoo! or Google finance tools to track and see how you do. I wouldn't suggest you put real money into it. You need to learn about research and timing and a bunch of other topics you can learn about here. I personally just stick to life cycle funds that are managed products that offer me a cruise control setting for investing.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"146632\",\n \"text\": \"\\\"Yes. There are several downsides to this strategy: You aren't taking into account commissions. If you pay $5 each time you buy or sell a stock, you may greatly reduce or even eliminate any possible gains you would make from trading such small amounts. This next point sounds obvious, but remember that you pay a commission on every trade regardless of profit, so every trade you make that you make at a loss also costs you commissions. Even if you make trades that are profitable more often than not, if you make quite a few trades with small amounts like this, your commissions may eat away all of your profits. Commissions represent a fixed cost, so their effect on your gains decreases proportionally with the amount of money you place at risk in each trade. Since you're in the US, you're required to follow the SEC rules on pattern day trading. From that link, \\\"\\\"FINRA rules define a “pattern day trader” as any customer who executes four or more “day trades” within five business days, provided that the number of day trades represents more than six percent of the customer’s total trades in the margin account for that same five business day period.\\\"\\\" If you trip this rule, you'll be required to maintain $25,000 in a margin brokerage account. If you can't maintain the balance, your account will be locked. Don't forget about capital gains taxes. Since you're holding these securities for less than a year, your gains will be taxed at your ordinary income tax rates. You can deduct your capital losses too (assuming you don't repurchase the same security within 30 days, because in that case, the wash sale rule prevents you from deducting the loss), but it's important to think about gains and losses in real terms, not nominal terms. The story is different if you make these trades in a tax-sheltered account like an IRA, but the other problems still apply. You're implicitly assuming that the stock's prices are skewed in the positive direction. Remember that you have limit orders placed at the upper and lower bounds of the range, so if the stock price decreases before it increases, your limit order at the lower bound will be triggered and you'll trade at a loss. If you're hoping to make a profit through buying low and selling high, you want a stock that hits its upper bound before hitting the lower bound the majority of the time. Unless you have data analysis (not just your intuition or a pattern you've talked yourself into from looking at a chart) to back this up, you're essentially gambling that more often than not, the stock price will increase before it decreases. It's dangerous to use any strategy that you haven't backtested extensively. Find several months or years of historical data, either intra-day or daily data, depending on the time frame you're using to trade, and simulate your strategy exactly. This helps you determine the potential profitability of your strategy, and it also forces you to decide on a plan for precisely when you want to invest. Do you invest as soon as the stock trades in a range (which algorithms can determine far better than intuition)? It also helps you figure out how to manage your risk and how much loss you're willing to accept. For risk management, using limit orders is a start, but see my point above about positively skewed prices. Limit orders aren't enough. In general, if an active investment strategy seems like a \\\"\\\"no-brainer\\\"\\\" or too good to be true, it's probably not viable. In general, as a retail investor, it's foolish to assume that no one else has thought of your simple active strategy to make easy money. I can promise you that someone has thought of it. Trading firms have quantitative researchers that are paid to think of and implement trading strategies all the time. If it's viable at any scale, they'll probably already have utilized it and arbitraged away the potential for small traders to make significant gains. Trust me, you're not the first person who thought of using limit orders to make \\\"\\\"easy money\\\"\\\" off volatile stocks. The fact that you're asking here and doing research before implementing this strategy, however, means that you're on the right track. It's always wise to research a strategy extensively before deploying it in the wild. To answer the question in your title, since it could be interpreted a little differently than the body of the question: No, there's nothing wrong with investing in volatile stocks, indexes, etc. I certainly do, and I'm sure many others on this site do as well. It's not the investing that gets you into trouble and costs you a lot of money; it's the rapid buying and selling and attempting to time the market that proves costly, which is what you're doing when you implicitly bet that the distribution of the stock's prices is positively skewed. To address the commission fee problem, assuming a fee of $8 per trade ... and a minimum of $100 profit per sale Commissions aren't your only problem, and counting on $100 profit per sale is a significant assumption. Look at point #4 above. Through your use of limit orders, you're making the implicit assumption that, more often than not, the price will trigger your upper limit order before your lower limit order. Here's a simple example; let's assume you have limit orders placed at +2 and -2 of your purchase price, and that triggering the limit order at +2 earns you $100 profit, while triggering the limit order at -2 incurs a loss of $100. Assume your commission is $5 on each trade. If your upper limit order is triggered, you earn a profit of 100 - 10 = 90, then set up the same set of limit orders again. If your lower limit order is triggered this time, you incur a loss of 100 + 10 = 110, so your net gain is 90 - 110 = -20. This is a perfect example of why, when taking into account transaction costs, even strategies that at first glance seem profitable mathematically can actually fail. If you set up the same situation again and incur a loss again (100 + 10 = 110), you're now down -20 - 110 = -130. To make a profit, you need to make two profitable trades, without incurring further losses. This is why point #4 is so important. Whenever you trade, it's critical to completely understand the risk you're taking and the bet you're actually making, not just the bet you think you're making. Also, according to my \\\"\\\"algorithm\\\"\\\" a sale only takes place once the stock rises by 1 or 2 points; otherwise the stock is held until it does. Does this mean you've removed the lower limit order? If yes, then you expose yourself to downside risk. What if the stock has traded within a range, then suddenly starts declining because of bad earnings reports or systemic risks (to name a few)? If you haven't removed the lower limit order, then point #4 still stands. However, I never specified that the trades have to be done within the same day. Let the investor open up 5 brokerage accounts at 5 different firms (for safeguarding against being labeled a \\\"\\\"Pattern Day Trader\\\"\\\"). Each account may only hold 1 security at any time, for the span of 1 business week. How do you control how long the security is held? You're using limit orders, which will be triggered when the stock price hits a certain level, regardless of when that happens. Maybe that will happen within a week, or maybe it will happen within the same day. Once again, the bet you're actually making is different from the bet you think you're making. Can you provide some algorithms or methods that do work for generating some extra cash on the side, aside from purchasing S&P 500 type index funds and waiting? When I purchase index funds, it's not to generate extra liquid cash on the side. I don't invest nearly enough to be able to purchase an index fund and earn substantial dividends. I don't want to get into any specific strategies because I'm not in the business of making investment recommendations, and I don't want to start. Furthermore, I don't think explicit investment recommendations are welcome here (unless it's describing why something is a bad idea), and I agree with that policy. I will make a couple of points, however. Understand your goals. Are you investing for retirement or a shorter horizon, e.g. some side income? You seem to know this already, but I include it for future readers. If a strategy seems too good to be true, it probably is. Educate yourself before designing a strategy. Research fundamental analysis, different types of orders (e.g., so you fully understand that you don't have control over when limit orders are executed), different sectors of the market if that's where your interests lie, etc. Personally, I find some sectors fascinating, so researching them thoroughly allows me to make informed investment decisions as well as learn about something that interests me. Understand your limits. How much money are you willing to risk and possibly lose? Do you have a risk management strategy in place to prevent unexpected losses? What are the costs of the risk management itself? Backtest, backtest, backtest. Ideally your backtesting and simulating should be identical to actual market conditions and incorporate all transaction costs and a wide range of historical data. Get other opinions. Evaluate those opinions with the same critical eye as I and others have evaluated your proposed strategy.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"492503\",\n \"text\": \"I will assume that you are not asking in the context of high frequency trading, as this is Personal Finance Stack Exchange. It is completely acceptable to trade odd lots for retail brokerage customers. The odd lot description that you provided in your link, from Interactive Brokers is correct. But even in that context, it says, regarding the acceptability of odd lots to stock exchanges: The exception is that odd lots can be routed to NYSE/ARCA/AMEX, but only as part of a basket order or as a market-on-close (MOC) order. Google GOOG is traded on the NASDAQ. Everything on the NASDAQ is electronic, and always has been. You will have no problem selling or buying less than 100 shares of Google. There is also an issue of higher commissions with odd lots: While trading commissions for odd lots may still be higher than for standard lots on a percentage basis, the popularity of online trading platforms and the consequent plunge in brokerage commissions means that it is no longer as difficult or expensive for investors to dispose of odd lots as it used to be in the past. Notice what it says about online trading making it easier, not more difficult, to trade odd lots.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"471131\",\n \"text\": \"Usually backtests for (long-term) strategies are evaluated on a end-of-day basis where you only consider close prices. If your strategy performs well in these backtests, hopes are that if you use a market-on-close (MOC) order your performance will not diverge too much from the backtest. The fact that it won't diverge much is important if you keep backtesting the strategy along with the real trading to see regime changes or similar. If you used end-of-day prices for the backtests but some arbitrary intraday market order, you'd have some difficulties to explain deviations between the two. What it is: MOC orders can be submitted during the day, but they won't be executed until shortly before the market (or more precise the current session) closes.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"251893\",\n \"text\": \"If you have a great technical trading system that gets you winning trading 80-85% of the time in backtesting, the question should be why are you not trading it? To get a better idea of how good your trading system is you should work out your expectancy per trade. This will tell you how much you should make on average for every trade you take. Expectancy not only considers your win rate but also you win size to loss size ratio. For example if you are getting winning trades 80% of the time but your average win size is $100, and your 20% of losses average $500, then you will still be losing money. You should be aiming for an average win size of at least 2.5 to 3 times you average loss size. This will provide you a profitable trading system even if your win rate is 50%. If your trading system is really that good and provides a win size of at least 2.5 times your loss size then you should be actively trading it. Also, if you put your trading system out there in the public domain together with your trading results you will actually find that, quite opposite to what the consensus above is, your results from your trading plan should actually improve further. The more people acting on the outcome of a signal in the same direction the higher the probability that the movement in the desired direction will actually occur. If you are looking to make money from your trading ideas, no one will pay anything unless you have real results to back it up. So if you are so confident about your system you should start trading it with real money. Of course you should start off small and build it up over time as your results eventuate as per your simulations.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"381195\",\n \"text\": \"i have been trading with dollarbird Trading firm for past 1 year there is absolutly no problem everything is fine you can google them to find anything about them.they have provided me with LASER trading platform which requires a bit of training as in to know the software but i can say one thing trading in US Equity market exp. is very diffrent from indian market they are very mature market and highly liqd and have good volatality to trade best equity market to trade with great trading platform you should have a exp. to trade on US equity it is diffrent\",\n \"title\": \"\"\n },\n {\n \"docid\": \"98532\",\n \"text\": \"Our Finance organization does much of their reporting out of Excel being fed out of SSAS cubes, and beyond that, there's significant need for PowerPivot charts, forecasting, and Monte Carlo simulation, as well as significant use of various plugins and VBA code. We kept Office 365 ProPlus around for Finance and HR. For the rest of the organization, they don't need particularly advanced capabilities for slides, drawing, or word processing, or light spreadsheet capability and we're quite content to output to PDF, Google Sheets, and other things as needed, as well as using cost free alternatives to MS Exchange/Outlook, Visio, and Project. The collaboration is a particular plus, and Google Hangouts is really convenient working from multiple sites/screen sharing. We've done our best to keep our data centralized and universally accessible, in lieu of living in Excel spreadsheets and MS Access databases as tribal knowledge.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"467373\",\n \"text\": \"After looking at both S&P GSCI Crude Oil Index Excess Return (INDEXSP:SPGSCLP) and CS VS 3x LC ETN NYSEARCA: UWTI they seem to track well (using Google Finance). I'm not seeing where your statement this ETN loses whether oil is gaining or not holds true. Both have posted a year-over-year loss. In the past year the Crude Oil index has fallen from a high of 494 on October 6, 2014 to a low of 213 as of today October 5th, 2015. So of course the UWTI will lose as well. Please also notice that that, as stated in the prospectus for UWTI: The ETNs are intended to be daily trading tools for sophisticated investors to manage daily trading risks. They are designed t o achieve their stated investment objectives on a daily basis, but their performance over different periods of time can differ significantly fr om their stated daily objectives. The ETNs are riskier than securities that have intermediate or long-term investment objectives, and may not be sui table for investors who plan to hold them for a period other than one day. You might want to look into investing in an ETF for long term investment goals and objectives. Oil ETF List\",\n \"title\": \"\"\n },\n {\n \"docid\": \"97180\",\n \"text\": \"Using any simulator will never be exactly the same as real trading. One reason is that a simulator will always execute your trades at the exact price you want, but that may not always happen in real life. For example, if you place a limit order to buy 1000 shares of a stock at 10.50, and the price drops down to exactly 10.50, then the simulator will execute your trade and you will have 1000 shares at 10.50. But in real life, the price of the stock may drop to 10.50, but other people may have buy orders ahead of you. If the price of the stock drops to 10.50 but then starts going up again, you may not get all the shares that you wanted (or you may not even get any shares at all) due to the fact that people were ahead of you. In real trading there is also slippage, which you don't see in a simulator. For example, if you have a stop order to sell 1000 shares of a stock if it drops to 7.50, then the simulator will sell all 1000 shares at 7.50 if the price drops to 7.50. But in real trading, if the price drops to 7.50, then you may not be able to sell all 1000 shares at 7.50 if there's not enough liquidity or the market is moving very fast. You may end up selling 100 shares at 7.50, 100 shares at 7.49, 100 shares at 7.48, 50 shares at 7.47, 50 shares at 7.46, 200 shares at 7.45, and 400 shares at 7.44. Another thing is that you don't experience the emotional aspect of trading with a simulator. If you buy a stock in a simulator and it goes down, it's not real money, so you may be more willing to hold it and wait for it to come back up. But if you are trading real money and the stock goes down, you may not be so willing to hold if it goes down. You may be more apt to sell the stock for a small loss before the loss gets too big.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"181425\",\n \"text\": \"\\\"Because an equity option can be constructed at essentially any price by two willing counterparties on an exchange, there are not enough ISINs to represent the entire (i.e. infinite) option chain for even a single stock on a single expiration date. As a result, ISINs are not generated for each individual possible options contract. Instead the ISIN is used only to refer to the \\\"\\\"underlying\\\"\\\" symbol, and a separate formula is used to refer to the specific option contract for that symbol: So that code you pasted is not an ISIN but rather the standard US equity option naming scheme that you need to provide in addition to the ISIN when talking to your broker. Note that ISINs and formulas for referring to option contracts in other countries can behave quite differently. Also, there are many countries and markets that don't need ISINs because the products in question only exist on a single exchange. In those cases the exchange is pretty much free to make up whatever ID scheme it wants. P.S. Now I'm curious how option chains are identified for strike prices above $99,999. I looked up the only stock I can think of that trades above that price (BRK.A), but it doesn't seem to have an option chain (or at least Google doesn't show it) ...\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"128281\",\n \"text\": \"\\\"The professional financial advisors do have tools which will take a general description of a portfolio and run monte-carlo simulations based on the stock market's historical behavior. After about 100 simulation passes they can give a statistical statement about the probable returns, the risk involved in that strategy, and their confidence in these numbers. Note that they do not just use the historical data or individual stocks. There's no way to guarantee that the same historical accidents would have occurred that made one company more successful than another, or that they will again. \\\"\\\"Past performance is no guarantee of future results\\\"\\\"... but general trends and patterns can be roughly modelled. Which makes that a good fit for those of us buying index funds, less good for those who want to play at a greater level of detail in the hope of doing better. But that's sorta the point; to beat market rate of return with the same kind of statistical confidence takes a lot more work.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"81865\",\n \"text\": \"This is going to be a bit of a shameless plug, but I've build a portfolio tracking website to track your portfolio and be able to share it (in read-only mode) as well. It is at http://frano.carelessmusings.com and currently in beta. Most portfolio trackers are behind a login wall and thus will lack the sharing function you are looking for. Examples of these are: Yahoo Finance, Google Finance, Reuters Portfolios, MorningStart Portfolios, and many others. Another very quick and easy solution (if you are not trading too often) is a shared google docs spreadsheet. Gdocs has integration with google finance and can retrieve prices for stocks by symbol. A spreadsheet can contain the following: Symbol, Quantity, Avg. Buy Price, Price, P/L, P/L% and so on. The current price and P/L data can be functions that use the google finance API. Hope this helps, and if you check out my site please let me know what you think and what I could change.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"241423\",\n \"text\": \"\\\"See Solid reading/literature for investment/retirement/income taxes? – not exactly the same question, but a great reading list for you. You are putting the cart before the horse here, first, you learn, then you invest. There's a large danger in confusing intelligent investing with \\\"\\\"fooling around\\\"\\\". The idea that you think you'd like to use derivatives without knowing how or why is a tough one. I suggest you go to Yahoo! Finance and set yourself up with a portfolio (click on the \\\"\\\"My Portfolios\\\"\\\" tab), in effect, creating your own simulated account. Assume you are starting with some reasonable amount of money, say $10,000, but not $1M, as part of real investing is to learn how to asset allocate the funds you have. Learning that way for a time is the smarter way to start. That said, individual stocks are not for everyone. Most investors can lead a successful investing life by using ETFs or mutual funds of one type or another. Learning to pick individual stocks can be a life's work, and if you put too little time into it, are likely to be disappointed. But learning by 'paper trading' can be a good learning experience nonetheless.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"371720\",\n \"text\": \"Most of stock trading occurs on what is called a secondary market. For example, Microsoft is traded on NASDAQ, which is a stock exchange. An analogy that can be made is that of selling a used car. When you sell a used car to a third person, the maker of your car is unaffected by this transaction and the same goes for stock trading. Still within the same analogy, when the car is first sold, money goes directly to the maker (actually more complicated than that but good enough for our purposes). In the case of stock trading, this is called an Initial Public Offering (IPO) / Seasoned Public Offering (SPO), for most purposes. What this means is that a drop of value on a secondary market does not directly affect earning potential. Let me add some nuance to this. Say this drop from 20$ to 10$ is permanent and this company needs to finance itself through equity (stock) in the future. It is likely that it would not be able to obtain as much financing in this matter and would either 1) have to rely more on debt and raise its cost of capital or 2) obtain less financing overall. This could potentially affect earnings through less cash available from financing. One last note: in any case, financing does not affect earnings except through cost of capital (i.e. interest paid) because it is neither revenue nor expense. Financing obtained from debt increases assets (cash) and liabilities (debt) and financing obtained from stock issuance increases assets (cash) and shareholder equity.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"445971\",\n \"text\": \"\\\"Back-testing itself is flawed. \\\"\\\"Past performance is no guarantee of future results\\\"\\\" is an important lesson to understand. Market strategies of one kind or another work until they don't. Edited in -- AssetPlay.net provides a tool that's halfway to what you are looking for. It only goes back to 1972, however. Just to try it, I compared 100% S&P to a 60/40 blend of S&P with 5 yr t-bills (a misnamed asset, 5 yr treasuries are 'notes' not 'bills') I found the mix actually had a better return with lower volatility. Now, can I count on that to work moving forward? Rates fell during most of this entire period so bonds/notes both looked pretty good. This is my point regarding the backtest concept. GeniusTrader appears more sophisticated, but command line work on PCs is beyond me. It may be worth a look for you, JP. ETF Replay appears to be another backtest tool. It has its drawbacks, however, (ETFs only)\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"206756\",\n \"text\": \"How would this trade behave IRL? I don't know how the simulation handles limit orders and bid/ask spreads to know it's feasible, but buying at 4.04 when the current ask is 8.00 seems unlikely. That would mean that all other sell orders between 8.00 and 4.04 were fulfilled, which means that there were very few sellers or that sell pressure spiked, both of which seem unlikely. In reality, it seems more likely that your order would have sat there until the ask dropped to $4.04 (if it ever did), and then you'd have to wait until the bid rose to $7.89 in order to sell them at that price. However, that kind of swing in option prices in not unrealistic. Options near at-the-money tend to move in price at about 50% of the change in the underlying, so if amazon suddenly dropped by $5, the option price could drop by $2.60 (from 6.66 to $4.04), and then rise back to $7.89 if the price rose $8 (which would be 1% swing and not unheard of intra-day). But it sounds like you got very lucky (or the simulation doesn't handle option trading realistically) - I've traded options in the past and have had some breaks similar to yours. I've also had bad breaks where I lost my entire investment (the options expire out-of-the money). So it should be a very limited part of your portfolio, and probably only used for risk management (e.g. buying put options to lock in some gains but keeping some upside potential).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"88105\",\n \"text\": \"Based on my experience with OpenQuant, which is a development platform for automated trading strategies (and therefore can be easily be used for backtesting your personal strategy), I can give a little insight into what you might look for in such a platform. OpenQuant is a coding environment, which reads data feeds from a variety of sources (more on that in the second point), and runs the code for your strategy on that data and gives you the results. The data could be imported from a live data feed or from historical data, either through numerous API's, CSV/Excel, etc. You can write your own strategies using the custom C# libraries included with the software, which spares you from implementing your own code for technical indicators, basic statistical functions, etc. Getting the data is another issue. You could use joe's strategy and calculate option prices yourself, although you need to exercise caution when doing this to test a strategy. However, there is no substitute for backtesting a strategy on real data. Markets change over time, and depending on how far back you're interested in testing your strategy, you may run into problems. The reason there is no substitute for using real data is that attempting to replicate the data may fail in some circumstances, and you need a method of verifying that the data you're generating is correct and realistic. Calculating a few values, comparing them to the real values, and calibrating accordingly is a good idea, but you have to decide for yourself how many checks you want to do. More is better, but it may not be enough to realistically test your strategy. Disclaimer: Lest you interpret my post as a shameless plug for the OpenQuant platform, I'll state that I found the interface awful (it looked vaguely like Office 2000 but ten years too late) and the documentation woefully incomplete. I last used the software in 2010, so it may have improved in the intervening years, but your mileage may vary. I only use it as an example to give some insight into what you might look for in a backtesting platform. When you actually begin trading, a different platform is likely in order. That being said, it responded fairly quickly and the learning curve wasn't too steep. The platform wasn't too expensive at the time (about $700 for a license with no data feeds, I think) but I was happy that the cost wasn't coming out of my pocket. It's only gotten more expensive and I'm not sure it's worth it.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"577585\",\n \"text\": \"Pivots Points are significant levels technical analysts can use to determine directional movement, support and resistance. Pivot Points use the prior period's high, low and close to formulate future support and resistance. In this regard, Pivot Points are predictive or leading indicators. There are at least five different versions of Pivot Points. I will focus on Standard Pivot Points here as they are the simplest. If you are looking to trade off daily charts you would work out your Pivot Points from the prior month's data. For example, Pivot Points for first trading day of February would be based on the high, low and close for January. They remain the same for the entire month of February. New Pivot Points would then be calculated on the first trading day of March using the high, low and close for February. To work out the Standard Pivot Points you use the High, Low and Close from the previous period (i.e. for daily charts it would be from the previous month) in the following formulas: You will now have 5 horizontal lines: P, R1, R2, S1 and S2 which will set the general tone for price action over the next month. A move above the Pivot Point P suggests strength with a target to the first resistance R1. A break above first resistance shows even more strength with a target to the second resistance level R2. The converse is true on the downside. A move below the Pivot Point P suggests weakness with a target to the first support level S1. A break below the first support level shows even more weakness with a target to the second support level S2. The second resistance and support levels (R2 & S2) can also be used to identify potentially overbought and oversold situations. A move above the second resistance level R2 would show strength, but it would also indicate an overbought situation that could give way to a pullback. Similarly, a move below the second support level S2 would show weakness, but would also suggest a short-term oversold condition that could give way to a bounce. This could be used together with a momentum indicator such as RSI or Stochastic to confirm overbought or oversold conditions. Pivot Points offer a methodology to determine price direction and then set support and resistance levels, however, it is important to confirm Pivot Point signals with other technical analysis indicators, such as candle stick reversal patterns, stochastic and general Support and Resistance Levels in the price action. These pivot points can be handy but I actually haven’t used them for trade setups and entries myself. I prefer to use candle sticks together with stochastic to determine potential turning points and then take out trades based on these. You can then use the Pivot Points Resistance and Support levels to help you estimate profit targets or areas to start becoming cautious and start tightening your stops. Say, for example, you have gone long from a signal you got a few days ago, you are now in profit and the price is now approaching R2 whilst the Stochastic is approaching overbought, you might want to start tightening your stop loss as you might expect some weakness in the price in the near future. If prices continue up you keep increasing your profits, if prices do reverse then you keep the majority of your existing profits. This would become part of your trade management. If you are after finding potential market turning points and take out trades based on these, then I would suggest using candlestick charting reversal patterns for your trade setups. The patterns I like to use most in my trading can be described as either the Hammer or One White Soldier for Bullish reversals and Shooting Star or One Black Crow for Bearish reversals. Below are diagrams of where to place your entries and exits on both Bullish and Bearish reversal patterns. Bullish Reversal Pattern So after some period of weakness in the price you would look for a bullish day where the price closes above the previous day’s high, you place your buy order here just before market close and place your initial stop just below the low of the day. You would apply this either for an uptrending stock where the price has retracted from or near the trendline or Moving Average, or a ranging stock where price is bouncing off the support line. The trade is reinforced if the Stochastic is in or near the oversold and crossing back upwards, volume on the up day is higher than volume on the down days, and the market as a whole is moving up as well. The benefit with this entry is that you are in early so you capture any bullish move up at the open of the next day, such as gaps. The drawbacks are that you need to be in front of your screen before market close to get your price close to the market close and you may get whipsawed if prices reverse at the open of the next day, thus being stopped out with a small loss. As the price moves up you would move your stop loss to just below the low of each day. Alternative Bullish Reversal Entry An alternative, entry would be to wait for after market close and then start your analysis (easier to do after market close than whilst the market is open and less emotions involved). Place a stop buy order to buy at the open of next trading day just above the high of the bullish green candle. Your stop is placed exactly the same, just below the low of the green bullish candle. The benefits of this alternative entry include you avoid the trade if the price reverses at the open of next day, thus avoiding a potential small loss (in other words you wait for further confirmation on the next trading day), and you avoid trading during market open hours where your emotions can get the better of you. I prefer to do my trading after market close so prefer this alternative. The drawback with this alternative is that you may miss out on bullish news prior to and at the next open, so miss out on some potential profits if prices do gap up at the open. This may also increase your loss on the trade if the prices gaps up then reverses and hits your stop on the same day. However, if you choose this method, then you will just need to incorporate this into your trading plan as potential slippage. Bearish Reversal Pattern So after some short period of strength in the price you would look for a bearish day where the price closes below the previous day’s low, you place your sell short order here just before market close and place your initial stop just above the high of the day. You would apply this either for an downtrending stock where the price has retracted from or near the trendline or Moving Average, or a ranging stock where price is bouncing off the resistance line. The trade is reinforced if the Stochastic is in or near the overbought and crossing back downwards, volume on the up day is higher than volume on the up days, and the market as a whole is moving down as well. The benefit with this entry is that you are in early so you capture any bearish move down at the open of the next day, such as gaps. The drawbacks are that you need to be in front of your screen before market close to get your price close to the market close and you may get whipsawed if prices reverse at the open of the next day, thus being stopped out with a small loss. As the price moves down you would move your stop loss to just above the high of each day. Alternative Bearish Reversal Entry An alternative, entry would be to wait for after market close and then start your analysis (easier to do after market close than whilst the market is open and less emotions involved). Place a stop sell short order to sell at the open of next trading day just below the low of the bearish red candle. Your stop is placed exactly the same, just above the high of the red bearish candle. The benefits of this alternative entry include you avoid the trade if the price reverses at the open of next day, thus avoiding a potential small loss (in other words you wait for further confirmation on the next trading day), and you avoid trading during market open hours where your emotions can get the better of you. I prefer to do my trading after market close so prefer this alternative. The drawback with this alternative is that you may miss out on bearish news prior to and at the next open, so miss out on some potential profits if prices do gap down at the open. This may also increase your loss on the trade if the prices gaps down then reverses and hits your stop on the same day. However, if you choose this method, then you will just need to incorporate this into your trading plan as potential slippage. You could also trade other candle stick patterns is similar ways. And with the long entries you can also use them to get into the market with longer term trend following strategies, you would usually just use a larger stop for longer term trading. To determine the size of your order you would use the price difference between your entry and your stop. You should not be risking more than 1% of your trading capital on any one trade. So if your trading capital is $20,000 your risk per trade should be $200. If you were looking to place your buy at 5.00 and had your initial stop at $4.60, you would divide $200 by $0.40 to get 500 stocks to buy. Using this form of money management you keep your losses down to a maximum of $200 (some trades may be a bit higher due to some slippage which you should allow for in your trading plan), which becomes your R-multiple. Your aim is to have your average win at 3R or higher (3 x your average loss), which will give you a positive expectancy even with a win ratio under 50%. Once you have written down your trading rules you can search stock charts for potential setups. When you find one you can backtest the chart for similar setup over the past few years. For each setup in the past jot down the prices you would have entered at, where you would have set your stop, work out your R, and go day by day, moving your stop as you go, and see where you would have been stopped out. Work out your profit or loss in terms of R for each setup and then add them up. If you get a positive R multiple, then this may be a good stock to trade on this setup. If you get a negative R multiple, then maybe give this stock a miss and look for the next setup. You can setup watch-lists of stocks that perform well for both long setups and short setups, and then trade these stocks when you get a new signal. It can take some time starting off, but once you have got your watch-lists for a particular setup, you just need to keep monitoring those stocks. You can create other watch-lists for other type of setups you have backtested as well.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"234892\",\n \"text\": \"Yes, exactly. VaR is just a single tailed confidence interval. To go from model to strategy, you need to design some kind of indicator (i.e. when to buy and when to short or stay out). In practice, this will look like a large matrix with values ranging from -1 to 1 (corresponding to shorting and holding respectively) for each security and each day (or hour, or minute, or tick, etc.), which you then just multiply with the matrix of the stock returns. The resulting matrix will be your daily returns for each stock, you can then just row sum for daily returns of a portfolio, or calculate a cumulative product for cumulative returns. A simple example of an indicator would be something like a value of 1 when the price of the stock is below the 30 day moving average, and 0 otherwise. You can use a battery of econometric models to design these indicators, but the rest of the strategy design is essentially the same, and it's *relatively* easy to build a one-size-fits-all back-testing code. I'll try to edit this post later and link a blog that goes through some of the code. Edit: [Here](http://www.signalplot.com/simple-machine-learning-model-trade-spy/) is a post that discusses implementing a simple ML strategy. You can ignore most of the content but if you go through the github, you'll see how the ML model is implemented as a strategy. An even easier example can be found from [the github connected to this post](http://www.signalplot.com/how-to-measure-the-performance-of-a-trading-strategy/), where the author is just using a totally arbitrary signal. As you can see, deriving a signal can be a ton of work, but once you have, actually simulating the strategy can be done in just a few lines of code. Hopefully the author won't mind me linking his page here, but I find his coding style to be very clean and good for educational purposes.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"383399\",\n \"text\": \"Algo traders/quants/market backtesters/coders/et al. I am looking to backtest basic things like the correlation of P/E, EV/EBITDA, etc. to market performance. I know a little R and Python. What is the easiest way to learn to backtest this sort of stuff? I want to eventually get into algo trading sort of stuff. I'd **greatly** appreciate it!\",\n \"title\": \"\"\n },\n {\n \"docid\": \"568043\",\n \"text\": \"\\\"Though you're looking to repeat this review with multiple securities and events at different times, I've taken liberty in assuming you are not looking to conduct backtests with hundreds of events. I've answered below assuming it's an ad hoc review for a single event pertaining to one security. Had the event occurred more recently, your full-service broker could often get it for you for free. Even some discount brokers will offer it so. If the stock and its options were actively traded, you can request \\\"\\\"time and sales,\\\"\\\" or \\\"\\\"TNS,\\\"\\\" data for the dates you have in mind. If not active, then request \\\"\\\"time and quotes,\\\"\\\" or \\\"\\\"TNQ\\\"\\\" data. If the event happened long ago, as seems to be the case, then your choices become much more limited and possibly costly. Below are some suggestions: Wall Street Journal and Investors' Business Daily print copies have daily stock options trading data. They are best for trading data on actively traded options. Since the event sounds like it was a major one for the company, it may have been actively traded that day and hence reported in the papers' listings. Some of the print pages have been digitized; otherwise you'll need to review the archived printed copies. Bloomberg has these data and access to them will depend on whether the account you use has that particular subscription. I've used it to get detailed equity trading data on defunct and delisted companies on specific dates and times and for and futures trading data. If you don't have personal access to Bloomberg, as many do not, you can try to request access from a public, commercial or business school library. The stock options exchanges sell their data; some strictly to resellers and others to anyone willing to pay. If you know which exchange(s) the options traded on, you can contact the exchange's market data services department and request TNS and / or TNQ data and a list of resellers, as the resellers may be cheaper for single queries.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"485757\",\n \"text\": \"I stumbled on the same discrepancy, and was puzzled by a significant difference between the two prices on ETR and FRA. For example, today is Sunday, and google shows the following closing prices for DAI. FRA:DAI: ETR:DAI: So it looks like there are indeed two different exchanges trading at different prices. Now, the important value here, is the last column (Volume). According to Wikipedia, the trading on Frankfort Stock Exchange is done today exclusively via Xetra platform, thus the volume on ETR:DAI is much more important than on FRA:DAI. Obviously, they Wikipedia is not 100% accurate, i.e. not all trading is done electronically via Xetra. According to their web-page, Frankfort exchange has a Specialist Trading on Frankfurt Floor service which has slightly different trading hours. I suspect what Google and Yahoo show as Frankfort exchange is this manual trading via a Specialist (opposed to Xetra electronic trading). To answer your question, the stock you're having is exactly the same, meaning if you bought an ETR:BMW you can still sell it on FRA (by calling a FRA Trading Floor Specialist which will probably cost you a fee). On the other hand, for the portfolio valuation and performance assessments you should only use ETR:BMW prices, because it is way more liquid, and thus better reflect the current market valuation.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"535470\",\n \"text\": \"\\\"With my current, limited knowledge (see end), I understand it the following way: Are share prices really described as \\\"\\\"memoryless\\\"\\\"? Yes. Is there a technical meaning of the term? What does it really mean? The meaning comes from Markov Models: Think of the behavior of the stock market over time as a Markov Chain, i.e. a probabilistic model with states and probabilistic transitions. A state is the current price of all stocks of the market, a transition is a step in time. Memoryless means that transitions that the stock market might make can be modelled by a relation from one state to another, i.e. it only depends on the current state. The model is a Markov Chain, as opposed to a more general Stochastic Process where the next state depends on more than the current state. So in a Markov Chain, all the history of one stock is \\\"\\\"encoded\\\"\\\" already in its current price (more precisely in all stock's prices). The memorylessness of stocks is the main statement of the Efficient Market Theory (EMT). If a company's circumstances don't change, then a drop in its share price is going to be followed by a rise later. So if the EMT holds, your statement above is not necessarily true. I personally belief the EMT is a good approximation - only large corporations (e.g. Renaissance Technologies) have enough ressources (hundreds of mathematicians, billions of $) to be able to leverage tiny non-random movements that stem from a not completely random, mostly chaotic market. The prices can of course change when the company's circumstances change, but they aren't \\\"\\\"memoryless\\\"\\\" either. A company's future state is influenced by its past. In the EMT, a stock's future state is only influenced by its past as much as is encoded in its current price (more precisely, the complete market's current state). Whether that price was reached by a drop or a rise makes no difference. The above is my believe, but I'm by far no finance expert. I am working professionally with probabilistic models, but have only read one book on finance: Kommer's \\\"\\\"Souverän investieren mit Indexfonds und ETFs\\\"\\\". It's supposed to contain many statements of Malkiel's \\\"\\\"A Random Walk Down Wall Street\\\"\\\".\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"127263\",\n \"text\": \"The article links to William Bernstein’s plan that he outlined for Business Insider, which says: Modelling this investment strategy Picking three funds from Google and running some numbers. The international stock index only goes back to April 29th 1996, so a run of 21 years was modelled. Based on 15% of a salary of $550 per month with various annual raises: Broadly speaking, this investment doubles the value of the contributions over two decades. Note: Rebalancing fees are not included in the simulation. Below is the code used to run the simulation. If you have Mathematica you can try with different funds. Notice above how the bond index (VBMFX) preserves value during the 2008 crash. This illustrates the rationale for diversifying across different fund types.\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":397,"cells":{"query_id":{"kind":"string","value":"10406"},"query":{"kind":"string","value":"Can you use external money to pay trading commissions in tax-free and tax-deferred accounts?"},"positive_passages":{"kind":"list like","value":[{"docid":"569953","text":"According to Publication 590, broker's commissions for stock transactions within an IRA cannot be paid in addition to the IRA contribution(s), but they are deductible as part of the contribution, or add to the basis if you are making a nondeductible contribution to a Traditional IRA. (Top of Page 10, and Page 12, column 1, in the 2012 edition of Pub 590). On the other hand, trustees' administrative fees can be paid from outside the IRA if they are billed separately, and are even deductible as a Miscellaneous Deduction on Schedule A of your income tax return (subject to the 2% of AGI threshold). A long time ago, when my IRA account balances were much smaller, I used to get a bill from my IRA custodian for a $20 annual administrative fee which I paid separately (but never got to deduct due to the 2% threshold). My custodian also allowed the option of doing nothing in which case the $20 would be collected from (and thus reduce) the amount of money in my IRA. Note that this does not apply to the expenses charged by the mutual funds that you might have in your IRA; these expenses are treated the same as brokerage commissions and must be paid from within the IRA.","title":""},{"docid":"361639","text":"Nice idea. When I started my IRAs, I considered this as well, and the answer from the broker was that this was not permitted. And, aside from transfers from other IRAs or retirement accounts, you can't 'deposit' shares to the IRA, only cash.","title":""}],"string":"[\n {\n \"docid\": \"569953\",\n \"text\": \"According to Publication 590, broker's commissions for stock transactions within an IRA cannot be paid in addition to the IRA contribution(s), but they are deductible as part of the contribution, or add to the basis if you are making a nondeductible contribution to a Traditional IRA. (Top of Page 10, and Page 12, column 1, in the 2012 edition of Pub 590). On the other hand, trustees' administrative fees can be paid from outside the IRA if they are billed separately, and are even deductible as a Miscellaneous Deduction on Schedule A of your income tax return (subject to the 2% of AGI threshold). A long time ago, when my IRA account balances were much smaller, I used to get a bill from my IRA custodian for a $20 annual administrative fee which I paid separately (but never got to deduct due to the 2% threshold). My custodian also allowed the option of doing nothing in which case the $20 would be collected from (and thus reduce) the amount of money in my IRA. Note that this does not apply to the expenses charged by the mutual funds that you might have in your IRA; these expenses are treated the same as brokerage commissions and must be paid from within the IRA.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"361639\",\n \"text\": \"Nice idea. When I started my IRAs, I considered this as well, and the answer from the broker was that this was not permitted. And, aside from transfers from other IRAs or retirement accounts, you can't 'deposit' shares to the IRA, only cash.\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"308150","text":"\"If I understand correctly, the Traditional IRA, if you have 401k with an employer already, has the following features: Actually, #1 and #2 are characteristics of Roth IRAs, not Traditional IRAs. Only #3 is a characteristic of a Traditional IRA. Whether you have a 401(k) with your employer or not makes absolutely no difference in how your IRAs are taxed for the vast majority of people. (The rules for IRAs are different if you have a very high income, though). You're allowed to have and contribute to both kinds of accounts. (In fact, I personally have both). Traditional IRAs are tax deferred (not tax-free as people sometimes mistakenly call them - they're very different), meaning that you don't have to pay taxes on the contributions or profits you make inside the account (e.g. from dividends, interest, profits from stock you sell, etc.). Rather, you pay taxes on any money you withdraw. For Roth IRAs, the contributions are taxed, but you never have to pay taxes on the money inside the account again. That means that any money you get over and above the contributions (e.g. through interest, trading profits, dividends, etc.) are genuinely tax-free. Also, if you leave any of the money to people, they don't have to pay any taxes, either. Important point: There are no tax-free retirement accounts in the U.S. The distinction between different kinds of IRAs basically boils down to \"\"pay now or pay later.\"\" Many people make expensive mistakes in their retirement strategy by not understanding that point. Please note that this applies equally to Traditional and Roth 401(k)s as well. You can have Roth 401(k)s and Traditional 401(k)s just like you can have Roth IRAs and Traditional IRAs. The same terminology and logic applies to both kinds of accounts. As far as I know, there aren't major differences tax-wise between them, with two exceptions - you're allowed to contribute more money to a 401(k) per year, and you're allowed to have a 401(k) even if you have a high income. (By way of contrast, people with very high incomes generally aren't allowed to open IRAs). A primary advantage of a Traditional IRA is that you can (in theory, at least) afford to contribute more money to it due to the tax break you're getting. Also, you can defer taxes on any profits you make (e.g. through dividends or selling stock at a profit), so you can grow your money faster.\"","title":""},{"docid":"350082","text":"I know of no way to answer your question without 'spamming' a particular investment. First off, if you are a USA citizen, max out your 401-K. Whatever your employer matches will be an immediate boost to your investment. Secondly, you want your our gains to be tax deferred. A 401-K is tax deferred as well as a traditional IRA. Thirdly, you probably want the safety of diversification. You achieve this by buying an ETF (or mutual fund) that then buys individual stocks. Now for the recommendation that may be called spamming by others : As REITs pass the tax liability on to you, and as an IRA is tax deferred, you can get stellar returns by buying a mREIT ETF. To get you started here are five: mREITs Lastly, avoid commissions by having your dividends automatically reinvested by using that feature at Scottrade. You will have to pay commissions on new purchases but your purchases from your dividend Reinvestment will be commission free. Edit: Taking my own advice I just entered orders to liquidate some positions so I would have the $ on hand to buy into MORL and get some of that sweet 29% dividend return.","title":""},{"docid":"51086","text":"\"The primary tax-sheltered investing vehicles in Canada include: The RRSP. You can contribute up to 18% of your prior year's earned income, up to a limit ($24,930 in 2015, plus past unused contribution allowance) and receive an income tax deduction for your contributions. In an RRSP, investments grow on a tax-deferred basis. No tax is due until you begin withdrawals. When you withdraw funds, the withdrawn amount will be taxed at marginal income tax rates in effect at that time. The RRSP is similar to the U.S. \"\"traditional\"\" IRA, being an individual account with pre-tax contributions, tax-deferred growth, and ordinary tax rates applied to withdrawals. Yet, RRSPs have contribution limits higher than IRAs; higher, even, than U.S. 401(k) employee contribution limits. But, the RRSP is dissimilar to the IRA and 401(k) since an individual's annual contribution allowance isn't use-it-or-lose-it—unused allowance accumulates. The TFSA. Once you turn 18, you can put in up to $5,500 each year, irrespective of earned income. Like the RRSP, contribution room accumulates. If you were 18 in 2009 (when TFSAs were introduced) you'd be able to contribute $36,500 if you'd never contributed to one before. Unlike the RRSP, contributions to a TFSA are made on an after-tax basis and you pay no tax when you withdraw money. The post-tax nature of the TFSA and completely tax-free withdrawals makes them comparable to Roth-type accounts in the U.S.; i.e. while you won't get a tax deduction for contributing, you won't pay tax on earnings when withdrawn. Yet, unlike U.S. Roth-type accounts, you are not required to use the TFSA strictly for retirement savings—there is no penalty for pre-retirement withdrawal of TFSA funds. There are also employer-sponsored defined benefit (DB) and defined contribution (DC) retirement pension plans. Generally, employees who participate in these kinds of plans have their annual RRSP contribution limits reduced. I won't comment on these kinds of plans other than to say they exist and if your employer has one, check it out—many employees lose out on free money by not participating. The under-appreciated RESP. Typically used for education savings. A lifetime $50,000 contribution limit per beneficiary, and you can put that all in at once if you're not concerned about maximizing grants (see below). No tax deduction for contributions, but investments grow on a tax-deferred basis. Original contributions can be withdrawn tax-free. Qualified educational withdrawals of earnings are taxed as regular income in the hands of the beneficiary. An RESP beneficiary is typically a child, and in a child's case the Canadian federal government provides matching grant money (called CESG) of 20% on the first $2500 contributed each year, up to age 18, to a lifetime maximum of $7200 per beneficiary. Grant money is subject to additional conditions for withdrawal. While RESPs are typically used to save for a child's future education, there's nothing stopping an adult from opening an RESP for himself. If you've never had one, you can deposit $50,000 of after-tax money to grow on a tax-deferred basis for up to 36 years ... as far as I understand. An adult RESP will not qualify for CESG. Moreover, if you use the RESP strictly as a tax shelter and don't make qualified educational withdrawals when the time comes, your original contributions still come out free of tax but you'll pay ordinary income tax plus 20% additional tax on the earnings portion. That's the \"\"catch\"\"*. *However, if at that time you have accumulated sufficient RRSP contribution room, you may move up to $50,000 of your RESP earnings into your RRSP without any tax consequences (i.e. also avoiding the 20% additional tax) at time of transfer. Perhaps there's something above you haven't considered. Still, be sure to do your own due diligence and to consult a qualified, experienced, and conflict-free financial advisor for advice particular to your own situation.\"","title":""},{"docid":"109540","text":"Guaranteed 8.2% annual return sounds too good to be true. Am I right? Are there likely high fees, etc.? You're right. Guaranteed annual return is impossible, especially when you're talking about investments for such a long period of time. Ponzi (and Madoff) schemed their investors using promises of guaranteed return (see this note in Wikipedia: In some cases returns were allegedly determined before the account was even opened.[72]). Her financial advisor doesn't charge by the hour--he takes a commission. So there's obviously some incentive to sell her things, even if she may not need them. Definitely not a good sign, if the advisor gets a commission from the sale then he's obviously not an advisor but a sales person. The problem with this kind of investment is that it is very complex, and it is very hard to track. The commission to the broker makes it hard to evaluate returns (you pay 10% upfront, and it takes awhile to just get that money back, before even getting any profits), and since you're only able to withdraw in 20 years or so - there's no real way to know if something wrong, until you get there and discover that oops- no money! Also, many annuity funds (if not all) limit withdrawals to a long period, i.e.: you cannot touch money for like 10 years from investment (regardless of the tax issues, the tax deferred investment can be rolled over to another tax deferred account, but in this case - you can't). I suggest you getting your own financial advisor (that will work for you) to look over the details, and talk to your mother if it is really a scam.","title":""},{"docid":"11998","text":"\"I have a couple other important considerations regarding external HSA accounts vs employer sponsored HSA accounts. Depending on your personal financial situation and goals; some people like to use HSA accounts as an extra retirement account (since the money can be withdrawn penalty free in retirement for non-medical expenses, and completely tax & penalty free at any time for medical expenses). If your intended use for the HSA account is an investment vehicle for retirement, then you may find more use/benefit out of an external provider that may provide more or better investment options than your employers HSA investment options. There can be a lot of additional value in those extra investment options over greater periods of time. Another VERY important consideration for FICA taxes (FICA includes Social Security & Medicare) that I don't believe was mentioned before - for those earners who are under the maximum social security wage limit, you are paying 6.2% of each paycheck into social security taxes. As others have mentioned you can \"\"save\"\" this tax through your employer’s plan if you set up the account to be funded pre-tax from your paychecks. However, in doing so, you are lowering your overall contributions into social security, which may lower your social security benefits in your retirement years! If this is ultimately going to lower your SSA benefits in retirement then that is a big future cost that may steer you against the pre-tax employer contributions. Think of social security as part of your retirement plan, not as a tax but instead as an additional check you put away for yourself for retirement every month. Of course, this is only an important consideration if SSA is still going to be around when you retire, but let's assume that it will be. This is not an issue for higher earners, earning well above the max SSA taxable wages. There is no wage limit on the 1.45% Medicare tax withholding's, and there is certainly no harm in saving Medicare taxes because it will not affect future Medicare benefits. So for taxpayers earning well over the max SSA wages, they will just save the 1.45% Medicare taxes without affecting their SSA contributions and resulting retirement benefits. So again, it all comes down to personal situations. Depending on your earnings and goals, employer plan may or may not be the way to go. Personally, for my lower earning clients, friends and family, I tend to recommend that they do whatever they can to maximize their social security benefits in retirement. So I would advise them to either use the external provider account, or the employer plan but with post-tax contributions so you don't lower the SSA withholding's but can still claim the income tax deduction on your tax return. YMMV -Dan\"","title":""},{"docid":"359515","text":"A 401-K is something you get through an employer. I recommend getting a self-directed IRA. You can open an IRA with Scottrade with $500 The money you put into an IRA is tax deferred, meaning that you do not have to pay taxes on profits. It may also lower your tax liability. Scottrade has a feature to automatically reinvest any dividends from the securities you own. This feature allows you to avoid commissions on those automatic purchases. Don't try to time the market. Pick a good ETF (exchange traded fund) that pays dividends. It will give you diversification. Avoid the urge to buy and sell constantly. This only gives commissions to the broker.","title":""},{"docid":"587768","text":"4.7 is a pretty low rate, especially if you are deducting that from your taxes. If you reduce the number by your marginal tax rate to get the real cost of the money you end up with a number that isn't far off from inflation, and also represents a pretty low 'yield' in terms of paying off the loan early. (e.g. if your marginal tax rate is 28%, then the net you are paying in interest after the tax deduction is 4.7 * .72 = 3.384) While I'm all for paying off loans with higher rates (since it's in effect the same as making that much risk free on the money) it doesn't make a lot of sense when you are down at 3.4 unless there is a strong 'security factor' (which really makes a difference to some folks) to be had that really helps you sleep at night. (to be realistic, for some folks close to retirement, there can be a lot to be said for the security of not having to worry about house payments, although you don't seem to be in that situation yet) As others have said, first make sure you have enough liquid 'emergency money' in something like a money market account, or a ladder of short term CD's If you are sure that the sprouts will be going to college, then there's a lot to be said for kicking a decent amount into a 529, Coverdell ESA (Educational Savings Account), uniform gift to minors account, or some combination of those. I'm not sure if any of those plans can be used for a kid that has not been born yet however. I'd recommend http://www.savingforcollege.com as a good starting point to get more information on your various options. As with retirement savings, money put in earlier has a lot more 'power' over the final balance due to compounding interest, so there's a lot to be said for starting early, although depending on what it takes to qualify for the plans there could be such a thing as too early ;-) ). There's nothing wrong with Managed mutual funds as long as the fund objective and investing style is in alignment with your objectives and risk tolerance; The fund is giving you a good return relative to the market as a whole; You are not paying high fees or load charges; You are not losing a lot to taxes. I would always look at the return after expenses when comparing to other options, and if the money is not in a tax deferred account, also look at what sort of tax burden you will be faced with. A fund that trades a lot will generate more short term gains which means more taxes than compared to a more passive fund. Anything lost to taxes is money lost to you so needs to come out of the total return when you calculate that. Sometimes such funds are better off as a choice inside an IRA or 401K, and you can instead use more tax efficient vehicles for money where you have to pay the taxes every year on the gains. The reason a lot of folks like index funds better is that: Given your described age, it's not appropriate now, but in the long run as you get closer to retirement, you may want to start looking at building up some investments that are geared more towards generating income, such as bonds, or depending on taxes where you live, Municipal bonds. In any case, the more money you can set aside for retirement now, both inside and outside of tax deferred accounts, the sooner you will get to the point of the 'critical mass' you need to retire, at that point you can work because you want to, not because you have to.","title":""},{"docid":"318338","text":"\"Assuming that the will that bequeathed the money to your son did not stipulate any restrictions or set up a trust to hold the money until your son turns 25, or something like that, I don't think you have much choice except to put the money in a UTMA account (which of course can be invested in whatever the trustee (which could be you, or you and your wife jointly) decides. Note: not a UGMA account since the money is not a gift. You also don't have any option except to turn the account over to your son when he turns eighteen. The point is, the investment can be in anything as long as the account is registered as a UTMA account. But do remember also that your son is entitled to sue you for breach of fiduciary duty if you don't take good care of the money, so that blowing it all in risky investments is also not a good idea. If you are worried about taxes and your son's income being taxed at your rate, one way of deferring the issue is to buy US Savings Bonds. The interest can be deferred from taxation until the bonds are redeemed. Edit added in response to JoeTaxpayer's comments: But a better strategy is to declare the accrued interest each year as unearned income of the child on the kiddie tax form that is part of your tax return, and pay the tax, if any, that results To ease your mind or conscience, think of the tax that you pay on your child's behalf as a gift to your child! In any case, there will likely not be much tax due since the first $950 of unearned income of a child is tax-free and the next $950 taxed at 10%. Then, when the bonds are cashed in, the interest that accrued (and was \"\"taxed\"\") in earlier years can be deducted from the interest (cash in price minus purchase price) that you (or your son) will be told is the interest that the bonds earned. Of course, if kiddie tax is not a concern (and it shouldn't be, given the amount available for investment), an even better strategy is to set up the UTMA account(s) in long-term investments in low-cost index funds or ETFs (as JoeTaxpayer suggests) and pay the tax, if any, as it comes due.\"","title":""},{"docid":"264023","text":"\"when you contribute to a 401k, you get to invest pre-tax money. that means part of it (e.g. 25%) is money you would otherwise have to pay in taxes (deferred money) and the rest (e.g. 75%) is money you could otherwise invest (base money). growth in the 401k is essentially tax free because the taxes on the growth of the base money are paid for by the growth in the deferred portion. that is of course assuming the same marginal tax rate both now and when you withdraw the money. if your marginal tax rate is lower in retirement than it is now, you would save even more money using a traditional 401k or ira. an alternative is to invest in a roth account (401k or ira). in which case the money goes in after tax and the growth is untaxed. this would be advantageous if you expect to have a higher marginal tax rate during retirement. moreover, it reduces tax risk, which could give you peace of mind considering u.s. marginal tax rates were over 90% in the 1940's. a roth could also be advantageous if you hit the contribution limits since the contributions are after-tax and therefore more valuable. lastly, contributions to a roth account can be withdrawn at any time tax and penalty free. however, the growth in a roth account is basically stuck there until you turn 60. unlike a traditional ira/401k where you can take early retirement with a SEPP plan. another alternative is to invest the money in a normal taxed account. the advantage of this approach is that the money is available to you whenever you need it rather than waiting until you retire. also, investment losses can be deducted from earned income (e.g. 15-25%), while gains can be taxed at the long term capital gains rate (e.g. 0-15%). the upshot being that even if you make money over the course of several years, you can actually realize negative taxes by taking gains and losses in different tax years. finally, when you decide to retire you might end up paying 0% taxes on your long term capital gains if your income is low enough (currently ~50k$/yr for a single person). the biggest limitation of this strategy is that losses are limited to 3k$ per year. also, this strategy works best when you invest in individual stocks rather than mutual funds, increasing volatility (aka risk). lastly, this makes filing your taxes more complicated since you need to report every purchase and sale and watch out for the \"\"wash sale\"\" rules. side note: you should contribute enough to get all the 401k matching your employer offers. even if you cash out the whole account when you want the money, the matching (typically 50%-200%) should exceed the 10% early withdrawal penalty.\"","title":""},{"docid":"388145","text":"Yes, absolutely. The HSA, when used for medical expenses, allows you to essentially pay for your medical expenses tax free. Even if you don't have extra room in your budget, you can fund the HSA as you incur medical expenses, then withdraw money to pay the expenses, and you'll see an immediate tax benefit at tax time. However, let's say that you have plenty of room in your budget and you don't have a lot of medical expenses. You already contribute the maximum to your 401(k) or IRA, and you want to do more. The HSA acts like a retirement account in this case, allowing you to contribute before-tax money and let it grow untaxed. The HSA does have a huge benefit that no other retirement account has. If you choose not to reimburse yourself for medical expenses, but you keep track of the unreimbursed expenses you incur, then you can reimburse yourself for these expenses at any point in the future completely tax free. Essentially, your contributions are treated like a traditional IRA, but your withdrawals are treated like a Roth IRA, and can be done at any age. If you don't acquire enough medical expenses, you can still withdraw whatever is left at age 65 and those withdrawals will be taxed like a traditional IRA. The HSA provides for tax-free contributions and growth if used for medical expenses, and tax-deferred growth if withdrawn after age 65 without medical expenses.","title":""},{"docid":"329596","text":"\"tl;dr Roth earnings are not necessarily \"\"tax deferred\"\", but they might be. This is a great question because IMHO, the use of the wording \"\"tax deferred\"\" is slightly misleading when talking about a Roth IRA (and Roth 401k too). The phrase \"\"tax deferred\"\" actually means you save tax now and you pay tax later, i.e. you \"\"defer\"\" the tax. As you pointed out, this is the normal terminology used for describing a Traditional IRA/401k. Earnings on a Roth IRA are tax free (not deferred), but only if your distributions are qualified. For the most part distributions are considered qualified if you wait until you are 59.5 years old before taking the money out, but there are some exceptions. If you choose to distribute more than your contributions, meaning you are now taking out earnings, the earnings are tax free only if your distribution is qualified. For example, if you take out the earnings before you are 59.5 (and no other exceptions apply), then you would pay tax on the earnings and also a 10% penalty. So, perhaps a better way to say it is that earnings in a Roth IRA are \"\"conditionally tax deferred\"\".\"","title":""},{"docid":"206442","text":"\"It is important to remember that the stock price in principle reflects the value of the company, so the market cap should drop upon issuance of the the dividend. However, the above reasoning neglects to consider taxes, which make the question a bit more interesting. The key fact is that different investors are going to get taxed on the dividend to varying degrees, ranging from 20% for qualified dividends in the USA for a high-income individual in a taxable account (and even worse for non-qualified dividends) to 0% for tax-exempt nonprofits, retirement accounts, and low-income individuals. The high-tax investors are going to be a bit averse to paying tax on that dividend, whereas the tax-free investors are not. Hence in a tax-rational market the tax-free investors are going to be the ones buying right before a dividend and the tax-paying investors will be buying right afterwards. Tax-exempt investors could in principle make some amount of money buying dividends to keep them off the tax-paying investors' books. (Of course, the strategy could backfire if too many people did it all at once.) That said, the tax-payers have the tax disincentive to prevent them from fully exploiting the opposite strategy of selling just before a dividend. In particular, they are subject to capital gains tax when they sell at a profit (unless they have enough compensating capital losses), and it is to their after-tax profit to defer taxation by not trading. That said, the stock market has well-known irrationality when it comes to considering tax consequences, so logic based on assumed rationality of the market does not always apply to the extent one would expect. The foremost example of tax-irrationality is the so-called \"\"dividend paradox\"\", which basically states that corporations should favor stock buybacks (or perhaps loan repayment) to the complete exclusion of dividends because capital gains are taxed less harshly than dividends in a variety of ways, some of which are subtle: 1) Historically (although not currently in the USA for qualified dividends) the tax rate was higher for dividends. (In Canada, for example, dividends are taxed at twice the rate of capital gains.) 2) If you die holding appreciated stock then you (meaning your heirs) completely escape US the capital gains tax on the accrual during your lifetime. 3) Capital gains tax can be deferred by simply not selling. In comparison to dividends, this is roughly equivalent to getting a tax-free loan from the government which is invested for profit and paid at a later date after inflation has eaten away at the real value of the loan. For example, if all your stock investments increase by 10%/year but you sell every year, in a high-tax bracket situation you're total after-tax return will be only 8% per year. In contrast, if you hold the same investments for many many years and then sell, your total return will be nearly 10% per year, because you only pay 20% once (at the end). 4) A capital gain can often be neutralized by a capital loss in another stock, so that no tax results. If you loose money on a stock that is paying dividends, you're still going to have to pay tax on that dividend. There are companies that borrow money to pay out that taxable-dividend each quarter, which seems like gross tax malpractice on the part of the CFO. (If the dividend paradox doesn't make sense, first consider the case that you owned ALL the shares of a company. It wouldn't matter to you at all on a pre-tax basis whether you got a $1000 company buyback or a $1000 dividend, because after the buyback/dividend you'd still own the entire company and $1000. The number of shares would be reduced, but objecting that you owned fewer shares after the buyback would be like saying you have become shorter if your height is measured in inches rather than centimeters.) [Of course, in the case of many shareholders you can get burned by failing to sell into the buyback when the share price is too high, but that is another matter.]\"","title":""},{"docid":"438038","text":"\"You don't want to do that. DON'T LIE TO THE IRS!!! We live overseas as well and have researched this extensively. You cannot make $50k overseas and then say you only made $45k to put $5k into retirement. I have heard from some accountants and tax attorneys who interpret the law as saying that the IRS considers Foreign Earned Income as NOT being compensation when computing IRA contribution limits, regardless of whether or not you exclude it. Publication 590-A What is Compensation (scroll down a little to the \"\"What Is Not Compensation\"\" section). Those professionals say that any amounts you CAN exclude, not just ones you actually do exclude. Then there are others that say the 'can' is not implied. So be careful trying to use any foreign-earned income to qualify for retirement contributions. I haven't ran across anyone yet who has gotten caught doing it and paid the price, but that doesn't mean they aren't out there. AN ALTERNATIVE IN CERTAIN CASES: There are two things you can do that we have found to have some sort of taxable income that is preferably not foreign so that you can contribute to a retirement account. We do this by using capital gains from investments as income. Since our AGI is always zero, we pay no short or long term capital gains taxes (as long as we keep short term capital gains lower than $45k) Another way to contribute to a Roth IRA when you have no income is to do an IRA Rollover. Of course, you need money in a tax-deferred account to do this, but this is how it works: I always recommend those who have tax-deferred IRA's and no AGI due to the FEIE to roll over as much as they can every year to a Roth IRA. That really is tax free money. The only tax you'll pay on that money is sales tax when you SPEND IT!! =)\"","title":""},{"docid":"535340","text":"\"As user quid states in his answer, all you need to do is open an account with a stock broker in order to gain access to the world's stock markets. If you are currently banking with one of the six big bank, then they will offer stockbroking services. You can shop around for the best commission rates. If you wish to manage your own investments, then you will open a \"\"self-directed\"\" account. You can shelter your investments from all taxation by opening a TFSA account with your stock broker. Currently, you can add $5,500 per year to your TFSA. Unused allowances from previous years can still be used. Thus, if you have not yet made any TFSA contributions, you can add upto $46,500 to your TFSA and enjoy the benefits of tax free investing. Investing in what you are calling \"\"unmanaged index funds\"\" means investing in ETFs (Exchange Traded Funds). Once you have opened your account you can invest in any ETFs traded on the stock markets accessible through your stock broker. Buying shares on foreign markets may carry higher commission rates, but for the US markets commissions are generally the same as they are for Canadian markets. However, in the case of buying foreign shares you will carry the extra cost and risk of selling Canadian dollars and buying foreign currency. There are also issues to do with foreign withholding taxes when you trade foreign shares directly. In the case of the US, you will also need to register with the US tax authorities. Foreign withholding taxes payable are generally treated as a tax credit with respect to Canadian taxation, so you will not be double taxed. In today's market, for most investors there is generally no need to invest directly in foreign market indices since you can do so indirectly on the Toronto stock market. The large Canadian ETF providers offer a wide range of US, European, Asian, and Global ETFs as well as Canadian ETFs. For example, you can track all of the major US indices by trading in Toronto in Canadian dollars. The S&P500, the Dow Jones, and the NASDAQ100 are offered in both \"\"currency hedged\"\" and \"\"unhedged\"\" forms. In addition, there are ETFs on the total US Market, US Small Caps, US sectors such as banks, and more exotic ETFs such as those offering \"\"covered call\"\" strategies and \"\"put write\"\" strategies. Here is a link to the BMO ETF website. Here is a link to the iShares (Canada) ETF website.\"","title":""},{"docid":"8861","text":"\"Sure. For starters, you can put it in a savings account. Don't laugh, they used to pay noticeable interest. You know, back in the olden days. You could buy an I-bond from Treasury Direct. They're a government savings bond that pays a specified amount of interest (currently 0%, I believe), plus the amount of the inflation rate (something like 3.5% currently, I believe). You don't get paid the money -- the I-bond grows in value till you sell it. You can open a discount brokerage account, and buy 1 or more shares of stock in a company you like. Discount brokerages generally have a minimum of $500 or so, but will waive that if you set the account up as an IRA. Scot Trade, for instance. (An IRA, in case you didn't know, is a type of account that's tax free but you can't touch it till you turn 59 1/2. It's meant to help you save for retirement.) Incidentally, watch out of \"\"small account\"\" fees that some brokerages might charge you. Generally they're annual or monthly charges they'd charge you to cover their costs on your account -- since they're certainly not going to make it in commissions. That IRA at Scot Trade is no-fee. Speaking of commissions, those will be a big chunk of that $100. It'll be like $7-$10 to buy that stock -- a pretty big bite. However, many of these discount brokerages also offer some mutual funds for no commission. Those mutual funds, in turn, have minimums too, but once again if your account's an IRA many will waive the minimum or set it low -- like $100.\"","title":""},{"docid":"473658","text":"ETFs offer the flexibility of stocks while retaining many of the benefits of mutual funds. Since an ETF is an actual fund, it has the diversification of its potentially many underlying securities. You can find ETFs with stocks at various market caps and style categories. You can have bond or mixed ETFs. You can even get ETFs with equal or fundamental weighting. In short, all the variety benefits of mutual funds. ETFs are typically much less expensive than mutual funds both in terms of management fees (expense ratio) and taxable gains. Most of them are not actively managed; instead they follow an index and therefore have a low turnover. A mutual fund may actively trade and, if not balanced with a loss, will generate capital gains that you pay taxes on. An ETF will produce gains only when shifting to keep inline with the index or you yourself sell. As a reminder: while expense ratio always matters, capital gains and dividends don't matter if the ETF or mutual fund is in a tax-advantaged account. ETFs have no load fees. Instead, because you trade it like a stock, you will pay a commission. Commissions are straight, up-front and perfectly clear. Much easier to understand than the various ways funds might charge you. There are no account minimums to entry with ETFs, but you will need to buy complete shares. Only a few places allow partial shares. It is generally harder to dollar-cost average into an ETF with regular automated investments. Also, like trading stocks, you can do those fancy things like selling short, buying on margin, options, etc. And you can pay attention to the price fluctuations throughout the day if you really want to. Things to make you pause: if you buy (no-load) mutual funds through the parent company, you'll get them at no commission. Many brokerages have No Transaction Fee (NTF) agreements with companies so that you can buy many funds for free. Still look out for that expense ratio though (which is probably paying for that NTF advantage). As sort of a middle ground: index funds can have very low expense ratios, track the same index as an ETF, can be tax-efficient or tax-managed, free to purchase, easy to dollar-cost average and easier to automate/understand. Further reading:","title":""},{"docid":"10089","text":"Congratulations on deciding to save for retirement. Since you cite Dave Ramsey as the source of your 15% number, what does he have to say about where to invest the money? If you want to have instantaneous penalty-free access to your retirement money, all you need to do is set up one or more ordinary accounts that you think of as your retirement money. Just be careful not to put the money into CDs since Federal law requires a penalty of three months interest if you cash in the CD before its maturity date (penalty!) or put the money into those pesky mutual funds that charge a redemption fee (penalty!) if you take the money out within x months of investing it where x can be anywhere from 3 to 24 or more. In Federal tax law (and in most state tax laws as well) a retirement account has special privileges accorded to it in that the interest, dividends, capital gains, etc earned on the money in your retirement account are not taxed in the year earned (as they would be in a non-retirement account), but the tax is either deferred till you withdraw money from the account (Traditional IRAs, 401ks etc) or is waived completely (Roth IRAs, Roth 401ks etc). In return for this special treatment, penalties are imposed (in addition to tax) if you withdraw money from your retirement account before age 59.5 which presumably is on the distant horizon for you. (There are some exceptions (including first-time home buying and extraordinary medical expenses) to this rule that I won't bother going into). But You are not required to invest your retirement money into such a specially privileged retirement account. It is perfectly legal to keep your retirement money in an ordinary savings account if you wish, and pay taxes on the interest each year. You can invest your retirement money into municipal bonds whose interest is free of Federal tax (and usually free of state tax as well if the municipality is located in your state of residence) if you like. You can keep your retirement money in a sock under your mattress if you like, or buy a collectible item (e.g. a painting) with it (this is not permitted in an IRA), etc. In short, if you are concerned about the penalties imposed by retirement accounts on early withdrawals, forgo the benefits of these accounts and put your retirement money elsewhere where there is no penalty for instant access. If you use a money management program such as Mint or Quicken, all you need to do is name one or more accounts or a portfolio as MyRetirementMoney and voila, it is done. But those accounts/portfolios don't have to be retirement accounts in the sense of tax law; they can be anything at all.","title":""},{"docid":"475397","text":"There is no advantage to using one type of account or the other if you are in the same tax bracket at retirement that you are in during your working years. However, for tax planning reasons, it is good to have some money in both a Roth and a traditional IRA plan. JoeTaxpayer has often advocated a good rule of thumb to use a Roth when your tax bracket is 15% or lower, and use a traditional account when in the 25% bracket or above. The reason for this rule of thumb is that you are less likely to be in the higher tax bracket when you are living off retirement savings unless you put away an awful lot of money between now and then. If you are making enough money to be paying a 25% marginal rate on some of the money you would be putting away for retirement, then by all means, put all of that money in a traditional 401k. If after contributing that portion of your savings taxed at the higher rate, you still have money to put away for retirement, put the rest in a Roth and pay the 15% taxes on it. When you are younger, it is likely that you are making less than you will a few years hence, and it is also likely that a larger portion of your income will be paying tax deductible interest on a mortgage. If those are true for you, then by all means, use the Roth. That was true of me when I was single and just getting started. When you do finally retire, it is possible that the tax brackets will be increased to match inflation, and if so, then there is no benefit to having tax free money at retirement vs. paying taxes on deferred accounts, but there is also usually more flexibility in when to spend money. You may find that you have a year where you have to spend a lot, so it is good to be able to pull money out without it increasing your marginal rate for that year, and other years where you spend relatively smaller amounts, and you can withdraw taxable money and pay a lower rate on that money. No one knows what the tax code will look like in 40 years, but having some money in each type of account will give you flexibility to minimize your tax bill at retirement.","title":""},{"docid":"173088","text":"\"What is a stock? A share of stock represents ownership of a portion of a corporation. In olden times, you would get a physical stock certificate (looking something like this) with your name and the number of shares on it. That certificate was the document demonstrating your ownership. Today, physical stock certificates are quite uncommon (to the point that a number of companies don't issue them anymore). While a one-share certificate can be a neat memento, certificates are a pain for investors, as they have to be stored safely and you'd have to go through a whole annoying process to redeem them when you wanted to sell your investment. Now, you'll usually hold stock through a brokerage account, and your holdings will just be records in a database somewhere. You'll pick a broker (more on that in the next question), instruct them to buy something, and they'll keep track of it in your account. Where do I get a stock? You'll generally choose a broker and open an account. You can read reviews to compare different brokerages in your country, as they'll have different fees and pricing. You can also make sure the brokerage firm you choose is in good standing with the financial regulators in your country, though one from a major national bank won't be unsafe. You will be required to provide personal information, as you are opening a financial account. The information should be similar to that required to open a bank account. You'll also need to get your money in and out of the account, so you'll likely set up a bank transfer. It may be possible to request a paper stock certificate, but don't be surprised if you're told this is unavailable. If you do get a paper certificate, you'll have to deal with considerably more hassle and delay if you want to sell later. Brokers charge a commission, which is a fee per trade. Let's say the commission is $10/trade. If you buy 5 shares of Google at $739/share, you'd pay $739 * 5 + $10 = $3705 and wind up with $3695 worth of stock in your account. You'd pay the same commission when you sell the stock. Can anyone buy/own/use a stock? Pretty much. A brokerage is going to require that you be a legal adult to maintain an account with them. There are generally ways in which a parent can open an account on behalf of an underage child though. There can be different types of restrictions when it comes to investing in companies that are not publicly held, but that's not something you need to worry about. Stocks available on the public stock market are available to, well, the public. How are stocks taxed? Taxes differ from country to country, but as a general rule, you do have to provide the tax authorities with sufficient information to determine what you owe. This means figuring out how much you purchased the stock for and comparing that with how much you sold it for to determine your gain or loss. In the US (and I suspect in many other countries), your brokerage will produce an annual report with at least some of this information and send it to the tax authorities and you. You or someone you hire to do your taxes will use that report to compute the amount of tax owed. Your brokerage will generally keep track of your \"\"cost basis\"\" (how much you bought it for) for you, though it's a good idea to keep records. If you refuse to tell the government your cost basis, they can always assume it's $0, and then you'll pay more tax than you owe. Finding the cost basis for old investments can be difficult many years later if the records are lost. If you can determine when the stock was purchased, even approximately, it's possible to look back at historical price data to determine the cost. If your stock pays a dividend (a certain amount of money per-share that a company may pay out of its profits to its investors), you'll generally need to pay tax on that income. In the US, the tax rate on dividends may be the same or less than the tax rate on normal wage income depending on how long you've held the investment and other rules.\"","title":""},{"docid":"69841","text":"A UTMA may or may not fit your situation. The main drawbacks to a UTMA account is that it will count against your child for financial aid (it counts as the child's asset). The second thing to consider is that taxes aren't deferred like in a 529 plan. The last problem of course is that when he turns 18 he gets control of the account and can spend the money on random junk (which may or may not be important to you). A 529 plan has a few advantages over a UTMA account. The grandparents can open the account with your son as the beneficiary and the money doesn't show up on financial aid for college (under current law which could change of course). Earnings grow tax free which will net you more total growth. You can also contribute substantially more without triggering the gift tax ~$60k. Also many states provide a state tax break for contributing to the state sponsored 529 plan. The account owner would be the grandparents so junior can't spend the money on teenage junk. The big downside to the 529 is the 10% penalty if the money isn't used for higher education. The flip side is that if the money is left for 20 years you will also have additional growth from the 20 years of tax free growth which may be a wash depending on your tax bracket and the tax rates in effect over those 20 years.","title":""},{"docid":"432902","text":"\"Your question is based on incorrect assumptions. Generally, there's no \"\"penalty\"\", per se, to make a withdrawal from your RRSP, even if you make a withdrawal earlier than retirement, however you define it. A precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant.* Our U.S. neighbours have a 10% penalty on non-hardship early withdrawals (before age 59 ½) from retirement accounts like the 401k and IRA. It's an additional measure designed to discourage early withdrawals, and raise more tax. Yet, in Canada, there is no similar penalty. Individual investments inside your RRSP may have associated penalties, such as the dreaded \"\"deferred sales charge\"\" (DSC) of some back-end loaded mutual funds, or such as LSVCC funds that generated additional special tax credits that could get clawed back. Yet, these early withdrawal penalties are distinct from the RRSP nature of your account. Choose your investments carefully to avoid these kinds of surprises. Rather, an RRSP is a tax-deferred account, and it works like this: The government allows you to claim a nice juicy tax deduction, which can reduce your income tax at your marginal rate in the year you make a contribution, or later if you should choose to defer the deduction. The resulting pre-tax money accumulated in your RRSP benefits from further tax deferral: assets can grow without attracting annual income tax on earned interest, dividends, or capital gains. You don't need to declare on your income tax return any of the income earned inside your RRSP, unlike a regular investment account. Here's the rub: Once you decide to withdraw money from your RRSP, the entire amount withdrawn is considered regular income in the year in which you make the withdrawal. Thus, your withdrawals are subject to income tax, and yes, at your marginal rate. This is always the case, whether before or after retirement. You mentioned two special programs: The Home Buyers' Plan (HBP), and the Lifelong Learning Plan (LLP). Neither the HBP nor the LLP permit tax-free withdrawals. Rather, each of these programs are special kinds of loans that you can borrow from your own RRSP. HBP and LLP loan money isn't taxed when you get it because you are required to pay it back, and you pay it back into your own RRSP: You always pay income tax at your marginal rate on your RRSP withdrawals.** * Above, I said a precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant. Yet, there are ages that matter: By the end of the year in which you turn 71, you are required to convert your RRSP to a RRIF. It's similar, but you can no longer contribute, and you must withdraw a minimum amount each year. Other circumstances related to age may qualify for minor tax relief intended for retirees, such as the Age Amount or the Pension Income Credit. Generally, such measures don't significantly change the fact that you pay income tax on RRSP withdrawals at your marginal rate – these measures raise the minimum you can take out without attracting tax, but most do nothing at the margin.** ** Exception: One might split eligible pension income with a spouse or common-law partner, which may reduce tax at the margin.\"","title":""},{"docid":"417388","text":"The 401(k) contribution is Federal tax free, when you make the contribution, and most likely State too. I believe that is true for California, specifically. There was a court case some years ago about people making 401(k) or IRA contributions in New York, avoiding the New York state income tax. Then they moved to Florida (no income tax), and took the money out. New York sued, saying they had to pay the New York income tax that had been deferred, but the court said no. So you should be able to avoid California state income tax, and then later if you were to move to, for example, Texas (no income tax), have no state income tax liability. At the Federal level, you will have different problems. You won't have the money; it will be held by the 401(k) trustee. When you try to access the money (cash the account out), you will have to pay the deferred taxes. Effectively, when you remove the money it becomes income in the year it is removed. You can take the money out at any time, but if you are less than 59 1/2 at the time that you take it, there is a 10% penalty. The agreement is that the Feds let you defer paying the tax because it is going to finance your retirement, and they will tax it later. If you take it out before 59 1/2, they figure you are not retired yet, and are breaking your part of the agreement. Of course you can generally leave the money in the 401(k) plan with your old employer and let it grow until you are 59.5, or roll it over into another 401(k) with a new employer (if they let you), or into an IRA. But if you have returned to your own country, having an account in the U.S. would introduce both investment risk and currency risk. If you are in another country when you want the money, the question would be where your U.S. residence would be. If you live in California, then go to, say France, your U.S. residence would still be California, and you would still owe California income tax. If you move from California to Texas and then to France, your U.S. residence would be Texas. This is pretty vague, as you might have heard in the Rahm Emanual case -- was he a resident of Chicago or Washington, D.C.? Same problem with Howard Hughes who was born in Texas, but then spent most his life in California, then to Nevada, then to Nicaragua, and the Bahamas. When he died Texas, California and Nevada all claimed him as a resident, for estate taxes. The important thing is to be able to make a reasonable case that you are a resident of where ever you want to be -- driver's license, mailing address, living quarters, and so on.","title":""},{"docid":"170717","text":"In the US, the key to understanding the benefits of retirement accounts is to understand capital gains taxes and how they work. Retirement accounts are designed for making investments throughout your career, then after several decades of contributions, withdrawing that money to pay for your needs when your full-time employment has concluded. Normally when you invest money in a brokerage account, if the value of your investment increases, and you sell in less than a year, those investments are considered short-term gains and taxed as ordinary income. If you hold that same investment for over a year, the same investment is taxed at a lower capital gains rate (depending on which tax bracket you are in during that year, the amount due could be up to 20%, but much lower than your regular income tax rate). When you place your money in a retirement account, you are choosing to either pay the tax due on the income when you put it in the account, or put the money in tax free and pay the tax when you withdraw (these are called tax-deferred accounts). When you have money invested several decades, the raw dollar amount increases greatly, but inflation is also reducing the value of those dollars. Imagine you bought some bonds that payed 4% over 40 years, but inflation was 2% during those same years. When you sell those bonds 40 years later, you will owe capital gains on the entire gain even though half of the gain came from inflation. Retirement accounts allow you to buy and sell according to your investment needs and goals without any consideration about whether the gains are short-term or long-term, and they also allow you to pay taxes just once, either when you put it in, or when you take it out, with no worries about whether you're paying taxes on inflated gains.","title":""},{"docid":"299690","text":"\"As other people have indicated, traditional IRAs are tax deductable for a particular year. Please note, though, that traditional IRAs are tax deferred (not tax-free) accounts, meaning that you'll have to pay taxes on any money you take out later regardless of why you're making the withdrawal. (A lot of people mistakenly call them tax free, which they're not). There is no such thing as a \"\"tax-free\"\" retirement account. Really, in terms of Roth vs. Traditional IRAs, it's \"\"pay now or pay later.\"\" With the exception of special circumstances like this, I recommend investing exclusively in Roth IRAs for money that you expect to grow much (or that you expect to produce substantial income over time). Just to add a few thoughts on what to actually invest in once you open your IRA, I strongly agree with the advice that you invest mostly in low-cost mutual funds or index funds. The advantage of an open-ended mutual fund is that it's easier to purchase them in odd increments and you may be able to avoid at least some purchase fees, whereas with an ETF you have to buy in multiples of that day's asking price. For example, if you were investing $500 and the ETF costs $200 per share, you could only purchase 2 shares, leaving $100 uninvested (minus whatever fee your broker charged for the purchase). The advantage of an ETF is that it's easy to buy or sell quickly. Usually, when you add money to a mutual fund, it'll take a few days for it to hit your account, and when you want to sell it'll similarly take a few days for you to get your money; when I buy an ETF the transaction can occur almost instantly. The fees can also be lower (if the ETF is just a passive index fund). Also, there's a risk with open-ended mutual funds that if too many people pull money out at once the managers could be forced to sell stocks at an unfavorable price.\"","title":""},{"docid":"38585","text":"This is something better asking a licensed professional (EA/CPA licensed in the US) who's also familiar with your home country tax law and the tax treaty your home country has with the US. Assuming no tax treaty and adverse tax consequences at home, you can have this scenario: The last step is critical - unless there's a tax treaty, not every country allows foreign tax credit (tax treaties usually have a provision to avoid double taxation), and you may end up paying both the US tax and local tax on the same money. If there's a tax treaty - step #4 is most likely guaranteed. Step #4 may not work in some places that would not consider the penalty as tax. Again - check it with an accountant proficient with the local law. Step #3 depends on your country. Some countries ignore foreign deferred compensation rules and consider the 401k amounts income to you when it was deposited (the US treats foreign tax deferred accounts this way, I believe that is also the case in India). So you should check locally. In this case you have probably paid taxes (or were exempt) on this amount when you earned it and will not pay taxes again. But then you might also not be able to claim the 10% back as credit. Leaving it is an option, although with such an amount is hardly worth it. You'll have to check how your country deals with foreign accounts of its citizens (the US, for example, puts an enormous reporting and tax burden on these, some countries forbid them altogether). This also applies to step #1.","title":""},{"docid":"335857","text":"\"You probably want to think about pools of money separately if they have separate time horizons or are otherwise not interchangeable. A classic example is your emergency fund (which has a potentially-immediate time horizon) vs. your retirement savings. The emergency fund would be all in cash or very short-term bonds, and would not count in your retirement asset allocation. Since the emergency fund usually has a capped value (a certain amount of money you want to have for emergencies) rather than a percentage of net worth value, this especially makes sense; you have to treat the emergency fund separately or you'd have to keep changing your asset allocation percentages as your net worth rises (hopefully) with respect to the capped emergency amount. Similarly, say you are saving for a car in 3 years; you'd probably invest that money very conservatively. Also, it could not go in tax-deferred retirement accounts, and when you buy the car the account will go to zero. So probably worth treating this separately. On the other hand, say you have some savings in tax-deferred retirement accounts and some in taxable accounts, but in both cases you're expecting to use the money for retirement. In that case, you have the same time horizon and goals, and it can pay to think about the taxable and nontaxable accounts as a whole. In particular you can use \"\"asset location\"\" (put less-tax-efficient assets in tax-deferred accounts). In this case maybe you would end up with mostly bonds in the tax-deferred accounts and mostly equities in the taxable accounts, for tax reasons; the asset allocation would only make sense considering all the accounts, since the taxable account would be too equity-heavy and the tax-deferred one too bond-heavy. There can be practical reasons to treat each account separately, too, though. For example if your broker has a convenient automatic rebalancing tool on their website, it probably only works within an account. Treating each account by itself would let you use the automatic rebalancing feature on the website, while a more complicated asset location strategy where you rebalance across multiple accounts might be too hard and in practice you wouldn't get around to it. Getting around to rebalancing could be more important than tax-motivated asset location. You could also take a keep-it-simple attitude: as long as your asset allocation is pretty balanced (say 40% bonds) and includes a cash allocation that would cover emergencies, you could just put all your money in one big portfolio, and think of it as a whole. If you have an emergency, withdraw from the cash allocation and then rebuild it over time; if you have a major purchase, you could redeem some bonds and then rebuild the bond portion over time. (When I say \"\"over time\"\" I'm thinking you might start putting new contributions into the now-underallocated assets, or you might dollar-cost-average back into them by selling bits of the now-overallocated assets.) Anyway there's no absolute rule, it depends on what's simple enough to be manageable for you in practice, and what separate shorter-horizon investing goals you have in addition to retirement. You can always make things complex but remember that a simple plan that happens in real life is better than a complex plan you don't keep up with in practice (or a complex plan that takes away from activities you'd enjoy more).\"","title":""},{"docid":"106501","text":"The $50k is subject to the appropriate income taxes, which may include FICA taxes including the employer share if you are self employed. The after tax money can then be invested with the amount invested being the cost basis (I.e., if you invest $40k you will have a cost basis of $40k). In future years you will have taxes due if any of those investments pay dividends (or capital gain distributions). Once you sell you will have a capital gain or loss that you will pay taxes on (or take a deduction if a loss). Now you can improve this picture if you are able to put some of your money into a retirement account (either a tax deductible or a ROTH). With retirement accounts you do not pay tax on the capital gains or dividends. If you use a tax deferred account your tax is higher but that is because you were also investing Uncle Sam's portion of your pay check.","title":""},{"docid":"396792","text":"\"Paypal linked with my bank account. 1.Can I use my Saving bank account to receive payments from my clients? Or is it necessary to open a current account? Yes you can get funds into your savings account. However it is advisable to keep a seperate account as it would help with your IT Returns. 2.I will be paying a certain % as commission on every sales to a couple of sales guys (who are not my employees but only working on commission). Can I show this as an expense in my IT returns? As you are earning as freelancer, you are eligible for certain deductions like Phone calls, Laptop, other hardware, payments to partners. It is important that you maintain a book of records. An accountant for a small fee of Rs 5 K should be able to help you. In the Returns you have to show Net income after all these deductions, there is no place to enter expenses. 3.Since I will be receiving all the payments in Euros so am I falling under a category of \"\"Exporter of services\"\"? The work you are doing can be Free Lancing. 4.Do I need an Import Export Code (IEC) for smoothly running this small business? You can run this without one as Free lancing. IEC would be when you grow big and are looking for various benefits under tax and pay different taxes and are incorporated as a company.\"","title":""},{"docid":"236732","text":"\"The 529 plan does outline your scenarios. There are stipulations for providing the funds should the child get the scholarship. If the child decides not to go into further education (vocational and community schools count), the money can be withdrawn with a 10% penalty and taxes paid on interest earnings. Taxes wouldn't have to be paid for contributions as taxes were already paid on that money by the gift giver. The 529 could also be transferred to another child in the family (including grandchildren). Here's an excerpt from www.savingforcollege.com: You'll never lose all of your savings. A 529 plan offers tax-free earnings and tax-free withdrawals as long as the money is used to pay for college. If you end up taking a non-qualified withdrawal, you'll incur income tax as well as a 10% penalty - but only on the earnings portion of the withdrawal. Since your contributions were made with after-tax money, they will never be taxed or penalized. You can avoid the penalty if you get a scholarship. There are a few special exceptions to the 10% penalty rule, including when the beneficiary becomes incapacitated, attends a U.S. Military Academy or gets a scholarship. In the case of a scholarship, non-qualified withdrawals up to the amount of the tax-free scholarship can be taken out penalty-free, but you'll have to pay income tax on the earnings. As Savingforcollege.com founder Joe Hurley likes to say, \"\"the scholarships have turned your tax-free 529 investment into a tax-deferred 529 investment\"\". Note, a 529 is ideal for the sum of money you are looking at. A proper trust, set up by a lawyer, will cost as much as $2000 to set up, and would require an annual tax return, both unnecessary burdens. To make matters worse, the trust counts as the child's asset where financial aid is concerned. The 529 counts, but to a much lesser extent.\"","title":""},{"docid":"114912","text":"The simplest explanation is that a traditional IRA is a method of deferring taxes. That is, normally you pay taxes on money you earn at the ordinary rate then invest the rest and only pay the capital gains rate. However, with a traditional IRA you don't pay taxes on the money when you earn it, you defer the payment of those taxes until you retire. So in the end it ends up being treated the same. That said, if you are strategic about it you can wind up paying less taxes with this type of account.","title":""}],"string":"[\n {\n \"docid\": \"308150\",\n \"text\": \"\\\"If I understand correctly, the Traditional IRA, if you have 401k with an employer already, has the following features: Actually, #1 and #2 are characteristics of Roth IRAs, not Traditional IRAs. Only #3 is a characteristic of a Traditional IRA. Whether you have a 401(k) with your employer or not makes absolutely no difference in how your IRAs are taxed for the vast majority of people. (The rules for IRAs are different if you have a very high income, though). You're allowed to have and contribute to both kinds of accounts. (In fact, I personally have both). Traditional IRAs are tax deferred (not tax-free as people sometimes mistakenly call them - they're very different), meaning that you don't have to pay taxes on the contributions or profits you make inside the account (e.g. from dividends, interest, profits from stock you sell, etc.). Rather, you pay taxes on any money you withdraw. For Roth IRAs, the contributions are taxed, but you never have to pay taxes on the money inside the account again. That means that any money you get over and above the contributions (e.g. through interest, trading profits, dividends, etc.) are genuinely tax-free. Also, if you leave any of the money to people, they don't have to pay any taxes, either. Important point: There are no tax-free retirement accounts in the U.S. The distinction between different kinds of IRAs basically boils down to \\\"\\\"pay now or pay later.\\\"\\\" Many people make expensive mistakes in their retirement strategy by not understanding that point. Please note that this applies equally to Traditional and Roth 401(k)s as well. You can have Roth 401(k)s and Traditional 401(k)s just like you can have Roth IRAs and Traditional IRAs. The same terminology and logic applies to both kinds of accounts. As far as I know, there aren't major differences tax-wise between them, with two exceptions - you're allowed to contribute more money to a 401(k) per year, and you're allowed to have a 401(k) even if you have a high income. (By way of contrast, people with very high incomes generally aren't allowed to open IRAs). A primary advantage of a Traditional IRA is that you can (in theory, at least) afford to contribute more money to it due to the tax break you're getting. Also, you can defer taxes on any profits you make (e.g. through dividends or selling stock at a profit), so you can grow your money faster.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"350082\",\n \"text\": \"I know of no way to answer your question without 'spamming' a particular investment. First off, if you are a USA citizen, max out your 401-K. Whatever your employer matches will be an immediate boost to your investment. Secondly, you want your our gains to be tax deferred. A 401-K is tax deferred as well as a traditional IRA. Thirdly, you probably want the safety of diversification. You achieve this by buying an ETF (or mutual fund) that then buys individual stocks. Now for the recommendation that may be called spamming by others : As REITs pass the tax liability on to you, and as an IRA is tax deferred, you can get stellar returns by buying a mREIT ETF. To get you started here are five: mREITs Lastly, avoid commissions by having your dividends automatically reinvested by using that feature at Scottrade. You will have to pay commissions on new purchases but your purchases from your dividend Reinvestment will be commission free. Edit: Taking my own advice I just entered orders to liquidate some positions so I would have the $ on hand to buy into MORL and get some of that sweet 29% dividend return.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"51086\",\n \"text\": \"\\\"The primary tax-sheltered investing vehicles in Canada include: The RRSP. You can contribute up to 18% of your prior year's earned income, up to a limit ($24,930 in 2015, plus past unused contribution allowance) and receive an income tax deduction for your contributions. In an RRSP, investments grow on a tax-deferred basis. No tax is due until you begin withdrawals. When you withdraw funds, the withdrawn amount will be taxed at marginal income tax rates in effect at that time. The RRSP is similar to the U.S. \\\"\\\"traditional\\\"\\\" IRA, being an individual account with pre-tax contributions, tax-deferred growth, and ordinary tax rates applied to withdrawals. Yet, RRSPs have contribution limits higher than IRAs; higher, even, than U.S. 401(k) employee contribution limits. But, the RRSP is dissimilar to the IRA and 401(k) since an individual's annual contribution allowance isn't use-it-or-lose-it—unused allowance accumulates. The TFSA. Once you turn 18, you can put in up to $5,500 each year, irrespective of earned income. Like the RRSP, contribution room accumulates. If you were 18 in 2009 (when TFSAs were introduced) you'd be able to contribute $36,500 if you'd never contributed to one before. Unlike the RRSP, contributions to a TFSA are made on an after-tax basis and you pay no tax when you withdraw money. The post-tax nature of the TFSA and completely tax-free withdrawals makes them comparable to Roth-type accounts in the U.S.; i.e. while you won't get a tax deduction for contributing, you won't pay tax on earnings when withdrawn. Yet, unlike U.S. Roth-type accounts, you are not required to use the TFSA strictly for retirement savings—there is no penalty for pre-retirement withdrawal of TFSA funds. There are also employer-sponsored defined benefit (DB) and defined contribution (DC) retirement pension plans. Generally, employees who participate in these kinds of plans have their annual RRSP contribution limits reduced. I won't comment on these kinds of plans other than to say they exist and if your employer has one, check it out—many employees lose out on free money by not participating. The under-appreciated RESP. Typically used for education savings. A lifetime $50,000 contribution limit per beneficiary, and you can put that all in at once if you're not concerned about maximizing grants (see below). No tax deduction for contributions, but investments grow on a tax-deferred basis. Original contributions can be withdrawn tax-free. Qualified educational withdrawals of earnings are taxed as regular income in the hands of the beneficiary. An RESP beneficiary is typically a child, and in a child's case the Canadian federal government provides matching grant money (called CESG) of 20% on the first $2500 contributed each year, up to age 18, to a lifetime maximum of $7200 per beneficiary. Grant money is subject to additional conditions for withdrawal. While RESPs are typically used to save for a child's future education, there's nothing stopping an adult from opening an RESP for himself. If you've never had one, you can deposit $50,000 of after-tax money to grow on a tax-deferred basis for up to 36 years ... as far as I understand. An adult RESP will not qualify for CESG. Moreover, if you use the RESP strictly as a tax shelter and don't make qualified educational withdrawals when the time comes, your original contributions still come out free of tax but you'll pay ordinary income tax plus 20% additional tax on the earnings portion. That's the \\\"\\\"catch\\\"\\\"*. *However, if at that time you have accumulated sufficient RRSP contribution room, you may move up to $50,000 of your RESP earnings into your RRSP without any tax consequences (i.e. also avoiding the 20% additional tax) at time of transfer. Perhaps there's something above you haven't considered. Still, be sure to do your own due diligence and to consult a qualified, experienced, and conflict-free financial advisor for advice particular to your own situation.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"109540\",\n \"text\": \"Guaranteed 8.2% annual return sounds too good to be true. Am I right? Are there likely high fees, etc.? You're right. Guaranteed annual return is impossible, especially when you're talking about investments for such a long period of time. Ponzi (and Madoff) schemed their investors using promises of guaranteed return (see this note in Wikipedia: In some cases returns were allegedly determined before the account was even opened.[72]). Her financial advisor doesn't charge by the hour--he takes a commission. So there's obviously some incentive to sell her things, even if she may not need them. Definitely not a good sign, if the advisor gets a commission from the sale then he's obviously not an advisor but a sales person. The problem with this kind of investment is that it is very complex, and it is very hard to track. The commission to the broker makes it hard to evaluate returns (you pay 10% upfront, and it takes awhile to just get that money back, before even getting any profits), and since you're only able to withdraw in 20 years or so - there's no real way to know if something wrong, until you get there and discover that oops- no money! Also, many annuity funds (if not all) limit withdrawals to a long period, i.e.: you cannot touch money for like 10 years from investment (regardless of the tax issues, the tax deferred investment can be rolled over to another tax deferred account, but in this case - you can't). I suggest you getting your own financial advisor (that will work for you) to look over the details, and talk to your mother if it is really a scam.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"11998\",\n \"text\": \"\\\"I have a couple other important considerations regarding external HSA accounts vs employer sponsored HSA accounts. Depending on your personal financial situation and goals; some people like to use HSA accounts as an extra retirement account (since the money can be withdrawn penalty free in retirement for non-medical expenses, and completely tax & penalty free at any time for medical expenses). If your intended use for the HSA account is an investment vehicle for retirement, then you may find more use/benefit out of an external provider that may provide more or better investment options than your employers HSA investment options. There can be a lot of additional value in those extra investment options over greater periods of time. Another VERY important consideration for FICA taxes (FICA includes Social Security & Medicare) that I don't believe was mentioned before - for those earners who are under the maximum social security wage limit, you are paying 6.2% of each paycheck into social security taxes. As others have mentioned you can \\\"\\\"save\\\"\\\" this tax through your employer’s plan if you set up the account to be funded pre-tax from your paychecks. However, in doing so, you are lowering your overall contributions into social security, which may lower your social security benefits in your retirement years! If this is ultimately going to lower your SSA benefits in retirement then that is a big future cost that may steer you against the pre-tax employer contributions. Think of social security as part of your retirement plan, not as a tax but instead as an additional check you put away for yourself for retirement every month. Of course, this is only an important consideration if SSA is still going to be around when you retire, but let's assume that it will be. This is not an issue for higher earners, earning well above the max SSA taxable wages. There is no wage limit on the 1.45% Medicare tax withholding's, and there is certainly no harm in saving Medicare taxes because it will not affect future Medicare benefits. So for taxpayers earning well over the max SSA wages, they will just save the 1.45% Medicare taxes without affecting their SSA contributions and resulting retirement benefits. So again, it all comes down to personal situations. Depending on your earnings and goals, employer plan may or may not be the way to go. Personally, for my lower earning clients, friends and family, I tend to recommend that they do whatever they can to maximize their social security benefits in retirement. So I would advise them to either use the external provider account, or the employer plan but with post-tax contributions so you don't lower the SSA withholding's but can still claim the income tax deduction on your tax return. YMMV -Dan\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"359515\",\n \"text\": \"A 401-K is something you get through an employer. I recommend getting a self-directed IRA. You can open an IRA with Scottrade with $500 The money you put into an IRA is tax deferred, meaning that you do not have to pay taxes on profits. It may also lower your tax liability. Scottrade has a feature to automatically reinvest any dividends from the securities you own. This feature allows you to avoid commissions on those automatic purchases. Don't try to time the market. Pick a good ETF (exchange traded fund) that pays dividends. It will give you diversification. Avoid the urge to buy and sell constantly. This only gives commissions to the broker.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"587768\",\n \"text\": \"4.7 is a pretty low rate, especially if you are deducting that from your taxes. If you reduce the number by your marginal tax rate to get the real cost of the money you end up with a number that isn't far off from inflation, and also represents a pretty low 'yield' in terms of paying off the loan early. (e.g. if your marginal tax rate is 28%, then the net you are paying in interest after the tax deduction is 4.7 * .72 = 3.384) While I'm all for paying off loans with higher rates (since it's in effect the same as making that much risk free on the money) it doesn't make a lot of sense when you are down at 3.4 unless there is a strong 'security factor' (which really makes a difference to some folks) to be had that really helps you sleep at night. (to be realistic, for some folks close to retirement, there can be a lot to be said for the security of not having to worry about house payments, although you don't seem to be in that situation yet) As others have said, first make sure you have enough liquid 'emergency money' in something like a money market account, or a ladder of short term CD's If you are sure that the sprouts will be going to college, then there's a lot to be said for kicking a decent amount into a 529, Coverdell ESA (Educational Savings Account), uniform gift to minors account, or some combination of those. I'm not sure if any of those plans can be used for a kid that has not been born yet however. I'd recommend http://www.savingforcollege.com as a good starting point to get more information on your various options. As with retirement savings, money put in earlier has a lot more 'power' over the final balance due to compounding interest, so there's a lot to be said for starting early, although depending on what it takes to qualify for the plans there could be such a thing as too early ;-) ). There's nothing wrong with Managed mutual funds as long as the fund objective and investing style is in alignment with your objectives and risk tolerance; The fund is giving you a good return relative to the market as a whole; You are not paying high fees or load charges; You are not losing a lot to taxes. I would always look at the return after expenses when comparing to other options, and if the money is not in a tax deferred account, also look at what sort of tax burden you will be faced with. A fund that trades a lot will generate more short term gains which means more taxes than compared to a more passive fund. Anything lost to taxes is money lost to you so needs to come out of the total return when you calculate that. Sometimes such funds are better off as a choice inside an IRA or 401K, and you can instead use more tax efficient vehicles for money where you have to pay the taxes every year on the gains. The reason a lot of folks like index funds better is that: Given your described age, it's not appropriate now, but in the long run as you get closer to retirement, you may want to start looking at building up some investments that are geared more towards generating income, such as bonds, or depending on taxes where you live, Municipal bonds. In any case, the more money you can set aside for retirement now, both inside and outside of tax deferred accounts, the sooner you will get to the point of the 'critical mass' you need to retire, at that point you can work because you want to, not because you have to.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"318338\",\n \"text\": \"\\\"Assuming that the will that bequeathed the money to your son did not stipulate any restrictions or set up a trust to hold the money until your son turns 25, or something like that, I don't think you have much choice except to put the money in a UTMA account (which of course can be invested in whatever the trustee (which could be you, or you and your wife jointly) decides. Note: not a UGMA account since the money is not a gift. You also don't have any option except to turn the account over to your son when he turns eighteen. The point is, the investment can be in anything as long as the account is registered as a UTMA account. But do remember also that your son is entitled to sue you for breach of fiduciary duty if you don't take good care of the money, so that blowing it all in risky investments is also not a good idea. If you are worried about taxes and your son's income being taxed at your rate, one way of deferring the issue is to buy US Savings Bonds. The interest can be deferred from taxation until the bonds are redeemed. Edit added in response to JoeTaxpayer's comments: But a better strategy is to declare the accrued interest each year as unearned income of the child on the kiddie tax form that is part of your tax return, and pay the tax, if any, that results To ease your mind or conscience, think of the tax that you pay on your child's behalf as a gift to your child! In any case, there will likely not be much tax due since the first $950 of unearned income of a child is tax-free and the next $950 taxed at 10%. Then, when the bonds are cashed in, the interest that accrued (and was \\\"\\\"taxed\\\"\\\") in earlier years can be deducted from the interest (cash in price minus purchase price) that you (or your son) will be told is the interest that the bonds earned. Of course, if kiddie tax is not a concern (and it shouldn't be, given the amount available for investment), an even better strategy is to set up the UTMA account(s) in long-term investments in low-cost index funds or ETFs (as JoeTaxpayer suggests) and pay the tax, if any, as it comes due.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"264023\",\n \"text\": \"\\\"when you contribute to a 401k, you get to invest pre-tax money. that means part of it (e.g. 25%) is money you would otherwise have to pay in taxes (deferred money) and the rest (e.g. 75%) is money you could otherwise invest (base money). growth in the 401k is essentially tax free because the taxes on the growth of the base money are paid for by the growth in the deferred portion. that is of course assuming the same marginal tax rate both now and when you withdraw the money. if your marginal tax rate is lower in retirement than it is now, you would save even more money using a traditional 401k or ira. an alternative is to invest in a roth account (401k or ira). in which case the money goes in after tax and the growth is untaxed. this would be advantageous if you expect to have a higher marginal tax rate during retirement. moreover, it reduces tax risk, which could give you peace of mind considering u.s. marginal tax rates were over 90% in the 1940's. a roth could also be advantageous if you hit the contribution limits since the contributions are after-tax and therefore more valuable. lastly, contributions to a roth account can be withdrawn at any time tax and penalty free. however, the growth in a roth account is basically stuck there until you turn 60. unlike a traditional ira/401k where you can take early retirement with a SEPP plan. another alternative is to invest the money in a normal taxed account. the advantage of this approach is that the money is available to you whenever you need it rather than waiting until you retire. also, investment losses can be deducted from earned income (e.g. 15-25%), while gains can be taxed at the long term capital gains rate (e.g. 0-15%). the upshot being that even if you make money over the course of several years, you can actually realize negative taxes by taking gains and losses in different tax years. finally, when you decide to retire you might end up paying 0% taxes on your long term capital gains if your income is low enough (currently ~50k$/yr for a single person). the biggest limitation of this strategy is that losses are limited to 3k$ per year. also, this strategy works best when you invest in individual stocks rather than mutual funds, increasing volatility (aka risk). lastly, this makes filing your taxes more complicated since you need to report every purchase and sale and watch out for the \\\"\\\"wash sale\\\"\\\" rules. side note: you should contribute enough to get all the 401k matching your employer offers. even if you cash out the whole account when you want the money, the matching (typically 50%-200%) should exceed the 10% early withdrawal penalty.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"388145\",\n \"text\": \"Yes, absolutely. The HSA, when used for medical expenses, allows you to essentially pay for your medical expenses tax free. Even if you don't have extra room in your budget, you can fund the HSA as you incur medical expenses, then withdraw money to pay the expenses, and you'll see an immediate tax benefit at tax time. However, let's say that you have plenty of room in your budget and you don't have a lot of medical expenses. You already contribute the maximum to your 401(k) or IRA, and you want to do more. The HSA acts like a retirement account in this case, allowing you to contribute before-tax money and let it grow untaxed. The HSA does have a huge benefit that no other retirement account has. If you choose not to reimburse yourself for medical expenses, but you keep track of the unreimbursed expenses you incur, then you can reimburse yourself for these expenses at any point in the future completely tax free. Essentially, your contributions are treated like a traditional IRA, but your withdrawals are treated like a Roth IRA, and can be done at any age. If you don't acquire enough medical expenses, you can still withdraw whatever is left at age 65 and those withdrawals will be taxed like a traditional IRA. The HSA provides for tax-free contributions and growth if used for medical expenses, and tax-deferred growth if withdrawn after age 65 without medical expenses.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"329596\",\n \"text\": \"\\\"tl;dr Roth earnings are not necessarily \\\"\\\"tax deferred\\\"\\\", but they might be. This is a great question because IMHO, the use of the wording \\\"\\\"tax deferred\\\"\\\" is slightly misleading when talking about a Roth IRA (and Roth 401k too). The phrase \\\"\\\"tax deferred\\\"\\\" actually means you save tax now and you pay tax later, i.e. you \\\"\\\"defer\\\"\\\" the tax. As you pointed out, this is the normal terminology used for describing a Traditional IRA/401k. Earnings on a Roth IRA are tax free (not deferred), but only if your distributions are qualified. For the most part distributions are considered qualified if you wait until you are 59.5 years old before taking the money out, but there are some exceptions. If you choose to distribute more than your contributions, meaning you are now taking out earnings, the earnings are tax free only if your distribution is qualified. For example, if you take out the earnings before you are 59.5 (and no other exceptions apply), then you would pay tax on the earnings and also a 10% penalty. So, perhaps a better way to say it is that earnings in a Roth IRA are \\\"\\\"conditionally tax deferred\\\"\\\".\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"206442\",\n \"text\": \"\\\"It is important to remember that the stock price in principle reflects the value of the company, so the market cap should drop upon issuance of the the dividend. However, the above reasoning neglects to consider taxes, which make the question a bit more interesting. The key fact is that different investors are going to get taxed on the dividend to varying degrees, ranging from 20% for qualified dividends in the USA for a high-income individual in a taxable account (and even worse for non-qualified dividends) to 0% for tax-exempt nonprofits, retirement accounts, and low-income individuals. The high-tax investors are going to be a bit averse to paying tax on that dividend, whereas the tax-free investors are not. Hence in a tax-rational market the tax-free investors are going to be the ones buying right before a dividend and the tax-paying investors will be buying right afterwards. Tax-exempt investors could in principle make some amount of money buying dividends to keep them off the tax-paying investors' books. (Of course, the strategy could backfire if too many people did it all at once.) That said, the tax-payers have the tax disincentive to prevent them from fully exploiting the opposite strategy of selling just before a dividend. In particular, they are subject to capital gains tax when they sell at a profit (unless they have enough compensating capital losses), and it is to their after-tax profit to defer taxation by not trading. That said, the stock market has well-known irrationality when it comes to considering tax consequences, so logic based on assumed rationality of the market does not always apply to the extent one would expect. The foremost example of tax-irrationality is the so-called \\\"\\\"dividend paradox\\\"\\\", which basically states that corporations should favor stock buybacks (or perhaps loan repayment) to the complete exclusion of dividends because capital gains are taxed less harshly than dividends in a variety of ways, some of which are subtle: 1) Historically (although not currently in the USA for qualified dividends) the tax rate was higher for dividends. (In Canada, for example, dividends are taxed at twice the rate of capital gains.) 2) If you die holding appreciated stock then you (meaning your heirs) completely escape US the capital gains tax on the accrual during your lifetime. 3) Capital gains tax can be deferred by simply not selling. In comparison to dividends, this is roughly equivalent to getting a tax-free loan from the government which is invested for profit and paid at a later date after inflation has eaten away at the real value of the loan. For example, if all your stock investments increase by 10%/year but you sell every year, in a high-tax bracket situation you're total after-tax return will be only 8% per year. In contrast, if you hold the same investments for many many years and then sell, your total return will be nearly 10% per year, because you only pay 20% once (at the end). 4) A capital gain can often be neutralized by a capital loss in another stock, so that no tax results. If you loose money on a stock that is paying dividends, you're still going to have to pay tax on that dividend. There are companies that borrow money to pay out that taxable-dividend each quarter, which seems like gross tax malpractice on the part of the CFO. (If the dividend paradox doesn't make sense, first consider the case that you owned ALL the shares of a company. It wouldn't matter to you at all on a pre-tax basis whether you got a $1000 company buyback or a $1000 dividend, because after the buyback/dividend you'd still own the entire company and $1000. The number of shares would be reduced, but objecting that you owned fewer shares after the buyback would be like saying you have become shorter if your height is measured in inches rather than centimeters.) [Of course, in the case of many shareholders you can get burned by failing to sell into the buyback when the share price is too high, but that is another matter.]\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"438038\",\n \"text\": \"\\\"You don't want to do that. DON'T LIE TO THE IRS!!! We live overseas as well and have researched this extensively. You cannot make $50k overseas and then say you only made $45k to put $5k into retirement. I have heard from some accountants and tax attorneys who interpret the law as saying that the IRS considers Foreign Earned Income as NOT being compensation when computing IRA contribution limits, regardless of whether or not you exclude it. Publication 590-A What is Compensation (scroll down a little to the \\\"\\\"What Is Not Compensation\\\"\\\" section). Those professionals say that any amounts you CAN exclude, not just ones you actually do exclude. Then there are others that say the 'can' is not implied. So be careful trying to use any foreign-earned income to qualify for retirement contributions. I haven't ran across anyone yet who has gotten caught doing it and paid the price, but that doesn't mean they aren't out there. AN ALTERNATIVE IN CERTAIN CASES: There are two things you can do that we have found to have some sort of taxable income that is preferably not foreign so that you can contribute to a retirement account. We do this by using capital gains from investments as income. Since our AGI is always zero, we pay no short or long term capital gains taxes (as long as we keep short term capital gains lower than $45k) Another way to contribute to a Roth IRA when you have no income is to do an IRA Rollover. Of course, you need money in a tax-deferred account to do this, but this is how it works: I always recommend those who have tax-deferred IRA's and no AGI due to the FEIE to roll over as much as they can every year to a Roth IRA. That really is tax free money. The only tax you'll pay on that money is sales tax when you SPEND IT!! =)\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"535340\",\n \"text\": \"\\\"As user quid states in his answer, all you need to do is open an account with a stock broker in order to gain access to the world's stock markets. If you are currently banking with one of the six big bank, then they will offer stockbroking services. You can shop around for the best commission rates. If you wish to manage your own investments, then you will open a \\\"\\\"self-directed\\\"\\\" account. You can shelter your investments from all taxation by opening a TFSA account with your stock broker. Currently, you can add $5,500 per year to your TFSA. Unused allowances from previous years can still be used. Thus, if you have not yet made any TFSA contributions, you can add upto $46,500 to your TFSA and enjoy the benefits of tax free investing. Investing in what you are calling \\\"\\\"unmanaged index funds\\\"\\\" means investing in ETFs (Exchange Traded Funds). Once you have opened your account you can invest in any ETFs traded on the stock markets accessible through your stock broker. Buying shares on foreign markets may carry higher commission rates, but for the US markets commissions are generally the same as they are for Canadian markets. However, in the case of buying foreign shares you will carry the extra cost and risk of selling Canadian dollars and buying foreign currency. There are also issues to do with foreign withholding taxes when you trade foreign shares directly. In the case of the US, you will also need to register with the US tax authorities. Foreign withholding taxes payable are generally treated as a tax credit with respect to Canadian taxation, so you will not be double taxed. In today's market, for most investors there is generally no need to invest directly in foreign market indices since you can do so indirectly on the Toronto stock market. The large Canadian ETF providers offer a wide range of US, European, Asian, and Global ETFs as well as Canadian ETFs. For example, you can track all of the major US indices by trading in Toronto in Canadian dollars. The S&P500, the Dow Jones, and the NASDAQ100 are offered in both \\\"\\\"currency hedged\\\"\\\" and \\\"\\\"unhedged\\\"\\\" forms. In addition, there are ETFs on the total US Market, US Small Caps, US sectors such as banks, and more exotic ETFs such as those offering \\\"\\\"covered call\\\"\\\" strategies and \\\"\\\"put write\\\"\\\" strategies. Here is a link to the BMO ETF website. Here is a link to the iShares (Canada) ETF website.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"8861\",\n \"text\": \"\\\"Sure. For starters, you can put it in a savings account. Don't laugh, they used to pay noticeable interest. You know, back in the olden days. You could buy an I-bond from Treasury Direct. They're a government savings bond that pays a specified amount of interest (currently 0%, I believe), plus the amount of the inflation rate (something like 3.5% currently, I believe). You don't get paid the money -- the I-bond grows in value till you sell it. You can open a discount brokerage account, and buy 1 or more shares of stock in a company you like. Discount brokerages generally have a minimum of $500 or so, but will waive that if you set the account up as an IRA. Scot Trade, for instance. (An IRA, in case you didn't know, is a type of account that's tax free but you can't touch it till you turn 59 1/2. It's meant to help you save for retirement.) Incidentally, watch out of \\\"\\\"small account\\\"\\\" fees that some brokerages might charge you. Generally they're annual or monthly charges they'd charge you to cover their costs on your account -- since they're certainly not going to make it in commissions. That IRA at Scot Trade is no-fee. Speaking of commissions, those will be a big chunk of that $100. It'll be like $7-$10 to buy that stock -- a pretty big bite. However, many of these discount brokerages also offer some mutual funds for no commission. Those mutual funds, in turn, have minimums too, but once again if your account's an IRA many will waive the minimum or set it low -- like $100.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"473658\",\n \"text\": \"ETFs offer the flexibility of stocks while retaining many of the benefits of mutual funds. Since an ETF is an actual fund, it has the diversification of its potentially many underlying securities. You can find ETFs with stocks at various market caps and style categories. You can have bond or mixed ETFs. You can even get ETFs with equal or fundamental weighting. In short, all the variety benefits of mutual funds. ETFs are typically much less expensive than mutual funds both in terms of management fees (expense ratio) and taxable gains. Most of them are not actively managed; instead they follow an index and therefore have a low turnover. A mutual fund may actively trade and, if not balanced with a loss, will generate capital gains that you pay taxes on. An ETF will produce gains only when shifting to keep inline with the index or you yourself sell. As a reminder: while expense ratio always matters, capital gains and dividends don't matter if the ETF or mutual fund is in a tax-advantaged account. ETFs have no load fees. Instead, because you trade it like a stock, you will pay a commission. Commissions are straight, up-front and perfectly clear. Much easier to understand than the various ways funds might charge you. There are no account minimums to entry with ETFs, but you will need to buy complete shares. Only a few places allow partial shares. It is generally harder to dollar-cost average into an ETF with regular automated investments. Also, like trading stocks, you can do those fancy things like selling short, buying on margin, options, etc. And you can pay attention to the price fluctuations throughout the day if you really want to. Things to make you pause: if you buy (no-load) mutual funds through the parent company, you'll get them at no commission. Many brokerages have No Transaction Fee (NTF) agreements with companies so that you can buy many funds for free. Still look out for that expense ratio though (which is probably paying for that NTF advantage). As sort of a middle ground: index funds can have very low expense ratios, track the same index as an ETF, can be tax-efficient or tax-managed, free to purchase, easy to dollar-cost average and easier to automate/understand. Further reading:\",\n \"title\": \"\"\n },\n {\n \"docid\": \"10089\",\n \"text\": \"Congratulations on deciding to save for retirement. Since you cite Dave Ramsey as the source of your 15% number, what does he have to say about where to invest the money? If you want to have instantaneous penalty-free access to your retirement money, all you need to do is set up one or more ordinary accounts that you think of as your retirement money. Just be careful not to put the money into CDs since Federal law requires a penalty of three months interest if you cash in the CD before its maturity date (penalty!) or put the money into those pesky mutual funds that charge a redemption fee (penalty!) if you take the money out within x months of investing it where x can be anywhere from 3 to 24 or more. In Federal tax law (and in most state tax laws as well) a retirement account has special privileges accorded to it in that the interest, dividends, capital gains, etc earned on the money in your retirement account are not taxed in the year earned (as they would be in a non-retirement account), but the tax is either deferred till you withdraw money from the account (Traditional IRAs, 401ks etc) or is waived completely (Roth IRAs, Roth 401ks etc). In return for this special treatment, penalties are imposed (in addition to tax) if you withdraw money from your retirement account before age 59.5 which presumably is on the distant horizon for you. (There are some exceptions (including first-time home buying and extraordinary medical expenses) to this rule that I won't bother going into). But You are not required to invest your retirement money into such a specially privileged retirement account. It is perfectly legal to keep your retirement money in an ordinary savings account if you wish, and pay taxes on the interest each year. You can invest your retirement money into municipal bonds whose interest is free of Federal tax (and usually free of state tax as well if the municipality is located in your state of residence) if you like. You can keep your retirement money in a sock under your mattress if you like, or buy a collectible item (e.g. a painting) with it (this is not permitted in an IRA), etc. In short, if you are concerned about the penalties imposed by retirement accounts on early withdrawals, forgo the benefits of these accounts and put your retirement money elsewhere where there is no penalty for instant access. If you use a money management program such as Mint or Quicken, all you need to do is name one or more accounts or a portfolio as MyRetirementMoney and voila, it is done. But those accounts/portfolios don't have to be retirement accounts in the sense of tax law; they can be anything at all.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"475397\",\n \"text\": \"There is no advantage to using one type of account or the other if you are in the same tax bracket at retirement that you are in during your working years. However, for tax planning reasons, it is good to have some money in both a Roth and a traditional IRA plan. JoeTaxpayer has often advocated a good rule of thumb to use a Roth when your tax bracket is 15% or lower, and use a traditional account when in the 25% bracket or above. The reason for this rule of thumb is that you are less likely to be in the higher tax bracket when you are living off retirement savings unless you put away an awful lot of money between now and then. If you are making enough money to be paying a 25% marginal rate on some of the money you would be putting away for retirement, then by all means, put all of that money in a traditional 401k. If after contributing that portion of your savings taxed at the higher rate, you still have money to put away for retirement, put the rest in a Roth and pay the 15% taxes on it. When you are younger, it is likely that you are making less than you will a few years hence, and it is also likely that a larger portion of your income will be paying tax deductible interest on a mortgage. If those are true for you, then by all means, use the Roth. That was true of me when I was single and just getting started. When you do finally retire, it is possible that the tax brackets will be increased to match inflation, and if so, then there is no benefit to having tax free money at retirement vs. paying taxes on deferred accounts, but there is also usually more flexibility in when to spend money. You may find that you have a year where you have to spend a lot, so it is good to be able to pull money out without it increasing your marginal rate for that year, and other years where you spend relatively smaller amounts, and you can withdraw taxable money and pay a lower rate on that money. No one knows what the tax code will look like in 40 years, but having some money in each type of account will give you flexibility to minimize your tax bill at retirement.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"173088\",\n \"text\": \"\\\"What is a stock? A share of stock represents ownership of a portion of a corporation. In olden times, you would get a physical stock certificate (looking something like this) with your name and the number of shares on it. That certificate was the document demonstrating your ownership. Today, physical stock certificates are quite uncommon (to the point that a number of companies don't issue them anymore). While a one-share certificate can be a neat memento, certificates are a pain for investors, as they have to be stored safely and you'd have to go through a whole annoying process to redeem them when you wanted to sell your investment. Now, you'll usually hold stock through a brokerage account, and your holdings will just be records in a database somewhere. You'll pick a broker (more on that in the next question), instruct them to buy something, and they'll keep track of it in your account. Where do I get a stock? You'll generally choose a broker and open an account. You can read reviews to compare different brokerages in your country, as they'll have different fees and pricing. You can also make sure the brokerage firm you choose is in good standing with the financial regulators in your country, though one from a major national bank won't be unsafe. You will be required to provide personal information, as you are opening a financial account. The information should be similar to that required to open a bank account. You'll also need to get your money in and out of the account, so you'll likely set up a bank transfer. It may be possible to request a paper stock certificate, but don't be surprised if you're told this is unavailable. If you do get a paper certificate, you'll have to deal with considerably more hassle and delay if you want to sell later. Brokers charge a commission, which is a fee per trade. Let's say the commission is $10/trade. If you buy 5 shares of Google at $739/share, you'd pay $739 * 5 + $10 = $3705 and wind up with $3695 worth of stock in your account. You'd pay the same commission when you sell the stock. Can anyone buy/own/use a stock? Pretty much. A brokerage is going to require that you be a legal adult to maintain an account with them. There are generally ways in which a parent can open an account on behalf of an underage child though. There can be different types of restrictions when it comes to investing in companies that are not publicly held, but that's not something you need to worry about. Stocks available on the public stock market are available to, well, the public. How are stocks taxed? Taxes differ from country to country, but as a general rule, you do have to provide the tax authorities with sufficient information to determine what you owe. This means figuring out how much you purchased the stock for and comparing that with how much you sold it for to determine your gain or loss. In the US (and I suspect in many other countries), your brokerage will produce an annual report with at least some of this information and send it to the tax authorities and you. You or someone you hire to do your taxes will use that report to compute the amount of tax owed. Your brokerage will generally keep track of your \\\"\\\"cost basis\\\"\\\" (how much you bought it for) for you, though it's a good idea to keep records. If you refuse to tell the government your cost basis, they can always assume it's $0, and then you'll pay more tax than you owe. Finding the cost basis for old investments can be difficult many years later if the records are lost. If you can determine when the stock was purchased, even approximately, it's possible to look back at historical price data to determine the cost. If your stock pays a dividend (a certain amount of money per-share that a company may pay out of its profits to its investors), you'll generally need to pay tax on that income. In the US, the tax rate on dividends may be the same or less than the tax rate on normal wage income depending on how long you've held the investment and other rules.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"69841\",\n \"text\": \"A UTMA may or may not fit your situation. The main drawbacks to a UTMA account is that it will count against your child for financial aid (it counts as the child's asset). The second thing to consider is that taxes aren't deferred like in a 529 plan. The last problem of course is that when he turns 18 he gets control of the account and can spend the money on random junk (which may or may not be important to you). A 529 plan has a few advantages over a UTMA account. The grandparents can open the account with your son as the beneficiary and the money doesn't show up on financial aid for college (under current law which could change of course). Earnings grow tax free which will net you more total growth. You can also contribute substantially more without triggering the gift tax ~$60k. Also many states provide a state tax break for contributing to the state sponsored 529 plan. The account owner would be the grandparents so junior can't spend the money on teenage junk. The big downside to the 529 is the 10% penalty if the money isn't used for higher education. The flip side is that if the money is left for 20 years you will also have additional growth from the 20 years of tax free growth which may be a wash depending on your tax bracket and the tax rates in effect over those 20 years.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"432902\",\n \"text\": \"\\\"Your question is based on incorrect assumptions. Generally, there's no \\\"\\\"penalty\\\"\\\", per se, to make a withdrawal from your RRSP, even if you make a withdrawal earlier than retirement, however you define it. A precise meaning for \\\"\\\"retirement\\\"\\\" with respect to RRSPs is largely irrelevant.* Our U.S. neighbours have a 10% penalty on non-hardship early withdrawals (before age 59 ½) from retirement accounts like the 401k and IRA. It's an additional measure designed to discourage early withdrawals, and raise more tax. Yet, in Canada, there is no similar penalty. Individual investments inside your RRSP may have associated penalties, such as the dreaded \\\"\\\"deferred sales charge\\\"\\\" (DSC) of some back-end loaded mutual funds, or such as LSVCC funds that generated additional special tax credits that could get clawed back. Yet, these early withdrawal penalties are distinct from the RRSP nature of your account. Choose your investments carefully to avoid these kinds of surprises. Rather, an RRSP is a tax-deferred account, and it works like this: The government allows you to claim a nice juicy tax deduction, which can reduce your income tax at your marginal rate in the year you make a contribution, or later if you should choose to defer the deduction. The resulting pre-tax money accumulated in your RRSP benefits from further tax deferral: assets can grow without attracting annual income tax on earned interest, dividends, or capital gains. You don't need to declare on your income tax return any of the income earned inside your RRSP, unlike a regular investment account. Here's the rub: Once you decide to withdraw money from your RRSP, the entire amount withdrawn is considered regular income in the year in which you make the withdrawal. Thus, your withdrawals are subject to income tax, and yes, at your marginal rate. This is always the case, whether before or after retirement. You mentioned two special programs: The Home Buyers' Plan (HBP), and the Lifelong Learning Plan (LLP). Neither the HBP nor the LLP permit tax-free withdrawals. Rather, each of these programs are special kinds of loans that you can borrow from your own RRSP. HBP and LLP loan money isn't taxed when you get it because you are required to pay it back, and you pay it back into your own RRSP: You always pay income tax at your marginal rate on your RRSP withdrawals.** * Above, I said a precise meaning for \\\"\\\"retirement\\\"\\\" with respect to RRSPs is largely irrelevant. Yet, there are ages that matter: By the end of the year in which you turn 71, you are required to convert your RRSP to a RRIF. It's similar, but you can no longer contribute, and you must withdraw a minimum amount each year. Other circumstances related to age may qualify for minor tax relief intended for retirees, such as the Age Amount or the Pension Income Credit. Generally, such measures don't significantly change the fact that you pay income tax on RRSP withdrawals at your marginal rate – these measures raise the minimum you can take out without attracting tax, but most do nothing at the margin.** ** Exception: One might split eligible pension income with a spouse or common-law partner, which may reduce tax at the margin.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"417388\",\n \"text\": \"The 401(k) contribution is Federal tax free, when you make the contribution, and most likely State too. I believe that is true for California, specifically. There was a court case some years ago about people making 401(k) or IRA contributions in New York, avoiding the New York state income tax. Then they moved to Florida (no income tax), and took the money out. New York sued, saying they had to pay the New York income tax that had been deferred, but the court said no. So you should be able to avoid California state income tax, and then later if you were to move to, for example, Texas (no income tax), have no state income tax liability. At the Federal level, you will have different problems. You won't have the money; it will be held by the 401(k) trustee. When you try to access the money (cash the account out), you will have to pay the deferred taxes. Effectively, when you remove the money it becomes income in the year it is removed. You can take the money out at any time, but if you are less than 59 1/2 at the time that you take it, there is a 10% penalty. The agreement is that the Feds let you defer paying the tax because it is going to finance your retirement, and they will tax it later. If you take it out before 59 1/2, they figure you are not retired yet, and are breaking your part of the agreement. Of course you can generally leave the money in the 401(k) plan with your old employer and let it grow until you are 59.5, or roll it over into another 401(k) with a new employer (if they let you), or into an IRA. But if you have returned to your own country, having an account in the U.S. would introduce both investment risk and currency risk. If you are in another country when you want the money, the question would be where your U.S. residence would be. If you live in California, then go to, say France, your U.S. residence would still be California, and you would still owe California income tax. If you move from California to Texas and then to France, your U.S. residence would be Texas. This is pretty vague, as you might have heard in the Rahm Emanual case -- was he a resident of Chicago or Washington, D.C.? Same problem with Howard Hughes who was born in Texas, but then spent most his life in California, then to Nevada, then to Nicaragua, and the Bahamas. When he died Texas, California and Nevada all claimed him as a resident, for estate taxes. The important thing is to be able to make a reasonable case that you are a resident of where ever you want to be -- driver's license, mailing address, living quarters, and so on.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"170717\",\n \"text\": \"In the US, the key to understanding the benefits of retirement accounts is to understand capital gains taxes and how they work. Retirement accounts are designed for making investments throughout your career, then after several decades of contributions, withdrawing that money to pay for your needs when your full-time employment has concluded. Normally when you invest money in a brokerage account, if the value of your investment increases, and you sell in less than a year, those investments are considered short-term gains and taxed as ordinary income. If you hold that same investment for over a year, the same investment is taxed at a lower capital gains rate (depending on which tax bracket you are in during that year, the amount due could be up to 20%, but much lower than your regular income tax rate). When you place your money in a retirement account, you are choosing to either pay the tax due on the income when you put it in the account, or put the money in tax free and pay the tax when you withdraw (these are called tax-deferred accounts). When you have money invested several decades, the raw dollar amount increases greatly, but inflation is also reducing the value of those dollars. Imagine you bought some bonds that payed 4% over 40 years, but inflation was 2% during those same years. When you sell those bonds 40 years later, you will owe capital gains on the entire gain even though half of the gain came from inflation. Retirement accounts allow you to buy and sell according to your investment needs and goals without any consideration about whether the gains are short-term or long-term, and they also allow you to pay taxes just once, either when you put it in, or when you take it out, with no worries about whether you're paying taxes on inflated gains.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"299690\",\n \"text\": \"\\\"As other people have indicated, traditional IRAs are tax deductable for a particular year. Please note, though, that traditional IRAs are tax deferred (not tax-free) accounts, meaning that you'll have to pay taxes on any money you take out later regardless of why you're making the withdrawal. (A lot of people mistakenly call them tax free, which they're not). There is no such thing as a \\\"\\\"tax-free\\\"\\\" retirement account. Really, in terms of Roth vs. Traditional IRAs, it's \\\"\\\"pay now or pay later.\\\"\\\" With the exception of special circumstances like this, I recommend investing exclusively in Roth IRAs for money that you expect to grow much (or that you expect to produce substantial income over time). Just to add a few thoughts on what to actually invest in once you open your IRA, I strongly agree with the advice that you invest mostly in low-cost mutual funds or index funds. The advantage of an open-ended mutual fund is that it's easier to purchase them in odd increments and you may be able to avoid at least some purchase fees, whereas with an ETF you have to buy in multiples of that day's asking price. For example, if you were investing $500 and the ETF costs $200 per share, you could only purchase 2 shares, leaving $100 uninvested (minus whatever fee your broker charged for the purchase). The advantage of an ETF is that it's easy to buy or sell quickly. Usually, when you add money to a mutual fund, it'll take a few days for it to hit your account, and when you want to sell it'll similarly take a few days for you to get your money; when I buy an ETF the transaction can occur almost instantly. The fees can also be lower (if the ETF is just a passive index fund). Also, there's a risk with open-ended mutual funds that if too many people pull money out at once the managers could be forced to sell stocks at an unfavorable price.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"38585\",\n \"text\": \"This is something better asking a licensed professional (EA/CPA licensed in the US) who's also familiar with your home country tax law and the tax treaty your home country has with the US. Assuming no tax treaty and adverse tax consequences at home, you can have this scenario: The last step is critical - unless there's a tax treaty, not every country allows foreign tax credit (tax treaties usually have a provision to avoid double taxation), and you may end up paying both the US tax and local tax on the same money. If there's a tax treaty - step #4 is most likely guaranteed. Step #4 may not work in some places that would not consider the penalty as tax. Again - check it with an accountant proficient with the local law. Step #3 depends on your country. Some countries ignore foreign deferred compensation rules and consider the 401k amounts income to you when it was deposited (the US treats foreign tax deferred accounts this way, I believe that is also the case in India). So you should check locally. In this case you have probably paid taxes (or were exempt) on this amount when you earned it and will not pay taxes again. But then you might also not be able to claim the 10% back as credit. Leaving it is an option, although with such an amount is hardly worth it. You'll have to check how your country deals with foreign accounts of its citizens (the US, for example, puts an enormous reporting and tax burden on these, some countries forbid them altogether). This also applies to step #1.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"335857\",\n \"text\": \"\\\"You probably want to think about pools of money separately if they have separate time horizons or are otherwise not interchangeable. A classic example is your emergency fund (which has a potentially-immediate time horizon) vs. your retirement savings. The emergency fund would be all in cash or very short-term bonds, and would not count in your retirement asset allocation. Since the emergency fund usually has a capped value (a certain amount of money you want to have for emergencies) rather than a percentage of net worth value, this especially makes sense; you have to treat the emergency fund separately or you'd have to keep changing your asset allocation percentages as your net worth rises (hopefully) with respect to the capped emergency amount. Similarly, say you are saving for a car in 3 years; you'd probably invest that money very conservatively. Also, it could not go in tax-deferred retirement accounts, and when you buy the car the account will go to zero. So probably worth treating this separately. On the other hand, say you have some savings in tax-deferred retirement accounts and some in taxable accounts, but in both cases you're expecting to use the money for retirement. In that case, you have the same time horizon and goals, and it can pay to think about the taxable and nontaxable accounts as a whole. In particular you can use \\\"\\\"asset location\\\"\\\" (put less-tax-efficient assets in tax-deferred accounts). In this case maybe you would end up with mostly bonds in the tax-deferred accounts and mostly equities in the taxable accounts, for tax reasons; the asset allocation would only make sense considering all the accounts, since the taxable account would be too equity-heavy and the tax-deferred one too bond-heavy. There can be practical reasons to treat each account separately, too, though. For example if your broker has a convenient automatic rebalancing tool on their website, it probably only works within an account. Treating each account by itself would let you use the automatic rebalancing feature on the website, while a more complicated asset location strategy where you rebalance across multiple accounts might be too hard and in practice you wouldn't get around to it. Getting around to rebalancing could be more important than tax-motivated asset location. You could also take a keep-it-simple attitude: as long as your asset allocation is pretty balanced (say 40% bonds) and includes a cash allocation that would cover emergencies, you could just put all your money in one big portfolio, and think of it as a whole. If you have an emergency, withdraw from the cash allocation and then rebuild it over time; if you have a major purchase, you could redeem some bonds and then rebuild the bond portion over time. (When I say \\\"\\\"over time\\\"\\\" I'm thinking you might start putting new contributions into the now-underallocated assets, or you might dollar-cost-average back into them by selling bits of the now-overallocated assets.) Anyway there's no absolute rule, it depends on what's simple enough to be manageable for you in practice, and what separate shorter-horizon investing goals you have in addition to retirement. You can always make things complex but remember that a simple plan that happens in real life is better than a complex plan you don't keep up with in practice (or a complex plan that takes away from activities you'd enjoy more).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"106501\",\n \"text\": \"The $50k is subject to the appropriate income taxes, which may include FICA taxes including the employer share if you are self employed. The after tax money can then be invested with the amount invested being the cost basis (I.e., if you invest $40k you will have a cost basis of $40k). In future years you will have taxes due if any of those investments pay dividends (or capital gain distributions). Once you sell you will have a capital gain or loss that you will pay taxes on (or take a deduction if a loss). Now you can improve this picture if you are able to put some of your money into a retirement account (either a tax deductible or a ROTH). With retirement accounts you do not pay tax on the capital gains or dividends. If you use a tax deferred account your tax is higher but that is because you were also investing Uncle Sam's portion of your pay check.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"396792\",\n \"text\": \"\\\"Paypal linked with my bank account. 1.Can I use my Saving bank account to receive payments from my clients? Or is it necessary to open a current account? Yes you can get funds into your savings account. However it is advisable to keep a seperate account as it would help with your IT Returns. 2.I will be paying a certain % as commission on every sales to a couple of sales guys (who are not my employees but only working on commission). Can I show this as an expense in my IT returns? As you are earning as freelancer, you are eligible for certain deductions like Phone calls, Laptop, other hardware, payments to partners. It is important that you maintain a book of records. An accountant for a small fee of Rs 5 K should be able to help you. In the Returns you have to show Net income after all these deductions, there is no place to enter expenses. 3.Since I will be receiving all the payments in Euros so am I falling under a category of \\\"\\\"Exporter of services\\\"\\\"? The work you are doing can be Free Lancing. 4.Do I need an Import Export Code (IEC) for smoothly running this small business? You can run this without one as Free lancing. IEC would be when you grow big and are looking for various benefits under tax and pay different taxes and are incorporated as a company.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"236732\",\n \"text\": \"\\\"The 529 plan does outline your scenarios. There are stipulations for providing the funds should the child get the scholarship. If the child decides not to go into further education (vocational and community schools count), the money can be withdrawn with a 10% penalty and taxes paid on interest earnings. Taxes wouldn't have to be paid for contributions as taxes were already paid on that money by the gift giver. The 529 could also be transferred to another child in the family (including grandchildren). Here's an excerpt from www.savingforcollege.com: You'll never lose all of your savings. A 529 plan offers tax-free earnings and tax-free withdrawals as long as the money is used to pay for college. If you end up taking a non-qualified withdrawal, you'll incur income tax as well as a 10% penalty - but only on the earnings portion of the withdrawal. Since your contributions were made with after-tax money, they will never be taxed or penalized. You can avoid the penalty if you get a scholarship. There are a few special exceptions to the 10% penalty rule, including when the beneficiary becomes incapacitated, attends a U.S. Military Academy or gets a scholarship. In the case of a scholarship, non-qualified withdrawals up to the amount of the tax-free scholarship can be taken out penalty-free, but you'll have to pay income tax on the earnings. As Savingforcollege.com founder Joe Hurley likes to say, \\\"\\\"the scholarships have turned your tax-free 529 investment into a tax-deferred 529 investment\\\"\\\". Note, a 529 is ideal for the sum of money you are looking at. A proper trust, set up by a lawyer, will cost as much as $2000 to set up, and would require an annual tax return, both unnecessary burdens. To make matters worse, the trust counts as the child's asset where financial aid is concerned. The 529 counts, but to a much lesser extent.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"114912\",\n \"text\": \"The simplest explanation is that a traditional IRA is a method of deferring taxes. That is, normally you pay taxes on money you earn at the ordinary rate then invest the rest and only pay the capital gains rate. However, with a traditional IRA you don't pay taxes on the money when you earn it, you defer the payment of those taxes until you retire. So in the end it ends up being treated the same. That said, if you are strategic about it you can wind up paying less taxes with this type of account.\",\n \"title\": \"\"\n }\n]"}}},{"rowIdx":398,"cells":{"query_id":{"kind":"string","value":"PLAIN-1574"},"query":{"kind":"string","value":"marketing"},"positive_passages":{"kind":"list like","value":[{"docid":"MED-5151","text":"Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.","title":"The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease."},{"docid":"MED-5086","text":"BACKGROUND: Acrylamide, a probable human carcinogen, was detected in various heat-treated carbohydrate-rich foods in 2002. The few epidemiologic studies done thus far have not shown a relationship with cancer. Our aim was to investigate the association between acrylamide intake and endometrial, ovarian, and breast cancer risk. METHODS: The Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline (1986), a random subcohort of 2,589 women was selected using a case cohort analysis approach for analysis. The acrylamide intake of subcohort members and cases was assessed with a food frequency questionnaire and was based on chemical analysis of all relevant Dutch foods. Subgroup analyses were done for never-smokers to eliminate the influence of smoking; an important source of acrylamide. RESULTS: After 11.3 years of follow-up, 327, 300, and 1,835 cases of endometrial, ovarian, and breast cancer, respectively, were documented. Compared with the lowest quintile of acrylamide intake (mean intake, 8.9 mug/day), multivariable-adjusted hazard rate ratios (HR) for endometrial, ovarian, and breast cancer in the highest quintile (mean intake, 40.2 mug/day) were 1.29 [95% confidence interval (95% CI), 0.81-2.07; P(trend)=0.18], 1.78 (95% CI, 1.10-2.88; P(trend)=0.02), and 0.93 (95% CI, 0.73-1.19; P(trend)=0.79), respectively. For never-smokers, the corresponding HRs were 1.99 (95% CI, 1.12-3.52; P(trend)=0.03), 2.22 (95% CI, 1.20-4.08; P(trend)=0.01), and 1.10 (95% CI, 0.80-1.52; P(trend)=0.55). CONCLUSIONS: We observed increased risks of postmenopausal endometrial and ovarian cancer with increasing dietary acrylamide intake, particularly among never-smokers. Risk of breast cancer was not associated with acrylamide intake.","title":"A prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer."},{"docid":"MED-4912","text":"Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.","title":"Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain."},{"docid":"MED-5146","text":"Cocoa powder is rich in polyphenols, such as catechins and procyanidins, and has been shown in a variety of subject models to inhibit oxidized LDL and atherogenesis. Our study evaluated plasma LDL cholesterol and oxidized LDL concentrations following the intake of different levels of cocoa powder (13, 19.5, and 26 g/d) in normocholesterolemic and mildly hypercholesterolemic humans. In this comparative, double-blind study, we examined 160 subjects who ingested either cocoa powder containing low-polyphenolic compounds (placebo-cocoa group) or 3 levels of cocoa powder containing high-polyphenolic compounds (13, 19.5, and 26 g/d for low-, middle-, and high-cocoa groups, respectively) for 4 wk. The test powders were consumed as a beverage after the addition of hot water, twice each day. Blood samples were collected at baseline and 4 wk after intake of the test beverages for the measurement of plasma lipids. Plasma oxidized LDL concentrations decreased in the low-, middle-, and high-cocoa groups compared with baseline. A stratified analysis was performed on 131 subjects who had a LDL cholesterol concentrations of > or =3.23 mmol/L at baseline. In these subjects, plasma LDL cholesterol, oxidized LDL, and apo B concentrations decreased, and the plasma HDL cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups. The results suggest that polyphenolic substances derived from cocoa powder may contribute to a reduction in LDL cholesterol, an elevation in HDL cholesterol, and the suppression of oxidized LDL.","title":"Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different leve..."},{"docid":"MED-5149","text":"BACKGROUND: Cocoa powder is rich in polyphenols such as catechins and procyanidins and has been shown in various models to inhibit LDL oxidation and atherogenesis. OBJECTIVE: We examined whether long-term intake of cocoa powder alters plasma lipid profiles in normocholesterolemic and mildly hypercholesterolemic human subjects. DESIGN: Twenty-five subjects were randomly assigned to ingest either 12 g sugar/d (control group) or 26 g cocoa powder and 12 g sugar/d (cocoa group) for 12 wk. Blood samples were collected before the study and 12 wk after intake of the test drinks. Plasma lipids, LDL oxidative susceptibility, and urinary oxidative stress markers were measured. RESULTS: At 12 wk, we measured a 9% prolongation from baseline levels in the lag time of LDL oxidation in the cocoa group. This prolongation in the cocoa group was significantly greater than the reduction measured in the control group (-13%). A significantly greater increase in plasma HDL cholesterol (24%) was observed in the cocoa group than in the control group (5%). A negative correlation was observed between plasma concentrations of HDL cholesterol and oxidized LDL. At 12 wk, there was a 24% reduction in dityrosine from baseline concentrations in the cocoa group. This reduction in the cocoa group was significantly greater than the reduction in the control group (-1%). CONCLUSION: It is possible that increases in HDL-cholesterol concentrations may contribute to the suppression of LDL oxidation and that polyphenolic substances derived from cocoa powder may contribute to an elevation in HDL cholesterol.","title":"Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-c..."},{"docid":"MED-4892","text":"OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.","title":"Egg Consumption and Risk of Type 2 Diabetes in Men and Women"},{"docid":"MED-2823","text":"Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.","title":"Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies"},{"docid":"MED-5003","text":"Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.","title":"Genistein inhibits differentiation of primary human adipocytes."},{"docid":"MED-5085","text":"In this study, the adhesion factors examined were time between frying and coating, surface oil content, chip temperature, oil composition, NaCl size, NaCl shape, and electrostatic coating. Three different surface oil content potato chips, high, low, and no, were produced. Oils used were soybean, olive, corn, peanut, and coconut. After frying, chips were coated immediately, after 1 d, and after 1 mo. NaCl crystals of 5 different particle sizes (24.7, 123, 259, 291, and 388 microm) were coated both electrostatically and nonelectrostatically. Adhesion of cubic, dendritic, and flake crystals was examined. Chips were coated at different temperatures. Chips with high surface oil had the highest adhesion of salt, making surface oil content the most important factor. Decreasing chip temperature decreased surface oil and adhesion. Increasing time between frying and coating reduced adhesion for low surface oil chips, but did not affect high and no surface oil chips. Changing oil composition did not affect adhesion. Increasing salt size decreased adhesion. Salt size had a greater effect on chips with lower surface oil content. When there were significant differences, cubic crystals gave the best adhesion followed by flake crystals then dendritic crystals. For high and low surface oil chips, electrostatic coating did not change adhesion of small size crystals but decreased adhesion of large salts. For no surface oil content chips, electrostatic coating improved adhesion for small salt sizes but did not affect adhesion of large crystals.","title":"Factors dominating adhesion of NaCl onto potato chips."},{"docid":"MED-4731","text":"BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.","title":"No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-..."},{"docid":"MED-5148","text":"CONTEXT: Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear. OBJECTIVE: To determine effects of low doses of polyphenol-rich dark chocolate on BP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled, investigator-blinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006. INTERVENTION: Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate. MAIN OUTCOME MEASURES: Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols. RESULTS: From baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by -2.9 (1.6) mm Hg (P < .001) and diastolic BP by -1.9 (1.0) mm Hg (P < .001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (P < .001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers. CONCLUSIONS: Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00421499.","title":"Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial."},{"docid":"MED-5153","text":"OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.","title":"Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function."},{"docid":"MED-4911","text":"Arsenic exposures contribute significantly to the burden of preventable disease worldwide, specifically related to increased risks of cancer, diabetes, and cardiovascular disease. Most exposures are associated with natural contamination of groundwater, which is difficult to mitigate when these sources are used for drinking water. An anthropogenic source of arsenic exposure stems from the widespread use of arsenical drugs in food-animal production in the United States and China, among many countries. This use results in residual contamination of food products from animals raised with the drugs, as well as environmental contamination associated with disposal of wastes from these animals. Land disposal of these wastes can contaminate surface and ground water, and the conversion of animal wastes into fertilizer pellets for home use as well as the introduction of animal waste incinerators may increase opportunities for exposure. As an intentional additive to animal feed, use of arsenical drugs is a preventable source of human exposure. The domestic practice of using these drugs in poultry production has been the subject of media attention and limited research, though the use of these drugs in domestic swine production and in the rapidly growing foreign animal production industry remains largely uncharacterized. This continued expansion of arsenical drug use may likely increase the burden of global human arsenic exposure and risk.","title":"The environmental and public health risks associated with arsenical use in animal feeds."},{"docid":"MED-5110","text":"Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.","title":"Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?"},{"docid":"MED-2810","text":"Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".","title":"Curcumin as \"Curecumin\": from kitchen to clinic."},{"docid":"MED-5089","text":"BACKGROUND: Acrylamide, a probable human carcinogen, was recently detected in various heat-treated carbohydrate-rich foods. Epidemiologic studies on the relation with cancer have been few and largely negative. OBJECTIVE: We aimed to prospectively examine the association between dietary acrylamide intake and renal cell, bladder, and prostate cancers. DESIGN: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women aged 55-69 y. At baseline (1986), a random subcohort of 5000 participants was selected for a case-cohort analysis approach using Cox proportional hazards analysis. Acrylamide intake was assessed with a food-frequency questionnaire at baseline and was based on chemical analysis of all relevant Dutch foods. RESULTS: After 13.3 y of follow-up, 339, 1210, and 2246 cases of renal cell, bladder, and prostate cancer, respectively, were available for analysis. Compared with the lowest quintile of acrylamide intake (mean intake: 9.5 microg/d), multivariable-adjusted hazard rates for renal cell, bladder, and prostate cancer in the highest quintile (mean intake: 40.8 microg/d) were 1.59 (95% CI: 1.09, 2.30; P for trend = 0.04), 0.91 (95% CI: 0.73, 1.15; P for trend = 0.60), and 1.06 (95% CI: 0.87, 1.30; P for trend = 0.69), respectively. There was an inverse nonsignificant trend for advanced prostate cancer in never smokers. CONCLUSIONS: We found some indications for a positive association between dietary acrylamide and renal cell cancer risk. There were no positive associations with bladder and prostate cancer risk.","title":"Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer."},{"docid":"MED-2322","text":"The global demand for more affordable therapeutics and concerns about side effects of commonly used drugs are refocusing interest on Eastern traditional medicines, particularly those of India and China.","title":"From exotic spice to modern drug?"},{"docid":"MED-5087","text":"Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted. (c) 2008 Wiley-Liss, Inc.","title":"Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study."},{"docid":"MED-2489","text":"A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.","title":"Agricultural policies, food and public health"},{"docid":"MED-5150","text":"A single-dose ingestion of flavanol-rich cocoa acutely reverses endothelial dysfunction. To investigate the time course of endothelial function during daily consumption of high-flavanol cocoa, we determined flow-mediated dilation (FMD) acutely (for up to 6 hours after single-dose ingestion) and chronically (administration for 7 days). The study population represented individuals with smoking-related endothelial dysfunction; in addition to FMD, plasma nitrite and nitrate were measured. The daily consumption of a flavanol-rich cocoa drink (3 x 306 mg flavanols/d) over 7 days (n=6) resulted in continual FMD increases at baseline (after overnight fast and before flavanol ingestion) and in sustained FMD augmentation at 2 hours after ingestion. Fasted FMD responses increased from 3.7 +/- 0.4% on day 1 to 5.2 +/- 0.6%, 6.1 +/- 0.6%, and 6.6 +/- 0.5% (each P < 0.05) on days 3, 5, and 8, respectively. FMD returned to 3.3 +/- 0.3% after a washout week of cocoa-free diet (day 15). Increases observed in circulating nitrite, but not in circulating nitrate, paralleled the observed FMD augmentations. The acute, single-dose consumption of cocoa drinks with 28 to 918 mg of flavanols led to dose-dependent increases in FMD and nitrite, with a maximal FMD at 2 hours after consumption. The dose to achieve a half-maximal FMD response was 616 mg (n=6). Generally applied biomarkers for oxidative stress (plasma, MDA, TEAC) and antioxidant status (plasma ascorbate, urate) remained unaffected by cocoa flavanol ingestion. The daily consumption of flavanol-rich cocoa has the potential to reverse endothelial dysfunction in a sustained and dose-dependent manner.","title":"Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week."},{"docid":"MED-4730","text":"We successfully optimized an analytical method using gel permeation chromatography followed by direct sample introduction comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry to quantify multiple groups of targeted persistent organic pollutants and halogenated natural products (HNPs) simultaneously in fish oil samples. This new method has a wider analytical scope than the traditional approach to use multiple methods to cover each class of compounds. Our analysis revealed that the relatively more volatile and lighter organic compounds, such as polychlorinated biphenyls (PCBs), organochlorine pesticides, and other smaller organohalogen compounds, were still present in two brands of \"PCB-free\" cod liver oils, albeit at much lower levels than in an untreated commercial sample. Moreover, the less volatile organic compounds, such as polybrominated diphenyl ethers and brominated HNPs, were detected at similar levels in all three cod liver oils. This suggests that the commercial molecular distillation treatment used for removal of organic/inorganic toxic contaminants is only effective for the lighter organic contaminants.","title":"Simultaneous quantitation of multiple classes of organohalogen compounds in fish oils with direct sample introduction comprehensive two-dimensional..."},{"docid":"MED-4943","text":"Fish and seal oil dietary supplements, marketed to be rich in omega-3 fatty acids, are frequently consumed by Canadians. Samples of these supplements (n = 30) were collected in Vancouver, Canada, between 2005 and 2007. All oil supplements were analyzed for polychlorinated biphenyls (PCBs) and organochlorine insecticides (OCs) and each sample was found to contain detectable residues. The highest SigmaPCB and SigmaDDT (1,1,1-trichloro-di-(4-chlorophenyl)ethane) concentrations (10400 ng/g and 3310 ng/g, respectively) were found in a shark oil sample while lowest levels were found in supplements prepared using mixed fish oils (anchovy, mackerel, and sardine) (0.711 ng SigmaPCB/g and 0.189 ng SigmaDDT/g). Mean SigmaPCB concentrations in oil supplements were 34.5, 24.2, 25.1, 95.3, 12.0, 5260, 321, and 519 ng/g in unidentified fish, mixed fish containing no salmon, mixed fish with salmon, salmon, vegetable with mixed fish, shark, menhaden (n = 1), and seal (n = 1), respectively. Maximum concentrations of the other OCs were generally observed in the seal oil. The hexachlorinated PCB congeners were the dominant contributors to SigmaPCB levels, while SigmaDDT was the greatest contributor to organochlorine levels. Intake estimates were made using maximum dosages on manufacturers' labels and results varied widely due to the large difference in residue concentrations obtained. Average SigmaPCB and SigmaDDT intakes were calculated to be 736 +/- 2840 ng/d and 304 +/- 948 ng/d, respectively.","title":"Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides."},{"docid":"MED-4893","text":"Background Prospective studies evaluating associations between food intake and risk of heart failure (HF) in diverse populations are needed. Objectives Relationships between incident HF (death or hospitalization) and intake of seven food categories (whole grains, fruits/vegetables, fish, nuts, high-fat dairy, eggs, red meat) were investigated in an observational cohort of 14,153 African-American and white adults, age 45 to 64 years, sampled from four US communities. Methods Between baseline (1987–1989) and Exam 3 (1993–1995), dietary intake was based on responses to a 66-item food frequency questionnaire administered at baseline; thereafter, intake was based on averaged baseline and Exam 3 responses. Hazard ratios (HR [95% CI]) for HF were calculated per 1–daily serving difference in food group intake. Results During a mean of 13 years, 1,140 HF hospitalizations were identified. After multivariable adjustment (energy intake, demographics, lifestyle factors, prevalent cardiovascular disease, diabetes, hypertension), HF risk was lower with greater whole-grain intake (0.93 [0.87, 0.99]), but HF risk was higher with greater intake of eggs (1.23 [1.08, 1.41]) and high-fat dairy (1.08 [1.01, 1.16]). These associations remained significant independent of intakes of the five other food categories, which were not associated with HF. Conclusions In this large, population-based sample of African-American and white adults, whole-grain intake was associated with lower HF risk, whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders.","title":"Incident Heart Failure Is Associated with Lower Whole-Grain Intake and Greater High-Fat Dairy and Egg Intake in the Atherosclerosis Risk in Communities (ARIC) Study"},{"docid":"MED-5062","text":"BACKGROUND: We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. METHODS: 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. FINDINGS: 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01-0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05-0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02-0.23], p=0.023) or mix B (0.17 [0.07-0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. INTERPRETATION: Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.","title":"Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled..."},{"docid":"MED-2783","text":"Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.","title":"Multitargeting by turmeric, the golden spice: From kitchen to clinic."},{"docid":"MED-2323","text":"Low molecular weight phenols of plant origin are undoubtedly semiochemicals although not all of them can be easily classified as typical allelochemicals, which straightforwardly benefit the releaser. We have selected and surveyed this particular class of secondary metabolites, which shares high chemical reactivity with intrinsic biocompatibility and affinity for variety of molecular targets gained through evolution, because their suitability as prospective lead compounds for medicinal chemistry seems high but relatively unexplored. In particular, plant phenolics could be perceived as a natural product library, which contains privileged scaffolds, as evidenced by examples of endogenous phenols, phytochemicals containing aryl hydroxyl groups and phenolic synthetic drugs. It is postulated that application of bio-chemo-informatic tools to such library can be helpful in pulling out new drug candidates as well as in validating ADMET compatibility and suitability of the old ones. After short survey of structural diversity represented by plant phenolics, we focus on the compounds which either have obvious dietary significance or rich record of pharmacological studies, or both. It can be seen that apart from growing use of phytochemicals in dietary supplements, slow progress through clinical trials towards new drug registration is observed in that category of natural products. Such waste of resources on the way of transformation from renewable materials to high tech/high value products aimed for improved human healthcare is deplorable and should be reformed in name of sustainability. We attempt to answer the question why popular plant phenolics with well established health benefits and reasonably well recognized molecular pharmacology (such as: catechins, curcumin, resveratrol, quercetin and its glycosides, genistein, silymarin) have difficulties in attaining registered drug or even IND level.","title":"Plant phenolics as drug leads -- what is missing?"},{"docid":"MED-5088","text":"Potato products contain high amounts of acrylamide, which sometimes exceeds the concentration of 1 mg/L. However, many strategies for acrylamide reduction in potato products are possible. In this work, the different approaches for reducing acrylamide formation have been reviewed, keeping in mind that in the application of strategies for acrylamide formation, the main criteria to be maintained are the overall organoleptic and nutritional qualities of the final product.","title":"Mitigation strategies to reduce acrylamide formation in fried potato products."},{"docid":"MED-2809","text":"Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.","title":"Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials"},{"docid":"MED-5063","text":"Evidence supports a trial period of eliminating colourings and preservatives from the diet","title":"Food additives and hyperactivity"},{"docid":"MED-5147","text":"There has been considerable work on the relationships between nutrition and the immune response, particularly on studies that have focused on adaptive responses. There is increasing recognition of the importance of innate immunity in host protection and initiation of cytokine networks. In this study, we examined the effect of select cocoa flavanols and procyanidins on innate responses in vitro. Peripheral blood mono-nuclear cells (PBMCs), as well as purified monocytes and CD4 and CD8 T cells, were isolated from healthy volunteers and cultured in the presence of cocoa flavanol fractions that differ from another by the degree of flavanol polymerization: short-chain flavanol fraction (SCFF), monomers to pentamers; and long-chain flavanol fraction (LCFF), hexamers to decamers. Parallel investigations were also done with highly purified flavanol monomers and procyanidin dimers. The isolated cells were then challenged with lipopolysaccharide (LPS) with quantitation of activation using CD69 and CD83 expression and analysis of secreted tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, and granulocyte macrophage colony-stimulating factor (GM-CSF). The chain length of flavanol fractions had a significant effect on cytokine release from both unstimulated and LPS-stimulated PBMCs. For example, there was a striking increase of LPS-induced synthesis of IL-1beta, IL-6, IL-10, and TNF-alpha in the presence of LCFF. LCFF and SCFF, in the absence of LPS, stimulated the production of GM-CSF. In addition, LCFF and SCFF increased expression of the B cell markers CD69 and CD83. There were also unique differential responses in the mononuclear cell populations studied. We conclude that the oligomers are potent stimulators of both the innate immune system and early events in adaptive immunity.","title":"Immune effects of cocoa procyanidin oligomers on peripheral blood mononuclear cells."},{"docid":"MED-5152","text":"OBJECTIVES: Strong evidence has secured aging as a powerful predictor of both cardiovascular risk and endothelial dysfunction, yet specific treatment is not available. We tested the hypothesis that vascular responsiveness to flavanol-rich cocoa increases with advancing age. We have previously shown that flavanol-rich cocoa induced peripheral vasodilation, improving endothelial function via a nitric oxide (NO)-dependent mechanism. METHODS: We studied blood pressure and peripheral arterial responses to several days of cocoa in 15 young (< 50 years) and 19 older (> 50) healthy subjects. RESULTS: The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME) induced significant pressor responses following cocoa administration only among the older subjects: systolic blood pressure (SBP) rose 13 +/- 4 mmHg, diastolic blood pressure (DBP) 6 +/- 2 mmHg (P = 0.008 and 0.047, respectively); SBP was significantly higher in the older subjects (P < 0.05). Flow-mediated vasodilation, measured by tonometry in the finger, was enhanced with flavanol-rich cocoa in both groups, but significantly more so among the old (P = 0.01). Finally, basal pulse wave amplitude (PWA) followed a similar pattern. Four to six days of flavanol-rich cocoa caused a rise in PWA in both groups. At peak vasodilation following acute cocoa intake on the final day, both groups showed a further, significant rise in PWA. The response in the older subjects was more robust; P < 0.05. L-NAME significantly reversed dilation in both groups. CONCLUSIONS: Flavanol-rich cocoa enhanced several measures of endothelial function to a greater degree among older than younger healthy subjects. Our data suggest that the NO-dependent vascular effects of flavanol-rich cocoa may be greater among older people, in whom endothelial function is more disturbed.","title":"Aging and vascular responses to flavanol-rich cocoa."},{"docid":"MED-2488","text":"Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.","title":"Food prices and blood cholesterol."},{"docid":"MED-4729","text":"In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources.","title":"Do Organohalogen Contaminants Contribute to Histopathology in Liver from East Greenland Polar Bears (Ursus maritimus)?"},{"docid":"MED-4732","text":"Background Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives In this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis. Methods PCB-77 or 2,2′,4,4,5,5′-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR)−/− mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE−/− mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis. Results Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol–3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor γ, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR−/− mice. ApoE−/− mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. Conclusions Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.","title":"Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis"},{"docid":"MED-5004","text":"BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.","title":"Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford."}],"string":"[\n {\n \"docid\": \"MED-5151\",\n \"text\": \"Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.\",\n \"title\": \"The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease.\"\n },\n {\n \"docid\": \"MED-5086\",\n \"text\": \"BACKGROUND: Acrylamide, a probable human carcinogen, was detected in various heat-treated carbohydrate-rich foods in 2002. The few epidemiologic studies done thus far have not shown a relationship with cancer. Our aim was to investigate the association between acrylamide intake and endometrial, ovarian, and breast cancer risk. METHODS: The Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline (1986), a random subcohort of 2,589 women was selected using a case cohort analysis approach for analysis. The acrylamide intake of subcohort members and cases was assessed with a food frequency questionnaire and was based on chemical analysis of all relevant Dutch foods. Subgroup analyses were done for never-smokers to eliminate the influence of smoking; an important source of acrylamide. RESULTS: After 11.3 years of follow-up, 327, 300, and 1,835 cases of endometrial, ovarian, and breast cancer, respectively, were documented. Compared with the lowest quintile of acrylamide intake (mean intake, 8.9 mug/day), multivariable-adjusted hazard rate ratios (HR) for endometrial, ovarian, and breast cancer in the highest quintile (mean intake, 40.2 mug/day) were 1.29 [95% confidence interval (95% CI), 0.81-2.07; P(trend)=0.18], 1.78 (95% CI, 1.10-2.88; P(trend)=0.02), and 0.93 (95% CI, 0.73-1.19; P(trend)=0.79), respectively. For never-smokers, the corresponding HRs were 1.99 (95% CI, 1.12-3.52; P(trend)=0.03), 2.22 (95% CI, 1.20-4.08; P(trend)=0.01), and 1.10 (95% CI, 0.80-1.52; P(trend)=0.55). CONCLUSIONS: We observed increased risks of postmenopausal endometrial and ovarian cancer with increasing dietary acrylamide intake, particularly among never-smokers. Risk of breast cancer was not associated with acrylamide intake.\",\n \"title\": \"A prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer.\"\n },\n {\n \"docid\": \"MED-4912\",\n \"text\": \"Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.\",\n \"title\": \"Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain.\"\n },\n {\n \"docid\": \"MED-5146\",\n \"text\": \"Cocoa powder is rich in polyphenols, such as catechins and procyanidins, and has been shown in a variety of subject models to inhibit oxidized LDL and atherogenesis. Our study evaluated plasma LDL cholesterol and oxidized LDL concentrations following the intake of different levels of cocoa powder (13, 19.5, and 26 g/d) in normocholesterolemic and mildly hypercholesterolemic humans. In this comparative, double-blind study, we examined 160 subjects who ingested either cocoa powder containing low-polyphenolic compounds (placebo-cocoa group) or 3 levels of cocoa powder containing high-polyphenolic compounds (13, 19.5, and 26 g/d for low-, middle-, and high-cocoa groups, respectively) for 4 wk. The test powders were consumed as a beverage after the addition of hot water, twice each day. Blood samples were collected at baseline and 4 wk after intake of the test beverages for the measurement of plasma lipids. Plasma oxidized LDL concentrations decreased in the low-, middle-, and high-cocoa groups compared with baseline. A stratified analysis was performed on 131 subjects who had a LDL cholesterol concentrations of > or =3.23 mmol/L at baseline. In these subjects, plasma LDL cholesterol, oxidized LDL, and apo B concentrations decreased, and the plasma HDL cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups. The results suggest that polyphenolic substances derived from cocoa powder may contribute to a reduction in LDL cholesterol, an elevation in HDL cholesterol, and the suppression of oxidized LDL.\",\n \"title\": \"Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different leve...\"\n },\n {\n \"docid\": \"MED-5149\",\n \"text\": \"BACKGROUND: Cocoa powder is rich in polyphenols such as catechins and procyanidins and has been shown in various models to inhibit LDL oxidation and atherogenesis. OBJECTIVE: We examined whether long-term intake of cocoa powder alters plasma lipid profiles in normocholesterolemic and mildly hypercholesterolemic human subjects. DESIGN: Twenty-five subjects were randomly assigned to ingest either 12 g sugar/d (control group) or 26 g cocoa powder and 12 g sugar/d (cocoa group) for 12 wk. Blood samples were collected before the study and 12 wk after intake of the test drinks. Plasma lipids, LDL oxidative susceptibility, and urinary oxidative stress markers were measured. RESULTS: At 12 wk, we measured a 9% prolongation from baseline levels in the lag time of LDL oxidation in the cocoa group. This prolongation in the cocoa group was significantly greater than the reduction measured in the control group (-13%). A significantly greater increase in plasma HDL cholesterol (24%) was observed in the cocoa group than in the control group (5%). A negative correlation was observed between plasma concentrations of HDL cholesterol and oxidized LDL. At 12 wk, there was a 24% reduction in dityrosine from baseline concentrations in the cocoa group. This reduction in the cocoa group was significantly greater than the reduction in the control group (-1%). CONCLUSION: It is possible that increases in HDL-cholesterol concentrations may contribute to the suppression of LDL oxidation and that polyphenolic substances derived from cocoa powder may contribute to an elevation in HDL cholesterol.\",\n \"title\": \"Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-c...\"\n },\n {\n \"docid\": \"MED-4892\",\n \"text\": \"OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.\",\n \"title\": \"Egg Consumption and Risk of Type 2 Diabetes in Men and Women\"\n },\n {\n \"docid\": \"MED-2823\",\n \"text\": \"Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.\",\n \"title\": \"Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies\"\n },\n {\n \"docid\": \"MED-5003\",\n \"text\": \"Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.\",\n \"title\": \"Genistein inhibits differentiation of primary human adipocytes.\"\n },\n {\n \"docid\": \"MED-5085\",\n \"text\": \"In this study, the adhesion factors examined were time between frying and coating, surface oil content, chip temperature, oil composition, NaCl size, NaCl shape, and electrostatic coating. Three different surface oil content potato chips, high, low, and no, were produced. Oils used were soybean, olive, corn, peanut, and coconut. After frying, chips were coated immediately, after 1 d, and after 1 mo. NaCl crystals of 5 different particle sizes (24.7, 123, 259, 291, and 388 microm) were coated both electrostatically and nonelectrostatically. Adhesion of cubic, dendritic, and flake crystals was examined. Chips were coated at different temperatures. Chips with high surface oil had the highest adhesion of salt, making surface oil content the most important factor. Decreasing chip temperature decreased surface oil and adhesion. Increasing time between frying and coating reduced adhesion for low surface oil chips, but did not affect high and no surface oil chips. Changing oil composition did not affect adhesion. Increasing salt size decreased adhesion. Salt size had a greater effect on chips with lower surface oil content. When there were significant differences, cubic crystals gave the best adhesion followed by flake crystals then dendritic crystals. For high and low surface oil chips, electrostatic coating did not change adhesion of small size crystals but decreased adhesion of large salts. For no surface oil content chips, electrostatic coating improved adhesion for small salt sizes but did not affect adhesion of large crystals.\",\n \"title\": \"Factors dominating adhesion of NaCl onto potato chips.\"\n },\n {\n \"docid\": \"MED-4731\",\n \"text\": \"BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.\",\n \"title\": \"No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-...\"\n },\n {\n \"docid\": \"MED-5148\",\n \"text\": \"CONTEXT: Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear. OBJECTIVE: To determine effects of low doses of polyphenol-rich dark chocolate on BP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled, investigator-blinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006. INTERVENTION: Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate. MAIN OUTCOME MEASURES: Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols. RESULTS: From baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by -2.9 (1.6) mm Hg (P < .001) and diastolic BP by -1.9 (1.0) mm Hg (P < .001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (P < .001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers. CONCLUSIONS: Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00421499.\",\n \"title\": \"Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial.\"\n },\n {\n \"docid\": \"MED-5153\",\n \"text\": \"OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.\",\n \"title\": \"Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function.\"\n },\n {\n \"docid\": \"MED-4911\",\n \"text\": \"Arsenic exposures contribute significantly to the burden of preventable disease worldwide, specifically related to increased risks of cancer, diabetes, and cardiovascular disease. Most exposures are associated with natural contamination of groundwater, which is difficult to mitigate when these sources are used for drinking water. An anthropogenic source of arsenic exposure stems from the widespread use of arsenical drugs in food-animal production in the United States and China, among many countries. This use results in residual contamination of food products from animals raised with the drugs, as well as environmental contamination associated with disposal of wastes from these animals. Land disposal of these wastes can contaminate surface and ground water, and the conversion of animal wastes into fertilizer pellets for home use as well as the introduction of animal waste incinerators may increase opportunities for exposure. As an intentional additive to animal feed, use of arsenical drugs is a preventable source of human exposure. The domestic practice of using these drugs in poultry production has been the subject of media attention and limited research, though the use of these drugs in domestic swine production and in the rapidly growing foreign animal production industry remains largely uncharacterized. This continued expansion of arsenical drug use may likely increase the burden of global human arsenic exposure and risk.\",\n \"title\": \"The environmental and public health risks associated with arsenical use in animal feeds.\"\n },\n {\n \"docid\": \"MED-5110\",\n \"text\": \"Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.\",\n \"title\": \"Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?\"\n },\n {\n \"docid\": \"MED-2810\",\n \"text\": \"Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \\\"Curecumin\\\".\",\n \"title\": \"Curcumin as \\\"Curecumin\\\": from kitchen to clinic.\"\n },\n {\n \"docid\": \"MED-5089\",\n \"text\": \"BACKGROUND: Acrylamide, a probable human carcinogen, was recently detected in various heat-treated carbohydrate-rich foods. Epidemiologic studies on the relation with cancer have been few and largely negative. OBJECTIVE: We aimed to prospectively examine the association between dietary acrylamide intake and renal cell, bladder, and prostate cancers. DESIGN: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women aged 55-69 y. At baseline (1986), a random subcohort of 5000 participants was selected for a case-cohort analysis approach using Cox proportional hazards analysis. Acrylamide intake was assessed with a food-frequency questionnaire at baseline and was based on chemical analysis of all relevant Dutch foods. RESULTS: After 13.3 y of follow-up, 339, 1210, and 2246 cases of renal cell, bladder, and prostate cancer, respectively, were available for analysis. Compared with the lowest quintile of acrylamide intake (mean intake: 9.5 microg/d), multivariable-adjusted hazard rates for renal cell, bladder, and prostate cancer in the highest quintile (mean intake: 40.8 microg/d) were 1.59 (95% CI: 1.09, 2.30; P for trend = 0.04), 0.91 (95% CI: 0.73, 1.15; P for trend = 0.60), and 1.06 (95% CI: 0.87, 1.30; P for trend = 0.69), respectively. There was an inverse nonsignificant trend for advanced prostate cancer in never smokers. CONCLUSIONS: We found some indications for a positive association between dietary acrylamide and renal cell cancer risk. There were no positive associations with bladder and prostate cancer risk.\",\n \"title\": \"Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer.\"\n },\n {\n \"docid\": \"MED-2322\",\n \"text\": \"The global demand for more affordable therapeutics and concerns about side effects of commonly used drugs are refocusing interest on Eastern traditional medicines, particularly those of India and China.\",\n \"title\": \"From exotic spice to modern drug?\"\n },\n {\n \"docid\": \"MED-5087\",\n \"text\": \"Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted. (c) 2008 Wiley-Liss, Inc.\",\n \"title\": \"Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study.\"\n },\n {\n \"docid\": \"MED-2489\",\n \"text\": \"A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.\",\n \"title\": \"Agricultural policies, food and public health\"\n },\n {\n \"docid\": \"MED-5150\",\n \"text\": \"A single-dose ingestion of flavanol-rich cocoa acutely reverses endothelial dysfunction. To investigate the time course of endothelial function during daily consumption of high-flavanol cocoa, we determined flow-mediated dilation (FMD) acutely (for up to 6 hours after single-dose ingestion) and chronically (administration for 7 days). The study population represented individuals with smoking-related endothelial dysfunction; in addition to FMD, plasma nitrite and nitrate were measured. The daily consumption of a flavanol-rich cocoa drink (3 x 306 mg flavanols/d) over 7 days (n=6) resulted in continual FMD increases at baseline (after overnight fast and before flavanol ingestion) and in sustained FMD augmentation at 2 hours after ingestion. Fasted FMD responses increased from 3.7 +/- 0.4% on day 1 to 5.2 +/- 0.6%, 6.1 +/- 0.6%, and 6.6 +/- 0.5% (each P < 0.05) on days 3, 5, and 8, respectively. FMD returned to 3.3 +/- 0.3% after a washout week of cocoa-free diet (day 15). Increases observed in circulating nitrite, but not in circulating nitrate, paralleled the observed FMD augmentations. The acute, single-dose consumption of cocoa drinks with 28 to 918 mg of flavanols led to dose-dependent increases in FMD and nitrite, with a maximal FMD at 2 hours after consumption. The dose to achieve a half-maximal FMD response was 616 mg (n=6). Generally applied biomarkers for oxidative stress (plasma, MDA, TEAC) and antioxidant status (plasma ascorbate, urate) remained unaffected by cocoa flavanol ingestion. The daily consumption of flavanol-rich cocoa has the potential to reverse endothelial dysfunction in a sustained and dose-dependent manner.\",\n \"title\": \"Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week.\"\n },\n {\n \"docid\": \"MED-4730\",\n \"text\": \"We successfully optimized an analytical method using gel permeation chromatography followed by direct sample introduction comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry to quantify multiple groups of targeted persistent organic pollutants and halogenated natural products (HNPs) simultaneously in fish oil samples. This new method has a wider analytical scope than the traditional approach to use multiple methods to cover each class of compounds. Our analysis revealed that the relatively more volatile and lighter organic compounds, such as polychlorinated biphenyls (PCBs), organochlorine pesticides, and other smaller organohalogen compounds, were still present in two brands of \\\"PCB-free\\\" cod liver oils, albeit at much lower levels than in an untreated commercial sample. Moreover, the less volatile organic compounds, such as polybrominated diphenyl ethers and brominated HNPs, were detected at similar levels in all three cod liver oils. This suggests that the commercial molecular distillation treatment used for removal of organic/inorganic toxic contaminants is only effective for the lighter organic contaminants.\",\n \"title\": \"Simultaneous quantitation of multiple classes of organohalogen compounds in fish oils with direct sample introduction comprehensive two-dimensional...\"\n },\n {\n \"docid\": \"MED-4943\",\n \"text\": \"Fish and seal oil dietary supplements, marketed to be rich in omega-3 fatty acids, are frequently consumed by Canadians. Samples of these supplements (n = 30) were collected in Vancouver, Canada, between 2005 and 2007. All oil supplements were analyzed for polychlorinated biphenyls (PCBs) and organochlorine insecticides (OCs) and each sample was found to contain detectable residues. The highest SigmaPCB and SigmaDDT (1,1,1-trichloro-di-(4-chlorophenyl)ethane) concentrations (10400 ng/g and 3310 ng/g, respectively) were found in a shark oil sample while lowest levels were found in supplements prepared using mixed fish oils (anchovy, mackerel, and sardine) (0.711 ng SigmaPCB/g and 0.189 ng SigmaDDT/g). Mean SigmaPCB concentrations in oil supplements were 34.5, 24.2, 25.1, 95.3, 12.0, 5260, 321, and 519 ng/g in unidentified fish, mixed fish containing no salmon, mixed fish with salmon, salmon, vegetable with mixed fish, shark, menhaden (n = 1), and seal (n = 1), respectively. Maximum concentrations of the other OCs were generally observed in the seal oil. The hexachlorinated PCB congeners were the dominant contributors to SigmaPCB levels, while SigmaDDT was the greatest contributor to organochlorine levels. Intake estimates were made using maximum dosages on manufacturers' labels and results varied widely due to the large difference in residue concentrations obtained. Average SigmaPCB and SigmaDDT intakes were calculated to be 736 +/- 2840 ng/d and 304 +/- 948 ng/d, respectively.\",\n \"title\": \"Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides.\"\n },\n {\n \"docid\": \"MED-4893\",\n \"text\": \"Background Prospective studies evaluating associations between food intake and risk of heart failure (HF) in diverse populations are needed. Objectives Relationships between incident HF (death or hospitalization) and intake of seven food categories (whole grains, fruits/vegetables, fish, nuts, high-fat dairy, eggs, red meat) were investigated in an observational cohort of 14,153 African-American and white adults, age 45 to 64 years, sampled from four US communities. Methods Between baseline (1987–1989) and Exam 3 (1993–1995), dietary intake was based on responses to a 66-item food frequency questionnaire administered at baseline; thereafter, intake was based on averaged baseline and Exam 3 responses. Hazard ratios (HR [95% CI]) for HF were calculated per 1–daily serving difference in food group intake. Results During a mean of 13 years, 1,140 HF hospitalizations were identified. After multivariable adjustment (energy intake, demographics, lifestyle factors, prevalent cardiovascular disease, diabetes, hypertension), HF risk was lower with greater whole-grain intake (0.93 [0.87, 0.99]), but HF risk was higher with greater intake of eggs (1.23 [1.08, 1.41]) and high-fat dairy (1.08 [1.01, 1.16]). These associations remained significant independent of intakes of the five other food categories, which were not associated with HF. Conclusions In this large, population-based sample of African-American and white adults, whole-grain intake was associated with lower HF risk, whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders.\",\n \"title\": \"Incident Heart Failure Is Associated with Lower Whole-Grain Intake and Greater High-Fat Dairy and Egg Intake in the Atherosclerosis Risk in Communities (ARIC) Study\"\n },\n {\n \"docid\": \"MED-5062\",\n \"text\": \"BACKGROUND: We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. METHODS: 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. FINDINGS: 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01-0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05-0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02-0.23], p=0.023) or mix B (0.17 [0.07-0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. INTERPRETATION: Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.\",\n \"title\": \"Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled...\"\n },\n {\n \"docid\": \"MED-2783\",\n \"text\": \"Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\",\n \"title\": \"Multitargeting by turmeric, the golden spice: From kitchen to clinic.\"\n },\n {\n \"docid\": \"MED-2323\",\n \"text\": \"Low molecular weight phenols of plant origin are undoubtedly semiochemicals although not all of them can be easily classified as typical allelochemicals, which straightforwardly benefit the releaser. We have selected and surveyed this particular class of secondary metabolites, which shares high chemical reactivity with intrinsic biocompatibility and affinity for variety of molecular targets gained through evolution, because their suitability as prospective lead compounds for medicinal chemistry seems high but relatively unexplored. In particular, plant phenolics could be perceived as a natural product library, which contains privileged scaffolds, as evidenced by examples of endogenous phenols, phytochemicals containing aryl hydroxyl groups and phenolic synthetic drugs. It is postulated that application of bio-chemo-informatic tools to such library can be helpful in pulling out new drug candidates as well as in validating ADMET compatibility and suitability of the old ones. After short survey of structural diversity represented by plant phenolics, we focus on the compounds which either have obvious dietary significance or rich record of pharmacological studies, or both. It can be seen that apart from growing use of phytochemicals in dietary supplements, slow progress through clinical trials towards new drug registration is observed in that category of natural products. Such waste of resources on the way of transformation from renewable materials to high tech/high value products aimed for improved human healthcare is deplorable and should be reformed in name of sustainability. We attempt to answer the question why popular plant phenolics with well established health benefits and reasonably well recognized molecular pharmacology (such as: catechins, curcumin, resveratrol, quercetin and its glycosides, genistein, silymarin) have difficulties in attaining registered drug or even IND level.\",\n \"title\": \"Plant phenolics as drug leads -- what is missing?\"\n },\n {\n \"docid\": \"MED-5088\",\n \"text\": \"Potato products contain high amounts of acrylamide, which sometimes exceeds the concentration of 1 mg/L. However, many strategies for acrylamide reduction in potato products are possible. In this work, the different approaches for reducing acrylamide formation have been reviewed, keeping in mind that in the application of strategies for acrylamide formation, the main criteria to be maintained are the overall organoleptic and nutritional qualities of the final product.\",\n \"title\": \"Mitigation strategies to reduce acrylamide formation in fried potato products.\"\n },\n {\n \"docid\": \"MED-2809\",\n \"text\": \"Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.\",\n \"title\": \"Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials\"\n },\n {\n \"docid\": \"MED-5063\",\n \"text\": \"Evidence supports a trial period of eliminating colourings and preservatives from the diet\",\n \"title\": \"Food additives and hyperactivity\"\n },\n {\n \"docid\": \"MED-5147\",\n \"text\": \"There has been considerable work on the relationships between nutrition and the immune response, particularly on studies that have focused on adaptive responses. There is increasing recognition of the importance of innate immunity in host protection and initiation of cytokine networks. In this study, we examined the effect of select cocoa flavanols and procyanidins on innate responses in vitro. Peripheral blood mono-nuclear cells (PBMCs), as well as purified monocytes and CD4 and CD8 T cells, were isolated from healthy volunteers and cultured in the presence of cocoa flavanol fractions that differ from another by the degree of flavanol polymerization: short-chain flavanol fraction (SCFF), monomers to pentamers; and long-chain flavanol fraction (LCFF), hexamers to decamers. Parallel investigations were also done with highly purified flavanol monomers and procyanidin dimers. The isolated cells were then challenged with lipopolysaccharide (LPS) with quantitation of activation using CD69 and CD83 expression and analysis of secreted tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, and granulocyte macrophage colony-stimulating factor (GM-CSF). The chain length of flavanol fractions had a significant effect on cytokine release from both unstimulated and LPS-stimulated PBMCs. For example, there was a striking increase of LPS-induced synthesis of IL-1beta, IL-6, IL-10, and TNF-alpha in the presence of LCFF. LCFF and SCFF, in the absence of LPS, stimulated the production of GM-CSF. In addition, LCFF and SCFF increased expression of the B cell markers CD69 and CD83. There were also unique differential responses in the mononuclear cell populations studied. We conclude that the oligomers are potent stimulators of both the innate immune system and early events in adaptive immunity.\",\n \"title\": \"Immune effects of cocoa procyanidin oligomers on peripheral blood mononuclear cells.\"\n },\n {\n \"docid\": \"MED-5152\",\n \"text\": \"OBJECTIVES: Strong evidence has secured aging as a powerful predictor of both cardiovascular risk and endothelial dysfunction, yet specific treatment is not available. We tested the hypothesis that vascular responsiveness to flavanol-rich cocoa increases with advancing age. We have previously shown that flavanol-rich cocoa induced peripheral vasodilation, improving endothelial function via a nitric oxide (NO)-dependent mechanism. METHODS: We studied blood pressure and peripheral arterial responses to several days of cocoa in 15 young (< 50 years) and 19 older (> 50) healthy subjects. RESULTS: The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME) induced significant pressor responses following cocoa administration only among the older subjects: systolic blood pressure (SBP) rose 13 +/- 4 mmHg, diastolic blood pressure (DBP) 6 +/- 2 mmHg (P = 0.008 and 0.047, respectively); SBP was significantly higher in the older subjects (P < 0.05). Flow-mediated vasodilation, measured by tonometry in the finger, was enhanced with flavanol-rich cocoa in both groups, but significantly more so among the old (P = 0.01). Finally, basal pulse wave amplitude (PWA) followed a similar pattern. Four to six days of flavanol-rich cocoa caused a rise in PWA in both groups. At peak vasodilation following acute cocoa intake on the final day, both groups showed a further, significant rise in PWA. The response in the older subjects was more robust; P < 0.05. L-NAME significantly reversed dilation in both groups. CONCLUSIONS: Flavanol-rich cocoa enhanced several measures of endothelial function to a greater degree among older than younger healthy subjects. Our data suggest that the NO-dependent vascular effects of flavanol-rich cocoa may be greater among older people, in whom endothelial function is more disturbed.\",\n \"title\": \"Aging and vascular responses to flavanol-rich cocoa.\"\n },\n {\n \"docid\": \"MED-2488\",\n \"text\": \"Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.\",\n \"title\": \"Food prices and blood cholesterol.\"\n },\n {\n \"docid\": \"MED-4729\",\n \"text\": \"In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources.\",\n \"title\": \"Do Organohalogen Contaminants Contribute to Histopathology in Liver from East Greenland Polar Bears (Ursus maritimus)?\"\n },\n {\n \"docid\": \"MED-4732\",\n \"text\": \"Background Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives In this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis. Methods PCB-77 or 2,2′,4,4,5,5′-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR)−/− mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE−/− mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis. Results Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol–3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor γ, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR−/− mice. ApoE−/− mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. Conclusions Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.\",\n \"title\": \"Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis\"\n },\n {\n \"docid\": \"MED-5004\",\n \"text\": \"BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.\",\n \"title\": \"Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford.\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"MED-1451","text":"OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. METHODS: Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. RESULTS: A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. CONCLUSIONS: Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.","title":"The link between workforce health and safety and the health of the bottom line: tracking market performance of companies that nurture a \"culture of..."},{"docid":"MED-3087","text":"Sixty random samples of bulk farm milk, market milk, locally manufactured processed cheese, and milk powder were collected to be analyzed for aluminum (Al) concentration using graphite furnace atomic absorption spectrometry (GFAAS). The results were compared with provisional acceptable permissible limits (PAPLs). The maximum estimated dietary intake (MEDI) of Al for the examined samples was calculated. In addition, an experimental study was conducted to determine the possible leaching of Al from cookware in milk during boiling. The obtained results showed that Al concentration in examined bulk farm milk samples was found to be negligible. In contrast, market milk revealed higher concentration, 65.0% of the examined samples were above the PAPLs. The results revealed significant difference of Al concentration among them. The Al levels in processed cheese wrapped in Al foil were significantly higher than those found in samples packed in glass containers with a significant difference of Al concentration between them. Also, 20% of the examined milk powder samples exceeded the PAPLs (0.01 to 0.4 mg/kg). The MEDI for Al in bulk farm milk, control market milk, market milk boiled in Al cookware, market milk boiled in stainless-steel cookware, processed cheese wrapped in Al foil, processed cheese packed in glass containers, and milk powder were calculated as 3.0%, 61.0%, 63.0%, 61.0%, 428.0%, 220.0%, and 166.0% from \"PTDI,\" respectively. The results of the experimental study showed no marked significant differences of Al concentration between market milk (control group) and those boiled in Al cookware, as well as to those boiled in stainless-steel cookware. PRACTICAL APPLICATION: The results of the present study indicate that Al level in milk kept in Al containers and dairy products packed in Al foil is beyond the permissible limits, suggesting health hazard. Therefore, all milk cans should be constructed of stainless steel, prevent the entrance of tap water into milk, and the processed cheese should be packed in glass containers and not wrapped in Al foil. Leaching of Al increased to a significant percent more during storage than during boiling, so milk should be kept in stainless steel or glass containers in the refrigerator.","title":"Prevalence and public health significance of aluminum residues in milk and some dairy products."},{"docid":"MED-4727","text":"The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.","title":"Dietary intake of organotin compounds in Finland: a market-basket study."},{"docid":"MED-3490","text":"Liquid dietary supplements represent a fast growing market segment, including botanically-based beverages containing mangosteen, acai, and noni. These products often resemble fruit juice in packaging and appearance, but may contain pharmacologically active ingredients. While little is known about the human health effects or safety of consuming such products, manufacturers make extensive use of low-quality published research to promote their products. This report analyzes the science-based marketing claims of two of the most widely consumed mangosteen liquid dietary supplements, and compares them to the findings of the research being cited. The reviewer found that analyzed marketing claims overstate the significance of findings, and fail to disclose severe methodological weaknesses of the research they cite. If this trend extends to other related products that are similarly widely consumed, it may pose a public health threat by misleading consumers into assuming that product safety and effectiveness are backed by rigorous scientific data.","title":"Science in Liquid Dietary Supplement Promotion: The Misleading Case of Mangosteen Juice"},{"docid":"MED-4366","text":"BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail (\"junk mail\"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.","title":"The marketing of dietary supplements in North America: the emperor is (almost) naked."},{"docid":"MED-1760","text":"OBJECTIVE: To examine the effects of cumulative, real-world marketing and brand exposures on young children by testing the influence of branding from a heavily marketed source on taste preferences. DESIGN: Experimental study. Children tasted 5 pairs of identical foods and beverages in packaging from McDonald's and matched but unbranded packaging and were asked to indicate if they tasted the same or if one tasted better. SETTING: Preschools for low-income children. PARTICIPANTS: Sixty-three children (mean +/- SD age, 4.6 +/- 0.5 years; range, 3.5-5.4 years). MAIN EXPOSURE: Branding of fast foods. OUTCOME MEASURES: A summary total taste preference score (ranging from -1 for the unbranded samples to 0 for no preference and +1 for McDonald's branded samples) was used to test the null hypothesis that children would express no preference. RESULTS: The mean +/- SD total taste preference score across all food comparisons was 0.37 +/- 0.45 (median, 0.20; interquartile range, 0.00-0.80) and significantly greater than zero (P<.001), indicating that children preferred the tastes of foods and drinks if they thought they were from McDonald's. Moderator analysis found significantly greater effects of branding among children with more television sets in their homes and children who ate food from McDonald's more often. CONCLUSION: Branding of foods and beverages influences young children's taste perceptions. The findings are consistent with recommendations to regulate marketing to young children and also suggest that branding may be a useful strategy for improving young children's eating behaviors.","title":"Effects of fast food branding on young children's taste preferences."},{"docid":"MED-4964","text":"The microbial quality of raw fillets of aquacultured catfish, salmon, tilapia, and trout was evaluated. A total of 272 fillets from nine local and nine Internet retail markets were tested. Mean values were 5.7 log CFU/g for total aerobic mesophiles, 6.3 log CFU/g for psychrotrophs, and 1.9 log most probable number (MPN) per gram for coliforms. Differences in these microbial levels between the two kinds of markets and among the four types of fish were not significant (P > 0.05), except that Internet trout fillets had about 0.8-log higher aerobic mesophiles than did trout fillets purchased locally. Although Escherichia coli was detected in 1.4, 1.5, and 5.9% of trout, salmon, and tilapia, respectively, no sample had > or = 1.0 log MPN/g. However, E. coli was found in 13.2% of catfish, with an average of 1.7 log MPN/g. About 27% of all fillets had Listeria spp., and a positive correlation between the prevalence of Listeria spp. and Listeria monocytogenes was observed. Internet fillets had a higher prevalence of both Listeria spp. and L. monocytogenes than did those fillets purchased locally. L. monocytogenes was present in 23.5% of catfish but in only 5.7, 10.3, and 10.6% of trout, tilapia, and salmon, respectively. Salmonella and E. coli O157 were not found in any sample. A follow-up investigation using catfish operation as a model revealed that gut waste exposed during evisceration is a potential source of coliforms and Listeria spp.","title":"Microbial quality of raw aquacultured fish fillets procured from Internet and local retail markets."},{"docid":"MED-1959","text":"Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.","title":"Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source."},{"docid":"MED-2751","text":"Recent data on fishmeal and fish-oil supply are presented identifying key producer countries and raw material sources and distinguishing between whole fish and by-products. The conversion of these raw materials into marine ingredients is discussed and global volumes presented. This is followed by a summary of the main countries using these marine ingredients over recent years. Uses of fishmeal and fish-oil by market segment are then presented. From this, a global mass balance of inputs and outputs is derived which allows the calculation of the input-to-output ratios (fish in:fish out; FIFO) for the main aquaculture production types to be made. Current areas of focus by the industry include the need to demonstrate sustainable practice, more strategic use of marine ingredients, greater use of fishery and land-animal by-products as well as vegetable substitutes, and novel sources of essential omega-3 fats, notably the long-chain polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Implications are drawn for future supply prospects of fishmeal and fish-oil and their future role in aquaculture, agriculture and human health. © 2013 The Fisheries Society of the British Isles.","title":"Global fishmeal and fish-oil supply: inputs, outputs and markets."},{"docid":"MED-2016","text":"BACKGROUND: Coeliac disease is a common, autoimmune disorder, for which the only treatment is lifelong adherence to a gluten-free diet. This study evaluates the economic burden of adhering to a gluten-free diet. METHODS: A market basket of products identified by name brand, weight or package size for both regular wheat-based products and gluten-free counterparts was developed. The differences in price between purchase venues, both type of store (general grocery store, an upscale grocery store and a health food store and four internet-based grocery sites) and region was also analysed. RESULTS: Availability of gluten-free products varied between the different venues, regular grocery stores carried 36%, while upscale markets carried 41%, and health food stores 94%, compared with 100% availability on the internet. Overall, every gluten-free product was more expensive than their wheat-based counterpart (P 9 h per day. Carriage of MRSA was higher in butchers than in the general community. Although five strains were probably of healthcare origin, the high incidence of t899 (CC9) suggests that cross-contamination from pork occurs frequently. Washing of hands after touching raw pork is advised. © 2012 Blackwell Verlag GmbH.","title":"Colonization of butchers with livestock-associated methicillin-resistant Staphylococcus aureus."},{"docid":"MED-4531","text":"Traditional herbal preparations used in Ayurveda, traditional Chinese medicine, traditional Tibetan medicine, and other Asian traditional medicine systems may contain significant amounts of mercury, arsenic or lead. Though deliberately incorporated in Asian traditional herbal preparations for therapeutic purposes, these constituents have caused intoxications worldwide. The aim of this study was therefore to determine mercury, arsenic, and lead levels in Asian traditional herbal preparations on the Dutch market. A total of 292 traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine were sampled between 2004 and 2007. Samples were mostly multi-ingredient traditional herbal preparations containing herbs and minerals. The labeling of less than 20% of the traditional herbal preparations suggested the presence of mercury, arsenic or lead. These elements were shown by inductively coupled mass spectrometry (ICP-MS) in 186 (64%) of 292 traditional herbal preparations. Estimated weekly mercury, arsenic, and lead intake levels were calculated for each traditional herbal preparation from the analytically determined concentrations and the recommended dose. A total of 59 traditional herbal preparations (20%) were likely to result in intakes of these elements significantly exceeding safety limits. Of these 59 traditional herbal preparations, intake estimates for 50 traditional herbal preparations significantly exceeded the safety limit for mercury (range = 1.4-1747 mg week(-1)); intake estimates for 26 traditional herbal preparations significantly exceeded the safety limit for arsenic (range = 0.53-427 mg week(-1)) and intake estimates for eight traditional herbal preparations were significantly above the safety limit for lead (range = 2.6-192 mg week(-1)). It is concluded that the mercury, arsenic, and lead contents of traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine remain a cause for concern and require strict control.","title":"Monitoring of mercury, arsenic, and lead in traditional Asian herbal preparations on the Dutch market and estimation of associated risks."},{"docid":"MED-4747","text":"In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.","title":"Hormonal growth promoting agents in food producing animals."},{"docid":"MED-5022","text":"The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.","title":"Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana."},{"docid":"MED-4922","text":"The discipline of glycobiology contributes to our understanding of human health and disease through research, most of which is published in peer-reviewed scientific journals. Recently, legitimate discoveries in glycobiology have been used as marketing tools to help sell plant extracts termed \"glyconutrients.\" The glyconutrient industry has a worldwide sales force of over half a million people and sells nearly half a billion dollars (USD) of products annually. Here we address the relationship between glyconutrients and glycobiology, and how glyconutrient claims may impact the public and our discipline.","title":"A \"glyconutrient sham\"."},{"docid":"MED-5215","text":"Punctal and canalicular plugs are widely used for both temporary and permanent occlusion of the lacrimal puncta in dry eyes. There are many designs and materials available on the market. While their efficacy in improving dry eye symptoms is widely proven, the gamut of complications associated with these devices have never been subject to a general review, although there are numerous case series in the literature associated with one particular device. This review aims to examine the track record of a variety of plugs currently in use, to review the management of complications, and propose strategies for both the prevention of these complications and their treatment.","title":"A review of the complications of lacrimal occlusion with punctal and canalicular plugs."},{"docid":"MED-3481","text":"The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer approaches for the treatment of obesity have involved inhibition of dietary triglyceride absorption via inhibition of pancreatic lipase (PL) as this is the major source of excess calories. Natural products provide a vast pool of PL inhibitors that can possibly be developed into clinical products. This article reviews various extracts and secondary metabolites from plants and microbial origin with PL inhibitory activity that can be focused for drug development programs.","title":"Pancreatic lipase inhibitors from natural sources: unexplored potential."},{"docid":"MED-3693","text":"Probiotics are widely used to prevent and treat several diseases. Many commercial products are available worldwide. However, there is no clear international or local legislation about them and previous studies showed that most of the tested products are not in conformity with international guidelines. The aim of this study was to determine if products available in the USA market in 2009 were correctly labeled in terms of quantity of viable bacteria, identification of species and cross contamination by species not on the label. Disturbingly, we found that only 4 of 13 products (31%) were in accordance with label claims. Our results suggest the need for adequate control of probiotic production as well as periodical screenings by competent organizations to monitor the effect of storage on product quality.","title":"Microbiological evaluation of commercial probiotic products available in the USA in 2009."},{"docid":"MED-3487","text":"Weight loss supplements often contain powerful pharmacoactive ingredients with the potential to cause harm. Trials used to determine product safety and effectiveness, meanwhile, tend to be small, of short duration, and frequently lack financial conflict of interest disclosures. These factors could conspire to place consumers at risk, especially when published research cited in advertising cloaks products with the suggestion that their safety and effectiveness have been proven by science. Examples of current and former weight loss products backed by potentially conflicted or low quality research include Metabolife-356, Hydroxycut, Xenadrine and LeptiCore. Published research, especially in the field of weight loss supplements, needs better conflict of interest disclosure, and regulators should consider how research findings are used in marketing claims.","title":"Science of weight loss supplements: Compromised by conflicts of interest?"},{"docid":"MED-4491","text":"Dry-cured ham is a traditional product with a strong presence in markets in the Mediterranean area. It is very popular with European consumers and is of enormous economic importance for the meat industry in the Mediterranean area. Although the great palatability of ham largely outweighs other considerations, aspects relating to health and wellbeing are increasingly important factors in consumer decisions. The potential role of ham in a context of healthy nutrition has not been clearly elucidated, especially considering that origins and production methods of dry-cured hams can induce differences in composition. The object of this review was on the one hand to provide an analysis of the components of dry-cured ham and their role in a healthy diet, and on the other hand to suggest possible strategies for improving its nutritional composition. 2009 Elsevier Ltd. All rights reserved.","title":"Nutritional composition of dry-cured ham and its role in a healthy diet."},{"docid":"MED-2673","text":"Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.","title":"Determination of microbial transglutaminase in meat and meat products."},{"docid":"MED-4535","text":"Herbal formulations are getting popular throughout the world and commercialized extensively for various medicinal properties. WHO has emphasized the need for quality assurance of herbal products, including testing of heavy metals and pesticides residues. In view of WHO guidelines, single herbal drugs used in herbal formulations were collected from local market, for testing heavy metals and persistent pesticides residue. Therefore, in the present case, we have examined few local samples of certain herbs viz. Emblica officinalis, Terminalia chebula, Terminalia belerica, and Withania somnifera. The present studies were selected for estimation of four heavy metals namely Arsenic, Cadmium, Lead, and Mercury. Apart from these, pesticide residue Viz. Organochlorine pesticides, Organophosphorus pesticides, and Pyrethroids were analyzed in the four samples of single crude drugs. Heavy metals and pesticide residue were found below detection limits in all the samples.","title":"Detection of toxic heavy metals and pesticide residue in herbal plants which are commonly used in the herbal formulations."},{"docid":"MED-4870","text":"Anatoxin-a is a potent neurotoxin produced by several species of cyanobacteria. This alkaloid may cause fatal intoxication to exposed organisms and this has raised concerns over the increasing popularity of food supplements containing cyanobacteria. These are being marketed with alleged health properties for animal and human consumption. These supplements most commonly contain the genera Spirulina (Arthrospira) and Aphanizomenon and their consumption represent a potential route for anatoxin-a exposure in cases where adequate quality control is not undertaken. In this work, several dietary supplements containing cyanobacteria from different commercial suppliers were evaluated for the presence of anatoxin-a by high performance liquid chromatography with fluorescence detection. Additionally, the presence of the previously derivatized anatoxin-a was confirmed by using Gas chromatography-mass spectrometry. A total of 39 samples were analysed in the study. Results showed that three of the samples (7.7%) contained anatoxin-a, at concentrations ranging from 2.50 to 33 microg g(-1). Quality control of cyanobacterial food supplements is required to avoid potential health effects in humans and animals.","title":"First detection of anatoxin-a in human and animal dietary supplements containing cyanobacteria."},{"docid":"MED-1268","text":"Most amyotrophic lateral sclerosis (ALS) cases occur sporadically. Some environmental triggers have been implicated, including beta-methylamino-L-alanine (BMAA), a cyanobacteria produced neurotoxin. This study aimed to identify environmental risk factors common to three sporadic ALS patients who lived in Annapolis, Maryland, USA and developed the disease within a relatively short time and within close proximity to each other. A questionnaire was used to identify potential risk factors for ALS among the cohort of patients. One common factor among the ALS patients was the frequent consumption of blue crab. Samples of blue crab from the patients' local fish market were tested for BMAA using LC-MS/MS. BMAA was identified in these Chesapeake Bay blue crabs. We conclude that the presence of BMAA in the Chesapeake Bay food web and the lifetime consumption of blue crab contaminated with BMAA may be a common risk factor for sporadic ALS in all three patients. Copyright © 2013 Elsevier Ltd. All rights reserved.","title":"Linking β-methylamino-L-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD."},{"docid":"MED-2018","text":"A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.","title":"Spectrum of gluten-related disorders: consensus on new nomenclature and classification"},{"docid":"MED-2143","text":"Many therapeutic agents had been used for the treatment of diabetes mellitus before insulin was discovered and several hundred plants have shown some extent of antidiabetic activity. This study tries to explore which agents were most widely used in Europe in the pre-insulin era. According to the scientific literature and the proprietary drug industry around 1900, more than 100 agents were considered to have hypoglycemic activity. Most of them seem to have been used only occasionally while some others were recommended and marketed to a large extent. Among the medicinal plants, Syzygium cumini (syn. S. jambolanum, Eugenia jambolana), Vaccinum myrtillus and Phaseolus sp. were most common, and other frequently used agents were opium, opium alkaloids, other alkaloids like quinine or Belladonna alkaloids, salicylates, alkaline substances like sodium (bi)carbonate and even strong poisons like arsenic or uranium salts. Syzygium jambolanum seed powder seems to be one of the most intensively studied antidiabetic agents of plant origin.","title":"Antidiabetic drugs used in Europe prior to the discovery of insulin."},{"docid":"MED-2726","text":"The 2011 UN high-level meeting on non-communicable diseases (NCDs) called for multisectoral action including with the private sector and industry. However, through the sale and promotion of tobacco, alcohol, and ultra-processed food and drink (unhealthy commodities), transnational corporations are major drivers of global epidemics of NCDs. What role then should these industries have in NCD prevention and control? We emphasise the rise in sales of these unhealthy commodities in low-income and middle-income countries, and consider the common strategies that the transnational corporations use to undermine NCD prevention and control. We assess the effectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with these industries and conclude that unhealthy commodity industries should have no role in the formation of national or international NCD policy. Despite the common reliance on industry self-regulation and public-private partnerships, there is no evidence of their effectiveness or safety. Public regulation and market intervention are the only evidence-based mechanisms to prevent harm caused by the unhealthy commodity industries. Copyright © 2013 Elsevier Ltd. All rights reserved.","title":"Profits and pandemics: prevention of harmful effects of tobacco, alcohol, and ultra-processed food and drink industries."}],"string":"[\n {\n \"docid\": \"MED-1451\",\n \"text\": \"OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. METHODS: Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. RESULTS: A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. CONCLUSIONS: Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.\",\n \"title\": \"The link between workforce health and safety and the health of the bottom line: tracking market performance of companies that nurture a \\\"culture of...\"\n },\n {\n \"docid\": \"MED-3087\",\n \"text\": \"Sixty random samples of bulk farm milk, market milk, locally manufactured processed cheese, and milk powder were collected to be analyzed for aluminum (Al) concentration using graphite furnace atomic absorption spectrometry (GFAAS). The results were compared with provisional acceptable permissible limits (PAPLs). The maximum estimated dietary intake (MEDI) of Al for the examined samples was calculated. In addition, an experimental study was conducted to determine the possible leaching of Al from cookware in milk during boiling. The obtained results showed that Al concentration in examined bulk farm milk samples was found to be negligible. In contrast, market milk revealed higher concentration, 65.0% of the examined samples were above the PAPLs. The results revealed significant difference of Al concentration among them. The Al levels in processed cheese wrapped in Al foil were significantly higher than those found in samples packed in glass containers with a significant difference of Al concentration between them. Also, 20% of the examined milk powder samples exceeded the PAPLs (0.01 to 0.4 mg/kg). The MEDI for Al in bulk farm milk, control market milk, market milk boiled in Al cookware, market milk boiled in stainless-steel cookware, processed cheese wrapped in Al foil, processed cheese packed in glass containers, and milk powder were calculated as 3.0%, 61.0%, 63.0%, 61.0%, 428.0%, 220.0%, and 166.0% from \\\"PTDI,\\\" respectively. The results of the experimental study showed no marked significant differences of Al concentration between market milk (control group) and those boiled in Al cookware, as well as to those boiled in stainless-steel cookware. PRACTICAL APPLICATION: The results of the present study indicate that Al level in milk kept in Al containers and dairy products packed in Al foil is beyond the permissible limits, suggesting health hazard. Therefore, all milk cans should be constructed of stainless steel, prevent the entrance of tap water into milk, and the processed cheese should be packed in glass containers and not wrapped in Al foil. Leaching of Al increased to a significant percent more during storage than during boiling, so milk should be kept in stainless steel or glass containers in the refrigerator.\",\n \"title\": \"Prevalence and public health significance of aluminum residues in milk and some dairy products.\"\n },\n {\n \"docid\": \"MED-4727\",\n \"text\": \"The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.\",\n \"title\": \"Dietary intake of organotin compounds in Finland: a market-basket study.\"\n },\n {\n \"docid\": \"MED-3490\",\n \"text\": \"Liquid dietary supplements represent a fast growing market segment, including botanically-based beverages containing mangosteen, acai, and noni. These products often resemble fruit juice in packaging and appearance, but may contain pharmacologically active ingredients. While little is known about the human health effects or safety of consuming such products, manufacturers make extensive use of low-quality published research to promote their products. This report analyzes the science-based marketing claims of two of the most widely consumed mangosteen liquid dietary supplements, and compares them to the findings of the research being cited. The reviewer found that analyzed marketing claims overstate the significance of findings, and fail to disclose severe methodological weaknesses of the research they cite. If this trend extends to other related products that are similarly widely consumed, it may pose a public health threat by misleading consumers into assuming that product safety and effectiveness are backed by rigorous scientific data.\",\n \"title\": \"Science in Liquid Dietary Supplement Promotion: The Misleading Case of Mangosteen Juice\"\n },\n {\n \"docid\": \"MED-4366\",\n \"text\": \"BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail (\\\"junk mail\\\"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.\",\n \"title\": \"The marketing of dietary supplements in North America: the emperor is (almost) naked.\"\n },\n {\n \"docid\": \"MED-1760\",\n \"text\": \"OBJECTIVE: To examine the effects of cumulative, real-world marketing and brand exposures on young children by testing the influence of branding from a heavily marketed source on taste preferences. DESIGN: Experimental study. Children tasted 5 pairs of identical foods and beverages in packaging from McDonald's and matched but unbranded packaging and were asked to indicate if they tasted the same or if one tasted better. SETTING: Preschools for low-income children. PARTICIPANTS: Sixty-three children (mean +/- SD age, 4.6 +/- 0.5 years; range, 3.5-5.4 years). MAIN EXPOSURE: Branding of fast foods. OUTCOME MEASURES: A summary total taste preference score (ranging from -1 for the unbranded samples to 0 for no preference and +1 for McDonald's branded samples) was used to test the null hypothesis that children would express no preference. RESULTS: The mean +/- SD total taste preference score across all food comparisons was 0.37 +/- 0.45 (median, 0.20; interquartile range, 0.00-0.80) and significantly greater than zero (P<.001), indicating that children preferred the tastes of foods and drinks if they thought they were from McDonald's. Moderator analysis found significantly greater effects of branding among children with more television sets in their homes and children who ate food from McDonald's more often. CONCLUSION: Branding of foods and beverages influences young children's taste perceptions. The findings are consistent with recommendations to regulate marketing to young children and also suggest that branding may be a useful strategy for improving young children's eating behaviors.\",\n \"title\": \"Effects of fast food branding on young children's taste preferences.\"\n },\n {\n \"docid\": \"MED-4964\",\n \"text\": \"The microbial quality of raw fillets of aquacultured catfish, salmon, tilapia, and trout was evaluated. A total of 272 fillets from nine local and nine Internet retail markets were tested. Mean values were 5.7 log CFU/g for total aerobic mesophiles, 6.3 log CFU/g for psychrotrophs, and 1.9 log most probable number (MPN) per gram for coliforms. Differences in these microbial levels between the two kinds of markets and among the four types of fish were not significant (P > 0.05), except that Internet trout fillets had about 0.8-log higher aerobic mesophiles than did trout fillets purchased locally. Although Escherichia coli was detected in 1.4, 1.5, and 5.9% of trout, salmon, and tilapia, respectively, no sample had > or = 1.0 log MPN/g. However, E. coli was found in 13.2% of catfish, with an average of 1.7 log MPN/g. About 27% of all fillets had Listeria spp., and a positive correlation between the prevalence of Listeria spp. and Listeria monocytogenes was observed. Internet fillets had a higher prevalence of both Listeria spp. and L. monocytogenes than did those fillets purchased locally. L. monocytogenes was present in 23.5% of catfish but in only 5.7, 10.3, and 10.6% of trout, tilapia, and salmon, respectively. Salmonella and E. coli O157 were not found in any sample. A follow-up investigation using catfish operation as a model revealed that gut waste exposed during evisceration is a potential source of coliforms and Listeria spp.\",\n \"title\": \"Microbial quality of raw aquacultured fish fillets procured from Internet and local retail markets.\"\n },\n {\n \"docid\": \"MED-1959\",\n \"text\": \"Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.\",\n \"title\": \"Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source.\"\n },\n {\n \"docid\": \"MED-2751\",\n \"text\": \"Recent data on fishmeal and fish-oil supply are presented identifying key producer countries and raw material sources and distinguishing between whole fish and by-products. The conversion of these raw materials into marine ingredients is discussed and global volumes presented. This is followed by a summary of the main countries using these marine ingredients over recent years. Uses of fishmeal and fish-oil by market segment are then presented. From this, a global mass balance of inputs and outputs is derived which allows the calculation of the input-to-output ratios (fish in:fish out; FIFO) for the main aquaculture production types to be made. Current areas of focus by the industry include the need to demonstrate sustainable practice, more strategic use of marine ingredients, greater use of fishery and land-animal by-products as well as vegetable substitutes, and novel sources of essential omega-3 fats, notably the long-chain polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Implications are drawn for future supply prospects of fishmeal and fish-oil and their future role in aquaculture, agriculture and human health. © 2013 The Fisheries Society of the British Isles.\",\n \"title\": \"Global fishmeal and fish-oil supply: inputs, outputs and markets.\"\n },\n {\n \"docid\": \"MED-2016\",\n \"text\": \"BACKGROUND: Coeliac disease is a common, autoimmune disorder, for which the only treatment is lifelong adherence to a gluten-free diet. This study evaluates the economic burden of adhering to a gluten-free diet. METHODS: A market basket of products identified by name brand, weight or package size for both regular wheat-based products and gluten-free counterparts was developed. The differences in price between purchase venues, both type of store (general grocery store, an upscale grocery store and a health food store and four internet-based grocery sites) and region was also analysed. RESULTS: Availability of gluten-free products varied between the different venues, regular grocery stores carried 36%, while upscale markets carried 41%, and health food stores 94%, compared with 100% availability on the internet. Overall, every gluten-free product was more expensive than their wheat-based counterpart (P 9 h per day. Carriage of MRSA was higher in butchers than in the general community. Although five strains were probably of healthcare origin, the high incidence of t899 (CC9) suggests that cross-contamination from pork occurs frequently. Washing of hands after touching raw pork is advised. © 2012 Blackwell Verlag GmbH.\",\n \"title\": \"Colonization of butchers with livestock-associated methicillin-resistant Staphylococcus aureus.\"\n },\n {\n \"docid\": \"MED-4531\",\n \"text\": \"Traditional herbal preparations used in Ayurveda, traditional Chinese medicine, traditional Tibetan medicine, and other Asian traditional medicine systems may contain significant amounts of mercury, arsenic or lead. Though deliberately incorporated in Asian traditional herbal preparations for therapeutic purposes, these constituents have caused intoxications worldwide. The aim of this study was therefore to determine mercury, arsenic, and lead levels in Asian traditional herbal preparations on the Dutch market. A total of 292 traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine were sampled between 2004 and 2007. Samples were mostly multi-ingredient traditional herbal preparations containing herbs and minerals. The labeling of less than 20% of the traditional herbal preparations suggested the presence of mercury, arsenic or lead. These elements were shown by inductively coupled mass spectrometry (ICP-MS) in 186 (64%) of 292 traditional herbal preparations. Estimated weekly mercury, arsenic, and lead intake levels were calculated for each traditional herbal preparation from the analytically determined concentrations and the recommended dose. A total of 59 traditional herbal preparations (20%) were likely to result in intakes of these elements significantly exceeding safety limits. Of these 59 traditional herbal preparations, intake estimates for 50 traditional herbal preparations significantly exceeded the safety limit for mercury (range = 1.4-1747 mg week(-1)); intake estimates for 26 traditional herbal preparations significantly exceeded the safety limit for arsenic (range = 0.53-427 mg week(-1)) and intake estimates for eight traditional herbal preparations were significantly above the safety limit for lead (range = 2.6-192 mg week(-1)). It is concluded that the mercury, arsenic, and lead contents of traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine remain a cause for concern and require strict control.\",\n \"title\": \"Monitoring of mercury, arsenic, and lead in traditional Asian herbal preparations on the Dutch market and estimation of associated risks.\"\n },\n {\n \"docid\": \"MED-4747\",\n \"text\": \"In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\\\"anabolics\\\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\\\"hormones\\\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \\\"legal natural levels\\\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \\\"pour on\\\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \\\"smart\\\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \\\"highly\\\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \\\"normal\\\" diet.\",\n \"title\": \"Hormonal growth promoting agents in food producing animals.\"\n },\n {\n \"docid\": \"MED-5022\",\n \"text\": \"The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.\",\n \"title\": \"Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana.\"\n },\n {\n \"docid\": \"MED-4922\",\n \"text\": \"The discipline of glycobiology contributes to our understanding of human health and disease through research, most of which is published in peer-reviewed scientific journals. Recently, legitimate discoveries in glycobiology have been used as marketing tools to help sell plant extracts termed \\\"glyconutrients.\\\" The glyconutrient industry has a worldwide sales force of over half a million people and sells nearly half a billion dollars (USD) of products annually. Here we address the relationship between glyconutrients and glycobiology, and how glyconutrient claims may impact the public and our discipline.\",\n \"title\": \"A \\\"glyconutrient sham\\\".\"\n },\n {\n \"docid\": \"MED-5215\",\n \"text\": \"Punctal and canalicular plugs are widely used for both temporary and permanent occlusion of the lacrimal puncta in dry eyes. There are many designs and materials available on the market. While their efficacy in improving dry eye symptoms is widely proven, the gamut of complications associated with these devices have never been subject to a general review, although there are numerous case series in the literature associated with one particular device. This review aims to examine the track record of a variety of plugs currently in use, to review the management of complications, and propose strategies for both the prevention of these complications and their treatment.\",\n \"title\": \"A review of the complications of lacrimal occlusion with punctal and canalicular plugs.\"\n },\n {\n \"docid\": \"MED-3481\",\n \"text\": \"The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer approaches for the treatment of obesity have involved inhibition of dietary triglyceride absorption via inhibition of pancreatic lipase (PL) as this is the major source of excess calories. Natural products provide a vast pool of PL inhibitors that can possibly be developed into clinical products. This article reviews various extracts and secondary metabolites from plants and microbial origin with PL inhibitory activity that can be focused for drug development programs.\",\n \"title\": \"Pancreatic lipase inhibitors from natural sources: unexplored potential.\"\n },\n {\n \"docid\": \"MED-3693\",\n \"text\": \"Probiotics are widely used to prevent and treat several diseases. Many commercial products are available worldwide. However, there is no clear international or local legislation about them and previous studies showed that most of the tested products are not in conformity with international guidelines. The aim of this study was to determine if products available in the USA market in 2009 were correctly labeled in terms of quantity of viable bacteria, identification of species and cross contamination by species not on the label. Disturbingly, we found that only 4 of 13 products (31%) were in accordance with label claims. Our results suggest the need for adequate control of probiotic production as well as periodical screenings by competent organizations to monitor the effect of storage on product quality.\",\n \"title\": \"Microbiological evaluation of commercial probiotic products available in the USA in 2009.\"\n },\n {\n \"docid\": \"MED-3487\",\n \"text\": \"Weight loss supplements often contain powerful pharmacoactive ingredients with the potential to cause harm. Trials used to determine product safety and effectiveness, meanwhile, tend to be small, of short duration, and frequently lack financial conflict of interest disclosures. These factors could conspire to place consumers at risk, especially when published research cited in advertising cloaks products with the suggestion that their safety and effectiveness have been proven by science. Examples of current and former weight loss products backed by potentially conflicted or low quality research include Metabolife-356, Hydroxycut, Xenadrine and LeptiCore. Published research, especially in the field of weight loss supplements, needs better conflict of interest disclosure, and regulators should consider how research findings are used in marketing claims.\",\n \"title\": \"Science of weight loss supplements: Compromised by conflicts of interest?\"\n },\n {\n \"docid\": \"MED-4491\",\n \"text\": \"Dry-cured ham is a traditional product with a strong presence in markets in the Mediterranean area. It is very popular with European consumers and is of enormous economic importance for the meat industry in the Mediterranean area. Although the great palatability of ham largely outweighs other considerations, aspects relating to health and wellbeing are increasingly important factors in consumer decisions. The potential role of ham in a context of healthy nutrition has not been clearly elucidated, especially considering that origins and production methods of dry-cured hams can induce differences in composition. The object of this review was on the one hand to provide an analysis of the components of dry-cured ham and their role in a healthy diet, and on the other hand to suggest possible strategies for improving its nutritional composition. 2009 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Nutritional composition of dry-cured ham and its role in a healthy diet.\"\n },\n {\n \"docid\": \"MED-2673\",\n \"text\": \"Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.\",\n \"title\": \"Determination of microbial transglutaminase in meat and meat products.\"\n },\n {\n \"docid\": \"MED-4535\",\n \"text\": \"Herbal formulations are getting popular throughout the world and commercialized extensively for various medicinal properties. WHO has emphasized the need for quality assurance of herbal products, including testing of heavy metals and pesticides residues. In view of WHO guidelines, single herbal drugs used in herbal formulations were collected from local market, for testing heavy metals and persistent pesticides residue. Therefore, in the present case, we have examined few local samples of certain herbs viz. Emblica officinalis, Terminalia chebula, Terminalia belerica, and Withania somnifera. The present studies were selected for estimation of four heavy metals namely Arsenic, Cadmium, Lead, and Mercury. Apart from these, pesticide residue Viz. Organochlorine pesticides, Organophosphorus pesticides, and Pyrethroids were analyzed in the four samples of single crude drugs. Heavy metals and pesticide residue were found below detection limits in all the samples.\",\n \"title\": \"Detection of toxic heavy metals and pesticide residue in herbal plants which are commonly used in the herbal formulations.\"\n },\n {\n \"docid\": \"MED-4870\",\n \"text\": \"Anatoxin-a is a potent neurotoxin produced by several species of cyanobacteria. This alkaloid may cause fatal intoxication to exposed organisms and this has raised concerns over the increasing popularity of food supplements containing cyanobacteria. These are being marketed with alleged health properties for animal and human consumption. These supplements most commonly contain the genera Spirulina (Arthrospira) and Aphanizomenon and their consumption represent a potential route for anatoxin-a exposure in cases where adequate quality control is not undertaken. In this work, several dietary supplements containing cyanobacteria from different commercial suppliers were evaluated for the presence of anatoxin-a by high performance liquid chromatography with fluorescence detection. Additionally, the presence of the previously derivatized anatoxin-a was confirmed by using Gas chromatography-mass spectrometry. A total of 39 samples were analysed in the study. Results showed that three of the samples (7.7%) contained anatoxin-a, at concentrations ranging from 2.50 to 33 microg g(-1). Quality control of cyanobacterial food supplements is required to avoid potential health effects in humans and animals.\",\n \"title\": \"First detection of anatoxin-a in human and animal dietary supplements containing cyanobacteria.\"\n },\n {\n \"docid\": \"MED-1268\",\n \"text\": \"Most amyotrophic lateral sclerosis (ALS) cases occur sporadically. Some environmental triggers have been implicated, including beta-methylamino-L-alanine (BMAA), a cyanobacteria produced neurotoxin. This study aimed to identify environmental risk factors common to three sporadic ALS patients who lived in Annapolis, Maryland, USA and developed the disease within a relatively short time and within close proximity to each other. A questionnaire was used to identify potential risk factors for ALS among the cohort of patients. One common factor among the ALS patients was the frequent consumption of blue crab. Samples of blue crab from the patients' local fish market were tested for BMAA using LC-MS/MS. BMAA was identified in these Chesapeake Bay blue crabs. We conclude that the presence of BMAA in the Chesapeake Bay food web and the lifetime consumption of blue crab contaminated with BMAA may be a common risk factor for sporadic ALS in all three patients. Copyright © 2013 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Linking β-methylamino-L-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD.\"\n },\n {\n \"docid\": \"MED-2018\",\n \"text\": \"A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.\",\n \"title\": \"Spectrum of gluten-related disorders: consensus on new nomenclature and classification\"\n },\n {\n \"docid\": \"MED-2143\",\n \"text\": \"Many therapeutic agents had been used for the treatment of diabetes mellitus before insulin was discovered and several hundred plants have shown some extent of antidiabetic activity. This study tries to explore which agents were most widely used in Europe in the pre-insulin era. According to the scientific literature and the proprietary drug industry around 1900, more than 100 agents were considered to have hypoglycemic activity. Most of them seem to have been used only occasionally while some others were recommended and marketed to a large extent. Among the medicinal plants, Syzygium cumini (syn. S. jambolanum, Eugenia jambolana), Vaccinum myrtillus and Phaseolus sp. were most common, and other frequently used agents were opium, opium alkaloids, other alkaloids like quinine or Belladonna alkaloids, salicylates, alkaline substances like sodium (bi)carbonate and even strong poisons like arsenic or uranium salts. Syzygium jambolanum seed powder seems to be one of the most intensively studied antidiabetic agents of plant origin.\",\n \"title\": \"Antidiabetic drugs used in Europe prior to the discovery of insulin.\"\n },\n {\n \"docid\": \"MED-2726\",\n \"text\": \"The 2011 UN high-level meeting on non-communicable diseases (NCDs) called for multisectoral action including with the private sector and industry. However, through the sale and promotion of tobacco, alcohol, and ultra-processed food and drink (unhealthy commodities), transnational corporations are major drivers of global epidemics of NCDs. What role then should these industries have in NCD prevention and control? We emphasise the rise in sales of these unhealthy commodities in low-income and middle-income countries, and consider the common strategies that the transnational corporations use to undermine NCD prevention and control. We assess the effectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with these industries and conclude that unhealthy commodity industries should have no role in the formation of national or international NCD policy. Despite the common reliance on industry self-regulation and public-private partnerships, there is no evidence of their effectiveness or safety. Public regulation and market intervention are the only evidence-based mechanisms to prevent harm caused by the unhealthy commodity industries. Copyright © 2013 Elsevier Ltd. All rights reserved.\",\n \"title\": \"Profits and pandemics: prevention of harmful effects of tobacco, alcohol, and ultra-processed food and drink industries.\"\n }\n]"}}},{"rowIdx":399,"cells":{"query_id":{"kind":"string","value":"5110"},"query":{"kind":"string","value":"Why does shorting a call option have potential for unlimited loss?"},"positive_passages":{"kind":"list like","value":[{"docid":"281533","text":"\"You are likely making an assumption that the \"\"Short call\"\" part of the article you refer to isn't making: that you own the underlying stock in the first place. Rather, selling short a call has two primary cases with considerably different risk profiles. When you short-sell (or \"\"write\"\") a call option on a stock, your position can either be: covered, which means you already own the underlying stock and will simply need to deliver it if you are assigned, or else uncovered (or naked), which means you do not own the underlying stock. Writing a covered call can be a relatively conservative trade, while writing a naked call (if your broker were to permit such) can be extremely risky. Consider: With an uncovered position, should you be assigned you will be required to buy the underlying at the prevailing price. This is a very real cost — certainly not an opportunity cost. Look a little further in the article you linked, to the Option strategies section, and you will see the covered call mentioned there. That's the kind of trade you describe in your example.\"","title":""}],"string":"[\n {\n \"docid\": \"281533\",\n \"text\": \"\\\"You are likely making an assumption that the \\\"\\\"Short call\\\"\\\" part of the article you refer to isn't making: that you own the underlying stock in the first place. Rather, selling short a call has two primary cases with considerably different risk profiles. When you short-sell (or \\\"\\\"write\\\"\\\") a call option on a stock, your position can either be: covered, which means you already own the underlying stock and will simply need to deliver it if you are assigned, or else uncovered (or naked), which means you do not own the underlying stock. Writing a covered call can be a relatively conservative trade, while writing a naked call (if your broker were to permit such) can be extremely risky. Consider: With an uncovered position, should you be assigned you will be required to buy the underlying at the prevailing price. This is a very real cost — certainly not an opportunity cost. Look a little further in the article you linked, to the Option strategies section, and you will see the covered call mentioned there. That's the kind of trade you describe in your example.\\\"\",\n \"title\": \"\"\n }\n]"},"negative_passages":{"kind":"list like","value":[{"docid":"140371","text":"To expand on the comment made by @NateEldredge, you're looking to take a short position. A short position essentially functions as follows: Here's the rub: you have unlimited loss potential. Maybe you borrow a share and sell it at $10. Maybe in a month you still haven't closed the position and now the share is trading at $1,000. The share lender comes calling for their share and you have to close the position at $1,000 for a loss of $990. Now what if it was $1,000,000 per share, etc. To avoid this unlimited loss risk, you can instead buy a put option contract. In this situation you buy a contract that will expire at some point in the future for the right to sell a share of stock for $x. You get to put that share on to someone else. If the underlying stock price were to instead rise above the put's exercise price, the put will expire worthless — but your loss is limited to the premium paid to acquire the put option contract. There are all sorts of advanced options trades sometimes including taking a short or long position in a security. It's generally not advisable to undertake these sorts of trades until you're very comfortable with the mechanics of the contracts. It's definitely not advisable to take an unhedged short position, either by borrowing someone else's share(s) to sell or selling an option (when you sell the option you take the risk), because of the unlimited loss potential described above.","title":""},{"docid":"118633","text":"\"There are three ways to do this. So far the answers posted have only mentioned two. The three ways are: Selling short means that you borrow stock from your broker and sell it with the intent of buying it back later to repay the loan. As others have noted, this has unlimited potential losses and limited potential gains. Your profit or loss will go $1:$1 with the movement of the price of the stock. Buying a put option gives you the right to sell the stock at a later date on a price that you choose now. You pay a premium to have this right, and if the stock moves against you, you won't exercise your option and will lose the premium. Options move non-linearly with the price of the stock, especially when the expiration is far in the future. They probably are not for a beginner, although they can be powerful if used properly. The third option is a synthetic short position. You form this by simultaneously buying a put option and selling short a call option, both at the same strike price. This has a risk profile that is very much like the selling the stock short, but you can accomplish it entirely with stock options. Because you're both buying an selling, in theory you might even collect a small net premium when you open. You might ask why you'd do this given that you could just sell the stock short, which certainly seems simpler. One reason is that it is not always possible to sell the stock short. Recall that you have to borrow shares from your broker to sell short. When many people want to short the stock, brokers will run out of shares to loan. The stock is then said to be \"\"hard to borrow,\"\" which effectively prevents further short selling of the stock. In this case the synthetic short is still potentially possible.\"","title":""},{"docid":"307518","text":"\"The stock market is not a zero-sum game. Some parts are (forex, some option trading), but plain old stock trading is not zero sum. That is to say, if you were to invest \"\"at random\"\", you would on average make money. That's because the market as a whole makes money - it goes up over time (6-10% annually, averaged over time). That's because you're not just gambling when you buy a stock; you're actually contributing money to a company (directly or indirectly), which it uses to fund activities that (on average) make money. When you buy Caterpillar stock, you're indirectly funding Caterpillar building tractors, which they then sell for a profit, and thus your stock appreciates in value. While not every company makes a profit, and thus not every stock appreciates in true value, the average one does. To some extent, buying index funds is pretty close to \"\"investing at random\"\". It has a far lower risk quotient, of course, since you're not buying a few stocks at random but instead are buying all stocks in an index; but buying stocks from the S&P 500 at random would on average give the same return as VOO (with way more volatility). So for one, you definitely could do worse than 50/50; if you simply sold the market short (sold random stocks short), you would lose money over time on average, above and beyond the transaction cost, since the market will go up over time on average. Secondly, there is the consideration of limited and unlimited gains or losses. Some trades, specifically some option trades, have limited potential gains, and unlimited potential losses. Take for example, a simple call option. If you sell a naked call option - meaning you sell a call option but don't own the stock - for $100, at a strike price of $20, for 100 shares, you make money as long as the price of that stock is under $21. You have a potential to make $100, because that's what you sold it for; if the price is under $20, it's not exercised, and you just get that $100, free. But, on the other hand, if the stock goes up, you could potentially be out any amount of money. If the stock trades at $24, you're out $400-100 = $300, right? (Plus transaction costs.) But what if it trades at $60? Or $100? Or $10000? You're still out 100 * that amount, so in the latter case, $1 million. It's not likely to trade at that point, but it could. If you were to trade \"\"at random\"\", you'd probably run into one of those types of situations. That's because there are lots of potential trades out there that nobody expects anyone to take - but that doesn't mean that people wouldn't be happy to take your money if you offered it to them. That's the reason your 16.66 vs 83.33 argument is faulty: you're absolutely right that if there were a consistently losing line, that the consistently winning line would exist, but that requires someone that is willing to take the losing line. Trades require two actors, one on each side; if you're willing to be the patsy, there's always someone happy to take advantage of you, but you might not get a patsy.\"","title":""},{"docid":"105231","text":"The important thing to realize is, what would you do, if you didn't have the call? If you didn't have call options, but you wanted to have a position in that particular stock, you would have to actually purchase it. But, having purchased the shares, you are at risk to lose up to the entire value of them-- if the company folded or something like that. A call option reduces the potential loss, since you are at worst only out the cost of the call, and you also lose a little on the upside, since you had to pay for the call, which will certainly have some premium over buying the underlying share directly. Risk can be defined as reducing the variability of outcomes, so since calls/shorts etc. reduce potential losses and also slightly reduce potential gains, they pretty much by definition reduce risk. It's also worth noting, that when you buy a call, the seller could also be seen as hedging the risk of price decreases while also guaranteeing that they have a buyer at a certain price. So, they may be more concerned about having cash flow at the right time, while at the same time reducing the cost of the share losing in value than they are losing the potential upside if you do exercise the option. Shorts work in the same way but opposite direction to calls, and forwards and futures contracts are more about cash flow management: making sure you have the right amount of money in the right currency at the right time regardless of changes in the costs of raw materials or currencies. While either party may lose on the transaction due to price fluctuations, both parties stand to gain by being able to know exactly what they will get, and exactly what they will have to pay for it, so that certainty is worth something, and certainly better for some firms than leaving positions exposed. Of course you can use them for speculative purposes, and a good number of firms/people do but that's not really why they were invented.","title":""},{"docid":"107045","text":"Rich's answer captures the basic essence of short selling with example. I'd like to add these additional points: You typically need a specially-privileged brokerage account to perform short selling. If you didn't request short selling when you opened your account, odds are good you don't have it, and that's good because it's not something most people should ever consider doing. Short selling is an advanced trading strategy. Be sure you truly grok selling short before doing it. Consider that when buying stock (a.k.a. going long or taking a long position, in contrast to short) then your potential loss as a buyer is limited (i.e. stock goes to zero) and your potential gain unlimited (stock keeps going up, if you're lucky!) Whereas, with short selling, it's reversed: Your loss can be unlimited (stock keeps going up, if you're unlucky!) and your potential gain is limited (i.e. stock goes to zero.) The proceeds you receive from a short sale – and then some – need to stay in your account to offset the short position. Brokers require this. Typically, margin equivalent to 150% the market value of the shares sold short must be maintained in the account while the short position is open. The owner of the borrowed shares is still expecting his dividends, if any. You are responsible for covering the cost of those dividends out of your own pocket. To close or cover your short position, you initiate a buy to cover. This is simply a buy order with the intention that it will close out your matching short position. You may be forced to cover your short position before you want to and when it is to your disadvantage! Even if you have sufficient margin available to cover your short, there are cases when lenders need their shares back. If too many short sellers are forced to close out positions at the same time, they push up demand for the stock, increasing price and deepening their losses. When this happens, it's called a short squeeze. In the eyes of the public who mostly go long buying stock, short sellers are often reviled. However, some people and many short sellers believe they are providing balance to the market and preventing it sometimes from getting ahead of itself. [Disambiguation: A short sale in the stock market is not related to the real estate concept of a short sale, which is when a property owner sells his property for less than he owes the bank.] Additional references:","title":""},{"docid":"272547","text":"\"Ok, I think what you're really asking is \"\"how can I benefit from a collapse in the price of gold?\"\" :-) And that's easy. (The hard part's making that kind of call with money on the line...) The ETF GLD is entirely physical gold sitting in a bank vault. In New York, I believe. You could simply sell it short. Alternatively, you could buy a put option on it. Even more risky, you could sell a (naked) call option on it. i.e. you receive the option premium up front, and if it expires worthless you keep the money. Of course, if gold goes up, you're on the hook. (Don't do this.) (the \"\"Don't do this\"\" was added by Chris W. Rea. I agree that selling naked options is best avoided, but I'm not going to tell you what to do. What I should have done was make clear that your potential losses are unlimited when selling naked calls. For example, if you sold a single GLD naked call, and gold went to shoot to $1,000,000/oz, you'd be on the hook for around $10,000,000. An unrealistic example, perhaps, but one that's worth pondering to grasp the risk you'd be exposing yourself to with selling naked calls. -- Patches) Alternative ETFs that work the same, holding physical gold, are IAU and SGOL. With those the gold is stored in London and Switzerland, respectively, if I remember right. Gold peaked around $1900 and is now back down to the $1500s. So, is the run over, and it's all downhill from here? Or is it a simple retracement, gathering strength to push past $2000? I have no idea. And I make no recommendations.\"","title":""},{"docid":"363043","text":"\"A covered call risks the disparity between the purchase price and the potential forced or \"\"called\"\" sale price less the premium received. So buy a stock for $10.00 believing it will drop you or not rise above $14.00 for a given period of days. You sell a call for a $1.00 agreeing to sell your stock for $14.00 and your wrong...the stock rises and at 14.00 or above during the option period the person who paid you the $1.00 premium gets the stock for a net effective price of $15.00. You have a gain of 5$. Your hypothecated loss is unlimited in that the stock could go to $1mil a share. That loss is an opportunity loss you still had a modest profit in actual $. The naked call is a different beast. you get the 1.00 in commission to sell a stock you don't own but must pay for that right. so lets say you net .75 in commission per share after your sell the option. as long as the stock trades below $14.00 during the period of the option you sold your golden. It rises above the strike price you must now buy that stock at market to fill the order when the counter party choses to exercise the option which results in a REAL loss of 100% of the stocks market price less the .75 a share you made. in the scenarios a 1000 shares that for up $30.00 a share over the strike price make you $5,000 in a covered call and lose you $29,250 in a naked call.Naked calls are speculative. Covered calls are strategic.\"","title":""},{"docid":"69395","text":"\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \"\"normal\"\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \"\"bag 'o cash\"\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \"\"Paper trade\"\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \"\"not long enough\"\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \"\"risk-free-rate\"\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\"","title":""},{"docid":"232880","text":"A long put - you have a small initial cost (the option premium) but profit as the stock goes down. You have no additional risk if the shock rises, even a lot. Short a stock - you gain if the stock drops, but have unlimited risk if it rises, the call mitigates this, by capping that rising stock risk. The profit/loss graph looks similar to the long put when you hold both the short position and the long call. You might consider producing a graph or spreadsheet to compare positions. You can easily sketch put, call, long stock, short stock, and study how combinations of positions can synthetically look like other positions. Often, when a stock has no shares to short, the synthetic short can help you put your stock position in place.","title":""},{"docid":"336541","text":"\"There is unlimited risk in taking a naked call option position. The only risk in taking a covered call position is that you will be required to sell your shares for less than the going market price. I don't entirely agree with the accepted answer given here. You would not lose the amount you paid to buy the shares. Naked Call Option Suppose take a naked call option position by selling a call option. Since there is no limit on how high the price of the underlying share can go, you can be forced to either buy back the option at a very high price, or, in the case that the option is exercised, you can be force. to buy the underlying shares at a very high price and then sell them to the option holder at a very low price. For example, suppose you sell an Apple call option with a strike price of $100 at a premium of $2.50, and for this you receive a payment of $250. Now, if the price of Apple skyrockets to, say, $1000, then you would either have to buy back the option for about $90,000 = 100 x ($1000-$100), or, if the holder exercised the option, then you would need to buy 100 Apple shares at the market price of $1000 per share, costing you $100,000, and then sell them to the option holder at the strike price of $100 for $10,000 = 100 x $100. In either case, you would show a loss of $90,000 on the share transaction, which would be slightly offset by a $250 credit for the premium you received selling the call. There is no limit on the potential loss since there is no limit on how high the underlying share price can go. Covered Call Option Consider now the case of a covered call option. Since you hold the underlying shares, any loss you make on the option position would be \"\"covered\"\" by the profit you make on the underlying shares. Again, suppose you own 100 Apple shares and sell a call option with a strike price of $100 at a premium of $2.50 to earn a payment of $250. If the price of Apple skyrockets to $1000, then there are again two possible scenarios. One, you buy back the option at a premium of about $900 costing you $90,000. In order to cover this cost you would then sell your 100 Apple shares at the market price of $1000 per share to realise $100,000 = 100 x $1000. On the other hand, if your option is exercised, then you would deliver your 100 Apple shares to the option holder at the contracted strike price of $100 per share, thus receiving just $10,000 = 100 x $100. The only \"\"loss\"\" is that you have had to sell your shares for much less than the market price.\"","title":""},{"docid":"209359","text":"When you short a stock, you can lose an unlimited amount of money if the trade goes against you. If the shorted stock gaps up overnight you can lose more money than you have in your account. The best case is you make 100% if the stock goes to zero. And then you have margin fees on top of that. With long positions, it's the other way around. Your max loss is 100% and your gains are potentially unlimited.","title":""},{"docid":"12542","text":"Short selling can be a good strategy to hedge, but you have almost unlimited downside. If a stock price skyrockets, you may be forced to cover your short by the brokerage before you want to or put up more capital. A smarter strategy to hedge, that limits your potential downside is to buy puts if you think the market is going down. Your downside is limited to the total amount that you purchased the put for and no more. Another way to hedge is to SELL calls that are covered because you own the shares the calls refer to. You might do this if you thought your stock was going to go down but you didn't want to sell your shares right now. That way the only downside if the price goes up is you give up your shares at a predetermined price and you miss out on the upside, but your downside is now diminished by the premium you were paid for the option. (You'd still lose money if the shares went down since you still own them, but you got paid the option premium so that helps offset that).","title":""},{"docid":"240215","text":"\"The process of borrowing shares and selling them is called shorting a stock, or \"\"going short.\"\" When you use money to buy shares, it is called \"\"going long.\"\" In general, your strategy of going long and short in the same stock in the same amounts does not gain you anything. Let's look at your two scenarios to see why. When you start, LOOT is trading at $20 per share. You purchased 100 shares for $2000, and you borrowed and sold 100 shares for $2000. You are both long and short in the stock for $2000. At this point, you have invested $2000, and you got your $2000 back from the short proceeds. You own and owe 100 shares. Under scenario A, the price goes up to $30 per share. Your long shares have gone up in value by $1000. However, you have lost $1000 on your short shares. Your short is called, and you return your 100 shares, and have to pay interest. Under this scenario, after it is all done, you have lost whatever the interest charges are. Under scenario B, the prices goes down to $10 per share. Your long shares have lost $1000 in value. However, your short has gained $1000 in value, because you can buy the 100 shares for only $1000 and return them, and you are left with the $1000 out of the $2000 you got when you first sold the shorted shares. However, because your long shares have lost $1000, you still haven't gained anything. Here again, you have lost whatever the interest charges are. As explained in the Traders Exclusive article that @RonJohn posted in the comments, there are investors that go long and short on the same stock at the same time. However, this might be done if the investor believes that the stock will go down in a short-term time frame, but up in the long-term time frame. The investor might buy and hold for the long term, but go short for a brief time while holding the long position. However, that is not what you are suggesting. Your proposal makes no prediction on what the stock might do in different periods of time. You are only attempting to hedge your bets. And it doesn't work. A long position and a short position are opposites to each other, and no matter which way the stock moves, you'll lose the same amount with one position that you have gained in the other position. And you'll be out the interest charges from the borrowed shares every time. With your comment, you have stated that your scenario is that you believe that the stock will go up long term, but you also believe that the stock is at a short-term peak and will drop in the near future. This, however, doesn't really change things much. Let's look again at your possible scenarios. You believe that the stock is a long-term buy, but for some reason you are guessing that the stock will drop in the short-term. Under scenario A, you were incorrect about your short-term guess. And, although you might have been correct about the long-term prospects, you have missed this gain. You are out the interest charges, and if you still think the stock is headed up over the long term, you'll need to buy back in at a higher price. Under scenario B, it turns out that you were correct about the short-term drop. You pocket some cash, but there is no guarantee that the stock will rise anytime soon. Your investment has lost value, and the gain that you made with your short is still tied up in stocks that are currently down. Your strategy does prevent the possibility of the unlimited loss inherent in the short. However, it also prevents the possibility of the unlimited gain inherent in the long position. And this is a shame, since you fundamentally believe that the stock is undervalued and is headed up. You are sabotaging your long-term gains for a chance at a small short-term gain.\"","title":""},{"docid":"171819","text":"\"There some specific circumstances when you would have a long-term gain. Option 1: If you meet all of these conditions: Then you've got a long-term gain on the stock. The premium on the option gets rolled into the capital gain on the stock and is not taxed separately. From the IRS: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010630 Option 2: If you didn't hold the underlying and the exercise of the call that you wrote resulted in a short position, you might also be able to get to a long-term gain by buying the underlying while keeping your short position open and then \"\"crossing\"\" them to close both positions after one year. (In other words, don't \"\"buy to cover\"\" just \"\"buy\"\" so that your account shows both a long and a short position in the same security. Your broker probably allows this, but if not you, could buy in a different account than the one with the short position.) That would get you to this rule: As a general rule, you determine whether you have short-term or long-term capital gain or loss on a short sale by the amount of time you actually hold the property eventually delivered to the lender to close the short sale. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010586 Option 1 is probably reasonably common. Option 2, I would guess, is uncommon and likely not worthwhile. I do not think that the wash sale rules can help string along options from expiration to expiration though. Option 1 has some elements of what you wrote in italics (I find that paragraph a bit confusing), but the wash sale does not help you out.\"","title":""},{"docid":"521644","text":"Buying the underlying asset will not completely hedge you, only what lies above 155 dollars (strike + price of option) - you still have the risk of losing everything but 5. You have a maximum earnings-potential of 55 dollars (strike of 150 - investment of 100 + option of 5) but you have a risk of losing 95$ (investment of 100 - option of 5). Say chance of winning everything or losing everything is 50-50, your expected outcome is 0.5 x -95 + 0.5 x 55 = -20$. Is this a great investment? Sure you don't know your odds - otherwise it would be a sure thing. You shouldn't sell the call option if you do not expect prices to go up - but in that case - why not just buy the underlying alone? Speculating in options is a dangerous game with infinite earnings-potential but also infinite loss potential. (Consider selling a call option and not buying the underlying and the price goes from 100 to 1.000.000.000).","title":""},{"docid":"22916","text":"On expiry, with the underlying share price at $46, we have : You ask : How come they substract 600-100. Why ? Because you have sold the $45 call to open you position, you must now buy it back to close your position. This will cost you $100, so you are debited for $100 and this debit is being represented as a negative (subtracted); i.e., -$100 Because you have purchased the $40 call to open your position, you must now sell it to close your position. Upon selling this option you will receive $600, so you are credited with $600 and this credit is represented as a positive (added) ; i.e., +$600. Therefore, upon settlement, closing your position will get you $600-$100 = $500. This is the first point you are questioning. (However, you should also note that this is the value of the spread at settlement and it does not include the costs of opening the spread position, which are given as $200, so you net profit is $500-$200 = $300.) You then comment : I know I am selling 45 Call that means : As a writer: I want stock price to go down or stay at strike. As a buyer: I want stock price to go up. Here, note that for every penny that the underlying share price rises above $45, the money you will pay to buy back your short $45 call option will be offset by the money you will receive by selling the long $40 call option. Your $40 call option is covering the losses on your short $45 call option. No matter how high the underlying price settles above $45, you will receive the same $500 net credit on settlement. For example, if the underlying price settles at $50, then you will receive a credit of $1000 for selling your $40 call, but you will incur a debit of $500 against for buying back your short $45 call. The net being $500 = $1000-$500. This point is made in response to your comments posted under Dr. Jones answer.","title":""},{"docid":"507828","text":"\"I'm adding to @Dilip's basic answer, to cover the additional points in your question. I'll assume you are referring to publicly traded stock options, such as those found on the CBOE, and not an option contract entered into privately between two specific counterparties (e.g. as in an employer stock option plan). Since you are not obligated to exercise a call option you purchased on the market, you don't need to maintain funds on account for possible exercising. You could instead let the option expire, or resell the option, neither of which requires funds available for purchase of the underlying shares. However, should you actually choose to exercise the call option (and usually this is done close to expiration, if at all), you will be required to fund your account much like if you bought the underlying shares in the first place. Call your broker to determine the exact rules and timing for when they need the money for a call-option exercise. And to expand on the idea of \"\"cancelling\"\" an option you purchased: No, you cannot \"\"cancel\"\" an option contract, per se. But, you are permitted to sell the call option to somebody else willing to buy, via the market. When you sell your call option, you'll either make or lose money on the sale – depending on the price of the underlying shares at the time (are they in- or out- of the money?), volatility in the market, and remaining time value. Once you sell, you're back to \"\"no position\"\". That's not the same as \"\"cancelled\"\", but you are out of the trade, whether at profit or loss. Furthermore, the option writer (i.e. the seller who \"\"sold to open\"\" a position, in writing the call in the first place) is also not permitted to cancel the option he wrote. However, the option writer is permitted to close out the original short position by simply buying back a matching call option on the market. Again, this would occur at either profit or loss based on market prices at the time. This second kind of buy order – i.e. made by someone who initially wrote a call option – is called a \"\"buy to close\"\", meaning the purchase of an offsetting position. (The other kind of buy is the \"\"buy to open\"\".) Then, consider: Since an option buyer is free to re-sell the option purchased, and since an option writer (who \"\"sold to open\"\" the new contract) is also free to buy back an offsetting option, a process known as clearing is required to match remaining buyers exercising the call options held with the remaining option writers having open short positions for the contract. For CBOE options, this clearing is performed by the Options Clearing Corporation. Here's how it works (see here): What is the OCC? The Options Clearing Corporation is the sole issuer of all securities options listed at the CBOE, four other U.S. stock exchanges and the National Association of Securities Dealers, Inc. (NASD), and is the entity through which all CBOE option transactions are ultimately cleared. As the issuer of all options, OCC essentially takes the opposite side of every option traded. Because OCC basically becomes the buyer for every seller and the seller for every buyer, it allows options traders to buy and sell in a secondary market without having to find the original opposite party. [...] [emphasis above is mine] When a call option writer must deliver shares to a call option buyer exercising a call, it's called assignment. (I have been assigned before, and it isn't pleasant to see a position called away that otherwise would have been very profitable if the call weren't written in the first place!) Also, re: \"\"I know my counter party cannot sell his shares\"\" ... that's not strictly true. You are thinking of a covered call. But, an option writer doesn't necessarily need to own the underlying shares. Look up Naked call (Wikipedia). Naked calls aren't frequently undertaken because a naked call \"\"is one of the riskiest options strategies because it carries unlimited risk\"\". The average individual trader isn't usually permitted by their broker to enter such an order, but there are market participants who can do such a trade. Finally, you can learn more about options at The Options Industry Council (OIC).\"","title":""},{"docid":"388754","text":"\"The question you are asking concerns the exercise of a short option position. The other replies do not appear to address this situation. Suppose that Apple is trading at $96 and you sell a put option with a strike price of $95 for some future delivery date - say August 2016. The option contract is for 100 shares and you sell the contract for a premium of $3.20. When you sell the option your account will be credited with the premium and debited with the broker commission. The premium you receive will be $320 = 100 x $3.20. The commission you pay will depend on you broker. Now suppose that the price of Apple drops to $90 and your option is exercised, either on expiry or prior to expiry. Then you would be obliged to take delivery of 100 Apple shares at the contracted option strike price of $95 costing you $9,500 plus broker commission. If you immediately sell the Apple shares you have purchased under your contract obligations, then assuming you sell the shares at the current market price of $90 you would realise a loss of $500 ( = 100x($95-$90) )plus commission. Since you received a premium of $320 when you sold the put option, your net loss would be $500-$320 = $180 plus any commissions paid to your broker. Now let's look at the case of selling a call option. Again assume that the price of Apple is $96 and you sell a call option for 100 shares with a strike price of $97 for a premium of $3.60. The premium you receive would be $360 = 100 x $3.60. You would also be debited for commission by your broker. Now suppose that the price of Apple shares rises to $101 and your option is exercised. Then you would be obliged to deliver 100 Apple shares to the party exercising the option at the contracted strike price of $97. If you did not own the shares to effect delivery, then you would need to purchase those shares in the market at the current market price of $101, and then sell them to the party exercising the option at the strike price of $97. This would realise an immediate loss of $400 = 100 x ($101-$97) plus any commission payable. If you did own the shares, then you would simply deliver them and possibly pay some commission or a delivery fee to your broker. Since you received $360 when you sold the option, your net loss would be $40 = $400-$360 plus any commission and fees payable to the broker. It is important to understand that in addition to these accounting items, short option positions carry with them a \"\"margin\"\" requirement. You will need to maintain a margin deposit to show \"\"good faith\"\" so long as the short option position is open. If the option you have sold moves against you, then you will be called upon to put up extra margin to cover any potential losses.\"","title":""},{"docid":"578022","text":"\"You owe no tax on the option transaction in 2015 in this case. How you ultimately get taxed depends on how you dispose of the position. If it expires, then you will have a short-term capital gain on the option position at expiration. If it is exercised, then the option is \"\"gone\"\" for tax purposes and your basis in the underlying is adjusted. From IRS Publication 550: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. In your case, this will be a long-term capital gain. For completeness, if you buy to cover the option back from the market before expiration or exercise, then it is also a short-term capital gain. Also, keep in mind that this all assumes that this covered call is \"\"qualified\"\" so that it does not count as a straddle. You can find more about that in Pub 550. https://www.irs.gov/publications/p550/ch04.html#en_US_2014_publink100010630 All of this is for US tax purposes.\"","title":""},{"docid":"557356","text":"\"There are two reasons why most options aren't exercised. The first is obvious, and the second, less so. The obvious: An option that's practically worthless doesn't get exercised. Options that reach expiry and remain unexercised are almost always worthless bets that simply didn't pay off. This includes calls with strikes above the current underlying price, and puts with strikes below it. A heck of a lot of options. If an option with value was somehow left to expire, it was probably a mistake, or else the transaction costs outweighed the value remaining; not quite worthless, but not \"\"worth it\"\" either. The less obvious: An option with value can be cancelled any time before expiration. A trader that buys an option may at some point show a gain sooner than anticipated, or a loss in excess of his tolerance. If a gain, he may want to sell before expiry to realize the gain sooner. Similarly, if a loss, he may want to take the loss sooner. In both cases, his capital is freed up and he can take another position. And — this is the key part — the other end matched up with that option sale is often a buyer that had created (written) exactly such an option contract in the first place – the option writer – and who is looking to get out of his position. Option writers are the traders responsible, in the first place, for creating options and increasing the \"\"open interest.\"\" Anybody with the right kind and level of options trading account can do this. A trader that writes an option does so by instructing his broker to \"\"sell to open\"\" a new instance of the option. The trader then has a short position (negative quantity) in that option, and all the while may be subject to the obligations that match the option's exercise rights. The only way for the option writer to get out of that short position and its obligations are these: Not by choice: To get assigned. That is to say: a buyer exercised the option. The writer has to fulfill his obligation by delivering the underlying (if a call) to the option holder, or buying the underlying (if a put) from the option holder. Not by choice: The option expires worthless. This is the ideal scenario for a writer because 100% of the premium received (less transaction costs) is profit. By choice: The writer is free to buy back exactly the same kind of option before expiry using a \"\"buy to close\"\" order with their broker. Once the option has been purchased with a \"\"buy to close\"\", it eliminates the short position and obligation. The option is cancelled. The open interest declines. Options thus cancelled just don't live long enough to either expire or be exercised.\"","title":""},{"docid":"268802","text":"Without commenting on your view of the TV market: Let's have a look at the main ways to get negative exposure: 1.Short the stocks Pros: Relatively Easy Cons: Interest rate, costs of shorting, linear bet 2.Options a. Write Calls b. Buy puts Pros: Convexity, leveraged, relatively cheap Cons: Zero Sum bet that expires with time, theta 3.Short Stock, Buy Puts, Write Calls Short X Units of each stock, Write calls on them , use call premiums to finance puts. Pros: 3x the power!, high kickout Cons: Unlimited pain","title":""},{"docid":"393418","text":"By buying the call option, you are getting the benefit of purchasing the underlying shares (that is, if the shares go up in value, you make money), but transferring the risk of the shares reducing in value. This is more apparent when you are using the option to offset an explicit risk that you hold. For example, if you have a short position, you are at unlimited risk of the position going up in value. You could decide you only want to take the risk that it might rise to $X. In that case, you could buy a call option with $X strike price. Then you have transferred the risk that the position goes over $X to the counterpart, since, even if the shares are trading at $X+$Y you can close out the short position by purchasing the shares at $X, while the option counterpart will lose $Y.","title":""},{"docid":"520098","text":"\"A derivative contract can be an option, and you can take a short (sell) position , much the same way you would in a stock. When BUYING options you risk only the money you put in. However when selling naked(you don't have the securities or cash to cover all potential losses) options, you are borrowing. Brokers force you to maintain a required amount of cash called, a maintenance requirement. When selling naked calls - theoretically you are able to lose an INFINITE amount of money, so in order to sell this type of options you have to maintain a certain level of cash in your account. If you fail to maintain this level you will enter into whats often referred to as a \"\"margin-call\"\". And yes they will call your phone and tell you :). Your broker has the right to liquidate your positions in order to meet requirements. PS: From experience my broker has never liquidated any of my holdings, but then again I've never been in a margin call for longer then a few days and never with a severe amount. The margin requirement for investors is regulated and brokers follow these regulations.\"","title":""},{"docid":"314478","text":"\"And what exactly do I profit from the short? I understand it is the difference in the value of the stock. So if my initial investment was $4000 (200 * $20) and I bought it at $3800 (200 * $19) I profit from the difference, which is $200. Do I also receive back the extra $2000 I gave the bank to perform the trade? Either this is extremely poorly worded or you misunderstand the mechanics of a short position. When you open a short position, your are expecting that the stock will decline from here. In a short position you are borrowing shares you don't own and selling them. If the price goes down you get to buy the same shares back for less money and return them to the person you borrowed from. Your profit is the delta between the original sell price and the new lower buy price (less commissions and fees/interest). Opening and closing a short position is two trades, a sell then a buy. Just like a long trade there is no maximum holding period. If you place your order to sell (short) 200 shares at $19, your initial investment is $3,800. In order to open your $3,800 short position your broker may require your account to have at least $5,700 (according to the 1.5 ratio in your question). It's not advisable to open a short position this close to the ratio requirement. Most brokers require a buffer in your account in case the stock goes up, because in a short trade if the stock goes up you're losing money. If the stock goes up such that you've exhausted your buffer you'll receive what's known as a \"\"margin call\"\" where your broker either requires you to wire in more money or sell part or all of your position at a loss to avoid further losses. And remember, you may be charged interest on the value of the shares you're borrowing. When you hold a position long your maximum loss is the money you put in; a position can only fall to zero (though you may owe interest or other fees if you're trading on margin). When you hold a position short your maximum loss is unlimited; there's no limit to how high the value of something can go. There are less risky ways to make short trades by using put options, but you should ensure that you have a firm grasp on what's happening before you use real money. The timing of the trades and execution of the trades is no different than when you take a plain vanilla long position. You place your order, either market or limit or whatever, and it executes when your trade criteria occurs.\"","title":""},{"docid":"242663","text":"\"Some thoughts on your questions in order, Duration: You might want to look at the longest-dated option (often a \"\"LEAP\"\"), for a couple reasons. One is that transaction costs (spread plus commission, especially spread) are killer on options, so a longer option means fewer transactions, since you don't have to keep rolling the option. Two is that any fundamentals-based views on stocks might tend to require 3-5 years to (relatively) reliably work out, so if you're a fundamental investor, a 3-6 month option isn't great. Over 3-6 months, momentum, short-term news, short squeezes, etc. can often dominate fundamentals in determining the price. One exception is if you just want to hedge a short-term event, such as a pending announcement on drug approval or something, and then you would buy the shortest option that still expires after the event; but options are usually super-expensive when they span an event like this. Strike: Strike price on a long option can be thought of as a tradeoff between the max loss and minimizing \"\"insurance costs.\"\" That is, if you buy a deeply in-the-money put or call, the time value will be minimal and thus you aren't paying so much for \"\"insurance,\"\" but you may have 1/3 or 1/2 of the value of the underlying tied up in the option and subject to loss. If you buy a put or call \"\"at the money,\"\" then you might have only say 10% of the value of the underlying tied up in the option and subject to loss, but almost the whole 10% may be time value (insurance cost), so you are losing 10% if the underlying stock price stays flat. I think of the deep in-the-money options as similar to buying stocks on margin (but the \"\"implied\"\" interest costs may be less than consumer margin borrowing rates, and for long options you can't get a margin call). The at-the-money options are more like buying insurance, and it's expensive. The commissions and spreads add significant cost, on top of the natural time value cost of the option. The annual costs would generally exceed the long-run average return on a diversified stock fund, which is daunting. Undervalued/overvalued options, pt. 1: First thing is to be sure the options prices on a given underlying make sense at all; there are things that \"\"should\"\" hold, for example a synthetic long or short should match up to an actual long or short. These kinds of rules can break, for example on LinkedIn (LNKD) after its IPO, when shorting was not permitted, the synthetic long was quite a bit cheaper than a real long. Usually though this happens because the arbitrage is not practical. For example on LNKD, the shares to short weren't really available, so people doing synthetic shorts with options were driving up the price of the synthetic short and down the price of the synthetic long. If you did actually want to be long the stock, then the synthetic long was a great deal. However, a riskless arbitrage (buy synthetic long, short the stock) was not possible, and that's why the prices were messed up. Another basic relationship that should hold is put-call parity: http://en.wikipedia.org/wiki/Put%E2%80%93call_parity Undervalued/overvalued options, pt. 2: Assuming the relationship to the underlying is sane (synthetic positions equivalent to actual positions) then the valuation of the option could focus on volatility. That is, the time value of the option implies the stock will move a certain amount. If the time value is high and you think the stock won't move much, you might short the option, while if the time value is low and you think the stock will move a lot, you might buy the option. You can get implied volatility from your broker perhaps, or Morningstar.com for example has a bunch of data on option prices and the implied components of the price model. I don't know how useful this really is though. The spreads on options are so wide that making money on predicting volatility better than the market is pretty darn hard. That is, the spread probably exceeds the amount of the mispricing. The price of the underlying is more important to the value of an option than the assumed volatility. How many contracts: Each contract is 100 shares, so you just match that up. If you want to hedge 100 shares, buy one contract. To get the notional value of the underlying multiply by 100. So say you buy a call for $30, and the stock is trading at $100, then you have a call on 100 shares which are currently priced at $10,000 and the option will cost $30*100=3,000. You are leveraged about 3 to 1. (This points to an issue with options for individual investors, which is that one contract is a pretty large notional value relative to most portfolios.)\"","title":""},{"docid":"326599","text":"Gold's valuation is so stratospheric right now that I wonder if negative numbers (as in, you should short it) are acceptable in the short run. In the long run I'd say the answer is zero. The problem with gold is that its only major fundamental value is for making jewelry and the vast majority is just being hoarded in ways that can only be justified by the Greater Fool Theory. In the long run gold shouldn't return more than inflation because a pile of gold creates no new wealth like the capital that stocks are a claim on and doesn't allow others to create new wealth like money lent via bonds. It's also not an important and increasingly scarce resource for wealth creation in the global economy like oil and other more useful commodities are. I've halfway-thought about taking a short position in gold, though I haven't taken any position, short or long, in gold for the following reasons: Straight up short-selling of a gold ETF is too risky for me, given its potential for unlimited losses. Some other short strategy like an inverse ETF or put options is also risky, though less so, and ties up a lot of capital. While I strongly believe such an investment would be profitable, I think the things that will likely rise when the flight-to-safety is over and gold comes back to Earth (mainly stocks, especially in the more beaten-down sectors of the economy) will be equally profitable with less risk than taking one of these positions in gold.","title":""},{"docid":"142110","text":"\"He didn't sell in the \"\"normal\"\" way that most people think of when they hear the term \"\"sell.\"\" He engaged in a (perfectly legitimate) technique known as short selling, in which he borrows shares from his broker and sells them immediately. He's betting that the price of the stock will drop so he can buy them back at a lower price to return the borrowed shares back to his broker. He gets to pocket the difference. He had about $37,000 of cash in his account. Since he borrowed ~8400 shares and sold them immediately at $2/share, he got $16,800 in cash and owed his broker 8400 shares. So, his net purchasing power at the time of the short sale was $37,000 + $16,800 - 4800 shares * $2/share. As the price of the stock changes, his purchasing power will change according to this equation. He's allowed to continue to borrow these 8400 shares as long as his purchasing power remains above 0. That is, the broker requires him to have enough cash on hand to buy back all of his borrowed shares at any given moment. If his purchasing power ever goes negative, he'll be subject to a margin call: the broker will make him either deposit cash into his account or close his positions (sell long positions or buy back short positions) until it's positive again. The stock jumped up to $13.85 the next morning before the market opened (during \"\"before-hours\"\" trading). His purchasing power at that time was $37,000 + $16,800 - 8400 shares * $13.85/share = -$62,540. Since his purchasing power was negative, he was subject to a margin call. By the time he got out, he had to pay $17.50/share to buy back the 8400 shares that he borrowed, making his purchasing power -$101,600. This $101,600 was money that he borrowed from his broker to buy back the shares to fulfill his margin call. His huge loss was from borrowing shares from his broker. Note that his maximum potential loss is unlimited, since there is no limit to how much a stock can grow. Evidently, he failed to grasp the most important concept of short selling, which is that he's borrowing stock from his broker and he's obligated to give that stock back whenever his broker wants, no matter what it costs him to fulfill that obligation.\"","title":""},{"docid":"16747","text":"\"The previous answers make valid points regarding the risks, and why you can't reasonably compare trading for profit/loss to a roll of the die. This answer looks at the math instead. Your assumption: I have an equal probability to make a profit or a loss. Is incorrect, for the reasons stated in other answers. However, the answer to your question: Can I also assume that probabilistically speaking, a trader cannot do worst than random? Is \"\"yes\"\". But only because the question is flawed. Consequently it's throwing people in all directions with their answers. But quite simply, in a truly random environment the worst case scenario, no matter how improbable, is that you lose over and over again until you have nothing left. This can happen in sequential rolls of the dice AND in trading securities/bonds/whatever. You could guess wrong for every roll of the die AND all of your stock picks could become worthless. Both outcomes result in $0 (assuming you do not gamble with credit). Tell me, which $0 is \"\"worse\"\"? Given the infinite number of plays that \"\"random\"\" implies, the chance of losing your entire bankroll exists in both scenarios, and that is enough by itself to make neither option \"\"worse\"\" than the other. Of course, the opposite is also true. You could only pick winners, with an unlimited upside potential, but again that could happen with either dice rolls or stock picks. It's just highly improbable. my chances cannot be worse than random and if my trading system has an edge that is greater than the percentage of the transaction that is transaction cost, then I am probabilistically likely to make a profit? Nope. This is where it all falls apart. Just because your chances of losing it all are similarly improbable, does not make you more likely to win with one method or the other. Regression to the mean, when given infinite, truly random outcomes, makes it impossible to \"\"have an edge\"\". Also, \"\"probabilistically\"\" isn't a word, but \"\"probably\"\" is.\"","title":""},{"docid":"147361","text":"\"Yes, long calls, and that's a good point. Let's see... if I bought one contract at the Bid price above... $97.13 at expiry of $96.43 option = out of the money =- option price(x100) = $113 loss. $97.13 at expiry of $97.00 option = out of the money =- option price(x100) = $77 loss. $97.13 at expiry of $97.14 option = in the money by 1-cent=$1/contract profit - option price(x100) = $1-$58 = $57 loss The higher strike prices have much lower losses if they expire with the underlying stock at- or near-the-money. So, they carry \"\"gentler\"\" downside potential, and are priced much higher to reflect that \"\"controlled\"\" risk potential. That makes sense. Thanks.\"","title":""},{"docid":"485760","text":"\"Do you want to do it pre or post correction? If you're bearish on the market the obvious thing to do is short an index. I would say this is kind of dumb. The main problem is that it may take months or years for the market to crash, and by then it will have gone up so much that even the crash doesn't bring you profit, and you're paying borrowing fees meanwhile as well. You need to watch the portfolio also, when you short sell you'll get a bunch of cash, which you most likely will want to invest, but once you invest it, the market can spike and pummel your short position, resulting in negative remaining cash (since you already spent it). At that point you get a margin call from your broker. If you check your account regularly, not a big deal, but bad things can happen if you treat it as a fire and forget strategy. These days they have inverse funds so you don't have to borrow anything. The fund manager borrows for you. I'd say those are much better. The less cumbersome choice is to simply sell call options on the index or buy puts. These are even cash options, so when you exercise you get/lose money, not shares. You can even arrange them so that your potential loss is capped. (but honestly, same goes for shorts - it's called a stop loss) You could also wait for the correction and buy the dip. Less worrying about shorts and such, but of course the issue is timing the crash. Usually the crashes are very quick, and there are several \"\"pre-crashes\"\" that look like it bottomed out but then it crashes more. So actually very difficult thing to tell. You have to know either exactly when the correction will be, or exactly what the price floor is (and set a limit buy). Hope your crystal ball works! Yet another choice is finding asset classes uncorrelated or even anticorrelated with the broader market. For instance some emerging markets (developing countries), some sectors, individual stocks that are not inflated, bonds, gold and so on can have these characteristics where if S&P goes down they go up. Buying those may be a safer approach since at least you are still holding a fundamentally valuable thing even if your thesis flops, meanwhile shorts and puts and the like are purely speculative.\"","title":""}],"string":"[\n {\n \"docid\": \"140371\",\n \"text\": \"To expand on the comment made by @NateEldredge, you're looking to take a short position. A short position essentially functions as follows: Here's the rub: you have unlimited loss potential. Maybe you borrow a share and sell it at $10. Maybe in a month you still haven't closed the position and now the share is trading at $1,000. The share lender comes calling for their share and you have to close the position at $1,000 for a loss of $990. Now what if it was $1,000,000 per share, etc. To avoid this unlimited loss risk, you can instead buy a put option contract. In this situation you buy a contract that will expire at some point in the future for the right to sell a share of stock for $x. You get to put that share on to someone else. If the underlying stock price were to instead rise above the put's exercise price, the put will expire worthless — but your loss is limited to the premium paid to acquire the put option contract. There are all sorts of advanced options trades sometimes including taking a short or long position in a security. It's generally not advisable to undertake these sorts of trades until you're very comfortable with the mechanics of the contracts. It's definitely not advisable to take an unhedged short position, either by borrowing someone else's share(s) to sell or selling an option (when you sell the option you take the risk), because of the unlimited loss potential described above.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"118633\",\n \"text\": \"\\\"There are three ways to do this. So far the answers posted have only mentioned two. The three ways are: Selling short means that you borrow stock from your broker and sell it with the intent of buying it back later to repay the loan. As others have noted, this has unlimited potential losses and limited potential gains. Your profit or loss will go $1:$1 with the movement of the price of the stock. Buying a put option gives you the right to sell the stock at a later date on a price that you choose now. You pay a premium to have this right, and if the stock moves against you, you won't exercise your option and will lose the premium. Options move non-linearly with the price of the stock, especially when the expiration is far in the future. They probably are not for a beginner, although they can be powerful if used properly. The third option is a synthetic short position. You form this by simultaneously buying a put option and selling short a call option, both at the same strike price. This has a risk profile that is very much like the selling the stock short, but you can accomplish it entirely with stock options. Because you're both buying an selling, in theory you might even collect a small net premium when you open. You might ask why you'd do this given that you could just sell the stock short, which certainly seems simpler. One reason is that it is not always possible to sell the stock short. Recall that you have to borrow shares from your broker to sell short. When many people want to short the stock, brokers will run out of shares to loan. The stock is then said to be \\\"\\\"hard to borrow,\\\"\\\" which effectively prevents further short selling of the stock. In this case the synthetic short is still potentially possible.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"307518\",\n \"text\": \"\\\"The stock market is not a zero-sum game. Some parts are (forex, some option trading), but plain old stock trading is not zero sum. That is to say, if you were to invest \\\"\\\"at random\\\"\\\", you would on average make money. That's because the market as a whole makes money - it goes up over time (6-10% annually, averaged over time). That's because you're not just gambling when you buy a stock; you're actually contributing money to a company (directly or indirectly), which it uses to fund activities that (on average) make money. When you buy Caterpillar stock, you're indirectly funding Caterpillar building tractors, which they then sell for a profit, and thus your stock appreciates in value. While not every company makes a profit, and thus not every stock appreciates in true value, the average one does. To some extent, buying index funds is pretty close to \\\"\\\"investing at random\\\"\\\". It has a far lower risk quotient, of course, since you're not buying a few stocks at random but instead are buying all stocks in an index; but buying stocks from the S&P 500 at random would on average give the same return as VOO (with way more volatility). So for one, you definitely could do worse than 50/50; if you simply sold the market short (sold random stocks short), you would lose money over time on average, above and beyond the transaction cost, since the market will go up over time on average. Secondly, there is the consideration of limited and unlimited gains or losses. Some trades, specifically some option trades, have limited potential gains, and unlimited potential losses. Take for example, a simple call option. If you sell a naked call option - meaning you sell a call option but don't own the stock - for $100, at a strike price of $20, for 100 shares, you make money as long as the price of that stock is under $21. You have a potential to make $100, because that's what you sold it for; if the price is under $20, it's not exercised, and you just get that $100, free. But, on the other hand, if the stock goes up, you could potentially be out any amount of money. If the stock trades at $24, you're out $400-100 = $300, right? (Plus transaction costs.) But what if it trades at $60? Or $100? Or $10000? You're still out 100 * that amount, so in the latter case, $1 million. It's not likely to trade at that point, but it could. If you were to trade \\\"\\\"at random\\\"\\\", you'd probably run into one of those types of situations. That's because there are lots of potential trades out there that nobody expects anyone to take - but that doesn't mean that people wouldn't be happy to take your money if you offered it to them. That's the reason your 16.66 vs 83.33 argument is faulty: you're absolutely right that if there were a consistently losing line, that the consistently winning line would exist, but that requires someone that is willing to take the losing line. Trades require two actors, one on each side; if you're willing to be the patsy, there's always someone happy to take advantage of you, but you might not get a patsy.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"105231\",\n \"text\": \"The important thing to realize is, what would you do, if you didn't have the call? If you didn't have call options, but you wanted to have a position in that particular stock, you would have to actually purchase it. But, having purchased the shares, you are at risk to lose up to the entire value of them-- if the company folded or something like that. A call option reduces the potential loss, since you are at worst only out the cost of the call, and you also lose a little on the upside, since you had to pay for the call, which will certainly have some premium over buying the underlying share directly. Risk can be defined as reducing the variability of outcomes, so since calls/shorts etc. reduce potential losses and also slightly reduce potential gains, they pretty much by definition reduce risk. It's also worth noting, that when you buy a call, the seller could also be seen as hedging the risk of price decreases while also guaranteeing that they have a buyer at a certain price. So, they may be more concerned about having cash flow at the right time, while at the same time reducing the cost of the share losing in value than they are losing the potential upside if you do exercise the option. Shorts work in the same way but opposite direction to calls, and forwards and futures contracts are more about cash flow management: making sure you have the right amount of money in the right currency at the right time regardless of changes in the costs of raw materials or currencies. While either party may lose on the transaction due to price fluctuations, both parties stand to gain by being able to know exactly what they will get, and exactly what they will have to pay for it, so that certainty is worth something, and certainly better for some firms than leaving positions exposed. Of course you can use them for speculative purposes, and a good number of firms/people do but that's not really why they were invented.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"107045\",\n \"text\": \"Rich's answer captures the basic essence of short selling with example. I'd like to add these additional points: You typically need a specially-privileged brokerage account to perform short selling. If you didn't request short selling when you opened your account, odds are good you don't have it, and that's good because it's not something most people should ever consider doing. Short selling is an advanced trading strategy. Be sure you truly grok selling short before doing it. Consider that when buying stock (a.k.a. going long or taking a long position, in contrast to short) then your potential loss as a buyer is limited (i.e. stock goes to zero) and your potential gain unlimited (stock keeps going up, if you're lucky!) Whereas, with short selling, it's reversed: Your loss can be unlimited (stock keeps going up, if you're unlucky!) and your potential gain is limited (i.e. stock goes to zero.) The proceeds you receive from a short sale – and then some – need to stay in your account to offset the short position. Brokers require this. Typically, margin equivalent to 150% the market value of the shares sold short must be maintained in the account while the short position is open. The owner of the borrowed shares is still expecting his dividends, if any. You are responsible for covering the cost of those dividends out of your own pocket. To close or cover your short position, you initiate a buy to cover. This is simply a buy order with the intention that it will close out your matching short position. You may be forced to cover your short position before you want to and when it is to your disadvantage! Even if you have sufficient margin available to cover your short, there are cases when lenders need their shares back. If too many short sellers are forced to close out positions at the same time, they push up demand for the stock, increasing price and deepening their losses. When this happens, it's called a short squeeze. In the eyes of the public who mostly go long buying stock, short sellers are often reviled. However, some people and many short sellers believe they are providing balance to the market and preventing it sometimes from getting ahead of itself. [Disambiguation: A short sale in the stock market is not related to the real estate concept of a short sale, which is when a property owner sells his property for less than he owes the bank.] Additional references:\",\n \"title\": \"\"\n },\n {\n \"docid\": \"272547\",\n \"text\": \"\\\"Ok, I think what you're really asking is \\\"\\\"how can I benefit from a collapse in the price of gold?\\\"\\\" :-) And that's easy. (The hard part's making that kind of call with money on the line...) The ETF GLD is entirely physical gold sitting in a bank vault. In New York, I believe. You could simply sell it short. Alternatively, you could buy a put option on it. Even more risky, you could sell a (naked) call option on it. i.e. you receive the option premium up front, and if it expires worthless you keep the money. Of course, if gold goes up, you're on the hook. (Don't do this.) (the \\\"\\\"Don't do this\\\"\\\" was added by Chris W. Rea. I agree that selling naked options is best avoided, but I'm not going to tell you what to do. What I should have done was make clear that your potential losses are unlimited when selling naked calls. For example, if you sold a single GLD naked call, and gold went to shoot to $1,000,000/oz, you'd be on the hook for around $10,000,000. An unrealistic example, perhaps, but one that's worth pondering to grasp the risk you'd be exposing yourself to with selling naked calls. -- Patches) Alternative ETFs that work the same, holding physical gold, are IAU and SGOL. With those the gold is stored in London and Switzerland, respectively, if I remember right. Gold peaked around $1900 and is now back down to the $1500s. So, is the run over, and it's all downhill from here? Or is it a simple retracement, gathering strength to push past $2000? I have no idea. And I make no recommendations.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"363043\",\n \"text\": \"\\\"A covered call risks the disparity between the purchase price and the potential forced or \\\"\\\"called\\\"\\\" sale price less the premium received. So buy a stock for $10.00 believing it will drop you or not rise above $14.00 for a given period of days. You sell a call for a $1.00 agreeing to sell your stock for $14.00 and your wrong...the stock rises and at 14.00 or above during the option period the person who paid you the $1.00 premium gets the stock for a net effective price of $15.00. You have a gain of 5$. Your hypothecated loss is unlimited in that the stock could go to $1mil a share. That loss is an opportunity loss you still had a modest profit in actual $. The naked call is a different beast. you get the 1.00 in commission to sell a stock you don't own but must pay for that right. so lets say you net .75 in commission per share after your sell the option. as long as the stock trades below $14.00 during the period of the option you sold your golden. It rises above the strike price you must now buy that stock at market to fill the order when the counter party choses to exercise the option which results in a REAL loss of 100% of the stocks market price less the .75 a share you made. in the scenarios a 1000 shares that for up $30.00 a share over the strike price make you $5,000 in a covered call and lose you $29,250 in a naked call.Naked calls are speculative. Covered calls are strategic.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"69395\",\n \"text\": \"\\\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \\\"\\\"normal\\\"\\\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \\\"\\\"bag 'o cash\\\"\\\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \\\"\\\"Paper trade\\\"\\\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \\\"\\\"not long enough\\\"\\\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \\\"\\\"risk-free-rate\\\"\\\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"232880\",\n \"text\": \"A long put - you have a small initial cost (the option premium) but profit as the stock goes down. You have no additional risk if the shock rises, even a lot. Short a stock - you gain if the stock drops, but have unlimited risk if it rises, the call mitigates this, by capping that rising stock risk. The profit/loss graph looks similar to the long put when you hold both the short position and the long call. You might consider producing a graph or spreadsheet to compare positions. You can easily sketch put, call, long stock, short stock, and study how combinations of positions can synthetically look like other positions. Often, when a stock has no shares to short, the synthetic short can help you put your stock position in place.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"336541\",\n \"text\": \"\\\"There is unlimited risk in taking a naked call option position. The only risk in taking a covered call position is that you will be required to sell your shares for less than the going market price. I don't entirely agree with the accepted answer given here. You would not lose the amount you paid to buy the shares. Naked Call Option Suppose take a naked call option position by selling a call option. Since there is no limit on how high the price of the underlying share can go, you can be forced to either buy back the option at a very high price, or, in the case that the option is exercised, you can be force. to buy the underlying shares at a very high price and then sell them to the option holder at a very low price. For example, suppose you sell an Apple call option with a strike price of $100 at a premium of $2.50, and for this you receive a payment of $250. Now, if the price of Apple skyrockets to, say, $1000, then you would either have to buy back the option for about $90,000 = 100 x ($1000-$100), or, if the holder exercised the option, then you would need to buy 100 Apple shares at the market price of $1000 per share, costing you $100,000, and then sell them to the option holder at the strike price of $100 for $10,000 = 100 x $100. In either case, you would show a loss of $90,000 on the share transaction, which would be slightly offset by a $250 credit for the premium you received selling the call. There is no limit on the potential loss since there is no limit on how high the underlying share price can go. Covered Call Option Consider now the case of a covered call option. Since you hold the underlying shares, any loss you make on the option position would be \\\"\\\"covered\\\"\\\" by the profit you make on the underlying shares. Again, suppose you own 100 Apple shares and sell a call option with a strike price of $100 at a premium of $2.50 to earn a payment of $250. If the price of Apple skyrockets to $1000, then there are again two possible scenarios. One, you buy back the option at a premium of about $900 costing you $90,000. In order to cover this cost you would then sell your 100 Apple shares at the market price of $1000 per share to realise $100,000 = 100 x $1000. On the other hand, if your option is exercised, then you would deliver your 100 Apple shares to the option holder at the contracted strike price of $100 per share, thus receiving just $10,000 = 100 x $100. The only \\\"\\\"loss\\\"\\\" is that you have had to sell your shares for much less than the market price.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"209359\",\n \"text\": \"When you short a stock, you can lose an unlimited amount of money if the trade goes against you. If the shorted stock gaps up overnight you can lose more money than you have in your account. The best case is you make 100% if the stock goes to zero. And then you have margin fees on top of that. With long positions, it's the other way around. Your max loss is 100% and your gains are potentially unlimited.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"12542\",\n \"text\": \"Short selling can be a good strategy to hedge, but you have almost unlimited downside. If a stock price skyrockets, you may be forced to cover your short by the brokerage before you want to or put up more capital. A smarter strategy to hedge, that limits your potential downside is to buy puts if you think the market is going down. Your downside is limited to the total amount that you purchased the put for and no more. Another way to hedge is to SELL calls that are covered because you own the shares the calls refer to. You might do this if you thought your stock was going to go down but you didn't want to sell your shares right now. That way the only downside if the price goes up is you give up your shares at a predetermined price and you miss out on the upside, but your downside is now diminished by the premium you were paid for the option. (You'd still lose money if the shares went down since you still own them, but you got paid the option premium so that helps offset that).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"240215\",\n \"text\": \"\\\"The process of borrowing shares and selling them is called shorting a stock, or \\\"\\\"going short.\\\"\\\" When you use money to buy shares, it is called \\\"\\\"going long.\\\"\\\" In general, your strategy of going long and short in the same stock in the same amounts does not gain you anything. Let's look at your two scenarios to see why. When you start, LOOT is trading at $20 per share. You purchased 100 shares for $2000, and you borrowed and sold 100 shares for $2000. You are both long and short in the stock for $2000. At this point, you have invested $2000, and you got your $2000 back from the short proceeds. You own and owe 100 shares. Under scenario A, the price goes up to $30 per share. Your long shares have gone up in value by $1000. However, you have lost $1000 on your short shares. Your short is called, and you return your 100 shares, and have to pay interest. Under this scenario, after it is all done, you have lost whatever the interest charges are. Under scenario B, the prices goes down to $10 per share. Your long shares have lost $1000 in value. However, your short has gained $1000 in value, because you can buy the 100 shares for only $1000 and return them, and you are left with the $1000 out of the $2000 you got when you first sold the shorted shares. However, because your long shares have lost $1000, you still haven't gained anything. Here again, you have lost whatever the interest charges are. As explained in the Traders Exclusive article that @RonJohn posted in the comments, there are investors that go long and short on the same stock at the same time. However, this might be done if the investor believes that the stock will go down in a short-term time frame, but up in the long-term time frame. The investor might buy and hold for the long term, but go short for a brief time while holding the long position. However, that is not what you are suggesting. Your proposal makes no prediction on what the stock might do in different periods of time. You are only attempting to hedge your bets. And it doesn't work. A long position and a short position are opposites to each other, and no matter which way the stock moves, you'll lose the same amount with one position that you have gained in the other position. And you'll be out the interest charges from the borrowed shares every time. With your comment, you have stated that your scenario is that you believe that the stock will go up long term, but you also believe that the stock is at a short-term peak and will drop in the near future. This, however, doesn't really change things much. Let's look again at your possible scenarios. You believe that the stock is a long-term buy, but for some reason you are guessing that the stock will drop in the short-term. Under scenario A, you were incorrect about your short-term guess. And, although you might have been correct about the long-term prospects, you have missed this gain. You are out the interest charges, and if you still think the stock is headed up over the long term, you'll need to buy back in at a higher price. Under scenario B, it turns out that you were correct about the short-term drop. You pocket some cash, but there is no guarantee that the stock will rise anytime soon. Your investment has lost value, and the gain that you made with your short is still tied up in stocks that are currently down. Your strategy does prevent the possibility of the unlimited loss inherent in the short. However, it also prevents the possibility of the unlimited gain inherent in the long position. And this is a shame, since you fundamentally believe that the stock is undervalued and is headed up. You are sabotaging your long-term gains for a chance at a small short-term gain.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"171819\",\n \"text\": \"\\\"There some specific circumstances when you would have a long-term gain. Option 1: If you meet all of these conditions: Then you've got a long-term gain on the stock. The premium on the option gets rolled into the capital gain on the stock and is not taxed separately. From the IRS: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010630 Option 2: If you didn't hold the underlying and the exercise of the call that you wrote resulted in a short position, you might also be able to get to a long-term gain by buying the underlying while keeping your short position open and then \\\"\\\"crossing\\\"\\\" them to close both positions after one year. (In other words, don't \\\"\\\"buy to cover\\\"\\\" just \\\"\\\"buy\\\"\\\" so that your account shows both a long and a short position in the same security. Your broker probably allows this, but if not you, could buy in a different account than the one with the short position.) That would get you to this rule: As a general rule, you determine whether you have short-term or long-term capital gain or loss on a short sale by the amount of time you actually hold the property eventually delivered to the lender to close the short sale. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010586 Option 1 is probably reasonably common. Option 2, I would guess, is uncommon and likely not worthwhile. I do not think that the wash sale rules can help string along options from expiration to expiration though. Option 1 has some elements of what you wrote in italics (I find that paragraph a bit confusing), but the wash sale does not help you out.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"521644\",\n \"text\": \"Buying the underlying asset will not completely hedge you, only what lies above 155 dollars (strike + price of option) - you still have the risk of losing everything but 5. You have a maximum earnings-potential of 55 dollars (strike of 150 - investment of 100 + option of 5) but you have a risk of losing 95$ (investment of 100 - option of 5). Say chance of winning everything or losing everything is 50-50, your expected outcome is 0.5 x -95 + 0.5 x 55 = -20$. Is this a great investment? Sure you don't know your odds - otherwise it would be a sure thing. You shouldn't sell the call option if you do not expect prices to go up - but in that case - why not just buy the underlying alone? Speculating in options is a dangerous game with infinite earnings-potential but also infinite loss potential. (Consider selling a call option and not buying the underlying and the price goes from 100 to 1.000.000.000).\",\n \"title\": \"\"\n },\n {\n \"docid\": \"22916\",\n \"text\": \"On expiry, with the underlying share price at $46, we have : You ask : How come they substract 600-100. Why ? Because you have sold the $45 call to open you position, you must now buy it back to close your position. This will cost you $100, so you are debited for $100 and this debit is being represented as a negative (subtracted); i.e., -$100 Because you have purchased the $40 call to open your position, you must now sell it to close your position. Upon selling this option you will receive $600, so you are credited with $600 and this credit is represented as a positive (added) ; i.e., +$600. Therefore, upon settlement, closing your position will get you $600-$100 = $500. This is the first point you are questioning. (However, you should also note that this is the value of the spread at settlement and it does not include the costs of opening the spread position, which are given as $200, so you net profit is $500-$200 = $300.) You then comment : I know I am selling 45 Call that means : As a writer: I want stock price to go down or stay at strike. As a buyer: I want stock price to go up. Here, note that for every penny that the underlying share price rises above $45, the money you will pay to buy back your short $45 call option will be offset by the money you will receive by selling the long $40 call option. Your $40 call option is covering the losses on your short $45 call option. No matter how high the underlying price settles above $45, you will receive the same $500 net credit on settlement. For example, if the underlying price settles at $50, then you will receive a credit of $1000 for selling your $40 call, but you will incur a debit of $500 against for buying back your short $45 call. The net being $500 = $1000-$500. This point is made in response to your comments posted under Dr. Jones answer.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"507828\",\n \"text\": \"\\\"I'm adding to @Dilip's basic answer, to cover the additional points in your question. I'll assume you are referring to publicly traded stock options, such as those found on the CBOE, and not an option contract entered into privately between two specific counterparties (e.g. as in an employer stock option plan). Since you are not obligated to exercise a call option you purchased on the market, you don't need to maintain funds on account for possible exercising. You could instead let the option expire, or resell the option, neither of which requires funds available for purchase of the underlying shares. However, should you actually choose to exercise the call option (and usually this is done close to expiration, if at all), you will be required to fund your account much like if you bought the underlying shares in the first place. Call your broker to determine the exact rules and timing for when they need the money for a call-option exercise. And to expand on the idea of \\\"\\\"cancelling\\\"\\\" an option you purchased: No, you cannot \\\"\\\"cancel\\\"\\\" an option contract, per se. But, you are permitted to sell the call option to somebody else willing to buy, via the market. When you sell your call option, you'll either make or lose money on the sale – depending on the price of the underlying shares at the time (are they in- or out- of the money?), volatility in the market, and remaining time value. Once you sell, you're back to \\\"\\\"no position\\\"\\\". That's not the same as \\\"\\\"cancelled\\\"\\\", but you are out of the trade, whether at profit or loss. Furthermore, the option writer (i.e. the seller who \\\"\\\"sold to open\\\"\\\" a position, in writing the call in the first place) is also not permitted to cancel the option he wrote. However, the option writer is permitted to close out the original short position by simply buying back a matching call option on the market. Again, this would occur at either profit or loss based on market prices at the time. This second kind of buy order – i.e. made by someone who initially wrote a call option – is called a \\\"\\\"buy to close\\\"\\\", meaning the purchase of an offsetting position. (The other kind of buy is the \\\"\\\"buy to open\\\"\\\".) Then, consider: Since an option buyer is free to re-sell the option purchased, and since an option writer (who \\\"\\\"sold to open\\\"\\\" the new contract) is also free to buy back an offsetting option, a process known as clearing is required to match remaining buyers exercising the call options held with the remaining option writers having open short positions for the contract. For CBOE options, this clearing is performed by the Options Clearing Corporation. Here's how it works (see here): What is the OCC? The Options Clearing Corporation is the sole issuer of all securities options listed at the CBOE, four other U.S. stock exchanges and the National Association of Securities Dealers, Inc. (NASD), and is the entity through which all CBOE option transactions are ultimately cleared. As the issuer of all options, OCC essentially takes the opposite side of every option traded. Because OCC basically becomes the buyer for every seller and the seller for every buyer, it allows options traders to buy and sell in a secondary market without having to find the original opposite party. [...] [emphasis above is mine] When a call option writer must deliver shares to a call option buyer exercising a call, it's called assignment. (I have been assigned before, and it isn't pleasant to see a position called away that otherwise would have been very profitable if the call weren't written in the first place!) Also, re: \\\"\\\"I know my counter party cannot sell his shares\\\"\\\" ... that's not strictly true. You are thinking of a covered call. But, an option writer doesn't necessarily need to own the underlying shares. Look up Naked call (Wikipedia). Naked calls aren't frequently undertaken because a naked call \\\"\\\"is one of the riskiest options strategies because it carries unlimited risk\\\"\\\". The average individual trader isn't usually permitted by their broker to enter such an order, but there are market participants who can do such a trade. Finally, you can learn more about options at The Options Industry Council (OIC).\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"388754\",\n \"text\": \"\\\"The question you are asking concerns the exercise of a short option position. The other replies do not appear to address this situation. Suppose that Apple is trading at $96 and you sell a put option with a strike price of $95 for some future delivery date - say August 2016. The option contract is for 100 shares and you sell the contract for a premium of $3.20. When you sell the option your account will be credited with the premium and debited with the broker commission. The premium you receive will be $320 = 100 x $3.20. The commission you pay will depend on you broker. Now suppose that the price of Apple drops to $90 and your option is exercised, either on expiry or prior to expiry. Then you would be obliged to take delivery of 100 Apple shares at the contracted option strike price of $95 costing you $9,500 plus broker commission. If you immediately sell the Apple shares you have purchased under your contract obligations, then assuming you sell the shares at the current market price of $90 you would realise a loss of $500 ( = 100x($95-$90) )plus commission. Since you received a premium of $320 when you sold the put option, your net loss would be $500-$320 = $180 plus any commissions paid to your broker. Now let's look at the case of selling a call option. Again assume that the price of Apple is $96 and you sell a call option for 100 shares with a strike price of $97 for a premium of $3.60. The premium you receive would be $360 = 100 x $3.60. You would also be debited for commission by your broker. Now suppose that the price of Apple shares rises to $101 and your option is exercised. Then you would be obliged to deliver 100 Apple shares to the party exercising the option at the contracted strike price of $97. If you did not own the shares to effect delivery, then you would need to purchase those shares in the market at the current market price of $101, and then sell them to the party exercising the option at the strike price of $97. This would realise an immediate loss of $400 = 100 x ($101-$97) plus any commission payable. If you did own the shares, then you would simply deliver them and possibly pay some commission or a delivery fee to your broker. Since you received $360 when you sold the option, your net loss would be $40 = $400-$360 plus any commission and fees payable to the broker. It is important to understand that in addition to these accounting items, short option positions carry with them a \\\"\\\"margin\\\"\\\" requirement. You will need to maintain a margin deposit to show \\\"\\\"good faith\\\"\\\" so long as the short option position is open. If the option you have sold moves against you, then you will be called upon to put up extra margin to cover any potential losses.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"578022\",\n \"text\": \"\\\"You owe no tax on the option transaction in 2015 in this case. How you ultimately get taxed depends on how you dispose of the position. If it expires, then you will have a short-term capital gain on the option position at expiration. If it is exercised, then the option is \\\"\\\"gone\\\"\\\" for tax purposes and your basis in the underlying is adjusted. From IRS Publication 550: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. In your case, this will be a long-term capital gain. For completeness, if you buy to cover the option back from the market before expiration or exercise, then it is also a short-term capital gain. Also, keep in mind that this all assumes that this covered call is \\\"\\\"qualified\\\"\\\" so that it does not count as a straddle. You can find more about that in Pub 550. https://www.irs.gov/publications/p550/ch04.html#en_US_2014_publink100010630 All of this is for US tax purposes.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"557356\",\n \"text\": \"\\\"There are two reasons why most options aren't exercised. The first is obvious, and the second, less so. The obvious: An option that's practically worthless doesn't get exercised. Options that reach expiry and remain unexercised are almost always worthless bets that simply didn't pay off. This includes calls with strikes above the current underlying price, and puts with strikes below it. A heck of a lot of options. If an option with value was somehow left to expire, it was probably a mistake, or else the transaction costs outweighed the value remaining; not quite worthless, but not \\\"\\\"worth it\\\"\\\" either. The less obvious: An option with value can be cancelled any time before expiration. A trader that buys an option may at some point show a gain sooner than anticipated, or a loss in excess of his tolerance. If a gain, he may want to sell before expiry to realize the gain sooner. Similarly, if a loss, he may want to take the loss sooner. In both cases, his capital is freed up and he can take another position. And — this is the key part — the other end matched up with that option sale is often a buyer that had created (written) exactly such an option contract in the first place – the option writer – and who is looking to get out of his position. Option writers are the traders responsible, in the first place, for creating options and increasing the \\\"\\\"open interest.\\\"\\\" Anybody with the right kind and level of options trading account can do this. A trader that writes an option does so by instructing his broker to \\\"\\\"sell to open\\\"\\\" a new instance of the option. The trader then has a short position (negative quantity) in that option, and all the while may be subject to the obligations that match the option's exercise rights. The only way for the option writer to get out of that short position and its obligations are these: Not by choice: To get assigned. That is to say: a buyer exercised the option. The writer has to fulfill his obligation by delivering the underlying (if a call) to the option holder, or buying the underlying (if a put) from the option holder. Not by choice: The option expires worthless. This is the ideal scenario for a writer because 100% of the premium received (less transaction costs) is profit. By choice: The writer is free to buy back exactly the same kind of option before expiry using a \\\"\\\"buy to close\\\"\\\" order with their broker. Once the option has been purchased with a \\\"\\\"buy to close\\\"\\\", it eliminates the short position and obligation. The option is cancelled. The open interest declines. Options thus cancelled just don't live long enough to either expire or be exercised.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"268802\",\n \"text\": \"Without commenting on your view of the TV market: Let's have a look at the main ways to get negative exposure: 1.Short the stocks Pros: Relatively Easy Cons: Interest rate, costs of shorting, linear bet 2.Options a. Write Calls b. Buy puts Pros: Convexity, leveraged, relatively cheap Cons: Zero Sum bet that expires with time, theta 3.Short Stock, Buy Puts, Write Calls Short X Units of each stock, Write calls on them , use call premiums to finance puts. Pros: 3x the power!, high kickout Cons: Unlimited pain\",\n \"title\": \"\"\n },\n {\n \"docid\": \"393418\",\n \"text\": \"By buying the call option, you are getting the benefit of purchasing the underlying shares (that is, if the shares go up in value, you make money), but transferring the risk of the shares reducing in value. This is more apparent when you are using the option to offset an explicit risk that you hold. For example, if you have a short position, you are at unlimited risk of the position going up in value. You could decide you only want to take the risk that it might rise to $X. In that case, you could buy a call option with $X strike price. Then you have transferred the risk that the position goes over $X to the counterpart, since, even if the shares are trading at $X+$Y you can close out the short position by purchasing the shares at $X, while the option counterpart will lose $Y.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"520098\",\n \"text\": \"\\\"A derivative contract can be an option, and you can take a short (sell) position , much the same way you would in a stock. When BUYING options you risk only the money you put in. However when selling naked(you don't have the securities or cash to cover all potential losses) options, you are borrowing. Brokers force you to maintain a required amount of cash called, a maintenance requirement. When selling naked calls - theoretically you are able to lose an INFINITE amount of money, so in order to sell this type of options you have to maintain a certain level of cash in your account. If you fail to maintain this level you will enter into whats often referred to as a \\\"\\\"margin-call\\\"\\\". And yes they will call your phone and tell you :). Your broker has the right to liquidate your positions in order to meet requirements. PS: From experience my broker has never liquidated any of my holdings, but then again I've never been in a margin call for longer then a few days and never with a severe amount. The margin requirement for investors is regulated and brokers follow these regulations.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"314478\",\n \"text\": \"\\\"And what exactly do I profit from the short? I understand it is the difference in the value of the stock. So if my initial investment was $4000 (200 * $20) and I bought it at $3800 (200 * $19) I profit from the difference, which is $200. Do I also receive back the extra $2000 I gave the bank to perform the trade? Either this is extremely poorly worded or you misunderstand the mechanics of a short position. When you open a short position, your are expecting that the stock will decline from here. In a short position you are borrowing shares you don't own and selling them. If the price goes down you get to buy the same shares back for less money and return them to the person you borrowed from. Your profit is the delta between the original sell price and the new lower buy price (less commissions and fees/interest). Opening and closing a short position is two trades, a sell then a buy. Just like a long trade there is no maximum holding period. If you place your order to sell (short) 200 shares at $19, your initial investment is $3,800. In order to open your $3,800 short position your broker may require your account to have at least $5,700 (according to the 1.5 ratio in your question). It's not advisable to open a short position this close to the ratio requirement. Most brokers require a buffer in your account in case the stock goes up, because in a short trade if the stock goes up you're losing money. If the stock goes up such that you've exhausted your buffer you'll receive what's known as a \\\"\\\"margin call\\\"\\\" where your broker either requires you to wire in more money or sell part or all of your position at a loss to avoid further losses. And remember, you may be charged interest on the value of the shares you're borrowing. When you hold a position long your maximum loss is the money you put in; a position can only fall to zero (though you may owe interest or other fees if you're trading on margin). When you hold a position short your maximum loss is unlimited; there's no limit to how high the value of something can go. There are less risky ways to make short trades by using put options, but you should ensure that you have a firm grasp on what's happening before you use real money. The timing of the trades and execution of the trades is no different than when you take a plain vanilla long position. You place your order, either market or limit or whatever, and it executes when your trade criteria occurs.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"242663\",\n \"text\": \"\\\"Some thoughts on your questions in order, Duration: You might want to look at the longest-dated option (often a \\\"\\\"LEAP\\\"\\\"), for a couple reasons. One is that transaction costs (spread plus commission, especially spread) are killer on options, so a longer option means fewer transactions, since you don't have to keep rolling the option. Two is that any fundamentals-based views on stocks might tend to require 3-5 years to (relatively) reliably work out, so if you're a fundamental investor, a 3-6 month option isn't great. Over 3-6 months, momentum, short-term news, short squeezes, etc. can often dominate fundamentals in determining the price. One exception is if you just want to hedge a short-term event, such as a pending announcement on drug approval or something, and then you would buy the shortest option that still expires after the event; but options are usually super-expensive when they span an event like this. Strike: Strike price on a long option can be thought of as a tradeoff between the max loss and minimizing \\\"\\\"insurance costs.\\\"\\\" That is, if you buy a deeply in-the-money put or call, the time value will be minimal and thus you aren't paying so much for \\\"\\\"insurance,\\\"\\\" but you may have 1/3 or 1/2 of the value of the underlying tied up in the option and subject to loss. If you buy a put or call \\\"\\\"at the money,\\\"\\\" then you might have only say 10% of the value of the underlying tied up in the option and subject to loss, but almost the whole 10% may be time value (insurance cost), so you are losing 10% if the underlying stock price stays flat. I think of the deep in-the-money options as similar to buying stocks on margin (but the \\\"\\\"implied\\\"\\\" interest costs may be less than consumer margin borrowing rates, and for long options you can't get a margin call). The at-the-money options are more like buying insurance, and it's expensive. The commissions and spreads add significant cost, on top of the natural time value cost of the option. The annual costs would generally exceed the long-run average return on a diversified stock fund, which is daunting. Undervalued/overvalued options, pt. 1: First thing is to be sure the options prices on a given underlying make sense at all; there are things that \\\"\\\"should\\\"\\\" hold, for example a synthetic long or short should match up to an actual long or short. These kinds of rules can break, for example on LinkedIn (LNKD) after its IPO, when shorting was not permitted, the synthetic long was quite a bit cheaper than a real long. Usually though this happens because the arbitrage is not practical. For example on LNKD, the shares to short weren't really available, so people doing synthetic shorts with options were driving up the price of the synthetic short and down the price of the synthetic long. If you did actually want to be long the stock, then the synthetic long was a great deal. However, a riskless arbitrage (buy synthetic long, short the stock) was not possible, and that's why the prices were messed up. Another basic relationship that should hold is put-call parity: http://en.wikipedia.org/wiki/Put%E2%80%93call_parity Undervalued/overvalued options, pt. 2: Assuming the relationship to the underlying is sane (synthetic positions equivalent to actual positions) then the valuation of the option could focus on volatility. That is, the time value of the option implies the stock will move a certain amount. If the time value is high and you think the stock won't move much, you might short the option, while if the time value is low and you think the stock will move a lot, you might buy the option. You can get implied volatility from your broker perhaps, or Morningstar.com for example has a bunch of data on option prices and the implied components of the price model. I don't know how useful this really is though. The spreads on options are so wide that making money on predicting volatility better than the market is pretty darn hard. That is, the spread probably exceeds the amount of the mispricing. The price of the underlying is more important to the value of an option than the assumed volatility. How many contracts: Each contract is 100 shares, so you just match that up. If you want to hedge 100 shares, buy one contract. To get the notional value of the underlying multiply by 100. So say you buy a call for $30, and the stock is trading at $100, then you have a call on 100 shares which are currently priced at $10,000 and the option will cost $30*100=3,000. You are leveraged about 3 to 1. (This points to an issue with options for individual investors, which is that one contract is a pretty large notional value relative to most portfolios.)\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"326599\",\n \"text\": \"Gold's valuation is so stratospheric right now that I wonder if negative numbers (as in, you should short it) are acceptable in the short run. In the long run I'd say the answer is zero. The problem with gold is that its only major fundamental value is for making jewelry and the vast majority is just being hoarded in ways that can only be justified by the Greater Fool Theory. In the long run gold shouldn't return more than inflation because a pile of gold creates no new wealth like the capital that stocks are a claim on and doesn't allow others to create new wealth like money lent via bonds. It's also not an important and increasingly scarce resource for wealth creation in the global economy like oil and other more useful commodities are. I've halfway-thought about taking a short position in gold, though I haven't taken any position, short or long, in gold for the following reasons: Straight up short-selling of a gold ETF is too risky for me, given its potential for unlimited losses. Some other short strategy like an inverse ETF or put options is also risky, though less so, and ties up a lot of capital. While I strongly believe such an investment would be profitable, I think the things that will likely rise when the flight-to-safety is over and gold comes back to Earth (mainly stocks, especially in the more beaten-down sectors of the economy) will be equally profitable with less risk than taking one of these positions in gold.\",\n \"title\": \"\"\n },\n {\n \"docid\": \"142110\",\n \"text\": \"\\\"He didn't sell in the \\\"\\\"normal\\\"\\\" way that most people think of when they hear the term \\\"\\\"sell.\\\"\\\" He engaged in a (perfectly legitimate) technique known as short selling, in which he borrows shares from his broker and sells them immediately. He's betting that the price of the stock will drop so he can buy them back at a lower price to return the borrowed shares back to his broker. He gets to pocket the difference. He had about $37,000 of cash in his account. Since he borrowed ~8400 shares and sold them immediately at $2/share, he got $16,800 in cash and owed his broker 8400 shares. So, his net purchasing power at the time of the short sale was $37,000 + $16,800 - 4800 shares * $2/share. As the price of the stock changes, his purchasing power will change according to this equation. He's allowed to continue to borrow these 8400 shares as long as his purchasing power remains above 0. That is, the broker requires him to have enough cash on hand to buy back all of his borrowed shares at any given moment. If his purchasing power ever goes negative, he'll be subject to a margin call: the broker will make him either deposit cash into his account or close his positions (sell long positions or buy back short positions) until it's positive again. The stock jumped up to $13.85 the next morning before the market opened (during \\\"\\\"before-hours\\\"\\\" trading). His purchasing power at that time was $37,000 + $16,800 - 8400 shares * $13.85/share = -$62,540. Since his purchasing power was negative, he was subject to a margin call. By the time he got out, he had to pay $17.50/share to buy back the 8400 shares that he borrowed, making his purchasing power -$101,600. This $101,600 was money that he borrowed from his broker to buy back the shares to fulfill his margin call. His huge loss was from borrowing shares from his broker. Note that his maximum potential loss is unlimited, since there is no limit to how much a stock can grow. Evidently, he failed to grasp the most important concept of short selling, which is that he's borrowing stock from his broker and he's obligated to give that stock back whenever his broker wants, no matter what it costs him to fulfill that obligation.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"16747\",\n \"text\": \"\\\"The previous answers make valid points regarding the risks, and why you can't reasonably compare trading for profit/loss to a roll of the die. This answer looks at the math instead. Your assumption: I have an equal probability to make a profit or a loss. Is incorrect, for the reasons stated in other answers. However, the answer to your question: Can I also assume that probabilistically speaking, a trader cannot do worst than random? Is \\\"\\\"yes\\\"\\\". But only because the question is flawed. Consequently it's throwing people in all directions with their answers. But quite simply, in a truly random environment the worst case scenario, no matter how improbable, is that you lose over and over again until you have nothing left. This can happen in sequential rolls of the dice AND in trading securities/bonds/whatever. You could guess wrong for every roll of the die AND all of your stock picks could become worthless. Both outcomes result in $0 (assuming you do not gamble with credit). Tell me, which $0 is \\\"\\\"worse\\\"\\\"? Given the infinite number of plays that \\\"\\\"random\\\"\\\" implies, the chance of losing your entire bankroll exists in both scenarios, and that is enough by itself to make neither option \\\"\\\"worse\\\"\\\" than the other. Of course, the opposite is also true. You could only pick winners, with an unlimited upside potential, but again that could happen with either dice rolls or stock picks. It's just highly improbable. my chances cannot be worse than random and if my trading system has an edge that is greater than the percentage of the transaction that is transaction cost, then I am probabilistically likely to make a profit? Nope. This is where it all falls apart. Just because your chances of losing it all are similarly improbable, does not make you more likely to win with one method or the other. Regression to the mean, when given infinite, truly random outcomes, makes it impossible to \\\"\\\"have an edge\\\"\\\". Also, \\\"\\\"probabilistically\\\"\\\" isn't a word, but \\\"\\\"probably\\\"\\\" is.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"147361\",\n \"text\": \"\\\"Yes, long calls, and that's a good point. Let's see... if I bought one contract at the Bid price above... $97.13 at expiry of $96.43 option = out of the money =- option price(x100) = $113 loss. $97.13 at expiry of $97.00 option = out of the money =- option price(x100) = $77 loss. $97.13 at expiry of $97.14 option = in the money by 1-cent=$1/contract profit - option price(x100) = $1-$58 = $57 loss The higher strike prices have much lower losses if they expire with the underlying stock at- or near-the-money. So, they carry \\\"\\\"gentler\\\"\\\" downside potential, and are priced much higher to reflect that \\\"\\\"controlled\\\"\\\" risk potential. That makes sense. Thanks.\\\"\",\n \"title\": \"\"\n },\n {\n \"docid\": \"485760\",\n \"text\": \"\\\"Do you want to do it pre or post correction? If you're bearish on the market the obvious thing to do is short an index. I would say this is kind of dumb. The main problem is that it may take months or years for the market to crash, and by then it will have gone up so much that even the crash doesn't bring you profit, and you're paying borrowing fees meanwhile as well. You need to watch the portfolio also, when you short sell you'll get a bunch of cash, which you most likely will want to invest, but once you invest it, the market can spike and pummel your short position, resulting in negative remaining cash (since you already spent it). At that point you get a margin call from your broker. If you check your account regularly, not a big deal, but bad things can happen if you treat it as a fire and forget strategy. These days they have inverse funds so you don't have to borrow anything. The fund manager borrows for you. I'd say those are much better. The less cumbersome choice is to simply sell call options on the index or buy puts. These are even cash options, so when you exercise you get/lose money, not shares. You can even arrange them so that your potential loss is capped. (but honestly, same goes for shorts - it's called a stop loss) You could also wait for the correction and buy the dip. Less worrying about shorts and such, but of course the issue is timing the crash. Usually the crashes are very quick, and there are several \\\"\\\"pre-crashes\\\"\\\" that look like it bottomed out but then it crashes more. So actually very difficult thing to tell. You have to know either exactly when the correction will be, or exactly what the price floor is (and set a limit buy). Hope your crystal ball works! Yet another choice is finding asset classes uncorrelated or even anticorrelated with the broader market. For instance some emerging markets (developing countries), some sectors, individual stocks that are not inflated, bonds, gold and so on can have these characteristics where if S&P goes down they go up. Buying those may be a safer approach since at least you are still holding a fundamentally valuable thing even if your thesis flops, meanwhile shorts and puts and the like are purely speculative.\\\"\",\n \"title\": \"\"\n }\n]"}}}],"truncated":false,"partial":false},"paginationData":{"pageIndex":3,"numItemsPerPage":100,"numTotalItems":2592,"offset":300,"length":100}},"jwt":"eyJhbGciOiJFZERTQSJ9.eyJyZWFkIjp0cnVlLCJwZXJtaXNzaW9ucyI6eyJyZXBvLmNvbnRlbnQucmVhZCI6dHJ1ZX0sImlhdCI6MTc1ODE5NDI5MSwic3ViIjoiL2RhdGFzZXRzL3Nza3RvcmEvbmZjb3JwdXMtc2NpZmFjdC1maXFhLWZldmVyLWNvbWJpbmUtNjQ4IiwiZXhwIjoxNzU4MTk3ODkxLCJpc3MiOiJodHRwczovL2h1Z2dpbmdmYWNlLmNvIn0.Ig-6D3SHRTqM-UtjHnWrmebIBOI9eJm4nmiTnqUrNnT5esuwFkpUBXtDEBd8Hp4dpjhRnOolDvtiei-U0mVTDA","displayUrls":true},"discussionsStats":{"closed":0,"open":0,"total":0},"fullWidth":true,"hasGatedAccess":true,"hasFullAccess":true,"isEmbedded":false,"savedQueries":{"community":[],"user":[]}}">
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Gareth Neame is a television executive.
|
[
{
"docid": "BBC",
"text": "The British Broadcasting Corporation ( BBC ) is a British public service broadcaster headquartered at Broadcasting House in London . The BBC is the world 's oldest national broadcasting organisation and the largest broadcaster in the world by number of employees . It employs over 20,950 staff in total , 16,672 of whom are in public sector broadcasting . The total number of staff is 35,402 when part-time , flexible , and fixed contract staff are included . The BBC is established under a Royal Charter and operates under its Agreement with the Secretary of State for Culture , Media and Sport . Its work is funded principally by an annual television licence fee which is charged to all British households , companies , and organisations using any type of equipment to receive or record live television broadcasts and ` iPlayer ' catch-up since 1 September 2016 . The fee is set by the British Government , agreed by Parliament , and used to fund the BBC 's radio , TV , and online services covering the nations and regions of the UK . Since 1 April 2014 , it has also funded the BBC World Service ( launched in 1932 as the BBC Empire Service ) , which broadcasts in 28 languages and provides comprehensive TV , radio , and online services in Arabic and Persian . Around a quarter of BBC revenues come from its commercial arm BBC Worldwide Ltd , which sells BBC programmes and services internationally and also distributes the BBC 's international 24-hour English-language news services BBC World News , and from BBC.com , provided by BBC Global News Ltd. .",
"title": ""
},
{
"docid": "Gareth_Neame",
"text": "Gareth Elwin Neame OBE ( born 8 March 1967 ) is a British Emmy and Golden Globe award winning television producer and executive . As an executive at the BBC , Neame was responsible for bringing a new wave of popular dramas to the screen including Spooks ( MI5 ) , State of Play , Hustle and New Tricks . Neame 's strategy significantly enhanced the independent production sector as a source of quality and commercial scripted television programmes .",
"title": ""
}
] |
[
{
"docid": "Neame",
"text": "Neame is a surname which may refer to : Basil Neame ( 1921 -- 2010 ) , English fruit grower Christopher Neame ( born 1947 ) , English actor Christopher Neame ( writer/producer ) ( 1942 -- 2011 ) , British film producer and screenwriter Douglas Neame ( 1901 -- 1988 ) , English hurdler Gareth Neame ( born 1967 ) , British television producer and executive Ivo Neame ( born 1981 ) , British jazz pianist and saxophonist Philip Neame ( 1888 -- 1978 ) , British Army lieutenant general and recipient of the Victoria Cross Rex Neame ( 1936 -- 2008 ) , English cricketer Ronald Neame ( 1911 -- 2010 ) , English film cinematographer , producer , screenwriter and director Stuart Neame , rugby union international who represented England from 1879 to 1880",
"title": ""
},
{
"docid": "Conviction_(2004_TV_series)",
"text": "Conviction is a British television crime drama that premiered on BBC Three on 7 November 2004 . The six-part series stars William Ash , David Warner , Ian Puleston-Davies , Reece Dinsdale , Nicholas Gleaves , Laura Fraser , Jason Watkins and Zoe Henry . The series was created and was written by Bill Gallagher ( previously known for Clocking Off and Out of the Blue ) , produced by Red Production Company , and directed by Marc Munden ( Vanity Fair , Canterbury Tales : The Knight 's Tale ) . The producer was Ann Harrison-Baxter ( The Second Coming , The Cops ) , with Nicola Shindler and Gareth Neame as executive producers for Red Production Company and the BBC respectively . The storyline was later used as the basis for the movie Blood , starring Paul Bettany , Mark Strong and Brian Cox .",
"title": ""
},
{
"docid": "The_Philanthropist_(TV_series)",
"text": "The Philanthropist was an American action drama series that premiered on NBC on Wednesday , June 24 , 2009 . The program was a limited summer series , principally filmed in South Africa . It opened to strong ratings , but saw a drop in viewers in subsequent weeks . The Philanthropist is a Carnival Films production in association with The Levinson/Fontana Company and Original Media . Tom Fontana , Barry Levinson , Peter Horton , Charlie Corwin , Gareth Neame , and Teri Weinberg served as executive producers . On October 21 , 2009 , the series was canceled by NBC . Fans attempts to keep the show on the air using Facebook and a charitable cause called `` Save The Philanthropist through Charity '' were unsuccessful .",
"title": ""
},
{
"docid": "Gareth_Davies_(television_producer)",
"text": "Gareth Davies ( fl . c. 2000 ) is a television producer . His first Hollywood producing credit was the 1970 film The Juggler of Notre Dame . Since , he has produced for television , particularly series including 69 episodes of Remington Steele ( two seasons each as producer and as co-executive producer ) from 1982 to 1986 , and 145 episodes of Buffy the Vampire Slayer from 1997 to 2003 . He should not be confused with the British television director and actor of the same name who was associated with the early work of television dramatist Dennis Potter .",
"title": ""
},
{
"docid": "Downton_Abbey",
"text": "Downton Abbey is a historical period drama television series created by Julian Fellowes and co-produced by Carnival Films and Masterpiece . It first aired on ITV in the United Kingdom on 26 September 2010 , and on PBS in the United States on 9 January 2011 as part of the Masterpiece Classic anthology . The series , set in the fictional Yorkshire country estate of Downton Abbey between 1912 and 1925 , depicts the lives of the aristocratic Crawley family and their domestic servants in the post-Edwardian era -- with the great events in history having an effect on their lives and on the British social hierarchy . Events depicted throughout the series include news of the sinking of the RMS Titanic in the first series ; the outbreak of the First World War , the Spanish influenza pandemic , and the Marconi scandal in the second series ; the Irish War of Independence leading to the formation of the Irish Free State in the third series ; the Teapot Dome scandal in the fourth series ; and the British general election of 1923 , the Jallianwala Bagh Massacre , and the Beer Hall Putsch in the fifth series . The sixth and final series introduces the rise of the working class during the interwar period and hints towards the eventual decline of the British aristocracy . Downton Abbey has received acclaim from television critics and won numerous accolades , including a Golden Globe Award for Best Miniseries or Television Film and a Primetime Emmy Award for Outstanding Miniseries or Movie . It was recognised by Guinness World Records as the most critically acclaimed English-language television series of 2011 . It earned the most nominations of any international television series in the history of the Primetime Emmy Awards , with twenty-seven in total ( after two series ) . It was the most watched television series on both ITV and PBS , and subsequently became the most successful British costume drama series since the 1981 television serial of Brideshead Revisited . By the third series , it had become one of the most widely watched television drama shows in the world . On 26 March 2015 , Carnival Films and ITV announced that the sixth series would be the last . It aired on ITV between 20 September 2015 and 8 November 2015 . The final episode , serving as the annual Christmas special , was broadcast on 25 December 2015 . Although there are no plans in place , there are strong rumours of a future film adaptation , with executive producer Gareth Neame saying that he was `` very interested '' and bookmakers Ladbrokes stating that `` it only looks like being a matter of time before the film is released '' .",
"title": ""
},
{
"docid": "Gareth_Penny",
"text": "Gareth Penny is non-Executive Chairman of Norilsk Nickel , the world 's largest producer of nickel and palladium and one of the leading producers of platinum and copper . MMC Norilsk Nickel , the largest diversified mining and metals company in Russia , is listed on the Moscow Exchange . Gareth is non-Executive Chairman of the Edcon Group , the largest non-food retailer in South Africa , with a clothing and footwear market share of nearly twice that of its nearest competitor . Gareth is a non-Executive Director and RemCo Chairman of Julius Bär Holding Limited , Switzerland 's leading , dedicated wealth manager . He also serves on the Senior Advisory Board of TowerBrook Capital Partners ( TCP ) , a successful New York and London based investment firm . Gareth is non-Executive Chairman of Pangolin Diamonds , an exciting diamond exploration company in Botswana , one of the world 's leading diamond producing countries . Pangolin is listed on the Canadian Exchange . Gareth has been a regular visiting Lecturer at the London Business School 's MBA and Sloane programmes . Gareth has worked in various forms of mining over the past three decades , and for 22 years he was with De Beers and Anglo American plc , the last five of which he was Group CEO of De Beers . During his tenure , Gareth was instrumental in reshaping not only the world 's largest diamond company , but also the diamond industry . He was the prime architect in the change to the De Beers business model , which replaced over 100 years of supply-side management in the rough diamond business , with demand-driven initiatives that have generated significant value creation for the company and the diamond industry . Gareth was voted Person of the Year in 2003 , by the authoritative jewellery industry magazine JCK ( Jewelers Circular Keystone ) , and holds Honorary Life Membership of the London Diamond Bourse and Club . On numerous occasions he has been included in the publication `` South Africa 's Leading Business Managers '' . Educated at Diocesan College ( Bishops ) in Cape Town and at Eton College , Gareth was a Rhodes Scholar at Oxford University , graduating with a Masters in Philosophy , Politics and Economics . Gareth is married to Kate and they have two children .",
"title": ""
},
{
"docid": "Gareth_Jones",
"text": "Gareth Jones may refer to : Gareth Stedman Jones ( born 1942 ) , British historian Gareth Jones ( journalist ) ( 1905 -- 1935 ) , Welsh journalist Gareth Jones ( music producer ) ( born 1954 ) , English music producer and engineer Gareth Jones ( politician ) ( born 1939 ) , member of the National Assembly for Wales Gareth Jones ( rugby player ) ( 1979 -- 2008 ) , Welsh rugby union player Gareth Jones ( presenter ) ( born 1961 ) , Welsh television presenter Gareth Jones ( actor ) ( 1925 -- 1958 ) , British actor Gareth Jones ( lawyer ) ( born 1930 ) , `` founding father '' of the English law of restitution and former professor of law at Cambridge University Gareth Jones ( conductor ) ( born 1960 ) , conductor of the Welsh National Opera chorus Gareth Jones ( researcher ) , professor of information technology in Dublin Gareth P. Jones , British children 's author Gareth Jones ( director ) ( born 1951 ) , British film and television director and screenwriter Gareth Jones ( EastEnders ) , fictional character better known as Andy Flynn Gareth Jones , lead singer and rhythm guitarist of the band People in Planes Gareth Paul Jones , Welsh software engineer",
"title": ""
},
{
"docid": "Gareth_Williams_(New_Zealand_actor)",
"text": "Gareth Williams ( born 13 July 1984 ) is a New Zealand born actor of television , film and theatre . He trained for a year with the Auckland Theatre Company at the prestigious Globe Theater in London . He then attained his Bachelor of Performing Arts at Toi : Whakaari Dramatic Arts College in 2006 . Williams has since had television roles in Facelift ( 2007 ) , This Is Not My Life ( 2009 ) , Legend of the Seeker ( 2010 ) , as well as some minor feature film roles . He has gained recognition through musical theatre , receiving positive reviews for his role as William Kemmler in the Indian Ink production of The Dentist 's Chair . Shannon Huse , reviewer for the New Zealand Herald , wrote `` Gareth Williams is suitably cadaver scary as William Kemmler , the ghost of the first man to be executed by electric chair who haunts Albert . He gives a charismatic performance that includes two ghoulish songs . '' He has also taken on such stage roles as Benvolio in Romeo and Juliet ( 2010 ) and ` The Balladeer ' in ` Assassins ' ( 2010 ) . Williams landed the supporting role of Vettius in Spartacus : Gods of the Arena ( 2011 ) .",
"title": ""
},
{
"docid": "Gareth_Edwards_(disambiguation)",
"text": "Gareth Edwards is a former Welsh rugby union footballer who played scrum-half . Gareth Edwards may also refer to : Gareth Edwards ( Berkshire cricketer ) ( born 1973 ) , English cricketer who played for Berkshire Gareth Edwards ( Welsh cricketer ) ( born 1976 ) , former Welsh cricketer , played for Glamorgan 1997 , Wales Minor Counties 1998 Gareth Edwards , co-founder of Image Metrics Gareth Edwards ( producer ) ( born 1965 ) , radio and television producer Gareth Edwards ( director ) ( born 1975 ) , film director",
"title": ""
},
{
"docid": "Gareth_Roberts",
"text": "Gareth Roberts may refer to : Gareth Roberts ( physicist ) ( 1940 -- 2007 ) , British physicist , engineer , and President of Wolfson College , Oxford Gareth Roberts ( rugby player ) ( born 1959 ) , Welsh rugby player Gareth Roberts ( writer ) ( born 1968 ) , British television writer Gareth Roberts ( footballer ) ( born 1978 ) , Welsh football player Gareth Roberts ( statistician ) ( born 1964 ) , British professor and Director of the Centre for Research in Statistical Methodology at University of Warwick Gareth Roberts ( ice hockey ) ( born 1986 ) , Irish ice hockey player Gareth Roberts ( co-driver ) ( 1987 -- 2012 ) , Welsh rally co-driver",
"title": ""
},
{
"docid": "Gareth_(The_Walking_Dead)",
"text": "Gareth is a fictional character from the American television series The Walking Dead portrayed by Andrew J. West . Gareth is based on Chris from the comic book series of the same name , according to West himself . Gareth is introduced at the end of season 4 . He is initially introduced as the welcoming yet mysterious leader of Terminus . However , his true motivations are revealed after Gareth forces Rick Grimes and his fellow survivors into train car A . At the beginning of season 5 , it is revealed Gareth and his entire community are cannibals . As the result of the actions by Carol Peletier , the group escapes , leaving many casualties of Terminus . Gareth , however , leads the remaining survivors to try to hunt down Rick 's group and eat them .",
"title": ""
},
{
"docid": "Gareth_Philips",
"text": "Gareth Philips is a television producer .",
"title": ""
},
{
"docid": "The_Choir:_Gareth's_Best_in_Britain",
"text": "The Choir : Gareth 's Best in Britain ( known as The Naked Choir for series 1 ) is a BBC Two television series that debuted in September 2015 . Presented by choirmaster Gareth Malone , the show features amateur choirs ( exclusively a cappella groups in series 1 ) competing to be chosen as the UK 's best .",
"title": ""
},
{
"docid": "Gareth_Cliff",
"text": "Gareth Cliff Rhydal ( born September , 24 1977 , Pretoria , South Africa ) is a South African radio and television personality . In January 2016 he won a court case to be reinstated as a judge on the television music competition show Idols South Africa on M-Net after being suspended for a perceived racist tweet .",
"title": ""
},
{
"docid": "Gareth_Jewell",
"text": "Gareth Jewell ( born 7th June 1983 ) is a Welsh television actor from Ammanford , Carmarthenshire .",
"title": ""
},
{
"docid": "Windom's_Way",
"text": "Windom 's Way is a 1957 British thriller film directed by Ronald Neame set during the Malayan Emergency . It was nominated for four British Academy of Film and Television Arts awards in 1958 .",
"title": ""
},
{
"docid": "Gareth_Jones_(presenter)",
"text": "Gareth Jones ( born 5 July 1961 ) , also known as `` Gaz Top '' , is a Welsh television presenter . He is also a Welsh language speaker . Best known for his work as a presenter of children 's television and science programmes such as How 2 and Get Fresh , he has more recently moved to presenting motorsport podcasts and directing and producing programmes .",
"title": ""
},
{
"docid": "Gareth_Wigan",
"text": "Gareth Wigan ( December 2 , 1931 -- February 13 , 2010 ) was a British agent , producer and studio executive known for working on such films as George Lucas 's Star Wars . His early recognition of the power of the global entertainment market allowed his employer , Sony Pictures Entertainment , to take advantage of films such as Crouching Tiger , Hidden Dragon .",
"title": ""
},
{
"docid": "Gareth_Jones_(director)",
"text": "Gareth Jones ( born 9 February 1951 ) is a British film and television director and screenwriter , owner of independent production company Scenario Films .",
"title": ""
},
{
"docid": "Gareth_Thomas_(actor)",
"text": "Gareth Daniel Thomas ( 12 February 1945 -- 13 April 2016 ) was a British actor . He was best known for his role as Roj Blake in the BBC science fiction television series Blake 's 7 , but appeared in many other films and television programmes , including Shem in the ITV sci-fi series Star Maidens and Adam Brake in the fantasy series Children of the Stones .",
"title": ""
},
{
"docid": "Shepherd_Neame_Kent_1",
"text": "Shepherd Neame Kent 1 is an English level 9 Rugby Union League and is made up of teams predominantly from south-east London and Kent . The teams play home and away matches from September through to April . The league champions move up to London 3 South East while the runners up play against the runners up of Sussex Spitfire 1 for the remaining place . Relegated teams drop down to Shepherd Neame Kent 2 .",
"title": ""
},
{
"docid": "Damaged_Goods_(Davies_novel)",
"text": "Damaged Goods is an original Doctor Who novel , released by Virgin Publishing in their New Adventures range of Doctor Who books in 1996 . It is the second and to date last piece of full-length prose fiction to have been published by the television scriptwriter Russell T Davies , who later became the chief writer and executive producer of the Doctor Who television series when it was revived in 2005 . Davies 's first professionally published fiction , a novelisation of his children 's television serial Dark Season , had been released by BBC Books in 1991 . In July 2014 it was announced that Big Finish Productions were to produce an audio drama adaptation of the novel , as part of their licensed Doctor Who range . The adaptation was released in April 2015 , available as a standalone title , or in a special box set with an adaptation of Gareth Roberts 's Fourth Doctor novel The Well-Mannered War .",
"title": ""
},
{
"docid": "Gareth_Edwards_(producer)",
"text": "Gareth Edwards ( born in 1965 ) is a radio and television producer and writer . He is the great-grandson of Hollywood pioneer Albert E. Smith , founder of Vitagraph Studios .",
"title": ""
},
{
"docid": "Gareth_Roberts_(writer)",
"text": "Gareth John Pritchard Roberts ( born 5 June 1968 ) is a British television screenwriter and novelist , best known for his work related to the science-fiction television series Doctor Who . He has also worked on various comedy series and soap operas . Roberts studied drama at the University of Winchester ( then King Alfred 's College ) and has also worked as a clerk at the Court of Appeal .",
"title": ""
},
{
"docid": "Stuart_Neame",
"text": "Stuart Neame was a rugby union international who represented England from 1879 to 1880 .",
"title": ""
},
{
"docid": "Ronald_Neame",
"text": "Ronald Elwin Neame CBE BSC ( 23 April 1911 -- 16 June 2010 ) was an English film cinematographer , producer , screenwriter and director . As cinematographer for the British war film One of Our Aircraft Is Missing ( 1943 ) , he received an Academy Award nomination for Best Special Effects . During a partnership with director David Lean , he produced Brief Encounter ( 1945 ) , Great Expectations ( 1946 ) , and Oliver Twist ( 1948 ) , receiving two Academy Award nominations for writing . Neame then moved into directing , and some notable films included , I Could Go On Singing ( 1963 ) , Judy Garland 's last film , The Prime of Miss Jean Brodie ( 1969 ) , which won Maggie Smith her first Oscar , Scrooge ( 1970 ) , starring Albert Finney , and the action-adventure disaster film The Poseidon Adventure ( 1972 ) . For his contributions to the film industry , Neame was appointed a Commander of the Order of the British Empire ( CBE ) , and received the BAFTA Academy Fellowship Award , the highest award the British Film Academy can give a filmmaker .",
"title": ""
},
{
"docid": "Christopher_Neame",
"text": "Christopher Neame ( born 12 September 1947 , London ) is an English actor now moved to the United States .",
"title": ""
},
{
"docid": "Shepherd_Neame_Kent_2",
"text": "Shepherd Neame Kent 2 is an English level 10 Rugby Union League and is made up of teams predominantly from south-east London and Kent . The teams play home and away matches from September through to April . Currently promoted teams move up to Shepherd Neame Kent 1 and there is no relegation although until the 2007-08 season teams could drop down to Kent 3 ( now folded ) . Now a single division , in the past Kent 2 was divided into regional divisions - Kent 2 East and Kent 2 West .",
"title": ""
},
{
"docid": "Basil_Neame",
"text": "Basil Desmond Neame CBE ( 14 October 1921 -- 25 February 2010 ) was a Kentish fruit grower and farmer .",
"title": ""
},
{
"docid": "Christopher_Neame_(writer/producer)",
"text": "Christopher Elwin Neame ( 24 December 1942 -- 12 June 2011 ) was a British film producer and screenwriter .",
"title": ""
}
] |
125110
|
Rockefeller University is in a state.
|
[
{
"docid": "New_York",
"text": "New York is a state in the northeastern United States , and is the 27th-most extensive , fourth-most populous , and seventh-most densely populated U.S. state . New York is bordered by New Jersey and Pennsylvania to the south and Connecticut , Massachusetts , and Vermont to the east . The state has a maritime border in the Atlantic Ocean with Rhode Island , east of Long Island , as well as an international border with the Canadian provinces of Quebec to the north and Ontario to the northwest . The state of New York , with an estimated 19.8 million residents in 2015 , is also referred to as New York State to distinguish it from New York City , the state 's most populous city and its economic hub . With an estimated population of 8.55 million in 2015 , New York City is the most populous city in the United States and the premier gateway for legal immigration to the United States . The New York Metropolitan Area is one of the most populous urban agglomerations in the world . New York City is a global city , exerting a significant impact upon commerce , finance , media , art , fashion , research , technology , education , and entertainment , its fast pace defining the term New York minute . The home of the United Nations Headquarters , New York City is an important center for international diplomacy and has been described as the cultural , financial , and media capital of the world , as well as the world 's most economically powerful city . New York City makes up over 40 % of the population of New York State . Two-thirds of the state 's population lives in the New York City Metropolitan Area , and nearly 40 % lives on Long Island . Both the state and New York City were named for the 17th-century Duke of York , future King James II of England . The next four most populous cities in the state are Buffalo , Rochester , Yonkers , and Syracuse , while the state capital is Albany . New York has a diverse geography . The southern part of the state consists of Long Island and several smaller associated islands , as well as New York City and the lower Hudson River Valley , most of which lie within the wider Atlantic Coastal Plain . The large region known as Upstate New York consists of several ranges of the wider Appalachian Mountains , including the Allegheny Plateau and Catskills along New York 's Southern Tier , and the Adirondack Mountains , Thousand Islands archipelago , and Saint Lawrence Seaway in the Northeastern lobe of the state . These more mountainous regions are bisected by two major river valleys -- the north-south Hudson River Valley and the east-west Mohawk River Valley , which forms the core of the Erie Canal . Western New York is considered part of the Great Lakes Region and straddles Lake Ontario and Lake Erie . Between the two lakes lies Niagara Falls . The central part of the state is dominated by the Finger Lakes , a popular vacation and tourist destination . New York had been inhabited by tribes of Algonquian and Iroquoian-speaking Native Americans for several hundred years by the time the earliest Europeans came to New York . The first Europeans to arrive were French colonists and Jesuit missionaries who arrived southward from settlements at Montreal for trade and proselytizing . In 1609 , the region was claimed by Henry Hudson for the Dutch , who built Fort Nassau in 1614 at the confluence of the Hudson and Mohawk rivers , where the present-day capital of Albany later developed . The Dutch soon also settled New Amsterdam and parts of the Hudson Valley , establishing the colony of New Netherland , a multicultural community from its earliest days and a center of trade and immigration . The British annexed the colony from the Dutch in 1664 . The borders of the British colony , the Province of New York , were similar to those of the present-day state . Many landmarks in New York are well known to both international and domestic visitors , with New York State hosting four of the world 's ten most-visited tourist attractions in 2013 : Times Square , Central Park , Niagara Falls ( shared with Ontario ) , and Grand Central Terminal . New York is home to the Statue of Liberty , a symbol of the United States and its ideals of freedom , democracy , and opportunity . In the 21st century , New York has emerged as a global node of creativity and entrepreneurship , social tolerance , and environmental sustainability . New York 's higher education network comprises approximately 200 colleges and universities , including Columbia University , Cornell University , New York University , and Rockefeller University , which have been ranked among the top 35 in the world .",
"title": ""
},
{
"docid": "Rockefeller_University",
"text": "The Rockefeller University is a center for scientific research , primarily in the biological and medical sciences , providing doctoral and postdoctoral education . Rockefeller is one of the most prestigious institutes for biomedical research in the world , and it is the oldest such institute in the United States . Of a 78 person faculty ( tenured and tenure-track , as of 2016 ) , 38 are members of the National Academy of Sciences , 18 are members of the National Academy of Medicine , 8 are Lasker Award recipients , and 5 are Nobel laureates . Rockefeller is located on the Upper East Side of Manhattan , between 63rd and 68th Streets along York Avenue . Richard P. Lifton -- previously the executive director of the Center for Human Genetics and Genomics at Yale University -- became the university 's eleventh president on September 1 , 2016 . The Rockefeller University Press publishes the Journal of Experimental Medicine , the Journal of Cell Biology , and The Journal of General Physiology .",
"title": ""
}
] |
[
{
"docid": "Richard_Rockefeller",
"text": "Richard Gilder Rockefeller ( January 20 , 1949 -- June 13 , 2014 ) was a family physician in Falmouth , Maine who practiced and taught medicine in Portland , Maine , from 1982 to 2000 . He was married and had two children and two stepchildren . A son of Margaret McGrath Rockefeller and banker David Rockefeller , he was a grandson of American financier John D. Rockefeller Jr. , and a great grandson of American business magnate and philanthropist John D. Rockefeller Sr. . He was chairman of the United States Advisory Board of Doctors Without Borders from 1989 until 2010 , and served on the board of Rockefeller University in New York City until 2006 . In the last few years of his life , Rockefeller was working to establish better worldwide methods of treatment for individuals suffering from post-traumatic stress disorder . Rockefeller was the founder and former chairman of Hour Exchange Portland , a service credit barter in Portland and throughout the state of Maine . He also served as chairman of the board of Maine Coast Heritage Trust from 2000 to 2006 . In addition to his degree from Harvard Medical School , Rockefeller held a master 's degree in Education , and was president of the Rockefeller Family Fund .",
"title": ""
},
{
"docid": "John_D._Rockefeller",
"text": "John Davison Rockefeller Sr. ( July 8 , 1839 -- May 23 , 1937 ) was an American oil industry business magnate and philanthropist . He is widely considered the wealthiest American of all time , and the richest person in modern history . Born into a large family in upstate New York , he was shaped by his con man father and religious mother . His family moved several times before eventually settling in Cleveland , Ohio . Rockefeller became an assistant bookkeeper at the age of 16 , and went into a business partnership with Maurice B. Clark and his brothers at 20 . After buying them out , he and his brother William founded Rockefeller & Andrews with Samuel Andrews . Instead of drilling for oil , he concentrated on refining . In 1867 , Henry Flagler entered the partnership . The Rockefeller , Andrews & Flagler company grew by incorporating local refineries . Rockefeller formally founded the Standard Oil Company , Inc. in 1870 as an Ohio partnership with his brother , Henry Flagler , Jabez A. Bostwick , Samuel Andrews , and a silent partner , Stephen V. Harkness . He ran it until 1897 . As kerosene and gasoline grew in importance , Rockefeller 's wealth soared and he became the richest person in the country , controlling 90 % of all oil in the United States at his peak . Oil was used throughout the country as a light source until the introduction of electricity and as a fuel after the invention of the automobile . Furthermore , Rockefeller gained enormous influence over the railroad industry , which transported his oil around the country . Standard Oil was the first great business trust in the United States . Rockefeller revolutionized the petroleum industry , and along with other key contemporary industrialists such as steel magnate Andrew Carnegie , defined the structure of modern philanthropy . The U.S. Supreme Court ruled in 1911 that Standard Oil must be dismantled for violation of federal anti-trust laws ; it was broken up into 34 separate entities that included companies that would become ExxonMobil , Chevron , and others ; some of them still having the largest revenue . Individual pieces of the company were worth more than the whole , and as shares of these doubled and tripled in value in their early years , Rockefeller became the country 's first billionaire with a fortune worth nearly 2 percent of the national economy . His peak net worth was estimated at $ 336 billion ( in 2007 USD ; inflation-adjusted ) in 1913 . Rockefeller spent the last 40 years of his life in retirement at his estate in Westchester County , New York . His fortune was mainly used to create the modern systematic approach of targeted philanthropy through the creation of foundations that had a major effect on medicine , education and scientific research . His foundations pioneered the development of medical research and were instrumental in the eradication of hookworm and yellow fever . Rockefeller was also the founder of both the University of Chicago and Rockefeller University and funded the establishment of Central Philippine University in the Philippines . He was a devout Northern Baptist , and supported many church-based institutions . Rockefeller adhered to total abstinence from alcohol and tobacco throughout his life . He was a faithful congregant of the Erie Street Baptist Mission Church , where he taught Sunday school , and served as a trustee , clerk , and occasional janitor . Religion was a guiding force throughout his life , and Rockefeller believed it to be the source of his success . Rockefeller was also considered a supporter of capitalism based on a perspective of social Darwinism , and was quoted often as saying `` The growth of a large business is merely a survival of the fittest '' .",
"title": ""
},
{
"docid": "Nelson_Rockefeller",
"text": "Nelson Aldrich Rockefeller ( July 8 , 1908 -- January 26 , 1979 ) was an American businessman and politician . He served as the 41st Vice President of the United States under President Gerald Ford from 1974 to 1977 , and previously as the 49th Governor of New York . He also served in the administrations of Presidents Franklin Roosevelt , Harry S. Truman , and Dwight Eisenhower . A member of the wealthy Rockefeller family , he was also a noted art collector , as well as administrator of Rockefeller Center . Rockefeller , a Republican , was often considered politically liberal and progressive , or in other cases moderate . He successfully altered the political platform of the Republican Party just before the 1960 Republican Convention in what is termed the Treaty of Fifth Avenue . In his time , liberals in the Republican Party were called `` Rockefeller Republicans '' . As governor of New York from 1959 to 1973 his achievements included the expansion of the State University of New York , efforts to protect the environment , the building of the Governor Nelson A. Rockefeller Empire State Plaza in Albany , increased facilities and personnel for medical care , and creation of the New York State Council on the Arts . After unsuccessfully seeking the Republican presidential nomination in 1960 , 1964 , and 1968 , he served as Vice President under President Gerald R. Ford . Ford had been the first vice president to be appointed under the provisions of the 25th Amendment , and ascended to the presidency following the August 1974 resignation of Richard Nixon over the Watergate Scandal , selecting Rockefeller as his replacement . Rockefeller retired from politics in 1977 and therefore decided not join the 1976 Republican national ticket with Ford . Ford later selected then-Senator Bob Dole from Kansas for his new running mate but ultimately lost the election to Democrat Jimmy Carter and his running mate , Walter Mondale . Rockefeller remains , as of 2017 , the last Vice President who declined to seek re-election . As a businessman he was president and later chairman of Rockefeller Center , Inc. , and he formed the International Basic Economy Corporation in 1947 . Rockefeller assembled a significant art collection and promoted public access to the arts . He served as trustee , treasurer , and president of the Museum of Modern Art , and founded the Museum of Primitive Art in 1954 . In the area of philanthropy , he founded the Rockefeller Brothers Fund in 1940 with his four brothers , and established the American International Association for Economic and Social Development in 1946 .",
"title": ""
},
{
"docid": "Rockefeller_University_Press",
"text": "The Rockefeller University Press ( RUP ) is a department of The Rockefeller University .",
"title": ""
},
{
"docid": "Rockefeller_Institute_of_Government",
"text": "The Nelson A. Rockefeller Institute of Government is a public policy research institute that conducts studies and related projects on state and local government and finance , American federalism , public management , and New York State issues . The Institute is located in Albany , New York , and is part of the State University of New York .",
"title": ""
},
{
"docid": "Alfred_Mirsky",
"text": "Alfred Ezra Mirsky ( October 17 , 1900 -- June 19 , 1974 ) was an American pioneer in molecular biology . Mirsky graduated from Harvard College in 1922 , after which he studied for two years at the Columbia University College of Physicians and Surgeons until 1924 when he moved to the University of Cambridge on a US National Research Council fellowship for the academic year 1924 -- 1925 . He received his PhD from Cambridge in 1926 , with a dissertation under Lawrence J. Henderson on the Haemoglobin molecule , completing work begun under Joseph Barcroft . On May 25 , 1926 Mirsky married Reba Paeff , who went on to become a renowned children 's author ; they had a daughter , Reba Goodman and a son , Jonathan Mirsky . In 1927 Mirsky was appointed Lab Assistant to Alfred E. Cohn at the then Rockefeller Institute for Medical Research , beginning his association with Rockefeller University . During a sabbatical year at the California Institute of Technology , Mirsky published a paper with Linus Pauling on the general theory of protein structure , suggesting that the structure of proteins are coiled in a specific configuration that accounts for the function in the body , and that the protein is denatured when that configuration is lost by breaking the hydrogen bonds that stabilize the structure . One of Mirsky 's more notorious contributions while at the Rockefeller Institute was his attempt to discredit Oswald Avery . Avery had correctly shown that DNA was likely the agent of heredity . However , Mirsky went to great lengths to block Avery 's discovery because of doubts that DNA was the sole genetic material . It is said he even urged the Karolinska Institute in Sweden not to award Avery the Nobel Prize . Eventually Mirsky 's efforts were successful . Avery did not win the prize , despite as Erwin Chargaff claims , Avery 's work was worth two Nobel Prizes . Mirsky became an official Member of the Rockefeller Institute in 1948 , and in 1950 was internationally congratulated for the `` grand discovery '' of DNA constancy , which proved the concept of DNA as the hereditary material . He served as an editor of The Journal of General Physiology in 1951 -- 1961 . Mirsky was made Professor in 1954 when the Institute became Rockefeller University . He was also elected to the United States National Academy of Sciences in the same year . Mirsky was highly involved in university affairs , and in 1959 he initiated a series of lectures for high school students , now named the Alfred E. Mirsky Holiday Lecture on Science in his honour . In 1962 Mirsky chose a new lab assistant from a pool of candidates , in choosing a woman , Ellie Donoghue , he set a precedent by making her the first female lab assistant in the Institute 's history , the very same position which he first held upon his initial association with Rockefeller Institute . Mirsky proceeded to entrust Ms. Donoghue with assistance in his research and the running of his laboratory , setting an early precedent for the advancement of women in the labs at Rockefeller University . Following retirement from his laboratory in an official capacity in 1964 , he served as librarian of the Rockefeller University from 1965 until 1972 , all the while being allowed to maintain his laboratory at the university for his personal research . He continued to make groundbreaking contributions to the study of cell nuclei in rodents and bovines in direct parallels to the structure of cell nuclei in humans . After his wife , Reba Paeff Mirsky , died in 1966 he donated her valuable jewelry collection , save for a few pieces distributed to family and close friends , to the university 's collection . This collection of jewelry , acquired during their many trips around the world , is a part of the university 's holdings to this day . He went on to marry fellow Rockefeller employee Sonia Wohl in 1967 . Mirsky became professor emeritus in 1971 , after forty-four years at the Rockefeller Institute and University . Mirsky traveled widely and was quite knowledgeable in archaeology and art history ; his priceless collection of art and historical objects was willed to the Rockefeller University upon his death in 1974 and remains in their permanent collection .",
"title": ""
},
{
"docid": "Rockefeller_College_(disambiguation)",
"text": "Rockefeller College may be taken as a shorthand reference to : The Nelson A. Rockefeller College of Public Affairs & Policy at the University at Albany , SUNY . The John D. Rockefeller 3rd College , or `` Rocky '' , a residential college at Princeton University .",
"title": ""
},
{
"docid": "Rockefeller_College_of_Public_Affairs_&_Policy",
"text": "The Nelson A. Rockefeller College of Public Affairs & Policy is a public policy school composed of the Departments of Public Administration & Policy and Political Science at the University at Albany , SUNY , United States . The department provides educational preparation for academic and public service careers , to undertake research on significant public problems and issues , and to assist in the continuing professional development of government executives . Rockefeller College has an enhanced interdisciplinary approach to its public policy mission . The College offers appropriate assistance to the governments of New York State and the United States , and to foreign governments and international organizations in meeting the responsibilities of contemporary citizenship and governance through special courses and conferences ; research and consultation ; and publications for the dissemination of information . The Rockefeller College of Public Affairs and Policy is located on the downtown campus of the University at Albany , SUNY , at 135 Western Avenue , Albany , New York . In 2008 , it was ranked 14th overall out of 253 schools of Public Affairs by U.S. News & World Report magazine . Rankings : Information Technology and Management - # 2 ( US News 2009 ) Public Affairs - # 14 ( US News 2009 ) Public Administration and Management - # 8 ( US News 2009 ) Public Finance and Budgeting - # 7 ( US News 2009 ) Public Policy Analysis - # 22 ( US News 2009 ) Non-Profit Management - # 18 ( US News 2009 )",
"title": ""
},
{
"docid": "Rockefeller_Institute",
"text": "Rockefeller Institute may refer to : The Rockefeller Institute of Government Rockefeller University , previously known as The Rockefeller Institute for Medical Research",
"title": ""
},
{
"docid": "Rockefeller_Foundation",
"text": "The Rockefeller Foundation is a private foundation based at 420 Fifth Avenue , New York City . It was established by the six-generation Rockefeller family . The Foundation was started by Standard Oil owner John D. Rockefeller ( `` Senior '' ) , along with his son John D. Rockefeller Jr. ( `` Junior '' ) , and Senior 's principal oil and gas business and philanthropic advisor , Frederick Taylor Gates , in New York State on May 14 , 1913 , when its charter was formally accepted by the New York State Legislature . Its stated mission is `` promoting the well-being of humanity throughout the world . '' Its activities have included : Financially supported education in the United States `` without distinction of race , sex or creed '' Helped establish the London School of Hygiene and Tropical Medicine in the United Kingdom ; Established the Johns Hopkins School of Public Health and Harvard School of Public Health , two of the first such institutions in the United States ; Established the School of Hygiene at the University of Toronto in 1927 ; Developed the vaccine to prevent yellow fever ; Helped The New School provide a haven for scholars threatened by the Nazis Some of its infamous activities include : Funding various German eugenics programs , including the laboratory of Otmar Freiherr von Verschuer , for whom Josef Mengele worked before he went to Auschwitz . Construction of the Kaiser Wilhelm Institute 's Institute for Brain Research with a $ 317,000 grant in 1929 , with continuing support for the Institute 's operations under Ernst Rüdin over the next several years . As of 2015 , the Foundation was ranked as the 39th largest U.S. foundation by total giving . By year-end 2008 assets were tallied at $ 3.1 billion from $ 4.6 billion in 2007 , with annual grants of $ 137 million .",
"title": ""
},
{
"docid": "Rick_Rockefeller-Silvia",
"text": "Rick Rockefeller-Silvia ( Richard London Rockefeller-Silvia ) ( born September 9 , 1984 , New York , USA ) is an equestrian athlete , equine breeder and former model . Rockefeller-Silvia first garnered media attention in 2005 during the inception of his sport horse breeding program , `` Dream Street Stallions '' . Rockefeller-Silvia publicly purchased and imported over a million dollars worth of breeding stock from Europe in a short period of time . Shortly thereafter , under the direction of Olympic Bronze Medalist Lisa Wilcox , Rockefeller-Silvia 's stallion , Lullaby , became the United States Equestrian Team 's alternate for the Young Horse World Championships in 2006 . That same year , Rockefeller-Silvia 's program took center stage , winning multiple `` United States Dressage Federation '' ` Horse of The Year ' titles . In 2007 , his stallion Starlight , set a record breaking year end score of ( 86 % ) , not only earning him the title of The United States Dressage Federation ( USDF ) `` Horse Of The Year '' . But , also a place in the USDF ` Hall of Fame ' , on the ` Traveling Trot Perpetual Trophy ' . Rockefeller-Silvia is the youngest owner in history to have had his program or stock recognized in the USDF ` Hall of Fame ' . That same year Rockefeller-Silvia ranked 8th nationally in the United States Equestrian Federation Grand Prix standings . In 2008 Rockefeller-Silvia won the title of ` Grand Champion ' of Dressage at Devon with Starlight , the youngest owner in history to do so , further signifying his successful contributions to equine breeding programs across the United States . Additionally , Starlight produced a 100 % ` first premium ' foal crop in 2008 , under Rockefeller-Silvia 's guidance . Rockefeller-Silvia has earned three ` top ten ' placements at the National Young Horse Championships . Including a Bronze medal at the `` 2010 National Young Horse Championships '' held in Wayne , Illinois . Rockefeller-Silvia earned the title of `` High Score Circuit Champion '' of the Global Dressage Festival 's '' inaugural year ( 2012 ) Wellington , Florida . At age 21 Rockefeller-Silvia competed internationally at the Grand Prix level ( Olympic level ) of equestrian sport successfully and was awarded a United States Dressage Federation Gold Medal in recognition of his excellence as an equestrian sports athlete . For nearly a decade Rockefeller-Silvia consistently ranked in the ` top ten ' owners in the United States of America ( United States Equestrian Federation ) with his winning string of horses .",
"title": ""
},
{
"docid": "Sharon_Percy_Rockefeller",
"text": "Sharon Lee Percy Rockefeller ( born December 10 , 1944 ) is the wife of former West Virginia Senator John Davison `` Jay '' Rockefeller IV and served as that state 's First Lady from 1977 to 1985 . She was born in Oakland , California , on December 10 , 1944 , a twin daughter of Senator Charles Harting Percy ( 1919 -- 2011 ) and Jeanne Valerie Dickerson , who died in 1947 . She earned a Bachelor 's degree at Stanford University and later studied at Morris Harvey College and West Virginia Wesleyan College . Her twin sister Valerie was murdered in 1966 at the family home by a mysterious intruder . Sharon married John Davison `` Jay '' Rockefeller IV ( born 1937 ) in 1967 . He is the son of John Davison Rockefeller III ( 1906 -- 1978 ) and Blanchette Ferry Hooker ( 1909 -- 1992 ) of the Rockefeller family . She and Jay have four children and six grandchildren . As First Lady of West Virginia , she promoted the Public Broadcasting Service , helped establish a centralized system to assist mentally handicapped children , and founded Mountain Artisans , a quilting business for low-income artisans . She also campaigned to lower utility costs and to improve care for the elderly . After Jay was elected to the United States Senate in 1985 , she became Chief executive officer of WETA-TV in Washington , D.C. . She is a former member of the Steering Committee of the Bilderberg Group . The Rockefellers live in Northwest district of Washington , DC and retain their permanent residence in Charleston , West Virginia . In 2005 Percy Rockefeller was diagnosed with colon cancer , undergoing chemotherapy and radiation therapy . Her cancer has since metastasized in the bones . Her experience prompted her to convince film maker Ken Burns to produce the 2015 documentary Cancer : The Emperor of All Maladies . It is adapted from the book of the same name by Siddhartha Mukherjee .",
"title": ""
},
{
"docid": "Edward_Harkness",
"text": "Edward Stephen Harkness ( January 22 , 1874 -- January 29 , 1940 ) was an American philanthropist . Given privately and through his family 's Commonwealth Fund , Harkness ' gifts to private hospitals , art museums , and educational institutions in the Northeastern United States were among the largest of the early twentieth century . His was a major benefactor to the Columbia University , Yale University , Harvard University , Phillips Exeter Academy , St. Paul 's School , the Metropolitan Museum of Art , as well as the University of St Andrews in Scotland . Harkness inherited his fortune from his father , Stephen V. Harkness , whose wealth was established by an early investment in Standard Oil , and his brother , Charles W. Harkness . In 1918 , he was ranked the 6th-richest person in the United States by Forbes magazine 's first `` Rich List '' , behind John D. Rockefeller , Henry Clay Frick , Andrew Carnegie , George Fisher Baker , and William Rockefeller .",
"title": ""
},
{
"docid": "Jay_Rockefeller",
"text": "John Davison `` Jay '' Rockefeller IV ( born June 18 , 1937 ) served as a United States Senator from West Virginia from 1985 to 2015 . He was first elected to the Senate in 1984 , while in office as Governor of West Virginia , a position he held from 1977 to 1985 . Rockefeller moved to Emmons , West Virginia to serve as a VISTA worker in 1964 , and was first elected to public office in the state , as a member of the House of Delegates , in 1966 . Rockefeller was later elected West Virginia Secretary of State in 1968 and was president of West Virginia Wesleyan College from 1973 to 1975 . He became the state 's senior senator when the long serving Sen. Robert Byrd died in June 2010 . As a great-grandson of oil tycoon John D. Rockefeller , he was the only serving politician of the prominent six-generation Rockefeller family during his tenure in the United States Senate and the only one to have held office as a Democrat in what has been a traditionally Republican dynasty , though he too was originally a Republican until he decided to run for office in what was then a strictly Democratic state . Rockefeller did not seek reelection in 2014 .",
"title": ""
},
{
"docid": "Founder's_Hall_(Rockefeller_University)",
"text": "Founder 's Hall was the first building built on the campus of The Rockefeller University ( formerly The Rockefeller Institute for Medical Research ) . Although there are still laboratories in the building , the space is now mostly used for administrative offices . It was declared a National Historic Landmark in 1974 . It is located at 66th Street and York Avenue , in Manhattan , New York City .",
"title": ""
},
{
"docid": "Charles_T._Bernard",
"text": "Charles Taylor Bernard , Sr. ( born 1927 ) , is an American retired businessman and politician formerly from Earle in Crittenden County in eastern Arkansas . He is best known as the 1968 Republican nominee for the United States Senate seat held by long-time Democrat J. William Fulbright of Fayetteville . Although Fulbright was comfortably re-elected , Bernard , later the Republican state chairman from 1971 to 1973 , was his strongest Republican opponent , for in all previous contests Fulbright had been returned to office unopposed or without significant opposition . In the primary , Fulbright had handily defeated James D. Johnson of Conway , a segregationist Democrat who had lost 1966 gubernatorial general election to Republican Winthrop Rockefeller . Fulbright won his final election with 59.2 percent to Bernard 's 40.2 percent . Bernard 's ticket mate , Governor Rockefeller , scored a second two-year term by defeating the Democrat Marion H. Crank of Foreman in Little River County in southwestern Arkansas . Crank had earlier defeated Johnson 's wife , Virginia Morris Johnson , in the Democratic gubernatorial runoff election . In 1970 , Bernard and then Republican State Representative George E. Nowotny of Fort Smith both considered running for governor had Rockefeller not sought a third term . Bernard won the state chairmanship to succeed Odell Pollard of Searcy in White County in balloting before the GOP State Committee held in Little Rock after Rockefeller 's defeat for governor in 1970 . Bernard defeated Rockefeller 's stated choice , William T. Kelly , Sr. , of Little Rock , the Pulaski County chairman , and Everett Ham , a Rockefeller aide . The vote was 137 for Bernard , 28 for Kelly , and 27 for Ham . Delegates then named Ham as the vice chairman . John L. Ward , a Rockefeller biographer , said that Rockefeller 's aides `` felt like Bernard and the party had kicked Rockefeller 's teeth in . '' Years later , Robert Faulkner , Rockefeller 's executive secretary in 1970 , said that Bernard 's victory for the chairmanship showed that many pre-Rockefeller Republicans in Arkansas `` could n't wait to throw out the Rockefeller influence and pick their own , more conservative , traditional Republican . '' Bernard operated One Hour Marvelizing dry cleaning establishments in eastern Arkansas . He is listed in 2013 as a resident of Naples , Florida .",
"title": ""
},
{
"docid": "Rockefeller_College",
"text": "John D. Rockefeller 3rd College , or `` Rocky '' , is one of six residential colleges at Princeton University , United States . It was founded in 1982 , making it the third residential college to be established at Princeton . It is named for John D. Rockefeller 3rd , Princeton Class of 1929 , who served as a major donor and longtime trustee of the University . The college is located in the northwestern corner of the Princeton campus and is largely composed of Collegiate Gothic style structures . Madison Hall , home of the college dining hall , office , and common spaces , and the dorms Holder Hall , Buyers Hall ( formerly `` East Blair Hall '' ) , and part of Campbell Hall are presently part of Rockefeller College . Witherspoon Hall , built in 1877 , is the oldest building in the college , and is characteristically Richardsonian Romanesque , a style which predates the Collegiate Gothic . The college is home to roughly 500 freshmen and sophomores and a small number of upperclassmen . The college staff is led by the master ( a faculty member ) , and also includes a dean , a director of studies , a college administrator , a college secretary , and two graduate student assistant masters . The current master of Rockefeller College is Jeff Nunokawa , Professor of English . A council of current students also contributes to college life , organizing trips , study breaks , and other opportunities . Beginning with the 2007 -- 2008 school year , Rockefeller College has , along with Princeton 's other residential colleges , catered to upperclassmen as well as underclassmen , with new programs and advising . However , the college houses no upperclassmen , with the exception of Residential College Advisors . Rocky is a two-year college , paired with the four-year Mathey College , located nearby . Rockyites who wish to live in a residential college past their sophomore year may move into one of the three four-year colleges , Whitman , Mathey , and Butler . Since Rocky is paired with Mathey College , priority for housing in Mathey is given to students who spent their first two years living in Rocky or Mathey . Therefore , although it is possible for a Rockyite to move into any of the three four-year colleges after sophomore year , it is most advantageous for him or her to move into Mathey . Rockefeller College 's common room , Holder Hall , and Blair Arch ( which adjoins Buyers Hall but is technically a part of Mathey College ) were all featured in the film A Beautiful Mind .",
"title": ""
},
{
"docid": "Rodman_Rockefeller",
"text": "Rodman Clark Rockefeller ( May 2 , 1932 -- May 14 , 2000 ) was an American businessman and philanthropist . He was the eldest son of former U.S. Vice President Nelson Aldrich Rockefeller and his wife Mary Todhunter `` Tod '' Clark , and was a fourth-generation member of the Rockefeller family . Rockefeller was vice president from 1968 to 1972 and chief executive from 1972 to 1980 of the International Basic Economy Corporation , a commercial genetics and agribusiness concern based in New York and incorporated by his father in 1946 . Its activities , all in Latin America , included developing corn production there and building thousands of low-cost homes in three places in Mexico . He was also chairman of IBEC Inc. a successor concern , from 1980 to 1985 , and of Arbor Acres Farm , based in Glastonbury , Connecticut , a seller of genetic material for poultry broiler stock , for some years . Rockefeller was co-chairman of the Mexico-United States Business Committee , an organization focusing on economic and political issues of interest to both nations ' business communities . The passage of the North American Free Trade Agreement in the mid-1990s has been called the culmination of his and the committee 's efforts . The honors he received included a prestigious Mexican decoration , the Order of the Aztec Eagle . He was on the board of the Rockefeller Brothers Fund for nine years . For many years , he was a trustee of Rockefeller Financial Services , which manages the family 's office ( known as `` Room 5600 '' ) , its investment companies and its many foundations . He was the head of the finance committee of Rockefeller Financial Services for many years and was a longtime trustee of Rockefeller Financial 's holding company , Rockefeller & Company . Rockefeller attended both Deerfield Academy and Dartmouth College . While at Dartmouth , he was a member of Green Key , co-editor of Dartmouth 's Freshman Handbook , and elected to Phi Beta Kappa . Rockefeller continued his education at Columbia University 's Graduate School of Business Administration and received his master 's degree . Rockefeller served as chairman of Pocantico Associates , a private capital and real estate investment company . He was also a trustee of the Institute of International Education , the Thomas Jefferson Memorial Foundation , the Museum of Modern Art , the Americas Society , and New York Blood Center . Rockefeller married Barbara Ann Olsen in 1953 and the couple had four children : Meile , Peter , Stuart , and Michael . That marriage ended in divorce in 1979 and he married the former Alexandra von Metzler , known as Sascha , in 1980 . Category : Rockefeller family Category : American businesspeople Category : American philanthropists Category : Deerfield Academy alumni Category :1932 births Category :2000 deaths Category : Columbia Business School alumni Category : Dartmouth College alumni Category : Clark banking family Category : Recipients of the Order of the Aztec Eagle Category : Dudley -- Winthrop family Category : American people of English descent Category : American people of German descent Category :20 th-century American businesspeople",
"title": ""
},
{
"docid": "Emil_C._Gotschlich",
"text": "Emil Claus Gotschlich is a professor emeritus at the Rockefeller University . He is best known for his development of the first meningitis vaccine in 1970 . Gotschlich received his M.D. from the New York University School of Medicine in 1959 . He interned at Bellevue Hospital in New York before joining The Rockefeller University 's Laboratory of Bacteriology and Immunology in 1960 . He was promoted to professor and senior physician at The Rockefeller University Hospital in 1978 . From 1996 to 2005 he served as the hospital 's vice president for medical sciences . He is a member of the National Academy of Sciences and its Institute of Medicine . He was the recipient of the 1978 Albert Lasker Clinical Medical Research Award .",
"title": ""
},
{
"docid": "Journal_of_Cell_Biology",
"text": "The Journal of Cell Biology is an international , peer-reviewed journal owned by The Rockefeller University and published by The Rockefeller University Press .",
"title": ""
},
{
"docid": "Marsh-Billings-Rockefeller_National_Historical_Park",
"text": "Marsh-Billings-Rockefeller National Historical Park is a United States National Historical Park in Woodstock , Vermont . The park preserves the site where Frederick Billings established a managed forest and a progressive dairy farm . The name honors Billings and the other owners of the property : George Perkins Marsh , Mary Montagu Billings French , Laurance Rockefeller , and Mary French Rockefeller . The Rockefellers transferred the property to the federal government in 1992 . It is the only unit of the United States National Park System in Vermont ( except for a portion of the Appalachian Trail ) .",
"title": ""
},
{
"docid": "Rockefeller_State_Park_Preserve",
"text": "__ NOTOC __ Rockefeller State Park Preserve is a state park in Sleepy Hollow , New York in the eastern foothills of the Hudson River in Westchester County . Common activities in the park include walking , jogging , running , horse-riding , birdwatching , and fishing . The park has a rich history and was donated to the State of New York over time by the Rockefeller Family beginning in 1983 . Rockefeller State Park Preserve is designated by the National Audubon Society as an Important Bird Area with over 180 species , and is known for its wildlife , carriage trails , and scenic vistas . The park 's 32 miles of carriage trails allow visitors to view the various habitats of the 1552 acre park , which include open meadows , dense forest , meandering brooks , wetlands , and the 24 acre Swan Lake . Rockefeller State Park Preserve abuts the Old Croton Aqueduct State Historic Park and Sleepy Hollow Cemetery . The preserve also abuts extensive private land owned by the Rockefeller family which is open to the public . The trails in the private area , still in use by the Rockefeller family and also open to the public , connect with those in the state park . Many of these trails were planned and laid out by John D. Rockefeller ( Sr. ) and his descendants . Access to these trails , and additional access to the state park trails , is available from Sleepy Hollow Road and Bedford Road/Route 448 in Sleepy Hollow . A section of the State Park is west of the Preserve , along the Hudson River , and is called the Rockwood Hall section . The Visitor Center in the Preserve also has a small art gallery that frequently displays paintings and photographic art works of local artists . Stone Barns Center for Food & Agriculture , `` a nonprofit farm and educational center designed to demonstrate , teach and promote sustainable , community-based food production '' , is located within walking distance of the preserve . The park is open year-round , from sunrise to sunset , and with office hours from 9a . m. to 4:30 p.m. . There is a fee for parking .",
"title": ""
},
{
"docid": "Harry_Frankfurt",
"text": "Harry Gordon Frankfurt ( born May 29 , 1929 ) is an American philosopher . He is professor emeritus of philosophy at Princeton University , where he taught from 1990 until 2002 , and previously taught at Yale University , Rockefeller University , and Ohio State University .",
"title": ""
},
{
"docid": "Rockefeller_Brothers_Fund",
"text": "The Rockefeller Brothers Fund ( RBF ) is a philanthropic foundation created and run by members of the Rockefeller family . It was founded in New York City in 1940 as the primary philanthropic vehicle for the five third-generation Rockefeller brothers : John D. Rockefeller III , Nelson , Laurance , Winthrop and David . It is distinct from the Rockefeller Foundation . The Rockefellers are an industrial , political , and banking family that made one of the world 's largest fortunes in the oil business during the late 19th and early 20th centuries . The Fund 's stated mission is to `` advance social change that contributes to a more just , sustainable , and peaceful world . '' The current president of RBF is Stephen Heintz , who was appointed to the post in 2000 . Valerie Rockefeller Wayne serve as RBF 's chairwoman . She succeeded Richard Rockefeller , the fifth child of David Rockefeller , who served as RBF 's chairman until his death in 2014 .",
"title": ""
},
{
"docid": "Peter_Elsbach",
"text": "Peter Elsbach ( born 1924 , Zeist ) is a Dutch physician . He is an emeritus professor of medicine at the New York University School of Medicine . He is specialized in biochemistry , infectious diseases and natural anti-bacterial host defense . In 1950 he obtained a degree in medicine from the University of Amsterdam . The next three years he was an intern at the local hospital . In 1953 he moved to the United States where he started residency training at the New York University School of Medicine . From 1956 to 1959 he did clinical fellowships at Rockefeller University . While at Rockefeller , he obtained his PhD in Medical Sciences from Leiden University in 1964 with his dissertation Uptake of Lipid by Phagocytic Cells . An Examination of the Role of Phagocytosis . He was elected a corresponding member of the Royal Netherlands Academy of Arts and Sciences in 1979 . He received an honorary degree from Lund University in 1993 . In 2008 he received honorary life membership of the International Endotoxin and Innate Immunity Society . Elsbach is a member of the American Society for Clinical Investigation .",
"title": ""
},
{
"docid": "Rockefeller_Drug_Laws",
"text": "The Rockefeller Drug Laws are the statutes dealing with the sale and possession of `` narcotic '' drugs in the New York State Penal Law . The laws are named after Nelson Rockefeller , who was the state 's governor at the time the laws were adopted . Rockefeller , a staunch supporter of the bill containing the laws , had Presidential ambitions and so wanted to raise his national posture by being `` tough on crime . '' If this strategy worked , he would no longer be seen as too liberal to be elected . He signed it on May 8 , 1973 . Under the Rockefeller drug laws , the penalty for selling spell = in 2 or more of heroin , morphine , `` raw or prepared opium , '' cocaine , or cannabis or possessing 4 oz or more of the same substances , was a minimum of 15 years to life in prison , and a maximum of 25 years to life in prison . The original legislation also mandated the same penalty for committing a violent crime while under the influence of the same drugs , but this provision was subsequently omitted from the bill and was not part of the legislation Rockefeller ultimately signed . The section of the laws applying to marijuana was repealed in 1977 , under the Democratic Governor Hugh Carey . The adoption of the Rockefeller drug laws gave New York State the distinction of having the toughest laws of its kind in the entire United States -- an approach soon imitated by the state of Michigan , which , in 1978 , enacted a `` 650-Lifer Law , '' which called for life imprisonment , without the possibility of parole for the sale , manufacture , or possession of at least 650 g of cocaine or any Schedule I or Schedule II opiate .",
"title": ""
},
{
"docid": "Rockefeller-Aldrich_family_political_line",
"text": "George Aldrich ( 1605-1683 ) , an immigrant from England , settled in Mendon , Massachusetts Bay Colony , in the mid 17th century . William Aldrich ( 1820-1885 ) , U.S. Representative from Illinois 1877-1883 , Wisconsin Assemblyman 1859 . Cousin of Nelson W. Aldrich . James Franklin Aldrich ( 1853-1933 ) , U.S. Representative from Illinois 1893-1897 . Son of William Aldrich . Nelson W. Aldrich ( 1841-1915 ) , U.S. Senator from Rhode Island 1881-1911 . ( Chairman of Senate Finance Committee ) , U.S. Representative from Rhode Island 1879-1881 , Rhode Island State Representative 1875-1877 , Cousin of William Aldrich . Richard S. Aldrich ( 1884-1941 ) , Rhode Island State Representative 1915-1916 , Rhodes Island State Senator 1917-1918 , U.S. Representative from Rhode Island 1923-1933 , delegate to the Republican National Convention 1924 . Son of Nelson W. Aldrich . Winthrop W. Aldrich ( 1885-1974 ) , U.S. Ambassador to Great Britain 1953-1957 . Son of Nelson W. Aldrich . Nelson Aldrich Rockefeller ( 1908-1979 ) , Vice President of the United States 1974-1977 . Governor of New York 1959-1973 , delegate to the Republican National Convention 1960 1964 , candidate for the Republican nomination for President of the United States 1960 1964 1968 1976 , Nephew of Richard S. Aldrich and Winthrop W. Aldrich . Winthrop Rockefeller ( 1912-1973 ) , Republican National Committeeman 1961 , delegate to the Republican National Convention 1964 , candidate for Governor of Arkansas 1964 , Governor of Arkansas 1967-1971 , candidate for the Republican nomination for President of the United States 1968 . Nephew of Richard S. Aldrich and Winthrop W. Aldrich . Richard S. Aldrich , candidate for U.S. Representative from New York 1962 , New York City Councilman . Son of Richard S. Aldrich . Charles H. Percy ( September 27 , 1919 -- September 17 , 2011 ) , delegate to the Republican National Convention 1960 , candidate for Governor of Illinois 1964 , U.S. Senator from Illinois 1967-1985 , candidate for the Republican nomination for President of the United States 1968 1976 . Father-in-law of John D. Rockefeller IV . John D. Rockefeller IV ( 1937 - ) , West Virginia House Delegate 1967-1968 , West Virginia Secretary of State 1969-1972 , candidate for Governor of West Virginia 1972 , Governor of West Virginia 1977-1985 , U.S. Senator from West Virginia 1985-2015 , delegate to the Democratic National Convention 2000 2004 . Nephew of Nelson A. Rockefeller and Winthrop Rockefeller . Winthrop Paul Rockefeller ( 1948-2006 ) , Lieutenant Governor of Arkansas 1996-2006 , candidate for the Republican nomination for Governor of Arkansas 2006 , withdrew nomination . Son of Winthrop Rockefeller . Mark Dayton ( 1947 - ) , candidate for U.S. Senate from Minnesota 1982 , Auditor of Minnesota 1991-1995 , U.S. Senator from Minnesota 2001-2007 , delegate to the Democratic National Convention 2004 , Governor of Minnesota from January 3 , 2011 . Former brother-in-law of John D. Rockefeller , IV ( Dayton divorced from Alida Rockefeller 1986 ) . NOTE : John D. Rockefeller IV and Winthrop Paul Rockefeller are also former third cousins by marriage of U.S. Senator William Proxmire .",
"title": ""
},
{
"docid": "Simon_Flexner",
"text": "Simon Flexner , M.D. ( March 25 , 1863 in Louisville , Kentucky -- May 2 , 1946 ) was a physician , scientist , administrator , and professor of experimental pathology at the University of Pennsylvania ( 1899 -- 1903 ) . He served as the first director of the Rockefeller Institute for Medical Research ( 1901 -- 1935 ) ( later developed as Rockefeller University ) and a trustee of the Rockefeller Foundation . He was also a friend and adviser to John D. Rockefeller Jr. . . Among Flexner 's most important achievements are studies into poliomyelitis and the development of serum treatment for meningitis . Among his lab assistants were Hideyo Noguchi and Cornelius Rhoads , later directors of Memorial Hospital and the Sloan-Kettering Institute , respectively . The bacteria species Shigella flexneri was named in recognition of Flexner . In addition , Flexner was the first to describe Flexner-Wintersteiner rosettes , a characteristic finding in retinoblastoma , a type of cancer .",
"title": ""
},
{
"docid": "Rockefeller_Chapel",
"text": "Rockefeller Chapel is a Gothic Revival chapel on the campus of the University of Chicago in Chicago , Illinois . A monumental example of Collegiate Gothic architecture , it was meant by patron John D. Rockefeller to be the `` central and dominant feature '' of the campus ; at 200.7 feet it is by covenant the tallest building on campus .",
"title": ""
},
{
"docid": "Mary_Rockefeller",
"text": "Mary Todhunter Clark Rockefeller ( June 17 , 1907 -- April 21 , 1999 ) was the first wife of Nelson Aldrich Rockefeller , a Governor of New York . She served as the First Lady of New York from 1959 until the Rockefellers ' divorce in March 1962 . After their divorce , Nelson Rockefeller served as the 41st Vice President of the United States .",
"title": ""
}
] |
209651
|
George W. Romney was married to a woman.
|
[
{
"docid": "Lenore_Romney",
"text": "Lenore LaFount Romney ( born Lenore Lafount but adopted the variation LaFount ; November 9 , 1908 -- July 7 , 1998 ) was an American actress and politician . The wife of businessman and politician George W. Romney , she was First Lady of Michigan from 1963 to 1969 . She was the Republican Party nominee for the U.S. Senate in 1970 from Michigan . Her youngest son , Mitt Romney , is a former Governor of Massachusetts and was the 2012 Republican presidential nominee . Lenore LaFount was born in Logan , Utah , and raised in Salt Lake City . She went to Latter-day Saints High School , where she developed an interest in drama and first met George Romney . She attended the University of Utah and George Washington University , graduating from the latter in 1929 . She studied acting at the American Laboratory Theatre in New York , then went to Hollywood where she became a bit player who appeared in a number of films with Metro-Goldwyn-Mayer . Turning down a contract offer with them , she married George Romney in 1931 . The couple had four children together ; she was a stay-at-home mother , eventually living in Bloomfield Hills , Michigan , while he became a success in business and politics . Lenore Romney was a popular First Lady of Michigan and was a frequent speaker at events and before civic groups . She was involved with many charitable , volunteer , and cultural organizations , including high positions with the Muscular Dystrophy Association , YWCA , and American Field Services , and also was active in the LDS Church of which she was a lifelong member . She was an asset to her husband 's 1968 presidential campaign . Although a traditionalist , she was an advocate for the greater involvement of women in business and politics . In 1970 , she was urged by her husband and state Republican Party officials to run against popular , two-term Democratic incumbent Senator Philip Hart . However , she struggled to establish herself as a serious candidate apart from her husband and failed to capture the support of conservatives within the party , only narrowly defeating State Senator Robert J. Huber in the party primary . Her difficulties continued in the general election and she lost to Hart by a two-to-one margin . She returned to volunteer activities during the 1970s , including stints on the boards of the National Center for Voluntary Action and the National Conference of Christians and Jews , and gave speeches to various organizations .",
"title": ""
},
{
"docid": "George_W._Romney",
"text": "George Wilcken Romney ( July 8 , 1907 -- July 26 , 1995 ) was an American businessman and Republican Party politician . He was chairman and president of American Motors Corporation from 1954 to 1962 , the 43rd Governor of Michigan from 1963 to 1969 , and the United States Secretary of Housing and Urban Development from 1969 to 1973 . He was the father of former Governor of Massachusetts and 2012 Republican presidential nominee Mitt Romney and the husband of former Michigan U.S. Senate candidate Lenore Romney . Romney was born to American parents living in the Mormon colonies in Mexico ; events during the Mexican Revolution forced his family to flee back to the United States when he was a child . The family lived in several states and ended up in Salt Lake City , Utah , where they struggled during the Great Depression . Romney worked in a number of jobs , served as a Mormon missionary in the United Kingdom , and attended several colleges in the U.S. but did not graduate from any of them . In 1939 he moved to Detroit and joined the American Automobile Manufacturers Association , where he served as the chief spokesman for the automobile industry during World War II and headed a cooperative arrangement in which companies could share production improvements . He joined Nash-Kelvinator in 1948 , and became the chief executive of its successor , American Motors Corporation , in 1954 . There he turned around the struggling firm by focusing all efforts on the compact Rambler car . Romney mocked the products of the `` Big Three '' automakers as `` gas-guzzling dinosaurs '' and became one of the first high-profile , media-savvy business executives . Devoutly religious , he presided over the Detroit Stake of The Church of Jesus Christ of Latter-day Saints . Having entered politics by participating in a state constitutional convention to rewrite the Michigan Constitution during 1961 -- 1962 , Romney was elected Governor of Michigan in 1962 . Re-elected by increasingly large margins in 1964 and 1966 , he worked to overhaul the state 's financial and revenue structure , greatly expanding the size of state government and introducing Michigan 's first state income tax . Romney was a strong supporter of the American Civil Rights Movement . He briefly represented moderate Republicans against conservative Republican Barry Goldwater during the 1964 U.S. presidential election . He requested the intervention of federal troops during the 1967 Detroit riot . Initially a front runner for the Republican nomination for President of the United States in the 1968 election , he proved an ineffective campaigner and fell behind Richard Nixon in polls . After a mid-1967 remark that his earlier support for the Vietnam War had been due to a `` brainwashing '' by U.S. military and diplomatic officials in Vietnam , his campaign faltered even more and he withdrew from the contest in early 1968 . After Nixon 's election as president , he appointed Romney as Secretary of Housing and Urban Development . Romney 's ambitious plans for housing production increases for the poor , and for open housing to desegregate suburbs , were modestly successful but often thwarted by Nixon . Romney left the administration at the start of Nixon 's second term in 1973 . Returning to private life , he advocated volunteerism and public service , and headed the National Center for Voluntary Action and its successor organizations from 1973 through 1991 . He also served as a regional representative of the Twelve within his church .",
"title": ""
}
] |
[
{
"docid": "Miles_Park_Romney",
"text": "Miles Park Romney ( August 18 , 1843 -- March 1904 ) was born in Nauvoo , Illinois , the son of Miles Romney . He was the president of the St. George Social Hall Company and the St. George Dramatic Association , and also served as a chief of police , attorney-at-law , newspaper editor , and architect . One of his sons , Gaskell Romney , was the father of George W. Romney and grandfather of Mitt Romney . Miles Park Romney became a builder , moved to Utah , married one woman , did mission work in England , returned to Utah and married another woman on orders from Brigham Young . He became quite prominent in the Mormon community , building Brigham Young 's home and helping to defeat a congressional anti-polygamy law . Miles Park Romney and his three wives and various children were then sent to settle St. Johns , Arizona , as part of the church leadership 's plan to settle across the entire American West . St. Johns was not particularly welcoming to the Mormon newcomers , with Romney , the editor of the local Mormon paper a particular target ; Romney became entangled in a non-Mormon led effort to try David King Udall , another prominent Mormon and bishop , for fraud involving a homestead application and after various threats to hang the lot of them , the polygamous Romney family was told to try Mexico instead . A polygamist , in the aftermath of the Edmunds Anti-Polygamy Act of 1882 ( later amended by the Edmunds -- Tucker Act , 1887 ) , Romney , on April 7 , 1885 , joined a party leaving Arizona to find land outside the U.S. , in the state of Chihuahua , Mexico , on which his family could settle , free from fear of his arrest . Romney died on February 26 , 1904 , in Colonia Dublan , Mexico . Romney 's five wives , in order of marriage , were Hannah Hood Hill ( 1862 ) , Caroline `` Carrie '' Lambourne ( 1867 ) , Catherine Jane Cottam ( 1873 ) , Alice Marie `` Annie '' Woodbury ( 1877 ) and Emily `` Millie '' Henrietta Eyring Snow ( 1897 ) . Romney married Hannah Hood Hill on May 10 , 1862 , at Salt Lake City , Utah .",
"title": ""
},
{
"docid": "George_Romney",
"text": "George Romney may refer to : George Romney ( painter ) ( 1734 -- 1802 ) , English portrait painter George S. Romney ( 1874 -- 1935 ) , president of the college now known as Brigham Young University-Idaho George W. Romney ( 1907 -- 1995 ) , businessman , Governor of Michigan , U.S. presidential candidate , Secretary of Housing & Urban Development , Mitt Romney 's father G. Scott Romney ( born 1941 ) , Michigan lawyer and politician , son of George W. Romney and brother of Mitt Romney G. Ott Romney ( 1892 -- 1973 ) , American football player , coach and college athletics administrator",
"title": ""
},
{
"docid": "George_W._Romney_Building",
"text": "The George W. Romney Building - ( `` The Romney Building '' ) is the Governor of Michigan 's main office , and houses other State of Michigan offices . The building is named after George W. Romney , the 43rd Governor and father of Mitt Romney . The building has a ten-story atrium , beginning on the fourth floor .",
"title": ""
},
{
"docid": "Gaskell_Romney",
"text": "Gaskell Romney ( September 22 , 1871 -- March 7 , 1955 ) is regarded as a father of the Romneys , a U.S. political family . Romney was born in St. George , in what was then the Utah Territory , the son of Miles Park Romney and Hannah Hood Hill . Gaskell Romney moved to Mexico when his father helped to found the Mormon colony in Colonia Dublán , Galeana , Chihuahua , Mexico , in 1885 . The Romney families lost their holdings in Chihuahua during the Mexican Revolution and in 1912 Romney moved back to the United States . Eventually he was reimbursed by the Mexican government for some of his losses . He married in 1895 to Anna Amelia Pratt . Romney was the father of six sons and one daughter : Maurice , Douglas , Miles , George W. Romney , Lawrence , Charles and Meryl . Gaskell himself was a candidate for County Commissioner 1931 as a Republican . He died in Salt Lake City , Utah , on March 7 , 1955 and is buried in Wasatch Lawn Memorial Park in the city .",
"title": ""
},
{
"docid": "George_S._Romney",
"text": "George Samuel Romney ( November 12 , 1874 -- December 19 , 1935 ) was the president of Ricks Academy at the end of the First World War . He was a key figure in helping it to survive the postwar depression . Romney was a member of The Church of Jesus Christ of Latter-day Saints ( LDS Church ) . He was born in St. George , Utah . When he was young his family moved to the Mormon colonies in Mexico so that his father could continue practicing plural marriage , which was illegal in the United States . After marrying and having several children , Romney returned to the United States at the start of the Mexican Revolution , specifically to flee the disruptive activities of Pancho Villa . By 1917 Romney was a faculty member at Brigham Young University in Provo , Utah . In the summer of that year Romney was appointed as principal of Ricks Academy to replace Andrew B. Christensen . In 1918 , the school was granted state certification . It was then renamed Ricks Normal College . By the time students returned for Fall Semester they not only had a new name , but they were now led by a president . Under Romney 's leadership the school instituted standards of dress and conduct that all students agreed to follow in 1922 . In 1923 , the name of the school was changed again to Ricks College , but Romney continued to lead it in its broadened mission . In 1930 Romney was replaced by Hyrum Manwaring . After his service as president of Ricks College , Romney served as president of the church 's Northern States Mission . He died while serving in this position and was replaced by Bryant S. Hinckley . Romney 's eldest son , Marion G. Romney , became an apostle and a member of the First Presidency of the LDS Church . Romney daughter , Catherine Romney Cheney , later became a cloistered nun in the Roman Catholic Church . Romney was an uncle of former Michigan governor George W. Romney .",
"title": ""
},
{
"docid": "Scott_Romney",
"text": "George Scott Romney ( born June 7 , 1941 ) is an American Republican politician and lawyer in the state of Michigan . He formerly sat on the Michigan State University Board of Trustees . A member of the Pratt-Romney family -- a well-known political family in Michigan -- he is the son of former Michigan Governor George W. Romney and brother of the former Massachusetts Governor and 2012 Republican presidential nominee Mitt Romney . He goes by the name of `` Scott '' in order to distinguish himself from his father .",
"title": ""
},
{
"docid": "Elwood_Romney",
"text": "Elwood Snow `` Woody '' Romney ( May 28 , 1911 -- August 24 , 1970 ) was an American basketball player and coach . He was an All-American at Brigham Young University ( BYU ) and later played semi-professionally . After his playing days , Romney coached at the college level and worked in other high-profile sports endeavors . Romney , a forward from St. George , Utah , starred at Dixie High School and played collegiately at Brigham Young from 1929 -- 33 . Romney led the Cougars to a pair of Rocky Mountain Conference titles . He was named a consensus All-American in 1931 and again made the Helms Athletic Foundation All-America team in 1932 . Romney scored 1,150 points in his BYU career . After the completion of his college career , Romney played semi-professional basketball with the Denver Athletic Club for two seasons . He then coached collegiately , first at Western State College for the 1935-36 season ( 13-7 record ) , then at the Colorado School of Mines from 1936 to 1939 ( 9-45 record ) . Romney was hired at Mines to also work in multiple sports , and during his tenure at Mines Romney also coached freshman football and was credited with creating a great deal of interest in intramural sports to where 300 students were taking part by the time he departed in 1939 . While living at Golden , Colorado Romney also sold automobiles and spearheaded the revival of the Golden Plunge , Golden 's community swimming pool , formulating a business plan and leading the successful community effort to purchase and reopen it on July 4 , 1938 . He owned and ran it successfully until selling it in October 1941 . After leaving coaching , Elwood Romney remained active in sports in Colorado . He was a key figure in founding the Western League , a minor-league baseball circuit , and served as league president . He also owned the Denver Bears franchise . In personal life , Romney was married to Ruth Hafen on June 26 , 1928 . They had three children : Jerry Elwood Romney , Janice Ruth Romney , and Jean Romney . Elwood Romney was the son of Erastus Snow Romney and Roxie Maria Stowell and grandson of Miles Park Romney and Annie Marie Woodbury . By this relation Elwood was a first cousin of George W. Romney and is ancestral cousin of his son Mitt Romney . Elwood Romney was inducted into the BYU Athletics Hall of Fame , the Helms Athletic Foundation Hall of Fame and the Utah Sports Hall of Fame . He died on August 24 , 1970 .",
"title": ""
},
{
"docid": "Romney_family",
"text": "The Romney family , prominent in U.S. politics and other professions , is most known for its connection with George W. Romney ( 1907 in Colonia Dublán , Galeana , Chihuahua , Mexico -- 1995 at Bloomfield Hills , Michigan ) , 43rd governor of Michigan ( 1963 -- 1969 ) and his son , Mitt Romney ( born 1947 in Detroit , Michigan ) , 70th governor of Massachusetts ( 2003 -- 2007 ) , and Republican nominee for the presidency of the United States in 2012 . George Romney 's father was Gaskell Romney ( 1871 in St. George , Utah -- 1955 in Salt Lake City , Utah ) , and his mother was Anna Amelia Pratt . Anna 's grandfather was renowned early Mormon leader Parley Parker Pratt . Based upon the family 's heritage going back to the first Mormon generation and to their modern-day prominence in business , politics , and as part of The Church of Jesus Christ of Latter-day Saints , authors Richard and Joan Ostling have written variously that the Romneys are `` an LDS political dynasty '' and that `` The Romneys are LDS royalty . '' The family is linked by marriage to the Smith family , and has a lateral relationship with the Matheson family , the Huntsman family , and the Eyring family . A branch of the Romneys reside in the Mormon colonies in Mexico . The Romney family emigrated to the United States from Dalton-in-Furness , England in the 1840s .",
"title": ""
},
{
"docid": "Ronna_Romney_McDaniel",
"text": "Ronna Romney McDaniel ( born 1973 ) is an American political operative . A member of the Republican Party , she is the current chairwoman of the Republican National Committee , and former chairwoman of the Michigan Republican Party . A third generation politician , McDaniel is the granddaughter of George W. Romney and the niece of Mitt Romney .",
"title": ""
},
{
"docid": "Milton_Romney",
"text": "Milton Addas Romney ( June 20 , 1899 -- November 1975 ) was a professional American football player who played in the offensive backfield for the Racine Legion from 1923 to 1924 and was a quarterback for the Chicago Bears from 1925 to 1928 . Romney played quarterback for the University of Chicago in the early 1920s when it had a winning varsity team , and was elected captain of the team in 1922 . After graduating from the U of Chicago in 1923 , Romney was head basketball coach at the University of Texas at Austin during the 1922 -- 23 season . He coached the Longhorns to a record of 11 -- 7 . Romney was born in Salt Lake City , Utah . He is the cousin of George W. Romney , father of former Massachusetts Governor and 2012 Republican Presidential Candidate Mitt Romney . Mitt Romney is his namesake and is a first cousin once removed .",
"title": ""
},
{
"docid": "National_Center_for_Voluntary_Action",
"text": "The National Center for Voluntary Action was an independent , private , non-profit organization that existed in the 1970s , and then extended on in merged forms , that sought to encourage volunteerism on the part of American citizens and organizations , assist in program development for voluntary efforts , and sought to make voluntary action an important force in American society . The organization had its origins in 1969 , the first year of the Nixon administration , when the Cabinet Committee on Voluntary Action was put into place . Led by United States Secretary of Housing and Urban Development George W. Romney , a study performed by this committee found a need for a national , non-governmental organization . Hence came the National Center for Voluntary Action , created in 1970 by executive order of the president . At its first meeting on February 20 , 1970 , Romney stressed the value of voluntary action as the `` fourth way '' of solving problems ( along with the federal government , state and local government , and private industry ) . In April 1970 , Henry Ford II became the organization 's first chair and Bud Wilkinson its first president . The organization launched a nationwide effort to develop Voluntary Action Centers ( previously known as Volunteer Bureaus ) as local volunteer centers to help people meet their needs through actions of volunteers . A heart-shaped logo was devised for the Voluntary Action Centers and used nationwide . It operated an information bank known as Clearinghouse . By October 1971 , Voluntary Action Centers had been established in 32 communities , with 30 more underway and 250 other communities having expressed interest . Wilkinson left in August 1970 . Lenore Romney , George 's wife , became a director of the organization , and a member of its executive committee by 1971 , and vice president by 1973 . Ford departed in 1972 , and W. Clement Stone , who was the treasurer , became acting chair . In 1973 , as he left the Nixon administration , George Romney became chair and CEO of the National Center for Voluntary Action . In 1976 , the organization sponsored a national Congress on Volunteerism and Citizenship in conjunction with the United States Bicentennial of that year . In 1979 , the National Center for Voluntary Action merged with another organization , the Colorado-based National Information Center on Volunteerism ( which had been in existence since 1970 , and as the National Information Center on Volunteers in Courts , since 1967 ) , and together became a new organization , VOLUNTEER : The National Center for Citizen Involvement . Romney remained as head of the new organization . The organization simplified its name to VOLUNTEER : The National Center in 1984 and to the National Volunteer Center in 1990 . Romney remained as chair of these organizations throughout this time . In 1991 , the organization merged into the Points of Light Foundation , which had been created in 1990 under the aegis of President George H.W. Bush . The merged organization also became known during the 2000s as the Points of Light Foundation and Volunteer Center National Network . That organization then in 2007 merged with the Atlanta-based Hands On Network to become the Points of Light Institute .",
"title": ""
},
{
"docid": "Massachusetts_liberal",
"text": "Massachusetts liberal is a phrase in American politics which is generally used as a pejorative political epithet by Republicans against Democrats who are from the Commonwealth of Massachusetts . It was most significantly used in the 1988 presidential race by Vice President George H.W. Bush against Governor Michael Dukakis , and again in the 2004 race by then-President George W. Bush against Senator John Kerry . The Democratic candidates ( Dukakis , Kerry ) lost both races . In the Republican 2012 presidential primary election Newt Gingrich used the phrase repeatedly against Mitt Romney , the former Governor of Massachusetts , whose main residence was a mansion in the state . Romney went on to win the nomination , but lost the Presidential election .",
"title": ""
},
{
"docid": "Romney_Sedgwick",
"text": "Richard Romney Sedgwick ( 29 May 1894 - 20 January 1972 ) was a British historian , civil servant and diplomat . He was the elder son of Professor Adam Sedgwick , 1854-1913 , and Laura Helen Elizabeth Robinson . He married Mana St David Hodson , daughter of Professor T.C.Hodson , in 1936 ; they had one son and one daughter . Sedgwick was educated at Weestminster School and Trinity College Cambridge . He became a Fellow of the College in 1919 . His work for The History of Parliament showed that the Whig versus Tory dichotomy survived in the reigns of George I and George II . Eveline Cruickshanks wrote a book on the Tories and the Jacobite Rising of 1745 and said : `` My greatest debt is to the late Romney Sedgwick , a staunch Whig , whose wit and erudition I greatly admired , for a series of discussions , heated at times , but , as I well know , much enjoyed on both sides '' .",
"title": ""
},
{
"docid": "Latter_Day_Saint_political_history",
"text": "This is a chronological listing of significant events surrounding Latter Day Saints seeking or winning political office . It refers primarily to members of The Church of Jesus Christ of Latter-day Saints ( LDS Church ) , but also some members of other Latter Day Saint movement religions , such as Community of Christ , formerly the Reorganized Church of Jesus Christ of Latter Day Saints ( RLDS ) . In addition to listing events chronologically , political firsts are noted . This list is very incomplete . 1838 John Corrill elected to the Missouri House of Representatives . This was the first Latter Day Saint elected to a state office in any state . 1841 William B. Smith elected to the Illinois House of Representatives . This was the first Latter Day Saint elected to a state office in Illinois . This was the first time a member of the Smith Family was elected to office . 1842 Joseph Smith elected Mayor of Nauvoo . 1844 Joseph Smith declares himself a candidate for President of the United States . He is assassinated during his campaign . This was the first Latter Day Saint to run for president . This was the first Latter Day Saint assassinated in office ( as Mayor of Nauvoo ) . 1850 Brigham Young is appointed Governor of Utah Territory . This is the first Latter Day Saint to hold a U.S. governorship . 1853 Jefferson Hunt is elected to the California State Assembly . This is the first Latter Day Saint elected to state office in California . James J. Strang is elected to the Michigan Legislature . This is the first Latter Day Saint elected to state office in Michigan . 1855 James J. Strang is reelected to the Michigan Legislature . 1858 Brigham Young removed from office as Governor of Utah . 1896 Utah gains statehood . Martha Hughes Cannon first woman elected to any state senate in U.S. history ( Utah ) . Heber Manning Wells elected Utah Governor . This is the first Latter Day Saint to be Utah governor since Brigham Young . This is the first Latter Day Saint to be elected governor of any state . Frank J. Cannon elected U.S. Senator from Utah First Latter-day Saint elected to the Senate . ( Cannon later left the LDS Church and became a bitter anti-Mormon . ) 1902 Reed Smoot elected to the U.S. Senate in Utah . First LDS Church General Authority elected to the Senate . 1911 Israel A. Smith elected to the Iowa State Legislature . First direct descendant of Latter Day Saint movement founder Joseph Smith to be elected to political office . 1922 George Sutherland appointed to the U.S. Supreme Court . 1928 J. Reuben Clark appointed U.S. Undersecretary of State . 1930 J. Reuben Clark appointed U.S. Ambassador to Mexico . 1940 Berkeley Bunker appointed U.S. Senator from Nevada . First Latter Day Saint to hold national office from Nevada . First Latter Day Saint U.S. Senator from outside Utah . 1944 Berkeley Bunker elected to U.S. House of Representatives from Nevada . 1953 Ezra Taft Benson appointed U.S. Secretary of Agriculture . Ivy Baker Priest appointed U.S. Treasurer . 1961 Stewart Udall appointed U.S. Secretary of the Interior . 1962 George W. Romney elected Governor of Michigan . 1968 George W. Romney declares candidacy for President of the United States ( as Republican ) . First Latter Day Saint to run for a major party 's presidential nomination . 1969 David Matthew Kennedy appointed U.S. Secretary of Treasury . George W. Romney appointed U.S. Secretary of Housing and Urban Development . 1976 Mo Udall declares candidacy for President of the United States ( as Democrat ) . 1980 Paula Hawkins elected to U.S. Senate from Florida . 1981 Terrel Bell appointed U.S. Secretary of Education . 1982 Bay Buchanan baptized into LDS Church as sitting U.S. Treasurer . Harry Reid wins election as a representative from Nevada . 1985 Jake Garn becomes first sitting U.S. Senator to fly in space . 1986 Harry Reid wins election as a Senator from Nevada . 1988 Evan Mecham impeached and removed from office as Governor of Arizona 1999 Three members of the Udall family serve in Congress simultaneously . Two are Latter-day Saint . 2000 Orrin Hatch declares candidacy for President of the United States ( as Republican ) . 2002 Mitt Romney elected Governor of Massachusetts . 2004 Harry Reid becomes the Democratic Leader of the United States Senate , and the Senate Minority leader 2005 Michael O. Leavitt appointed U.S. Secretary of Health and Human Services . 2007 Harry Reid becomes Senate Majority Leader Mitt Romney announces his candidacy for the U.S. presidency . 2011 Mitt Romney announces his candidacy for the U.S. presidency . First Latter Day Saint to receive a major party 's presidential nomination . Jon Huntsman , Jr. announces his candidacy for the U.S. presidency . Political History",
"title": ""
},
{
"docid": "The_Concerns_of_a_Citizen",
"text": "The Concerns of a Citizen is a book written by the Governor of Michigan , George W. Romney , and published during his campaign for the Republican presidential nomination in January 1968 .",
"title": ""
},
{
"docid": "Julian_Marsham,_8th_Earl_of_Romney",
"text": "Julian Charles Marsham , 8th Earl of Romney ( born 1948 , of Gayton Hall ) is an English peer . Romney is the son of Col. Peter William Marsham , a grandson of Charles Marsham , 4th Earl of Romney , and his wife Hersey , the granddaughter of Thomas Coke , 2nd Earl of Leicester . He was educated at Eton and became a land agent and farmer . In 1975 , he married Catriona Ann , the daughter of Sir Robert Christie Stewart , by whom he has two sons and one daughter : Major David Charles Marsham , Viscount Marsham ( b. 1977 ) ; married Katherine F. Phillips , has issue Hon. Michael Julian Marsham ( b. 1979 ) married Hon. Lucy Harriet Beaumont , daughter of Wentworth Peter Ismay Beaumont , 4th Viscount Allendale Lady Laura Clare Marsham ( b. 1984 ) , married James Meade , son of Olympian Richard Meade He succeeded his second cousin once removed , Michael Marsham , 7th Earl of Romney , in the earldom in 2004 . In 2007 , Lord Romney served as High Sheriff of Norfolk .",
"title": ""
},
{
"docid": "Matt_Rhoades",
"text": "Matthew `` Matt '' Rhoades ( born February 3 , 1974 ) is an American political consultant and strategist for the Republican National Committee . In the 2000 presidential election , he worked as a research analyst for the Republican National Committee assisting in the Florida recount . In the 2004 presidential election , Rhoades was director of opposition research for the campaign to re-elect President George W. Bush and Vice-President Dick Cheney . In the 2008 presidential bid of Mitt Romney , Rhoades was director of communications . Rhoades is cited as a pioneer in using less conventional outlets , such as the Drudge Report and America Rising , to influence the public image about candidates who oppose his clients . He was the manager of Mitt Romney 's 2012 campaign for the presidency . Rhoades received his B.A. at the Maxwell School of Citizenship and Public Affairs at Syracuse University in 1997 and his M.A. from the Graduate School of Political Management at George Washington University in 1999 .",
"title": ""
},
{
"docid": "Thomas_D._Rath",
"text": "Thomas D. Rath is a former Attorney General of New Hampshire . He is founder of the law firm of Rath , Young and Pignatelli . President George H. W. Bush appointed Rath to be a director of the Legal Services Corporation . Rath chaired the senatorial campaigns of Warren Rudman and Judd Gregg . He assisted actively with the confirmation of Supreme Court Justice David Souter by the United States Senate . He served as a senior advisor to the presidential campaigns of George W. Bush , Howard Baker , Mitt Romney , Robert Dole , and Lamar Alexander . He has served as a delegate to the Republican National Convention in 1984 , 1988 , 1992 , 1996 , 2000 , 2004 , and 2008 . He is the past National Committeeman from New Hampshire to the Republican Party .",
"title": ""
},
{
"docid": "Keith_Romney",
"text": "Keith Bradford Romney ( May 9 , 1929 -- January 21 , 2015 ) was the son of Vernon Romney . In 1960 , the first condominium in the continental United States , Graystone Manor , was built in Salt Lake City , Utah . The legal counsel for the project , Keith B. Romney is also credited with authoring the Utah Condominium Act of 1960 . Romney also played an advisory role in the creation of condominium legislation with every other legislature in the U.S. Business Week hailed Romney as the `` Father of Condominiums '' . In fact , Romney is said to have discovered the word `` condominio '' at an ancient site in Europe , and formed the word `` condominium '' to name the legislation . He soon after formed a partnership with Don W. Pihl called Keith Romney Associates , which was widely recognized throughout the 1970s as America 's preeminent condominium consulting firm . He was a largest financial supporter of his brother , politician Vernon B. Romney .",
"title": ""
},
{
"docid": "Elaine_Chao",
"text": "Elaine Lan Chao ( ; born March 26 , 1953 ) is an American politician who is the 18th and current United States Secretary of Transportation . She is a member of the Republican Party . Born in Taipei , Taiwan , Chao was the first Asian American woman and the first Taiwanese American in U.S. history to be appointed to a President 's Cabinet . She served as the 24th United States Secretary of Labor under President George W. Bush from 2001 to 2009 , and as Deputy Secretary of Transportation and Director of the Peace Corps under President George H. W. Bush . She spent four years as the president of the United Way of America . On November 29 , 2016 , President-elect Donald Trump nominated Chao to serve as the Secretary of Transportation . She was confirmed by the Senate on January 31 , 2017 , in a 93 -- 6 vote . Chao is married to Senator Mitch McConnell of Kentucky , who has been the Senate Majority Leader since January 3 , 2015 .",
"title": ""
},
{
"docid": "George_Romney_presidential_campaign,_1968",
"text": "George Romney ran for the 1968 Republican Party nomination in the 1968 United States presidential election . Romney was the Governor of Michigan and automaker who focused his campaign on the issues of fiscal responsibility , welfare reform , and the Vietnam War . If elected , he would have been the first Mormon president .",
"title": ""
},
{
"docid": "La_Teresita",
"text": "La Teresita is an historic Cuban cuisine restaurant with affiliated market and bakery in Tampa , Florida , in the West Tampa region . La Teresita opened in 1972 as a market . La Teresita is owned by the Capedevila family . A grocery market is located on the other side of a side street off West Columbus Drive from the restaurant and bakery . Founders Maximino and Coralia Capdevila emigrated from Cuba in 1962 after Fidel Castro came to power . They established the business as a grocery store and sold sandwiches . The family business gradually grew over time . The restaurant has been described as a being regarded by politicians `` as a place to be seen '' , and visits from President George W. Bush , John Kerry , Al Gore and Mitt Romney have occurred . In 2007 Mitt Romney held a campaign stop at the restaurant . Romnney also attended the restaurant in 2012 .",
"title": ""
},
{
"docid": "Harold_A._Lafount",
"text": "Harold Arundel Lafount ( January 5 , 1880 -- October 21 , 1952 ) was an American businessman who served on the Federal Radio Commission from 1927 to 1934 . He was the father of Lenore Romney ; the father-in-law of businessman and politician George W. Romney ; and the maternal grandfather of businessman and politician Mitt Romney . English-born , Lafount moved to the United States as a teenager and grew up in Utah . He managed several local businesses and was active in The Church of Jesus Christ of Latter-day Saints . Appointed to the Federal Radio Commission by President Calvin Coolidge , he was in charge of the zone covering the Western United States . Lafount played an important part in developments and decisions regarding the regulation of the broadcasting industry in the U.S. , favoring perspectives that saw radio broadcasting as a fundamentally commercial enterprise . He was also an early influence in making radio airtime available to political candidates and parties . Lafount later managed a number of well-known radio stations in the northeastern United States on behalf of Arde Bulova and served as president of the National Independent Broadcasters . A licensing issue regarding a station Lafount co-owned resulted in a protracted regulatory and legal matter that was finally decided in the U.S. Supreme Court .",
"title": ""
},
{
"docid": "Ray_Washburne",
"text": "Ray Willets Washburne ( born August 7 , 1960 ) is an American businessman , investor , and political fundraiser . Washburne was born in Dallas , Texas in 1960 , and was raised in Highland Park , later graduating from Southern Methodist University . In 1997 he married Heather Hill , a descendant of H. L. Hunt . Washburne is a co-founder of the M Crowd Restaurant Group , owning forty-six restaurants , which includes the Mi Cocina and Taco Diner restaurant chains . In addition to restaurants , he also has other real-estate developments in several states , and is the CEO of Charter Holdings . In 2009 , Washburne and his wife Heather , along with Stephen Summers and his spouse Elisa Summers , who is Heather 's sister , in 2009 bought the Highland Park Village , an upscale shopping center in Dallas , for $ 170 million . Washburne was actively involved in raising money for George W. Bush 's presidential campaigns in both 2000 and 2004 , and in the following years continued to raise money for the Republican Party . Later in the 2012 presidential election , he backed Mitt Romney , the Republican Party 's nominee , and became the campaign 's Texas co-chair , while also raising money . Following the 2012 election , in which Romney was defeated , Washburne became the finance chairman of the Republican National Committee , during which he raised $ 160 million , and two years later in 2015 , he became a part of Chris Christie 's 2016 campaign for president , serving as the finance director . Christie subsequently conceded in the race , and after Donald Trump emerged as the Republican front-runner , Washburne raised money for the campaign and became the vice chairman of the Trump Victory Committee .",
"title": ""
},
{
"docid": "Romney_Cottage",
"text": "Romney Cottage is an early-18th century home located in the Ormsgill area of Barrow-in-Furness , Cumbria , England . Also known as High Cocken it is most noted as being the residence of painter George Romney , an early member of the famed Romney family . Having been born in nearby Dalton-in-Furness , Romney lived in High Cocken between the ages of 8 and 21 before relocating to Kendal and eventually London . Romney Cottage was granted Grade II listed status in 1976 .",
"title": ""
},
{
"docid": "Country_club_Republican",
"text": "`` Country Club Republican '' also known as a `` Country Club Conservative '' or `` Establishment Republican '' is an expression employed , usually pejoratively , to describe certain members of the Republican Party in the United States . Some of the characteristics attributed to country club Republicans are higher than average income or inherited wealth , fiscally conservative opinions but with liberal , moderate or indifferent views on social issues such as abortion , censorship , and gay rights . Also , they are more likely to have attended prestigious colleges and universities than other Republican Party members . Politicians said to be country club Republicans include : President George H. W. Bush , son and also President George W. Bush , and his brother former Governor of Florida Jeb Bush , former Massachusetts Governor and presidential candidate Mitt Romney , former governor of New Jersey Thomas Kean , and Texas Senator Kay Bailey Hutchison .",
"title": ""
},
{
"docid": "Lenore_(disambiguation)",
"text": "Lenore may refer to : Arts and entertainment : `` Lenore '' , a poem by Edgar Allan Poe `` Lenore '' ( ballad ) , a 1773 poem by Gottfried August Bürger Symphony No. 5 ( Raff ) , a symphony by Joachim Raff entitled `` Lenore '' the title character of Lenore , the Cute Little Dead Girl , a comic series Places : Lenore , Idaho , an unincorporated community Lenore , West Virginia , an unincorporated community Lake Lenore ( Washington ) Lenore Lake ( Saskatchewan ) , Canada People : Lenore Blum ( born 1942 ) , mathematician and professor of computer science Lenore J. Coffee ( 1896 -- 1984 ) , American screenwriter , playwright and novelist Lenore Kandel ( 1932-2009 ) , American poet Lenore Kight ( 1911-2000 ) , American swimmer Lenore Marshall ( 1899-1971 ) , American poet , novelist and activist Lenore Muraoka ( born 1955 ) , American golfer Lenore Raphael ( born 1942 ) , American jazz pianist and educator Lenore Romney ( 1908-1998 ) , wife of American businessman and politician George W. Romney and mother of politician Mitt Romney Lenore Skenazy , American newspaper columnist Lenore Tawney ( 1907 -- 2007 ) , American artist Lenore Ulric ( 1892 -- 1970 ) , American stage and film star Lenore Zann ( born 1959 ) , Canadian politician and actress",
"title": ""
},
{
"docid": "Washington_Bottom_Farm",
"text": "Ridgedale ( also known as Washington Bottom Farm , Ridge Dale , and as the George W. Washington House and Farm ) is a 19th-century Greek Revival plantation house and farm on a plateau overlooking the South Branch Potomac River north of Romney , West Virginia , United States . The populated area adjacent to Washington Bottom Farm is known as Ridgedale . The farm is connected to West Virginia Route 28 via Washington Bottom Road ( West Virginia Secondary Route 28/3 ) . Ridgedale , constructed in 1835 , was the residence of gentleman farmer George William Washington , a descendant of George Washington 's great-great-grandfather Reverend Lawrence Washington . The farm is currently the private residence of Carol and Mike Shaw .",
"title": ""
},
{
"docid": "Alex_Castellanos",
"text": "Alejandro `` Alex '' Castellanos ( born 1954 ) is a Cuban American political consultant . He has worked on electoral campaigns for Republican candidates including Bob Dole , George W. Bush , Jeb Bush , and Mitt Romney . In 2008 , Castellanos , a partner at National Media Inc. , co-founded Purple Strategies , a bipartisan communications firm . Castellanos is also a regular guest commentator on Meet the Press and a contributor for CNN .",
"title": ""
},
{
"docid": "Roy_Abernethy",
"text": "Roy Abernethy ( September 29 , 1906 , Pennsylvania -- February 28 , 1977 , Jupiter , Florida ) was an executive in the American automobile industry , serving as CEO of American Motors Corporation ( AMC ) from February 1962 to January 1967 . Prior to his tenure at AMC , Abernethy had been with Packard Motors and Willys-Overland . Abernethy replaced George W. Romney , who resigned from AMC to become Governor of Michigan .",
"title": ""
}
] |
4020
|
How will the New credit reporting rules affect people who are already struggling financially?
|
[
{
"docid": "30623",
"text": "From my understanding by paying your bills more than 5 days late will not lead you into bankruptcy or stop you from getting a new loan in the future, however it may mean that lenders offer you credit at a higher interest rate. This of course would not help you as you are already struggling with your finances. However, no matter how bad you think things might be for you financially, there are always things you can do to improve your situation. Set a Budget The first thing you must do is to set a budget. List down all sources of income you receive each month, including any allowances. Then list all your sources of expenses and spending. List all your bills such as rent, telephone, electricity, car maintenance, credit card and other loans. Keep a diary for a month for all your discretionary spending - including coffees, lunches, and other odd bits and ends. You can also talk with your existing lenders and come to some agreement on reducing you interest rates on your debts and the repayments. But remember any reduction in repayments may increase your repayment period and the total interest you have to pay in the long term. If you need help setting up your budget here are some links to resources you can download to help you get started: Once you set up your budget you want your total income to be more than your total expenses. If it isn't you will be getting further and further behind each month. Some things you can do are to increase your income - get a job/second job, sell some unwanted items, or start a small home business. Some things you can do to reduce your expenses - make coffees and lunches at home before going out and buying these, pay off higher interest debts first, consolidate all your debts into a lower interest rate loan, reduce discretionary spending to an absolute minimum, cancel all unnecessary services, etc. Debt Consolidation In regards to a Debt Consolidation for your existing personal loans and credit cards into a single lower interest rate loan can be a good idea, but there are some pitfalls you should consider. Manly, if you are taking out a loan with a lower interest rate but a longer term to pay it off, you may end up paying less in monthly repayments but will end up paying more interest in the long run. If you do take this course of action try to keep your term to no longer than your current debt's terms, and try to keep your repayments as high as possible to pay the debt off as soon as possible and reduce any interest you have to pay. Again be wary of the fine print and read the PDS of any products you are thinking of getting. Refer to ASIC - Money Smart website for more valuable information you should consider before taking out any debt consolidation. Assistance improving your skills and getting a higher paid job If you are finding it hard to get a job, especially one that pays a bit more, look into your options of doing a course and improving your skills. There is plenty of assistance available for those wanting to improve their skills in order to improve their chances of getting a better job. Check out Centrelink's website for more information on Payments for students and trainees. Other Action You Can Take If you are finding that the repayments are really getting out of hand and no one will help you with any debt consolidation or reducing your interest rates on your debts, as a last resort you can apply for a Part 9 debt agreement. But be very careful as this is an alternative to bankruptcy, and like bankruptcy a debt agreement will appear on your credit file for seven years and your name will be listed on the National Personal Insolvency Index forever. Further Assistance and Help If you have trouble reading any PDS, or want further information or help regarding any issues I have raised or any other part of your financial situation you can contact Centrelink's Financial Information Service. They provide a free and confidential service that provides education and information on financial and lifestyle issues to all Australians. Learn how to manage your money so you can get out of your debt and can lead a much more comfortable and less stressful life into the future.",
"title": ""
}
] |
[
{
"docid": "587778",
"text": "Freezing your credit should be the default configuration. EDIT: More info on Why. Basically you're adding a password to your credit report access. https://www.privacyrights.org/consumer-guides/identity-theft-monitoring-services 4. Is there a low-cost alternative to monitoring services? The best low-cost alternative to credit monitoring services is a security freeze. A security freeze locks your credit files at the three credit reporting agencies (Equifax, Experian, and TransUnion) until you unlock your file with a password or PIN. The freeze stops new accounts from being established by imposters because potential creditors are not able to check your credit report or credit score, the standard procedure when financial accounts are opened. Any potential creditors’ requests for access to your credit files will be denied. However, a security freeze cannot stop misuse of your existing bank or credit accounts. You still must check the monthly statements on your current accounts for any erroneous charges or debits. Generally, you will pay no more than $30 for a lifetime of security freeze protection. In some circumstances (identity theft victims and senior citizens in some states), this protection may be free. With a security freeze, your credit reports cannot be seen by prospective creditors, insurance companies, landlords, utilities, or for employment screening. However, you may lift the freeze when necessary to allow a company to check your credit report. This is easily done by means of a password. It is important to realize that a security freeze does not prevent existing creditors from seeing your credit report. While a security freeze may be the best available deterrent to new account fraud, it may not be the best solution for everyone. It can be cumbersome for individuals who frequently apply for credit, are contemplating a new mortgage, or who plan to change jobs. On the other hand, a security freeze is particularly well-suited for seniors who are no longer in the market for new credit. And a freeze provides protection for individuals affected by data breaches involving Social Security numbers, as well as victims of identity theft or mail theft. For a more complete discussion of the pros and cons of security freezes, read this report in Consumer Reports. Brian Krebs' post How I Learned to Stop Worrying and Embrace the Security Freeze is a primer on what you can do to avoid becoming a victim of identity theft. Fees, supporting documentation, and procedures for placing a security freeze vary from state to state and among the three credit reporting agencies. The web sites of each of the credit reporting agencies provide state-specific instructions for placing a security freeze. The websites of each of the credit reporting agencies provide state-specific instructions for placing a security freeze. Equifax Experian TransUnion",
"title": ""
},
{
"docid": "47441",
"text": "Your credit score is really bad, and it's highly unlikely anyone will be willing to give you a mortgage, especially if you still have bad debt showing up on your credit report. What would help? Well, clearing off any bad debt would be a good place to start. Ideally, you want to get your credit rating up above 680, though that may be optimistic here. Note, though, that bad debt falls off your credit report after a while. Exactly how long depends on your province. Note that making partial payment, or even just acknowledging the debt, will reset the 'timer', however. I mention this, though, because you mention some of your debt is from 5 or 6 years ago. It may be just about to fall off. It would also help if you can show that your credit is so bad because of mistakes from a number of years ago, but you've been making payments and staying on top of all debts for the past few years, if that's the case. Also, it would help if you had a reasonable downpayment. 20% minimum, but you'll be a lower credit risk if you are able to put down 50 - 75%. You could also consider having someone with good credit co-sign the mortgage. Note that most people will not be willing to do this, as they take on substantial financial risk. All that said, there are some institutions which specialise in dealing with no credit or bad credit customers. You pay more fees and will pay a vastly higher interest rate, but this may be a good option for you. Check out mortgage brokers specialising in high-risk clients. You can also consider a rent-to-own, but almost all the advice I've ever seen say to avoid these if you can. One late payment and you may lose all the equity you think you've been building up. Note that things may be different if you are moving from the U.S. to Canada, and have no credit history in Canada. In that case, you may have no credit rather than bad credit. Most banks still won't offer you a mortgage in this case, but some lenders do target recent immigrants. Don't rule out renting. For many people, regardless of their credit rating, renting is a better option. The monthly payments may be lower, you don't need a downpayment, you don't have to pay realtor and legal fees (and pay again if you need to move). A couple of sites provide more information on how your credit rating affects your possibility of getting a mortgage, and how to get mortgages with bad credit: http://mortgages.ca/credit-score-needed-mortgage-canada/ and http://mortgages.ca/mortgage-solutions/new-to-canada-financing/, along with http://www.ratehub.ca/mortgage-blog/2013/11/how-to-get-a-mortgage-with-bad-credit/",
"title": ""
},
{
"docid": "444074",
"text": "This might be a bit of r/conspiracy thinking but: DOL fiducary rule has siginfcatly altered investment companies ability to make money on qualifed accounts. Many are still struggling to figure out how to adopt, monitor and be in compliance with it. This will hit the insurance companies hard too especially variable annuities providers since it is that much more difficult to justify their high cost products for rollovers unders DOL. If you reduce the limit to 2,400 people are going to have to find other places to put money to continue to save. If you already saving 18,000 or 10,000 or 5,000 a year your going to need a new place to put that money. What other products are there that are tax deferred for non qualifed money? after tax annuities. And since these dollars are no longer in qualified plans they are not subjected to the DOL fiducary rules. If a variable annuity company comes out with a hybrid Qualified / non qualified account that allows you to have one contract with two accounts in it, the fix is in. So maybe the insurance companies or the financial services companies lobbying groups or supported think tanks came up with the idea and served it to the government. My tin foil hat is bolted on.",
"title": ""
},
{
"docid": "520205",
"text": "Patience is the key here, I hate to say! There are five factors to FICO credit scores: Payment history is adversely affected by late payments - so always pay on time, otherwise your report will be haunted for seven years! 👻 Credit utilization has to do with how much of your available credit is currently in use - lower is better, but 0% isn't good either because they want to see that you're using credit. 10% or less is a good goal, and try to keep any single card balance to 30% or less when its statement close date rolls around. Credit history is based on the average age of all of your accounts, cards or otherwise, the older the better. Don't close either of your other cards (because that would cause your average account age to fall), and make sure to use the store card at least occasionally, because lenders sometimes decide to close unused lines of credit. Credit mix has to do with the different types of credit you hold and is why your bank's website suggested taking out a loan. It also has to do with the number of accounts overall; I've never found a satisfactory answer for what the sweet spot is, but I suspect it's in the 6-12 range? You wouldn't want to get several new ones at the same time because... New credit is affected by the credit inquiries (hard pulls) that occur when you apply for new cards or loans. Inquiries stay on your report for two years before falling off. This is almost certainly where your score dropped. You also mentioned not knowing if some hospital bills are still affecting your score. You'll want to review your credit reports and find out, plus checking your credit reports regularly is a really great habit to get into because errors (and fraud) can and do happen. There are three credit reporting agencies: Experian, Equifax, and TransUnion, and you'll want to review all three. You can get one free report from each of them every year: https://www.usa.gov/credit-reports It can take a couple of months for a new credit account to show up on your credit report, so your score should recover and go even higher once that happens. Sit tight, as annoying as that is!",
"title": ""
},
{
"docid": "293363",
"text": "\"As documented in MyFICO (http://www.myfico.com/credit-education/whats-in-your-credit-score/), there are several factors that affect credit scores. Payment history (35%) The first thing any lender wants to know is whether you've paid past credit accounts on time. This is one of the most important factors in a FICO® Score. As @Ben Miller mentioned, checking your credit report to determine whether or not late payments were reported to credit bureaus will give you a sense of whether or not this was effected. You mentioned several bounced payments, which certainly could have caused this. This would be my largest concern with a closed account, is to investigate why and what was reported to the bureaus, and in turn, other lenders. Also, since this has the highest impact on credit scores (35%), it's arguably, the most important. This is further detailed here, which details the public record and late payment effect on your score. Amounts owed (30%) Having credit accounts and owing money on them does not necessarily mean you are a high-risk borrower with a low FICO® Score....However, when a high percentage of a person's available credit is been used, this can indicate that a person is overextended, and is more likely to make late or missed payments. Given that this card was closed, whatever your credit limit was is now no longer added into your total credit limit. However, your utilization on that card is gone (assuming it gets paid off), depending on any other credit lines, and since you reported \"\"heavy use\"\" that could be a positive impact, though likely not. Length of credit history (15%) In general, a longer credit history will increase your FICO® Scores. However, even people who haven't been using credit long may have high FICO Scores, depending on how the rest of the credit report looks. Depending how old your card was, and particularly since this was your only credit card, it will likely impact your average age of credit lines, depending on other lines of credit (loans etc) you have open. This accounts for about 15% of your score, so not as large of an impact as the first two. Credit mix in use (10%) FICO Scores will consider your mix of credit cards, retail accounts, installment loans, finance company accounts and mortgage loans. Given that this was your only credit card, your loan mix has been reduced (possibly to none). New credit (10%) Research shows that opening several credit accounts in a short period of time represents a greater risk - especially for people who don't have a long credit history. This focuses on credit inquiries, which as you mentioned, you will likely have another either re-opening this credit card or opening another at some point in the future. Regardless, paying off the rest of that card is a priority, as interest rates on average credit cards are over 13%, and often higher (source). This rate comes into play when not paying the balance in full every month, and also as @Ben Miller suggested, I would not utilize a credit card without being able to pay it in full. It can often be a dangerous cycle of debt.\"",
"title": ""
},
{
"docid": "223948",
"text": "How would the economy affect Dell? * Sales revenue (look at financial reports since 2008), especially in enterprise-level sales for small businesses * Research and development - are they investing in creating new products now, or making minor adjustments to older lines? The lack of available credit in the economy might affect this decision. Connect this with the next part of your project - with their current course, are Dell's products going to be relevant in 3 years? * Supply issues - any recent supplier changes due to economic hardship? Any evidence of outsourcing/insourcing based upon the current economy? Also, there is currently a massive shortage in hard drives due to floods in Thailand. Just some thoughts.",
"title": ""
},
{
"docid": "192641",
"text": "It may or may not be a good idea to borrow money from your family; there are many factors to consider here, not the least of which is what you would do if you got in serious financial trouble and couldn't make your scheduled payments on the loan. Would you arrange with them to sell the property ASAP? Or could they easily manage for a few months without your scheduled payments if it were necessary? A good rule of thumb that some people follow when lending to family is this: don't do it unless you're 100% OK with the possibility that they might not pay you back at all. That said, your question was about credit scores specifically. Having a mortgage and making on-time payments would factor into your score, but not significantly more heavily than having revolving credit (eg a credit card) and making on time payments, or having a car loan or installment loan and making on time payments. I bought my house in 2011, and after years of paying the mortgage on time my credit score hasn't changed at all. MyFico has a breakdown of factors affecting your credit score here: http://www.myfico.com/crediteducation/whatsinyourscore.aspx. The most significant are a history of on-time payments, low revolving credit utilization (carrying a $4900 balance on a card with a $5000 limit is bad, carrying a $10 balance on the same card is good), and overall length of your credit history. As to credit mix, they have this to say: Types of credit in use Credit mix determines 10% of my FICO Score The FICO® Score will consider your mix of credit cards, retail accounts, installment loans, finance company accounts and mortgage loans. It's not necessary to have one of each, and it's not a good idea to open credit accounts you don’t intend to use. The credit mix usually won’t be a key factor in determining your FICO Score—but it will be more important if your credit report does not have a lot of other information on which to base a score. Have credit cards – but manage them responsibly Having credit cards and installment loans with a good payment history will raise your FICO Score. People with no credit cards tend to be viewed as a higher risk than people who have managed credit cards responsibly.",
"title": ""
},
{
"docid": "277477",
"text": "The details of credit score calculation tend to change periodically, but the fundamentals are mostly consistent. Pay your bills, keep your average account age high, overpay your credit card minimums, and keep your overall debt low. And do soft pulls on your credit report to see what's happening. First, the simplest route: pay all your bills early or on time. Automatic deduction may be useful in this regard, especially for bills with predictable amounts. A corollary to this tip is to never leave an unpaid bill. What often happens to young people is in the course of moving around they leave the final bill unpaid and it gets reported to collections. Make sure you follow up online with all bills, even after canceling the service. Second, average account age and oldest account age matter. Open an account like a credit card and never close it, so you'll have an older account (hopefully a zero-fee card). Try to keep other accounts open rather than closing them (no need to cancel a zero-fee credit card) so your average account age stays higher. A card that works on internal systems (like a gift card) is not going to show up on a credit report; a card that works like any VISA/MC is likely going to show up. The rule of thumb is if they need your SSN to run a credit check for the application, then the card will appear on a credit report. You can pull your credit report to find out if the card is listed (you may have to allow time for lag before the card appears, but I'm not sure how long that might be). Third, a tip for extra credit score is to pay more than the minimum required on credit card bills. You can achieve this by either using your credit card at least once a month or by leaving a small hanging balance each month so there's always something to overpay next month. Credit card reporting will be either: unpaid, underpaid, minimum paid, or overpaid. Minimum payment helps your score and overpayment helps more. If you can use your credit card every month, that will give you something to overpay every month. Otherwise, you can leave a small debt left on the card but still pay over the monthly minimum. However, your total debt load, especially debt carried on your cards, counts against your score; aim for less than 10% of your limit. Finally, of course, is to pull your credit report periodically. You need to know what others are seeing. Since debt load utilization matters, make sure the reported card maximum is correct on your credit report. Talk to your bank or account issuer if the limit is wrong. If a collection appears, then you need to handle it. Often you can negotiate with the collector, but be careful to negotiate how they will report the resolution. You want them to agree to remove any negative information (either in exchange for payment or because of a mistake). Failing that, you want them to mark it paid in full or satisfied in full; letting them notate your score that you only partially paid is what you want to avoid, since it most signals someone with cash flow problems and credit issues. They control their reporting to credit bureaus, so if the person on the phone demurs, ask to speak to their supervisor or someone with negotiating authority. Try to get any agreements in writing. Remember that your total debt load is a factor in your credit score. Home loans and student loans do affect credit score. If you take on a smaller home loan, then it will affect your credit less harshly (and leave you with smaller monthly payments).",
"title": ""
},
{
"docid": "345697",
"text": "\"It all comes down to how the loan itself is structured and reported - the exact details of how they run the loan paperwork, and how/if they report the activity on the loan to one of the credit bureaus (and which one they report to). It can go generally one of three ways: A) The loan company reports the status to a credit reporting agency on behalf of both the initiating borrower and the cosigner. In this scenario, both individuals get a new account on their credit report. Initially this will generally drop related credit scores somewhat (it's a \"\"hard pull\"\", new account with zero history, and increased debt), but over time this can have a positive effect on both people's credit rating. This is the typical scenario one might logically expect to be the norm, and it effects both parties credit just as if they were a sole signor for the loan. And as always, if the loan is not paid properly it will negatively effect both people's credit, and the owner of the loan can choose to come after either or both parties in whatever order they want. B) The loan company just runs the loan with one person, and only reports to a credit agency on one of you (probably the co-signor), leaving the other as just a backup. If you aren't paying close attention they may even arrange it where the initial party wanting to take the loan isn't even on most of the paperwork. This let the person trying to run the loan get something accepted that might not have been otherwise, or save some time, or was just an error. In this case it will have no effect on Person A's credit. We've had a number of question like this, and this isn't really a rare occurrence. Never assume people selling you things are necessarily accurate or honest - always verify. C) The loan company just doesn't report the loan at all to a credit agency, or does so incorrectly. They are under no obligation to report to credit agencies, it's strictly up to them. If you don't pay then they can report it as something \"\"in collections\"\". This isn't the typical way of doing business for most places, but some businesses still operate this way, including some places that advertise how doing business with them (paying them grossly inflated interest rates) will \"\"help build your credit\"\". Most advertising fraud goes unpunished. Note: Under all of the above scenarios, the loan can only effect the credit rating attached to the bureau it is reported to. If the loan is reported to Equifax, it will not help you with a TransUnion or Experian rating at all. Some loans report to multiple credit bureaus, but many don't bother, and credit bureaus don't automatically copy each other. It's important to remember that there isn't so much a thing as a singular \"\"consumer credit rating\"\", as there are \"\"consumer credit ratings\"\" - 3 of them, for most purposes, and they can vary widely depending on your reported histories. Also, if it is only a short-term loan of 3-6 months then it is unlikely to have a powerful impact on anyone's credit rating. Credit scores are formulas calibrated to care about long-term behavior, where 3 years of perfect credit history is still considered a short period of time and you will be deemed to have a significant risk of default without more data. So don't expect to qualify for a prime-rate mortgage because of a car loan that was paid off in a few months; it might be enough to give you a score if you don't have one, but don't expect much more. As always, please remember that taking out a loan just to improve credit is almost always a terrible idea. Unless you have a very specific reason with a carefully researched and well-vetted plan that means that it's very important you build credit in this specific way, you should generally focus on establishing credit in ways that don't actually cost you any money at all. Look for no fee credit cards that you pay in full each month, even if you have to start with credit-building secured card plans, and switch to cash-value no-fee rewards cards for a 1-3% if you operate your financial life in a way that this doesn't end up manipulating your purchasing decisions to cost you money. Words to the wise: \"\"Don't let the credit score tail wag the personal financial dog!\"\"\"",
"title": ""
},
{
"docid": "280140",
"text": "The first thing you need to know is that getting a new social security number will not erase your credit history. In fact, using a name change or a social security number change to get out of debt is considered fraud in most jurisdictions and you can be arrested for it. As soon as you are issued a new social security number, your old number and new number are linked in the government and credit bureau files. Everything that was on your old credit report will appear on your new credit report. The second big thing to know is if you suspect that your social security number has been used fraudulently in regards to credit, stop reading this right now, immediately call one of the three major credit bureaus (Experian, TransUnion, or Equifax), and place what's called an initial fraud alert. You only need to call one of the three. The one you call will notify the other two. This places a flag on your credit file at all three bureaus which says that your identity may have been stolen and any financial institution which is processing an application for credit should immediately contact you at the phone number you provide. The alert is good for 90 days and you can renew it as many times as you wish. I suggest using TransUnion as your one call because I've called them when my identity was stolen, and they're automated system is very well designed. Now that that is out of the way... you said that they have your email address, but it is very unusual for people to be contacted by email for a debt. In fact, I would automatically disregard any emails about debts. Every legitimate financial institution I've ever come across will either call you or send mail to your last known address. Regarding what's being reported on your credit report, you need to type a letter to each credit bureau which is reporting the information telling them who you are and that you are disputing this information on your report. Mail it to the bureaus by certified mail with return receipt. Under United States law they are required to verify the information on your report, if you dispute it, and remove the information if they are unable to verify it. In many cases, it's too much of a hassle and the bureaus just remove the information. The other thing I'll leave you with is that you said you've only had credit in the past six months. Six months is not enough time to build an adequate credit profile. You really need to be strategic about your credit score. Every time you apply for credit, it drags the score just a little bit lower. Your question wasn't really about building credit, so I'll spare you the novel on that, but I would encourage you to seek out one of the many resources which are readily available online. I am not an attorney. This is not legal advice. You should consult with an attorney who is licensed to practice law in your particular jurisdiction.",
"title": ""
},
{
"docid": "87402",
"text": "\"They have forever to collect a balance from you. Furthermore they can add whatever penalties and fees they wish to increase that balance. Worst of all, they don't have to remind you or send you bills or any other notification. You owed it when you left the office. (There very well could be local laws that require notifications, but that isn't really the issue here.) That dentist has every right to deny you service until you settle the account. Forever. The statute of limitations on collecting that debt via court: http://www.bankrate.com/finance/savings/when-does-your-debt-expire.aspx Which covers the rules on HOW LONG they have to collect the debt. Owing the money is one thing, but the rules and tools that you creditor has to collect the debt are another. You are probably worried about them suing you. But if you don't pay the debt (or settle in some way), that dentist can refuse to provide services to you, even if they write off the debt. Ways you can be punished by your dentist for not paying the bill are: Depending on your jurisdiction and/or type of debt, they typically only report it on your credit (if they are reporting at all) for 7 years. Even if you pay and settle the account, it will still be reported on your credit report for 7 years. The difference is how it is reported. They can report that \"\"user133466 is a super reliable person who always pays debts on time\"\". They can say \"\"user133466 is a flake who pays, but takes a while to pay\"\". Or they can say \"\"user133466 is a bad person to provide services before collecting money, because user133466 don't pay bills\"\". Other people considering lending you money are going to read these opinions and decide accordingly if they want to deal with you or not. And they can say that for 7 years. The idea of credit reporting is that you settle up as soon as possible and get your credit report to reflect the truth. One popular way to collect a debt to is to sue you for it. There, each state has a different time period on how long a creditor has to sue you for a debt. http://www.bankrate.com/finance/credit-cards/state-statutes-of-limitations-for-old-debts-1.aspx If you pay part of the debt, that will often reset the clock on the statute of limitations, so be sure any partial or negotiated settlements state very clearly, in writing, that payment is considered payment in full on the debt. Then you keep that record forever. There are other interesting points in the Fair Debt Collection Practices Act. See Debt collectors calling? Know your rights. They can only contact you in certain ways, they must respond to you in certain ways, and they have limits on what they can say, who they can say it to, and when they can say it. There are protections from mean or vicious bill collectors, but that doesn't sound like who you are dealing with. I don't know that the FDCPA is a tool you need to use in this case. You should negotiate your debt and try your best to settle up. From your post, both parties dropped the ball, and both parties should give a little. You should pay no or minor late fees, and the doctor should report your credit positively when you do so. If you both made honest mistakes, they both parties should acknowledge that and be fair, and not defensive. This is not legal advice. But you owe the debt, so you should settle up. I don't think it is fair for you to not pay because they didn't mail you a paper. However I also do not think it is fair for the doctor to run up fees and not remind you of the bill. Finally, you didn't bring up insurance or many other details. Those details can change the answer.\"",
"title": ""
},
{
"docid": "486729",
"text": "Someone else might be able to provide more details - but generally yes, of course. International corporations can pursue debt collection across borders - whether or not they do is a matter of convenience rather than law. My understanding is that a company's ability to report on your credit report is dependent on their membership in Equifax, USA etc. - so while most of your credit is country by country, international companies or companies with any relationship in other countries can follow you cross-border if they find out your new address and report the debt w/ that address. Since virtually every major company has some American affiliate, I wouldn't hold my breath that you can escape it indefinitely ESPECIALLY since you don't already have the debt, and have the power to actually pay for the service that you're using. Also - this is an incredibly scummy thing to do, and no matter how you dress it up as a financial decision it's just theft. Would you leave the country without paying your landlord? Without paying for groceries or other physical goods? Why is stealing from a telecom company any different?",
"title": ""
},
{
"docid": "116243",
"text": "Your credit score is definitely affected by the age of your credit accounts, so if you frequently close one card and open another new one, you're adversely affecting the overall average age of accounts. This is something to consider and whether it is worth what you're trying to achieve. Sometimes, if you're a good customer and are insistent enough, you can simply call your credit card company and use the threat of closing your account in favor of another card that offers something attractive to get your current bank to sweeten its incentives to keep your business. I know many people who've done this with real success, and they spare themselves the hassle of obtaining a new card and suffering the short term consequences on their credit report. This might be an avenue worth trying before you just close the account and move on. I hope this helps. Good luck!",
"title": ""
},
{
"docid": "237353",
"text": "Where was it reported that it was six figures per month? It isn't clear from the article what Mandiant's scope was that they were brought in under. I'm not even sure the way it reads that Mandiant found the Apache Struts-based breach while investigating the breach they were brought in for. Also, companies with an emphasis on IT like Equifax vary greatly in how they handle out-of-budget projects, and so far as I've read, it wasn't revealed how Mandiant's project was procured. Equifax is going to be a case study in business schools on the handling of this incident, and what not getting in front of a crisis looks like (for comparison, see how the Tylenol tampering was handled). Equifax should have reached out to all affected and said they automatically put a freeze on their records, and all affected now have an account created if they didn't already have an account, 7 years of free 100 freeze/unfreeze requests per year, 52 free credit report requests per year, and credit monitoring. If I was on the board, I would have told the CEO to make a generous offer to buy out LifeLock and put all affected onto their most comprehensive plan while working behind the scenes to revamp IT and information security, as well as rethink the industry. It would have been expensive as hell to do, but this is starting to grow into a Wells Fargo-scale career ending and industry-defining incident, and whatever cost savings they thought they got by cutting so many corners that enabled this breach and the weak response might get wiped out for the next 100 years of potential savings as odds increase weekly they'll be forced to adopt more regulatory oversight in the future. If they quietly get LifeLock's most comprehensive plan for all US federal and state legislators though, then they probably will escape real reform and might skate by on the weak response.",
"title": ""
},
{
"docid": "443487",
"text": "Generally, credit card networks (as opposed to debit/ATM cards that may or may not have Visa/MC logos) have a rule that a merchant must accept any credit card with their logo. Visa rules for merchants in the US say it explicitly: Accept all types of valid Visa cards. Although Visa card acceptance rules may vary based on country specific requirements or local regulations, to offer the broadest possible range of payment options to cardholder customers, most merchants choose to accept all categories of Visa debit, credit, and prepaid cards.* Unfortunately the Visa site for China is in Chinese, so I can't find similar reference there. You can complain against a merchant who you think had violated Visa rules here. That said, its not a law, its a contract between the merchant processor and the Visa International organization, and merchants are known to break these rules here and there (most commonly - refusing to accept foreign cards, including in the US). Also, local laws may affect these contracts (for example, in the US it is legal to set minimum amount requirements when accepting credit cards). This only affects credit card processing, and merchants that don't accept credit cards may still accept debit cards since those work in different networks, under a different set of rules. Those who accept credit cards, are also required to accept debit cards (at least if used as credit).",
"title": ""
},
{
"docid": "508070",
"text": "Nothing will happen. It will not affect your credit score. You are not in trouble. :) Assuming that you didn't already agree to a purchase contract, you are not obligated to purchase simply because you had a pre-approval credit check done. However, even if you did, since they aren't shipping yet, you could probably cancel. If you are in doubt, talk to customer service to ensure that they aren't planning on shipping one to you. They did check your credit report (known as a hard pull), and this does temporarily affect your credit score. However, it affects it the same whether you complete the purchase or not. If you have another credit check done with another seller, it will result in another hard pull, affecting your credit score a little more. But I wouldn't worry about a few hard pulls if you need to do some shopping. Just don't go overboard, and you'll be fine.",
"title": ""
},
{
"docid": "517215",
"text": "\"There's many concrete answers, but there's something circular about your question. The only thing I can think of is that phone service providers ask for credit report when you want to start a new account but I am sure that could be worked around if you just put down a cash deposit in some cases. So now the situation is flipped - you are relying on your phone company's credit! Who is to say they don't just walk away from their end of the deal now that you have paid in full? The amount of credit in this situation is conserved. You just have to eat the risk and rely on their credit, because you have no credit. It doesn't matter how much money you have - $10 or $10000 can be extorted out of you equally well if you must always pay for future goods up front. You also can't use that money month-by-month now, even in low-risk investments. Although, they will do exactly that and keep the interest. And I challenge your assumption that you will never default. You are not a seraphic being. You live on planet earth. Ever had to pay $125,000 for a chemo treatment because you got a rare form of cancer? Well, you won't be able to default on your phone plan and pay for your drug (or food, if you bankrupt yourself on the drug) because your money is already gone. I know you asked a simpler question but I can't write a good answer without pointing out that \"\"no default\"\" is a bad model, it's like doing math without a zero element. By the way, this is realistic. It applies to renting in, say, New York City. It's better to be a tenant with credit who can withhold rent in issue of neglected maintenance or gross unfair treatment, than a tenant who has already paid full rent and has left the landlord with little market incentive to do their part.\"",
"title": ""
},
{
"docid": "403969",
"text": "\"You promised to pay the loan if he didn't. That was a commitment, and I recommend \"\"owning\"\" your choice and following it through to its conclusion, even if you never do that again. TLDR: You made a mistake: own it, keep your word, and embrace the lesson. Why? Because you keep your promises. (Nevermind that this is a rare time where your answer will be directly recorded, in your credit report.) This isn't moralism. I see this as a \"\"defining moment\"\" in a long game: 10 years down the road I'd like you to be wise, confident and unafraid in financial matters, with a healthy (if distant) relationship with our somewhat corrupt financial system. I know austerity stinks, but having a strong financial life will bring you a lot more money in the long run. Many are leaping to the conclusions that this is an \"\"EX-friend\"\" who did this deliberately. Don't assume this. For instance, it's quite possible your friend sold the (car?) at a dealer, who failed to pay off this note, or did and the lender botched the paperwork. And when the collector called, he told them that, thinking the collector would fix it, which they don't do. The point is, you don't know: your friend may be an innocent party here. Creditors generally don't report late payments to the credit bureaus until they're 30 days late. But as a co-signer, you're in a bad spot: you're liable for the payments, but they don't send you a bill. So when you hear about it, it's already nearly 30 days late. You don't get any extra grace period as a co-signer. So you need to make a payment right away to keep that from going 30 late, or if it's already 30 late, to keep it from going any later. If it is later determined that it was not necessary for you to make those payments, the lender should give them back to you. A less reputable lender may resist, and you may have to threaten small claims court, which is a great expense to them. Cheaper to pay you. They say France is the nation of love. They say America is the nation of commerce. So it's not surprising that here, people are quick to burn a lasting friendship over a temporary financial issue. Just saying, that isn't necessarily the right answer. I don't know about you, but my friends all have warts. Nobody's perfect. Financial issues are just another kind of wart. And financial life in America is hard, because we let commerce run amok. And because our obsession with it makes it a \"\"loaded\"\" issue and thus hard to talk about. Perhaps your friend is in trouble but the actual villain is a predatory lender. Point is, the friendship may be more important than this temporary adversity. The right answer may be to come together and figure out how to make it work. Yes, it's also possible he's a human leech who hops from person to person, charming them into cosigning for him. But to assume that right out of the gate is a bit silly. The first question I'd ask is \"\"where's the car?\"\" (If it's a car). Many lenders, especially those who loan to poor credit risks, put trackers in the car. They can tell you where it is, or at least, where it was last seen when the tracker stopped working. If that is a car dealer's lot, for instance, that would be very informative. Simply reaching out to the lender may get things moving, if there's just a paperwork issue behind this. Many people deal with life troubles by fleeing: they dread picking up the phone, they fearfully throw summons in the trash. This is a terrifying and miserable way to deal with such a situation. They learn nothing, and it's pure suffering. I prefer and recommend the opposite: turn into it, deal with it head-on, get ahead of it. Ask questions, google things, read, become an expert on the thing. Be the one calling the lender, not the other way round. This way it becomes a technical learning experience that's interesting and fun for you, and the lender is dreading your calls instead of the other way 'round. I've been sued. It sucked. But I took it on boldly, and and actually led the fight and strategy (albeit with counsel). And turned it around so he wound up paying my legal bills. HA! With that precious experience, I know exactly what to do... I don't fear being sued, or if absolutely necessary, suing. You might as well get the best financial education. You're paying the tuition!\"",
"title": ""
},
{
"docid": "110953",
"text": "I do this all the time, my credit rating over time plotted on a graph looks like saw blades going upward on a slope I use a credit alert service to get my credit reports quarterly, and I know when the credit agencies update their files (every three months), so I never have a high balance at those particular times Basically, I use the negative hard pulls to propel my credit score upwards with a the consequentially lowered credit utilization ratio, and the credit history. So here is how it works for me, but I am not an impulse buyer and I wouldn't recommend it for most people as I have seen spending habits: Month 1: charge cards, pay minimum balance (raises score multiple points) Month 2: PAY OFF ALL CREDIT CARDS, massive deleveraging using actual money I already have (raises score multiple points) Month 3: get credit report showing low balance, charge cards, pay minimum balance ask for extensions of credit, AND followup on new credit line offers (lowers score several points per credit inquiry) Month 4: charge cards, pay minimum balance, discretionally approving hard pulls - always have room for one or two random hard pulls, such as for a new cell phone contract, or renting a car, or employment, etc Month 5: PAY OFF CREDIT CARDS using actual money you have. (the trick is to NEVER really go above a 15% credit utilization ratio, and to never overleverage. Tricky because very quickly you will get enough credit to go bankrupt) Month 6: get credit report showing low balances, a slight dip in score from last quarter, but still high continue.",
"title": ""
},
{
"docid": "421575",
"text": "Are financial institutions less likely to lend me money because of my age Yes. But they are especially unlikely to loan you money because you have little income. or because they know I avoid interest by paying things off aggressively? This won't affect them. But you might ask yourself how much credit history you have. Credit history can include all of loans, credit cards, rent, utilities, etc. You mention three loans. But you don't mention rent or utilities. You may simply not have much credit history, even if what you do have is good. But again, the biggest thing that they will look at is your income history. If you have a small income, then it doesn't matter what your payment history is. They don't want to loan money to people who need money. They want to loan money to people who don't need to borrow but are instead bringing a future purchase into the present. The ideal recipient is someone who has a high income and spends it all every month. Such a person is likely to borrow heavily but be able to keep up the payments. Obsessing about your ability to borrow is probably the wrong approach. Instead focus on how you can meet your goals without borrowing. Eventually your ability to pay will catch up. Then they'll offer you money. Of course, you might not need it then. Note that when I say little income, I'm talking about their perspective. You may be fully on track and making decent money or even very good money for your age. But they're looking for people who are mature in their careers and regularly bringing home large sums but who spend it faster than they can get it.",
"title": ""
},
{
"docid": "353980",
"text": "\"The biggest (but still temporary) ding you'll see on your credit score from opening a new account is from the low average (and low minimum) account age. This will have a stronger effect than the hard pull of the credit report, which is still a factor (but not much of one if you only have 1-2 pulls in the past couple years). Having a lower average account age increases your risk to lenders. Your average will go up by one month per month, and each time you open an account it will suffer a drop proportional to the number of accounts you already had open before. So if you want to have a more \"\"solid\"\" credit score that stays strong in the face of new accounts in the future, it's better to open a few more accounts now (assuming you can ride out the temporary drop in score and aren't planning to go e.g. mortgage-shopping in the very near future). Having an additional line of credit will also likely cause your credit card utilization (total balance / total credit limit, expressed as a percentage) to decrease, which would tend to increase your credit score, counteracting the age factor, unless your utilization is already extremely low (which it probably is given your monthly account payoffs). There are various credit score simulators out there, from places that show you your credit score, and you can put in a hypothetical new card account to see the immediate likely impact for your particular situation. You identified other costs, such as risk of fraud and fees. You should check your statements once in a while even if you're not using the card, just to make sure no one else is. The bit of additional time required for this is a nonzero cost of having an open credit card account. So is the additional hassle of dealing with having the card stolen etc. if you carry it in your wallet and your wallet's stolen. If you have an account with zero activity for some number of years, the bank may close it automatically and that can reflect negatively on a credit report (as a bank closure of the account, the reason is often obscured). Check your terms and conditions and/or have some activity every so often to prevent this from happening. Some of the otherwise most attractive credit cards have monthly or annual fees, which will cost you, and you won't want to close those because it would then reduce your credit score (e.g. by reducing the total available credit and increasing your utilization percentage) - so the solution is don't apply for credit cards that have monthly/annual fees. There are plenty of good cards without those fees. With a credit score that high, you can get cards that have some very good benefits and rewards programs, as well as some with great introductory offers. Though I'm not familiar with details of Amazon's offer, $80 cash up-front with nothing else seems unlikely to be among your best options. I would think that for at least some of the fee-free cards available to you, the benefits exceed the costs, and you could \"\"cash in\"\" some of the benefits of your good credit record to get those benefits (i.e. this is one of those things you work hard to build good credit for), while also building your long-term reputation for repayment reliability. Also be aware as you shop around for cards that credit card companies pay fairly high referral fees to websites that send customers their way, so if you want you can think about who you're supporting when you click the link that takes you to an application you complete, and choose to support a site you think is providing a useful consumer-focused service. As factors affecting your credit score in addition to payment history (i.e. making regular payments as agreed on the new account will help you), Equifax lists:\"",
"title": ""
},
{
"docid": "170481",
"text": "Good credit is calculated (by many lenders) by taking your FICO score which is calculated based upon what is in your credit report. Building credit generally means building up your FICO score. Your FICO score is impacted my many factors, one small one of which is your utilization ratio of your installment loans like student loans. This is the ratio of the current balance to your original balance. To improve your score (slightly) you would want a lower ratio. I would recommend paying your student loan down to 75% ratio as fast as you can and then you can go back to $50/month. A much better way to improve your FICO score is to have revolving credit. Your student loans are not revolving, they are installment loans. Therefore, you should open at least one credit card (assuming you currently have none) right away. The longer you have had a credit card open, the better your FICO score gets. Your revolving credit utilization ratio is way more important than your installment loan ratio. Therefore, to maximize your FICO, try to never have more than 10% utilization on your revolving credit report to the credit bureaus each month. Only the current month's ratio affects your score at any given moment. You can ensure you don't go above 10% by paying your balance before the statement cuts each month to get it below 10% way before any payment would be due. (You should always pay your remaining credit card statement balance in full each month by the due date after the statement cuts to avoid any interest charges.) Note that there is a slight FICO advantage to having at least one major bank credit card instead of just only credit union credit cards. Also, never let all your revolving credit report a zero balance in a month, you must always have at least $1 reporting to the credit bureaus on at least one of your open credit cards or your FICO score will take a big negative hit. If you cannot get a normal credit card, go to a credit union and find one that offers secured credit cards, or a bank that does. A secured credit card is where you place a deposit with the bank that they hold and give you a credit limit to match your security. Ideally it would be a card that graduates to unsecured after your demonstrate good history with them. For example, the Navy Federal Credit Union secured card unsecures for many people. I also believe the Wells Fargo Bank credit card (you can join if there is a family member who served or a roomate who did) also will unsecure. The reason you want it to unsecure and not be forced to open a new account to get an unsecured account is that you want your average age and oldest age of open revolving credit accounts to be as high as possible as this is another impact on your FICO score. Credit unions that anyone can join include, Digital Federal Credit Union, the Pentagon Federal Credit Union (which offers a secured card that does not graduate), and The State Department Federal Credit Union (also offers secured card that I think does not graduate). One other method to boost your FICO score is to get added as an authorized user on one of your parent's credit cards that has been open a long time. Not all lenders will report such an authorized user, however, ones that are known to do so are: Bank of America, Citi Bank, and Capital One. It is a good sign that it will report if they ask for the social security number of the authorized user. However, note that the Authorized User addition can have no impact if the lender is using one of the newer versions of the FICO scoring model, only the older versions reward you for the age of accounts for which you are an authorized user. A very long term boost is to open your first American Express card underwritten directly by Amex such as their Zync card which is pretty easy to get. The advantage of American express is that they remember the date your first credit card was opened with them and if you open new accounts in the future they will back date the date of their opening to match the date your first card was opened. If you let your membership lapse, be sure to record the account number and date opened in your personal files so that you can help them locate it again if you reopen as they can have trouble if it has been on the order of ten years or more. Finally, note that the number of accounts opened in the last twelve months is a small negative mark on your score (along with number of inquiries), so if you open a lot of accounts all at once, in addition to bringing down your average age of accounts, you will also get dinged for how many were opened in the last year.",
"title": ""
},
{
"docid": "574122",
"text": "Yes you can do this yourself. I cannot speak for all the credit repair companies, but generally they are not reputable. Even if they are trustworthy, they cannot do anything you cannot do yourself. Freeze your credit. Lock it down and prevent any new activity. This is for safety and I want you to do it so you know where you stand. Get a copy of your free copies of the three credit reports from https://www.annualcreditreport.com/ (this is the only free, official place to get your reports) Sign up for a free credit score estimation site like http://www.CreditKarma.com or http://www.CreditSesame.com (These sites make money by selling affiliate offers, but you can easily ignore them) You can't get your exact FICO score, but they letter grades they provide help you understand where you stand. Dispute anything that is not accurate. Get wrong items corrected with the credit agency. Ignore collectors who are not showing up on your report. If they aren't reporting you, so what? Let your own moral compass be your guide if you pay those debts or not. Negotiate a payment amount with the debtors you owe. If you are dealing with a debt collector, there isn't any point in paying the full amount. You owed the money to somebody else, and they sold it to the debt collector, therefore in my mind they are as whole as they feel like being. It is up to you how much you pay, but you are already going to suffer (and have suffered) the credit ramifications. No sense in wasting money when they will very likely settle for dimes on the dollar. Don't let them bully you around. I suggest understand your rights and protections as offered by the Fair Debt Collection Practices Act Before you pay anybody anything, get it IN WRITING Wait and follow up. Make sure they report it correctly. I would probably tackle them in order of age, newest first. Don't bother with debts that are more than, or nearly seven years old. Anything that old is or will fall off of the credit report soon, and your score will start to rise. Paying on those debts will refresh them and they will harm you longer. We can debate the ethics of that advice in the comments, but if you want your score to raise, I suggest just waiting about anything over six years old while you tackle the newer ones. This is a SLOW process. Your credit score will still take a couple years to heal once you fix your report. But that is the point of the score after all. It is a history of how you handle money and debt.",
"title": ""
},
{
"docid": "500261",
"text": "FICO is a financial services company, whose customers are financial services companies. Their products are for the benefit of their customers, not consumers. The purpose of the credit score system is two-fold. First, the credit score is intended to make it easy for lending institutions (FICO's customers) to assess the risk of loans that they make. This is probably based on science, although the FICO studies and even the FICO score formula are proprietary secrets. The second purpose of the credit score is to incentivize consumers into borrowing money. And they have done a great job of that. If you think you might need a loan in the future, perhaps a mortgage or a car loan, you need a credit score. And the only way to get a credit score is to start borrowing money now that you don't need. Yes, someone with a good income and a long history of paying utility bills on time would be a great credit risk for a mortgage. However, that person will have no credit score, and therefore be declared by FICO as a bad credit risk. On the other hand, someone with a low income, who struggles, but succeeds, to make the minimum payment on their credit card, would have a better credit score. The advice offered to the first person is start borrowing money now, even though you don't need it. I'm not anti-credit card. I use a credit card responsibly, paying it off in full every month. I use it for the convenience. I don't worry at all about my credit score, but I've been told it is great. However, there are some people that cannot use a credit card responsibly. The temptation is too great. Perhaps they are like problem gamblers, I don't know. But FICO and the financial services industry have created a system that makes a credit card a necessity in many ways. These are the people that get hurt in the current system.",
"title": ""
},
{
"docid": "489376",
"text": "Your contributions that you've already made are made and done, and will not disappear. What the Windfall Elimination Provision does is make sure that people do not collect the subsidized low-income payments while also collecting a full pension. People who did not pay anything into SS are able to collect money - less, but still something - from the system. Prior to this provision, people on full pensions who were exempt from SS contributions (such as teachers in many places) were able to still collect those amounts (which were never earned through contributions) even though they had quite significant pensions; that led to subsidies being given to people that didn't have as much need for them, as opposed to the indigent people who did need them. In your case, earning for 20+ years and then presumably only earning a small pension, you may be affected by this, but not necessarily severely. First of all, you are limited in how much your total reduction is to the lesser of a bit over $400 ($413 in 2015) or half your pension amount per month; so if you earn a $200 in pension monthly, your SS benefits are reduced by $100 monthly at most. Second, your percentage (and total cap) is reduced if you have over 20 years of credited work at 62 by 10% per credited year, and if you hit 30 years it's eliminated. So if you have 25 years right now, your total reduction is more like $200 at most. You also have an option to keep earning via credited work. Do some part-time work or summer work, for example. Sell things online. Whatever you need to do in order to get more years of credited work such that you end up with 30 years at 62. That will then increase your benefits back to the full amount. This article published on Nasdaq's website explains how this works in detail, including tables of benefit reductions. And, log in to ssa.gov to check how many years of creditable coverage you have and to see if you can get to 30 years and avoid any issues with this at all.",
"title": ""
},
{
"docid": "479095",
"text": "\"Curious, why are you interested in building/improving your credit score? Is it better to use your card and pay off the bill completely every month? Yes. How is credit utiltization calculated? Is it average utilization over the month, or total amount owed/credit_limit per month? It depends on how often your bank reports your balances to the reporting agencies. It can be daily, when your statement cycle closes, or some other interval. How does credit utilization affect your score? Closest to zero without actually being zero is best. This translates to making some charges, even $1 so your statement shows a balance each statement that you pay off. This shows as active use. If you pay off your balance before the statement closes, then it can sometimes be reported as inactive/unused. Is too much a bad thing? Yes. Is too little a bad thing? Depends. Being debt free has its advantages... but if your goal is to raise your credit score, then having a low utilization rate is a good metric. Less than 7% utilization seems to be the optimal level. \"\"Last year we started using a number, not as a recommendation, but as a fact that most of the people with really high FICO scores have credit utilization rates that are 7 percent or lower,\"\" Watts said. Read more: http://www.bankrate.com/finance/credit-cards/how-to-bump-up-your-credit-score.aspx Remember that on-time payment is the most important factor. Second is how much you owe. Third is length of credit history. Maintain these factors in good standing and you will improve your score: http://www.myfico.com/CreditEducation/WhatsInYourScore.aspx\"",
"title": ""
},
{
"docid": "409573",
"text": "A financial institution is not obligated to offer you a loan. They will only offer you a loan if they believe that they will make money off you. They use all the info available in order to determine if offering you a loan is profitable. In short, whether they offer you a loan, and the interest rate they charge for that loan, is based on a few things: How much does it cost the bank to borrow money? [aka: how much does the bank need to pay people who have savings accounts with them?]; How much does the bank need to spend in order to administer the loan? [ie: the loan officer's time, a little time for the IT guy who helps around the office, office space they are renting in order to allow the transaction to take place]; and How many people will 'default' and never be able to repay their loan? [ex: if 1 out of 100 people default on their loans, then every one of those 100 loans needs to be charged an extra 1% in order to recover the money the bank will lose on the person who defaults]. What we are mostly interested in here is #3: how likely are you to default? The bank determines that by determining your income, your assets, your current debts outstanding, your past history with payments (also called a credit score), and specifically to mortgages, how much the house is worth. If you don't have a long credit history, and because you don't have a long income history, and because you are putting <10% down on the condo [20% is often a good % to strive for, and paying less than that can often imply you will need mandatory mortgage insurance, depending on jurisdiction] the bank is a little more uncertain about your likelihood to pay. Banks don't like uncertainty, and they can deal with that uncertainty in two ways: (1) They can charge you a higher interest rate; OR (2) They can refuse you the loan. Now just because one bank refuses you a loan, doesn't mean all will - but being refused by one bank is probably a good indication that many / most institutions would refuse you, because they all use very similar analytical tools to determine your 'risk level'. If you are refused a loan, you can try again at another institution, or you can wait, save a larger down payment, and build your credit history by faithfully paying your credit card every month, paying your utilities, and making your car and rent payments on time. This will give the banks more comfort that you will have the ability to pay your mortgage every month, and a larger down payment will give them comfort that if the housing market dips, you won't owe more than the house is worth. My parting shot is this: If you are new in your career with no income history, be very careful about buying a property immediately, even if you get approved. A good rule of thumb is to only buy a property when you plan on living there for at least 5 years, or else you are likely to lose money overall, after factoring closing costs and maintenance fees. If you are refused a loan, that's probably a good sign that you aren't financially ready yet, but even if a bank approves you for a loan, you might not be ready yet either.",
"title": ""
},
{
"docid": "100721",
"text": "a) Nothing would support this company going back to $.50 per share b) Fundamentally the market for this sectors has been obliterated and the fundamentals don't look like they will improve. Similar companies experience what this one is and will be going through, they borrow the hilt and hope they can pump enough oil and sell the oil at a high price. Oil goes below, WAYYY below the price they can sell it at and even break even, so they are burning cash until they declare bankruptcy. This company is not an exception. So here is what to look at on their balance sheet: assets and liabilities. Liabilities are debt. Their debt is over 50% of their assets, that debt has interest and there is NO WAY they are making a profit. Their website's last financial statement is from September 30th.. LOL, so they haven't even released a quarterly financial statement in two quarters straight, so have they released anything? Given what we know about the dire state of the entire oil drilling industry, lets see if these guys are the exception to the rule (spoiler; they aren't) February 15th, 2015 http://www.marketwatch.com/story/strategic-oil-gas-ltd-provides-operations-update-2015-02-19-16173591 The Company prudently elected to stop the winter Muskeg drilling program in order to preserve capital. So now they aren't even getting new assets to resale, they aren't making any money from that operation, their debt still has interest payments though. Approximately 700 Boe/d of production has been shut-in by suspending operations at Bistcho, Cameron Hills and Larne, which are not economic at current commodity prices. Predictable. Also, you should notice from their actual financial statements (from 6 months ago, lol) (when the price of oil was over 100% higher than it is today, lol), this company already wasn't a good performer. They have been financing themselves by doing private placements, by issuing shares to investors that are not you, and diluting the share value of ALL OTHER SHAREHOLDERS. Dead in the water. I got this from skimming their financial report, without even being familiar with how canadian companies report. Its just bad news. You shouldn't be married to this investment.",
"title": ""
},
{
"docid": "11126",
"text": "1) How long have you had the car? Generally, accounts that last more than a year are kept on your credit report for 7 years, while accounts that last less than a year are only kept about 2 years (IIRC - could someone correct me if that last number is wrong?). 2) Who is the financing through? If it's through a used car dealer, there's a good chance they're not even reporting it to the credit bureaus (I had this happen to me; the dealer promised he'd report the loan so it would help my credit, I made my payments on time every time, and... nothing ever showed up. It pissed me off, because another positive account on my credit report would have really helped my score). Banks and brand name dealers are more likely to report the loan. 3) What are your expected long term gains on the stocks you're considering selling, and will you have to pay capital gains on them when you do sell them? The cost of selling those stocks could possibly be higher than the gain from paying off the car, so you'll want to run the numbers for a couple different scenarios (optimistic growth, pessimistic, etc) and see if you come out ahead or not. 4) Are there prepayment penalties or costs associated with paying off the car loan early? Most reputable financiers won't include such terms (or they'll only be in effect during the first few months of the loan), but again it depends on who the loan is through. In short: it depends. I know people hate hearing answers like that, but it's true :) Hopefully though, you'll be able to sit down and look at the specifics of your situation and make an informed decision.",
"title": ""
},
{
"docid": "40821",
"text": "\"I'm afraid you have missed a few of the outcomes commonly faced by millions of Americans, so I would like to take a moment to discuss a wider range of outcomes that are common in the United States today. Most importantly, some of these happen before retirement is ever reached, and have grave consequences - yet are often very closely linked to financial health and savings. Not planning ahead long-term - 10-20+ years - is generally associated with not planning ahead even for the next few months, so I'll start there. The most common thing that happens is the loss of a job, or illness/injury that put someone out of work. 6 in 10 adults in the US have less than $500 in savings, so desperation can set in very quickly, as the very next paycheck will be short or missing. Many of these Americans have no other source of saved money, either, so it's not like they can draw on retirement savings, as they don't have that either. Even if they are able to get another job or recover enough to get back to work in a few weeks, this can set off a desperate cycle. Those who have lost their jobs to technical obsolescence, major economic downturns, or large economic changes are often more severely affected. People once making excellent, middle-class (or above) wages with full benefits find they cannot find work that pays even vaguely similarly. In the past this was especially common in heavy labor jobs like manufacturing, meat-packing, and so on, but more recently this has happened in financial sectors and real estate/construction during the 2008 economic events. The more resilient people had padding, switched careers, and found other options - the less resilient, didn't. Especially during the 1970s and 1980s, many people affected by large losses of earning potential became sufficiently desperate that they fell heavily (or lost their functioning status) into substance abuse, including alcohol and drugs (cocaine and heroine being especially popular in this segment of the population). Life disruption - made even more major by a lack of savings - is a key trigger to many people who are already at risk of issues like substance addiction, mental health, or any ongoing legal issues. Another common issue is something more simple, like loss of transportation that threatens their ability to hold their job, and a lack of alternatives available through support networks, savings, family, and public transit. If their credit is bad, or their income is new, they may find even disreputable companies turn them away, or even worse - the most disreputable companies welcome them in with high interest and hair-trigger repossession policies. The most common cycle of desperation I have seen usually starts with banking over-drafts, and its associated fees. People who are afraid and desperate start to make increasingly desperate, short-sighted choices, as tunnel-vision sets in and they are unable to consider longer-term strategy as they focus on holding on to what they have and survival. Many industries have found this set of people quite profitable, including high-interest \"\"check cashing\"\", payday loans, and title loans (aka legal loan sharks), and it is not rare that desperate people are encouraged to get on increasing cycles of loan amounts and fees that worsen their financial situation in exchange for short-term relief. As fees, penalties, and interest add up, they lose more and more of their already strained income to stay afloat. Banks that are otherwise reputable and fair may soon blacklist them and turn them away, and suddenly only the least reputable and most predatory places offer to help at all - usually with a big smile at first, and almost always with awful strings attached. Drugs and alcohol are often readily available nearby and their use can easily turn from recreational to addictive given the allure of the escapism it offers, especially for those made vulnerable by increasing stress, desperation, loss of hope, isolation, and fear. Those who have not been within the system of poverty and desperation often do not see just how many people actively work to encourage bad decision making, with big budgets, charm, charisma, and talent. The voices of reason, trying to act as beacons to call people to take care of themselves and their future, are all too easily drowned out in the roar of a smooth and enticing operation. I personally think this is one of the greatest contributions of the movement to build personal financial health and awareness, as so many great people find ever more effective ways of pointing out the myriad ways people try to bleed your money out of you with no real concern for your welfare. Looking out for your own well-being and not being taking in by the wide array of cons and bad deals is all too often fighting against a strong societal current - as I'm sure most of our regular contributors are all too aware! With increasing desperation often comes illegal maneuvers, often quite petty in nature. Those with substance abuse issues often start reselling drugs to others to try to cover lost income or \"\"get ahead\"\", with often debilitating results on long-term earning potential if they get caught (which can include cost barriers to higher education, even if they do turn their life around). I think most people are surprised by how little and petty things can quickly cycle out of control. This can include things like not paying minor parking or traffic tickets, which can snowball from the $10-70 range into thousands of dollars (due to non-payment often escalating and adding additional penalties, triggering traffic stops for no other reason, etc.), arrest, and more. The elderly are not exempt from this system, and many of America's elderly spend their latter years in prison. While not all are tied to financial desperation as I've outlined above, a deeper look at poverty, crime, and the elderly will be deeply disturbing. Some of these people enter the system while young, but some only later in life. Rather than homelessness being something that only happens after people hit retirement, it often comes considerably earlier than that. If this occurs, the outcome is generally quite a bit more extreme than living off social security - some just die. The average life expectancy of adults who are living on the street is only about 64 years of age - only 2 years into early retirement age, and before full retirement age (which could of course be increased in the next 10-20 years, even if life expectancy and health of those without savings don't improve). Most have extremely restricted access to healthcare (often being emergency only), and have no comforts of home to rest and recuperate when they become ill or injured. There are many people dedicated to helping, yet the help is far less than the problem generally, and being able to take advantage of most of the help (scheduling where to go for food, who to talk to about other services, etc) heavily depends on the person not already suffering from conditions that limit their ability to care for themselves (mental conditions, mobility impairments, etc). There is also a shockingly higher risk of physical assault, injury, and death, depending on where the person goes - but it is far higher in almost every case, regardless. One of the chief problems in considering only retirement savings, is it assumes that you'll only have need for the savings and good financial health once you reach approximately the age of 62 (if it is not raised before you get there, which it has been multiple times to-date). As noted above, if homelessness occurs and becomes longstanding before that, the result is generally shortened lifespan and premature death. The other major issue of health is that preventative care - from simple dentistry to basic self-care, adequate sleep and rest, a safe place to rejuvenate - is often sacrificed in the scrambling to survive and limited budget. Those who develop chronic conditions which need regular care are more severely affected. Diabetic and injury-related limb loss, as one example, are far more likely for those without regular support resources - homeless, destitute, or otherwise. Other posters have done a great job in pointing out a number of the lesser-known governmental programs, so I won't list them again. I only note the important proviso that this may be quite a bit less in total than you think. Social Security on average pays retired workers $1300 a month. It was designed to avoid an all-too-common occurrence of simple starvation, rampant homelessness, and abject poverty among a large number of elderly. No guarantee is made that you won't have to leave your home, move away from your friends and family if you live in an expensive part of the country, etc. Some people get a bit more, some people get quite a bit less. And the loss of family and friend networks - especially to such at-risk groups - can be incredibly damaging. Note also that those financially desperate will be generally pushed to take retirement at the minimum age, even though benefits would be larger and more livable if they delayed their retirement. This is an additional cost of not having other sources of savings, which is not considered by many. Well, yes, many cannot retire whether they want to or not. I cannot find statistics on this specifically, but many are indeed just unable to financially retire without considerable loss. Social Security and other government plans help avoid the most desperate scenarios, but so many aspects of aging is not covered by insurance or affordable on the limited income that aging can be a cruel and lonely process for those with no other financial means. Those with no savings are not likely to be able to afford to regularly visit children and grandchildren, give gifts on holidays, go on cruises, enjoy the best assistive care, or afford new technological devices to assist their aging (especially those too new and experimental to be covered by the insurance plans they have). What's worse - but most people do not plan for either - is that diminished mental and physical capacity can render many people unable to navigate the system successfully. As we've seen here, many questions are from adult children trying to help their elderly parents in retirement, and include aging parents who do not understand their own access to social security, medicaid/medicare, assistive resources, or community help organizations. What happens to those aging without children or younger friend networks to step in and help? Well, we don't really have a replacement for that. I am not aware of any research that quantifies just how many in the US don't take advantage of the resources they are fully qualified to make use of and enjoy, due to a lack of education, social issues (feeling embarrassed and afraid), or inability to organize and communicate effectively. A resource being available is not very much help for those who don't have enough supportive resources to make use of it - which is very hard to effectively plan for, yet is exceedingly common. Without one's own independent resources, the natural aging and end of life process can be especially harsh. Elderly who are economically and food insecure experience far heightened incidence of depression, asthma, heart attack, and heart failure, and a host of other maladies. They are at greater risk for elder-abuse, accidental death, life-quality threatening conditions developing or worsening, and more. Scare-tactics aren't always persuasive, and they do little to improve the lives of many because the people who need to know it most generally just don't believe it. But my hope here is that the rather highly educated and sophisticated audience here will see a little more of the harsher world that their own good decisions, good fortune, culture, and position in society shields them from experiencing. There is a downside to good outcomes, which is that it can cause us to be blind to just how extremely different is the experience of others. Not all experience such terrible outcomes - but many hundreds of thousands in the US alone - do, and sometimes worse. It is not helpful to be unrealistic about this: life is not inherently kind. However, none of this suggests that being co-dependent or giving up your own financial well-being is necessary or advised to help others. Share your budgeting strategies, your plans for the future, your gentle concerns, and give of your time and resources as generously as you can - within your own set budgets and ensuring your own financial well-being. And most of all - do not so easily give up on your family and friends, and count them as life-long hopeless ne'er-do-wells. Let's all strive to be good, kind, honest, and offer non-judgmental support and advice to the best of our ability to the people we care about. It is ultimately their choice - restricted by their own experiences and abilities - but need not be fate. People regularly disappoint, but sometimes they surprise and delight. Take care of yourself, and give others the best chance you can, too.\"",
"title": ""
}
] |
5617
|
New or Used Car Advice for Recent College Grad
|
[
{
"docid": "256803",
"text": "Never buy a new car if cost is an issue. A big chunk of the price will disappear to depreciation as you drive it off the lot. If you want a shiny new car with the latest equipment (and if you can afford it!), buy a lightly-used car. Normally I would recommend a 1-3 year old car. 95% of the value, with a big cost savings. But this depends on your financial situation. Given that you just need a commuter car for mostly highway driving, in a place where the weather is easier on cars, you could be fine with a 5-6 year old import. Camry's, Accords, Civics, etc are all well-built, reliable, and affordable due to their numbers. As for financing, shop around. Don't blindly use dealer financing. Check with banks and especially local credit unions and see what rate they can offer you. Then, when you are ready to go, get pre-approved (this is when they pull your credit) and get the car.",
"title": ""
},
{
"docid": "341252",
"text": "17.5 thousand miles/year is pretty high mileage. You could find an Accord or Civic of comparable age with much lower mileage than that, and it wouldn't be a stretch for someone (even with your limited credit history) to get a loan on an old car like that. You might try to have your parents cosign on a loan depending on their financial circumstances. That's how I bought my first car 13 years ago. The biggest surprise you might want to consider is the cost of full collision auto coverage which will be required by whatever bank you finance through. Get quotes for that before signing any papers. (I spent $2000 more on a motorcycle because the more powerful one cost $2000 less/year to insure just a few years after I bought that first car.) Speaking of which, another thing to consider given the nice LA weather is a motorcycle. The total cost of ownership is much lower than a car. You will probably not want to pursue that option if you do not have medical insurance, and you may not want to anyway.",
"title": ""
}
] |
[
{
"docid": "338663",
"text": "But.. what I really want to know.... is it illegal, particularly the clause REQUIRING a trade in to qualify for the advertised price? The price is always net of all the parts of the deal. As an example they gave the price if you have $4000 trade in. If you have no trade in, or a trade in worth less than 4K, your final price for the new car will be more. Of course how do you know that the trade in value they are giving you is fair. It could be worth 6K but they are only giving you a credit of 4K. If you are going to trade in a vehicle while buying another vehicle the trade in should be a separate transaction. I always get a price quote for selling the old car before visiting the new car dealer. I do that to have a price point that I can judge while the pressure is on at the dealership.. Buying a car is a complex deal. The price, interest rate, length of loan, and the value of the trade in are all moving parts. It is even more complex if a lease is involved. They want to adjust the parts to be the highest profit that you are willing to agree to, while you think that you are getting a good deal. This is the fine print: All advertised amounts include all Hyundai incentives/rebates, dealer discounts and $2500 additional down from your trade in value. +0% APR for 72 months on select models subject to credit approval through HMF. *No payments or 90 days subject to credit approval. Value will be added to end of loan balance. 15MY Sonata - Price excludes tax, title, license, doc, and dealer fees. MSRP $22085- $2036 Dealer Discount - $500 HMA Lease Cash - $500 HMA Value Owner Coupon - $1000 HMA Retail Bonus Cash - $500 HMA Military Rebate - $500 HMA Competitive Owner Coupon - $400 HMA College Grad Rebate - $500 HMA Boost Program - $4000 Trade Allowance = Net Price $12149. On approved credit. Certain qualifications apply to each rebate. See dealer for details. Payment is 36 month lease with $0 due at signing. No security deposit required. All payment and prices include HMA College Grad Rebate, HMA Military Rebate, HMA Competitive Owner Coupon and HMA Valued Owner Coupon. Must be active military or spouse of same to qualify for HMA Military Rebate. Must graduate college in the next 6 months or within the last 2 years to qualify for HMA College Grad rebate. Must own currently registered Hyundai to qualify for HMA Valued Owner Coupon. Must own qualifying competitive vehicle to qualify for HMA Competitive Owner Coupon.",
"title": ""
},
{
"docid": "270877",
"text": "First, don't borrow any more money. You're probably bankrupt right now at that income level. 2k/month is poverty level income, especially in some of the higher cost of living areas of California. At $2k per month of income, and $1300 of rent and utilities, you've only got 700 a month for food. The student loans are probably in deferment while your husband is in school. If so, keep them that way and deal with them when he lands a career track goal after grad school. The car loan is more than you can afford. Seriously consider selling the car to get rid of the note. Then use the cash flow that was going to the car loan to pay off the 'other' debt. A car is usually a luxury, but if it is necessary, be sure it is one that doesn't include a loan. Budget all of your income (consider using YNAB or something like it). Include a budget item to build an emergency fund. Live within your means and look for ways to supplement your income. With three of your own, you'd probably make an excellent baby sitter. As for the inheritance, find a low risk, liquid investment, such as 12 month CDs or savings bonds. Something that you can liquidate without penalty if an emergency arises. Save the money for if you get into a situation where there is no other way out. Hopefully you can have your emergency fund built up so that you don't need to draw on the inheritance. Set a date, grad school + landing + 90 days. If you reach that date and haven't had to use the inheritance, and you have a good emergency fund, put the inheritance in a retirement fund and forget about it. Why retirement fund and not a college fund for the kids? The best gift you can give them is to remain financially independent throughout your life. If you get to the point where you are fully funding your tax advantaged retirement savings, and you are ready to start wealth-building, that is the time to take part of that cash flow and set it aside for college funds.",
"title": ""
},
{
"docid": "468879",
"text": "\"As someone who has a very similar debt amount and environment (new grad, nice new paying job, want a car, etc), I'd like to share something with you. Life has unexpected costs. Luckily I didn't buy that new car the first few months out of college like I had planned to; I'm glad that I didn't because, as a fledgling \"\"adult\"\", despite having lived on my own while in college while working part-to-full time there are some things you just don't realize until it either happens or it happens to someone else. Here are some of those things: I could go on but I won't. $95K is good money and I would definitely recommend spending it a bit to enjoy yourself. But I would honestly tell you that taking your monthly expenses, adding a few hundred on top of that and then multiplying that sum by 3 would be a smart savings amount before picking up a car loan. Maybe that's an excessive savings but I've seen way too many people burn out over their cost-of-living and their failure to adjust appropriately when shit hits the fan. So instead of having to deal with the stab at your pride when having to lower the cost/quality of living that you'll probably grow accustomed to at a $95K salary, just prepare for the worst. Oh, and did I mention... A NEW JOB IS NOT A SECURE JOB Consider yourself to likely be the first asset dropped from the company if even the tiniest thing goes wrong. I know way too many people who were fresh hires at Intel, Boeing, and a few other big tech companies that pay around what you make and, despite being bad asses in college, they were dropped like a bad habit when their employers hit rough patches. To those even more experienced than me, please feel free to add to the list. I'd personally love to know them myself.\"",
"title": ""
},
{
"docid": "244986",
"text": "\"I support the strategy to buy a less expensive car at the outset and then save for that more expensive car. You mentioned that you would be able to save $9000 by the time you had to start making payments. That sounds like a great budget for car shopping. For $9k you can get a dependable used car. If you find the right high-yield savings account you can get around 2% on your $500/month direct deposit. That's a difference of about 5% when you add in the 2.9% interest that you would have been paying on the loan. (You can't find such a low risk investment that would yield 5% these days.) Also, at that rate (2%) you would have $27k saved up in less than 52 months, or over $31k in 60 months. Then you could buy a BMW with cash! And I'm sure they would give you a cash discount. Alternatively you could be just finishing paying off the loan and might already be looking at the next car you'll take a loan out for. The point is not that you have to completely deprive yourself for the rest of your life. But by not taking out a loan you were certainly come out ahead in 5-10 years time. Also, one common mistake that new grads make is thinking that they are rich right out of college. Yes, you definitely have a nice salary and \"\"could afford it\"\" by most people's standards. I have a coworker that graduated and started work a year ago. He first bought a brand new Subaru. Why Subaru I do not know, but that is what he thought he wanted. After driving the car for a few months he decided for a few reasons that it was not what he wanted. So he sold the car (for a loss) and bought a slightly used Nissan Z. He has since decided that he needs a more practical car for day to day driving to minimize the abuse that his Z takes. So he has bought another car. This time a low budget Honda. Had he started with a low budget car he could be driving the same car to work right now, but have a good chunk of savings for a new car instead of a loan and a car that he drives only occasionally.\"",
"title": ""
},
{
"docid": "515060",
"text": "I completely agree that there are experts that recognize it as a very serious problem, and I agree that it is a serious problem that could cause a large recession or crash (my large chunk of remaining loans definitely agrees). My point is that this article isn't looking at economic data. It's looking at a survey of recent college grads and asking them to rank the risk of student loan debt vs the risk of North Korea. I wouldn't consider that a very useful indicator.",
"title": ""
},
{
"docid": "207591",
"text": "To answer your question, the $30 and it accrues monthly if you carry the balance forward. However, don't do that. Only use your credit card on things you can immediately pay off right away. Don't pay extra money for things and don't pay for things you can't afford. As a recent college grad, I've seen way too many people have $1,000+ in credit card debt while in school. That's just nutty. If you have any other questions let me know.",
"title": ""
},
{
"docid": "373645",
"text": "I used to like Applebee's when I was in Undergrad and Grad school... it was open late, it was relatively cheap (late night specials), and the food was better than your average college fair. I recently went back with my SO for some nostalgia at like 8:30 p.m. and I realized very quickly that: * Late night specials start at 10:00 p.m. - who the fuck stays out that late to eat on a weeknight? * Food was awful, definitely went downhill from what I remember * And it was super overpriced - like 9.99 for wings as an appetizer GTFO here Applebee's",
"title": ""
},
{
"docid": "250672",
"text": "I respectfully disagree with @JohnFX's comment regarding new vs used. (John knows what is talking about though; he gave an awesome answer on buying a car: What are some tips for getting the upper hand in car price negotiations?) The answer to your question is based on whether or you not you can stand to have a small, loud, cheap but reliable car for the next 10 or 15 years. If you plan to keep your new car until it dies 20 years from now, then a new car can be a fine choice. I just bought a car and the difference between my 2013 Hyundai and a comparable 2012 Hyundai wasn't much. Furthermore, it was hard to even find a 2012 (which justifies the higher price from dealerships and the private market). Doing math in my head told me the reduced usage I will get out of the car wasn't offset by the slightly lower price. Depending on the specific age, insurance on newer cars can be cheaper than insurance on older cars. (But you have to have carry more insurance, so consider that as well.) There might not be a different between a 2010 and a 2012, but there will likely be for a 2005 and the 2013. New cars can be cheaper to operate. Lower fuel costs, better safety and possibly pollution costs. They are tuned up and you know everything about their history. Repairs and factory warranties might not be available on a used car, so if you car turns out to be a problem, your out of pocket is limited. These programs don't mean anything. Get an independent certified mechanic to check out any used car you buy. If the dealer won't let you get the car checked out, then they aren't worth your business. Certified cars don't justify their cost according to consumer reports, they are more for marketing than reliability. Don't waste money on a third party warranty. Either the car is good and doesn't need it, or it needs a warranty and you shouldn't buy it. If you new car comes with a factory warranty, that is fine. Radio host Clark Howard is indifferent if you want to purchase a factory warranty separately, but never a third party. Just out of college, you probably will be better off spending the least amount of money you can for a good used car. If for no other reason, this likely isn't going to be your car in the near future. (Only you can answer that) If you have a feeling you won't keep your tiny car well into your 30s, then definitely don't buy a new car. Also, my experience only applies to my make and model. Certain models of cars keep their value and the difference between new and used isn't much for the most recent model years. But there are many more makes and models that don't pan out that way.",
"title": ""
},
{
"docid": "485318",
"text": "As a recent college grad who switched to his own car insurance, many of the things I did myself are reflected here. The #1 thing I did was find out what coverages I had, what coverages some friends of mine had (car enthusiasts mostly - they're the most informed on this stuff), and then figured out what kind of coverages I wanted. From there, I went around getting quotes from anyone and everyone and eventually built out a sizeable spreadsheet that made it obvious which company was going to offer me the best rate at a given coverage level. Something else to remember - not all insurance companies look at past accidents and violations (speeding, etc) the same. In my search, I found some have a 3-year scope on accidents and violations, while others were as much as 5 years. So, if your driving record isn't a shining example (mine isn't perfect), you could potentially save money by considering insurance through a company that will see fewer violations/incidents than another because of the size of their scope. I ended up saving $25/mo by choosing a company that had a 3-year scope, which was on the cusp of when my last violation/incident occurred. Insurance companies will also give out discounts for younger drivers based on GPA average. If you have kids and they maintain a high GPA, you might be able to get a discount there. Not all companies offer it, so if they do it's worth finding out how much it is",
"title": ""
},
{
"docid": "10284",
"text": "Source: I'm recently (2 years) out of college (Info Sciences + Technology degree) Disclaimer: Speaking from limited personal experience (see above) A lot of corporate recruiters like the prospect of hiring recent college grads of because of the location flexibility they have (typically own no real estate, are not married, and have no children). If you get a job with Amazon and relocate, take a year to settle your finances, then determine if purchasing a house is something you can manage. If you don't have a savings set aside for a reasonable down payment on a house, you'll get hit with a mortgage insurance payment each month =\\, and that's not fun. Don't try to do too much at once, and make sure you have a full assessment of your finances before making any major purchases. I follow this general rule: Every few months, I fully re-assess our expenditures, and see what we can cut out or cut back on, put a bit into savings, and put the rest against outstanding student loans.",
"title": ""
},
{
"docid": "397915",
"text": "\"For finance, you need to have a strong handle on how to use Excel. I don't mean \"\"I can write some formulas and make a complicated worksheet\"\", I mean \"\"I know the VBA language and can utilize macros and specific coding to streamline processes and eliminate some tasks\"\". Having VBA on your resume is a definite plus, especially in addition to the CFA L1/L2 candidacy. [Here's a great resource for learning VBA](http://www.excel-vba-easy.com/). In addition to VBA, the ability to use R (the stats program) can also be incredibly helpful. That's a whole new beast than Excel, and has amazing capabilities that are almost perfect for finance. [Here's a resource](http://www.statmethods.net/) for learning the programming, but it requires a strong understanding of statistical methods and maybe another stats program like SPSS. If you Google \"\"learn R quickly\"\" or something like that, you can come up with something. It sounds like you're a Seattlite (Amazon, Boeing, Russell), and so am I. If you'd like help networking, feel free to PM me. I'm a recent college grad, and over the past few years, I've built a pretty solid network in the investments community here. I can at least connect you to people that might be able to help out. If nothing else, I can at least give a ton more resources to learn from. Edit: Also, Russell often uses LinkedIn to find new hires to interview. If you have a lot of groups and stuff in common with the HR team, you pop up higher in their searches. Look up their HR team, and find out what groups they're in, what companies they follow, etc. Also, do you know if you want to go into corp. finance or investments? Two very different games.\"",
"title": ""
},
{
"docid": "237189",
"text": "\"The advice to \"\"Only invest what you can afford to lose\"\" is good advice. Most people should have several pots of money: Checking to pay your bills; short term savings; emergency fund; college fund; retirement. When you think about investing that is the funds that have along lead time: college and retirement. It is never the money you need to pay your bills. Now when somebody is young, the money they have decided to invest can be in riskier investments. You have time to recover. Over time the transition is made to less risky investments because the recovery time is now limited. For example putting all your college savings for your recent high school graduate into the stock market could have devastating consequences. Your hear this advice \"\"Only invest what you can afford to lose\"\" because too many people ask about hove to maximize the return on the down payment for their house: Example A, Example B. They want to use vehicles designed for long term investing, for short term purposes. Imagine a 10% correction while you are waiting for closing.\"",
"title": ""
},
{
"docid": "461325",
"text": ">Huh? Agriculture is down to single digits as part of the GDP. What does that have to do with a gold standard and monetary policy? I was being sarcastic. >But as soon as the USA left the gold exchange standard, total factor productivity began to dramatically stagnate. Correlation doesn't equal causation. Remember that this is also the same time that European, Japanese, and Soviet economies were picking back up after WW2. Global production picked up and there was more international competition. >Because our massive debt is doing so well for us? In the beginning it looks nice because there is very little pain and is practically unnoticible, but as we see current events playing out in the US and to a greater extent Europe which isnt as tightly knit economically as the US, fiat currency has huge problems. The EU cannot print money in the same way the USA can. If anything the Euro is a cautionary tale about currency's with too stringent printing limitations. Along with tying together a set of countries at vastly different levels of economic development. The USA is not anywhere near the point of no return, and seeing as we can finance our debt at ridiculously low rates compared to the rest of the world, it would be much simpler to do that, than try and restructure the entire monetary system of the USA. >Established over what? the last 40 years? We are at about 80-90 years now. >Thats hardly enough time to call practical fact when the gold standard existed for hundreds and thousands of years. The gold standard has not been in use for hundreds of thousands of years. Nor was it the only currency previous to fiat. >I am not sure why you think that the USA is in such a great position. The american dream is faultering if you're just starting out in life. Just ask any number of recent college grads who are increasingly living with parents, not getting married and can't find jobs. I don't think asking my local college grad is a good way of determining the USA's macro-economic situation. You're absolutely right that there is a major major disparity of wealth problem. But the gold standard isn't the reason for that. Unemployment Insurance and Welfare are also comically small portions of the budget. If you wanna talk about cutting spending, Defense and Medicare are where it's at. And you don't even have to hurt old people or soldiers to fix them.",
"title": ""
},
{
"docid": "16606",
"text": "\"Given the state of the economy, and the potential of a rough near future for us recent grads (i.e. on/off work), I would recommend holding off on large purchases while your life is in flux. This includes both a NEW car and purchasing a house. My short answer is: you need a reliable vehicle, so purchase a used car, from a major dealer (yes this will add a fairly high premium, but easier financing), that is 4-5 years old, or more. Barring the major dealer purchase, be sure to get a mechanic to check out a vehicle, many will offer this service for a reasonable payment. As people point out, cars these days will run for another 100k miles. You will NOT have to pay anywhere near $27,000 for this vehicle. You may need to leverage your 10k for a loan if you choose to finance, but it should not be a problem, especially as you seem to imply an established credit history. In addition to this, start saving your money for the house you would like to eventually get. We have no idea where you live, but, picking rough numbers, assuming a 2 year buy period, 20% down, and a $250,000 home, the down payment alone will require you to save ~$2,000/month starting now. Barring either of these options, max out your money to tax sheltered accounts (your Roth IRA, work 401k, or a regular IRA) asap. Obviously, do not deplete your emergency fund, if anything, increase it. 10k can be burned through in a heartbeat. Long Answer: I purchased a brand new car, right out of school, at a reasonable interest rate. Like you, I can afford this vehicle, however, if someone were to come to me today (3.5 years later) and offer me the opportunity to take it back and purchase a 4-5 year used vehicle, at a 4-5 year used car price, albeit at a much higher interest rate (since I financed), it would be about a 0.02 second decision. I like my car, but, I'd like the differential cash savings between it and a reliable used car more. $27,000 is also fairly expensive for a new vehicle, there are many, very nice vehicles, for 21-23k. I still would not consider these priced appropriate to spend your money on them, but they exist. However, you do very much need a reliable vehicle, and I think you should get one. On the home front, your $400 all inclusive rent is insanely cheap. Many people spend more than that on property tax and PMI each year, so anyone who throws the \"\"You're throwing money away!\"\" line at you is blowing smoke to justify their own home purchase. Take the money you would have spent on a mortgage, and squirrel it away. Do your own due diligence and research the home market in your area and decide for yourself if you think home prices have bottomed and will stay there, have further to go, or are going to begin to rise. That is a decision only you can make for yourself. I'd add a section about getting expenses under control, but you said you could save 50% of your takehome pay. This is an order of magnitude above the average. Good job. Try doing 50% for 4 months, then calculate your actual amount. Then try to beat it.\"",
"title": ""
},
{
"docid": "228342",
"text": "Right- and that's exactly what Amazon wants. YOUTH. They'll take every last bit of youthful energy and enthusiasm that a recent grad has to offer, use it up, and burn them out. Rinse and repeat. They're a despair factory. Honestly, this is the formula that the average large tech company has mastered. I know they are good experience and it's hard not to recommend them to recent grads, but man the people I knew from there when I lived in Seattle were depressed and demoralized by the experience.",
"title": ""
},
{
"docid": "155376",
"text": "\">They lie right to your face. \"\"Borrow tens of thousands of dollars to give to us, it will totally work out...for us.\"\" I don't believe they verbalize those last two words. They pretty much end it with a period after the \"\"work out\"\" part. And then of course, they produce that BS statistic that college grads make a \"\"million dollars more over their career\"\". I mean really? Which grads are those? You mean the ones who graduated circa 45-50 (or more) years ago (when very few people had college degrees)? And in exactly what inflation-adjusted time-frame was that \"\"million dollars\"\"? Was it 1960 dollars? 1980 dollars? 2000 dollars? Because a million bucks, while still not pocket change even in 2012, was worth a LOT more the further you go back.\"",
"title": ""
},
{
"docid": "204227",
"text": "Stay away from college debt. You can't default on it. Your wages will be garnished if you're unable to pay it back. Even when your and old man, they will garnish your social security money. In effect college debt makes you an indentured servant. Maybe even worse than the 7 years of servitude people served in early America. Lots of grads are working in restaurants and retail stores.... even some computer science grads. There is great risk in the college investment compared to 40 years ago when it was a sure thing. Do not take debt for college. If that means you can't go to college then so be it. You're future self will than you.",
"title": ""
},
{
"docid": "433066",
"text": "\"Consumer Reports offers a service that can tell you detailed actual cost to a dealer for a specific model and accessories -- real cost after rebates, not just invoice price. It costs a bit to order these reports, but if you are serious about buying a new car they are a highly recommended tool -- cu is independent and will give you the best info available, and simply walking into the dealership with the report in your hand can save huge amounts of negotiating. \"\"If you can give it to me for $500 over the real price, as shown here, I'll sign now.\"\" Of course, standard advice is that it's usually better to buy a recent-model used car. I believe cu has other reports that can help you determine what a fair price is in that case, but usually I just bring it to a trusted garage and pay them to tell me exactly how much work it needs and whether they think it's worth the asking price.\"",
"title": ""
},
{
"docid": "385600",
"text": "For some ideas on investing priority guidelines, see Oversimplify it for me: the correct order of investing. Congratulations on being debt free! My advice to you is to do what you can to remain debt free. You could certainly invest the money; it will earn much more over the long-term in a stock mutual fund than it would left in a savings account. However, if you need any of this money in the next few years, it would be a shame if it lost money in the short-term. How much do you need to finish grad school? Don't invest that money in the stock market, because you will need it over the next few years. Likewise, think about other expenses that are coming up. Will your car need to be replaced in the next couple of years? Will you have enough income to meet your living expenses while you are in grad school, or will you need some of this to money to help with that? Finally, it would be good to keep some extra as an emergency fund, so you can easily pay for any unexpected expenses that come up. If you can make it through grad school debt free, you will be much better off than if you invest all the money but take out student loans in the process. After you've accounted for all of that, whatever is left of the money could definitely be invested. If your goal is to start a retirement fund, an index mutual fund invested inside a Roth IRA is a great place to start.",
"title": ""
},
{
"docid": "347849",
"text": "First thing to do right now, is to see if there's somewhere equally liquid, equally risk free you can park your cash for higher rate of return. You can do this now, and decide how much to move into less liquid investments on your own pace. When I was in grad school, I opened a Roth IRA. These are fantastic things for young people who want to keep their options open. You can withdraw the contributions without penalty any time. The earnings are tax free on retirement, or for qualified withdrawls after five years. Down payments on a first home qualify for example. As do medical expenses. Or you can leave it for retirement, and you'll not pay any taxes on it. So Roth is pretty flexible, but what might that investment look like? It in depends on your time horizon; five years is pretty short so you probably don't want to be too stock market weighted. Just recognize that safe short term investments are very poorly rewarded right now. However, you can only contribute earnings in the year they are made, up to a 5000 annual maximum. And the deadline for 2010 is gone. So you'll have to move this into an IRA over a number of years, and have the earnings to back it. So in the meanwhile, the obvious advice to pay down your credit card bills & save for emergencies applies. It's also worth looking at health and dental insurance, as college students are among the least likely to have decent insurance. Also keep a good chunk on hand in liquid accounts like savings or checking for emergencies and general poor planning. You don't want to pay bank fees like I once did because I mis-timed a money transfer. It's also great for negotiating when you can pay in cash up front; my car insurance for example, will charge you more for monthly payments than for every six months. Or putting a huge chunk down on a car will pretty much guarantee the best available dealer financing.",
"title": ""
},
{
"docid": "551329",
"text": "oh yea, I read where if you become a plumber (for example), the average college grad (who is immediately employed post grad) doesn't catch up to the plumber's gross earnings and nest egg until age 59. in this economy, the grad may never catch up",
"title": ""
},
{
"docid": "52522",
"text": "\"This article is silly. We have a functioning labor market. Wages are balanced by supply and demand. We don't need more regulation to \"\"fix\"\" it. I think the market is effectively bifurcated. You have skilled jobs being well paid, and candidates can easily switch. For instance entry-level Computer Science grads regularly make $60k and have multiple offers. If you're highly skilled, life is good, economically. I think the jobs that require trade-skills are also under supplied. The roofer in the article is an example. These folks also get reasonable pay and steady work, certainly enough for a middle class lifestyle. If you're a low-skill worker, then life is much harder. There are job shortages, wages are low, and employees suffer. One complication is that many students go to college, but graduate without marketable skills. This leaves them to compete against low-skill workers. So college grads suffer from \"\"low\"\" wages, and non-college grads suffer from increased competition. I'm surprised so many people still take on college debt to get degrees that offer little to no wage premium. Minimum wage hikes can help a little. In Seattle they found no job loss from the first small minimum wage hike (and an increase in employee well-being). The second hike was larger and created significant job losses (enough that total wages paid were flat). I think this means that some jobs don't generate enough value to be paid $15/hr. The TL-DR is get skills to lead an easier economic life.\"",
"title": ""
},
{
"docid": "320583",
"text": "Each of us makes our own way in life, making choices based upon or own needs and desires. Some of us choose to live simple lives, others choose more complex lives where we earn and spend more. There are several points which one should examine and consider. Consider that the market for new cars is not the entire population, but only the fraction of the population that can afford to spend $20,000+ for a new car (at $400+/month payments). You quickly realize that most people making below median income cannot afford to purchase a new car. They buy used cars, from the pool of cars left after depreciation has reduced the price of the car by half (or more). One rule of thumb might be to spend < 10% of your income on transportation. Which might allow for a $400-500/month car payment for half of families. And when you keep a car for 10 years, that can mean two cars, one payment-free. Consider that a new Honda Accord or Toyota Camry is $20-30,000 which is 2/3 to 3/4 the price of a new luxury car. When I purchased my (used) Civic several years ago, the price was nearly 1/2 the price of a new luxury car. I recently purchased a (used) luxury car (7 year old, 70,000 miles) less than 1/3 the new price. The leather interior looks new, more amenities, better performance than my Civic, the car runs well, and with proper maintenance, I expect to drive it for 2-3 years and pass it along to one of my children.",
"title": ""
},
{
"docid": "451170",
"text": "Your long-term saving targets will include retirement, kids' college, house, etc. Medium-term might be your college, or a car. Short-term might be a vacation somewhere or a new laptop. In all cases saving, then spending money you do have is better than spending money you don't have. I think that's the first takeaway of this truism. However, I also believe 10% is said as a retirement target. Retirement is very important and this advice is stressed by many financial planners because it's very easy to underestimate how expensive it is. By the same token, it's recommended that you spend 2 months' salary on an engagement ring, and that particular truism can be traced back to a DeBeers ad. I personally don't know whether 10% as a retirement target is sage - it sounds right but I haven't followed it for a variety of reasons. Please corroborate against multiple sources and apply to your own financial person.",
"title": ""
},
{
"docid": "319403",
"text": "As a recent college graduate that's my main piece of advice to every incoming freshman... Take gens eds... If you want to be a paleontologist you are not going to take a semester in Africa to dig up bones your first semester. First semester you are going to take English 101, biology, geography and college algebra so that the rest of your classes make sense.",
"title": ""
},
{
"docid": "102628",
"text": "New cars are sold for about $500 over their blue book value. They drop in value by about 20% their first year. Used cars are sold for about $2,500 above their blue book. They depreciate like normal. My advice based on my personal experience is to get a new car. When buying a used car, remember that the previous owner sold it for a reason. You are buying someone else's problems. Average car is flipped every 4 years when it takes 5 years to pay it off. Don't do that...keep it for 5+ years if you get a new car. My knowledge comes from being a Chevrolet car salesman. This info is generalized and about 10 years old.",
"title": ""
},
{
"docid": "134063",
"text": "Plus you already have money in a 529 plan that is meant for college expenses (and cannot be used to pay student loans) - use that money for what it's for. I disagree with @DStanley, as a current college student I would say to take out loans. Most of the time I am against loans though. So WHY? There are very few times you will receive loans at 0% interest (for 4+ years). You have money saved currently, but you do not know what the future entails. If you expend all of your money on tuition and your car breaks down, what do you do? You can not used student loans to pay for your broken car.Student loans, as long as they are subsidized, serve as a wonderful risk buffer. You can pay off your loans with summer internships and retain the initial cash you had for additional activities that make college enjoyable, i.e - Fraternity/ Sorority, clubs, dinners, and social nights. Another benefit to taking these loans would assist in building credit, with an additional caveat being to get a credit card. In general, debt/loans/credit cards are non-beneficial. But, you have to establish debt to allow others to know that you can repay. Establishing this credit rating earlier than later is critical to cheaper interest rates on (say) a mortgage. You have made it through, you have watched your expenses, and you can pay your debt. Finish It. If you do it right, you will not have loans when you graduate, you will have a stunning credit rating, and you will have enjoyed college to its fullest potential (remember, you only really go through it once.) But this is contingent on: Good luck, EDIT: I did not realize the implication of this penalty which made me edit the line above to include: (to the extent you can per year) For now, student loan repayment isn't considered a qualified educational expense. This means that if you withdraw from a 529 to pay your debts, you may be subject to income taxes and penalties.Source Furthermore, Currently, taxpayers who use 529 plan money for anything other than qualified education expenses are subject to a 10% federal tax penalty. Source My advice with this new knowledge, save your 529 if you plan on continuing higher education at a more prestigious school. If you do not, use it later in your undergraduate years.",
"title": ""
},
{
"docid": "162519",
"text": "\"Numbers: Estimate you still owe around 37000 (48500 - 4750, 5% interest, 618 per month payment). Initial price, down payment, payments made - none of these mean anything. Ask your lender, \"\"What is the payoff of the current loan?\"\" Next, sell or trade the current vehicle. Compare to the amount owed. Any shortfall has to be repaid, out of pocket, or in some cases added to the price of the new car and included in the principal of the new loan. You cannot calculate how much you still owe the way you have, because it totally ignores interest. Advice on practicality: Don't do this. You will be upside down even worse on the new car from the instant you drive off the lot. Sell the current vehicle, find a way to pay the difference - one that doesn't involve financing. Cut your losses on the upside down vehicle. Then purchase a new vehicle. I'm in the \"\"Pay cash for gently used\"\" school, YMMV. Another option is to go to your bank. Refinance your car now to get a lower interest rate. Pay as much of the principal as you can. Keep that car until it is paid off. Then you will not be upside down. If you're asking how to use the estimator on the webpage. Put the payoff in the downpayment as a negative and the trade in value in the trade in spot. Expect the payment to go up significantly. Another opinion that might be practical advice. Nothing we say here will convince your financially responsible spouse that this is a good idea.\"",
"title": ""
},
{
"docid": "155727",
"text": "\">I've found most of my personal success looking for work by way of the burgeoning technical recruiter industry - they know a bit more than an HR 'bot', either mechanical or human (haha), about the reality of technical requirements for a job and are able to find you if you just know where to place yourself. Yes, that is another way \"\"around\"\" the HR bot-ery. But it tends to be expensive (granted the \"\"company\"\" doing the hiring does the paying, but I can guarantee you that the cost inevitably comes OUT of the possible salary/benefits of the hiree). >Getting solicited for a job by way of your LinkedIn profile is a much easier way of finding work than the futile carpet-bombing of large corporate HR machines, no doubt. Yes, alas... that seems to be about the only way that most people (including ironically enough college grads with HR & MBA degrees) seem to think about jobs: the \"\"carpet bombing\"\" of HR departments combined with the continual scanning of \"\"jobs\"\" listings. I want to weep every time some college grad tells me they were \"\"taught\"\" to use Monster.com (et al) as a *primary* means of obtaining a position. I mean seriously, USE those research and networking skills that you claim to have to FIND a company that you WANT to work for, and then find a way to get a position in that company. It is an ACTIVE thing, not a \"\"passive\"\" one. People who do that tend to actually GET (one of the) jobs they want, rather than being \"\"stuck\"\" in something where... well, they were the first ones to make an offer...\"",
"title": ""
},
{
"docid": "597467",
"text": "Yeah, the 12% assumption is divorced from reality. That is a full 5% higher than the real return on the S&P for the last sixty years. But buying a used car rather than borrowing for a new one is solid-gold advice. It may take more iterations to get to the nice car because of things like taxes, transaction costs, repairs, etc., but staying out of debt (or saving up as much as possible to get a reliable car) is excellent advice.",
"title": ""
}
] |
4590
|
Is a fixed-price natural gas or electricity contract likely to save money?
|
[
{
"docid": "267233",
"text": "In my area, the fixed prices are based on an average. My gas company will look at my previous months (six months if I remember correctly) payments and give me an average based on that amount. Then I am contracted for a year based on that average. If I lower my costs, I'm under contract and will not see the savings but if I go over for some reason, I will save money there. It really depends on how your utility companies work so I would check with them, look at your previous billing cycles and determine if the plan will possibly save you money. Of course some things can't be planned for such as the economic downturn like someone else mentioned.",
"title": ""
},
{
"docid": "580406",
"text": "I would argue: Because the company only offers you this if it can make money from it. What you are basically doing is betting against the company.",
"title": ""
},
{
"docid": "263050",
"text": "\"I have some numbers to share that may help. I've been tracking my home's natural gas consumption in a spreadsheet for years. Much of that time I'd only been interested in the quantity used – to measure my home's efficiency after certain upgrades – but in 2006 I also started tracking the \"\"Gas Supply Charge\"\" costs from my local utility, Enbridge, in Ontario, Canada. My numbers are for the gas commodity only (i.e. excluding delivery and customer charges.) I've never been on a fixed-price contract, so the numbers are supposed to be reflective of market rates. However, the numbers do differ from real \"\"spot prices\"\" because Enbridge estimates gas costs up-front and then applies a \"\"gas cost adjustment\"\" at later dates if their estimate was wrong. Natural gas cost per cubic meter for Chris's home http://img686.imageshack.us/img686/6406/naturalgascosts3priorye.png Since 2006, natural gas prices have been generally falling. The last cost I have on file, from my November 2009 bill, is 12.9 cents per cubic meter – being ~20 cents gas supply rate, less gas cost adjustment of ~7 cents. My average cost over that nearly 4 year period, January 2006 through November 2009, was 38.4 cents per cubic meter. Considering the current 5-year fixed rate I found is about 29 cents per cubic meter, there is a substantial premium to locking in when compared to current market rates. However, one can see that during the last 4 years, market prices did substantially exceed that rate for quite some time. Furthermore, when I last looked at those 5-year fixed rates perhaps a year or more ago, I couldn't find a company charging less than 39 cents per cubic meter. So, contract rates have fallen as well. Consequently, if we are at a natural gas price low and the economy is to recover, I tend to agree with Cart's answer and suggest it could be a good time to consider a fixed-rate contract. But, do your own due diligence and read the fine print if you go for it. UPDATE: In the interest of full disclosure, shortly after I did my own research above, I signed up for my first ever fixed-rate natural gas contract. :-)\"",
"title": ""
},
{
"docid": "662",
"text": "I can only speak to natural gas but I imagine the answer for electricity is the same. In general, yes, it is better to lock into a fixed price contract as in the long run, natural gas prices increase over time. However, if you locked (signed a fixed price contract) in prior to the economic downturn, most likely you were better off not doing so but the key is long-term. http://en.wikipedia.org/wiki/Natural_gas_prices However, do your research as fixed priced contracts vary considerably from company to company. http://www.energyshop.com/ I think it's a good time to sign a fixed-term contract right now as I don't see prices coming down much further with global economies are now recovering from the downturn. HTH",
"title": ""
},
{
"docid": "283100",
"text": "\"The answer to this question will vary considerably by state and how utilities are regulated in your area. In New York, ESCOs (Energy Supply Companies) are almost always a ripoff for consumers versus the old-style regulated utility (in NY the utility supply markups are tightly regulated, but ESCOs are less regulated). You also need to really understand the marketplace rules for \"\"locking in\"\" a price. If you can lock in the July price for natural gas for a year, that rocks. There are other factors as well. But even then its a real bet, since weather and supply factors can have a dramatic effect on gas prices in the winter. IMO, the best bet is to run with the market rates and bank the efficiency improvements that you build into your home over time. Some utilities offer \"\"budget plans\"\" that smooth out your payments without interest -- I'd recommend that route if predictable bills are your goal.\"",
"title": ""
}
] |
[
{
"docid": "583490",
"text": "You are correct that the price fixed when the contract is made is set and maybe there are a few institutions that don't actually bother to track the future after they initiate the contract. But most parties likely track the contracts fairly carefully for a number of reasons. The big deal is that while the price the contract is set, and if you did a perfect hedge maybe the value of the contract and the thing you are hedging is then fixed, the value of that futures contract by itself changes and this is important. The biggest reason is as JB mentions above most futures contracts settle up on a daily basis as the price of the underlying changes. This happens to limit the losses when for large price changes and one party owes a bunch of money on a futures contract and (for that reason or a different one) goes bankrupt. If the other party is using the contract to hedge a sale or asset maybe this risk is minimal but maybe that expected sale doesn't happen or maybe the party is using futures for speculation. There is no way to know built into the contract if a party is really hedging or not so people naturally want to limit this default risk. There are many other reasons to track profit and loss as well: There are likely even more reasons as well that I'm missing but hopefully that gives you an idea.",
"title": ""
},
{
"docid": "108090",
"text": "He's comfortably middle class, but not wealthy. The Tesla was purchased in a multi-owner shared arrangement, and the solar panels were installed by a company that supplies the capital for the panels with a long-term agreement to supply power to the homeowner and takes care of the more complex business agreements to feed back power to the grid. The situation on paper looks like a long term break even - but we'll have to see. Overall, even if he's paying a bit more in electric cost, the arrangement gives a lot of stability in exchange. To me it's clear that going electric car + renewable electric is a long-term good on the principle of becoming nationally independent from geopolitical enganglements, but also more towards becoming individually independent in terms of being isolated from instability in gas prices, utility prices, and even in times of natural disaster.",
"title": ""
},
{
"docid": "179726",
"text": "> Are occasional use grid-scale natural gas plants economically viable compared to distributed gas generators? Yes, a good question. I'm sure that ecologically a grid-scale natural gas plant is better than distributed as it will have higher efficiency and better maintenance. But I can see that the overhead of the grid (needs to be maintained too) may be too big economically and people may decide to drop of the grid entirely. Where I live natural gas is not that widespread outside the cities, so this is probably not viable to most people. On the other hand we already today get 15% of your electricity from hydro storage, so on a national level, we are not too far from the presumed 20%. However, currently the pumped hydro storage plants have economic problems, because solar is eating their traditional high-price peak around lunch time.",
"title": ""
},
{
"docid": "462944",
"text": "> It's much cheaper, [U.S. coal production and coal-fired electricity generation expected to rise in near term](https://www.eia.gov/todayinenergy/detail.php?id=29872) >**In 2017 and 2018, as natural gas prices are expected to increase**, coal is expected to regain some share of the electricity generation mix, and coal production is expected to increase slightly. The past decline in coal production has not been uniform across the three major coal-producing regions in the United States. *** >its only loss to coal is ease of storage. and amount. >the United States has enough natural gas to last about **86 years.** https://www.eia.gov/tools/faqs/faq.php?id=58&t=8 >coal production since the industrial revolution, recoverable domestic coal reserves at current mining levels would last **222 years.**",
"title": ""
},
{
"docid": "465732",
"text": "\"Home Improvements that improve the home's Energy Efficiency are currently eligible for federal tax credits. This includes renewable energy equipment (solar panels, etc.) and Nonbusiness Energy Property Tax Credit. The credit is 30% of the cost. From Intuit Turbo Tax: Energy Tax Credit: Equipment and materials can qualify for the Nonbusiness Energy Property Credit only if they meet technical efficiency standards set by the Department of Energy. The manufacturer can tell you whether a particular item meets those standards. For this credit, the IRS distinguishes between two kinds of upgrades. The first is \"\"qualified energy efficiency improvements,\"\" and it includes the following: •Home insulation •Exterior doors •Exterior windows and skylights •Certain roofing materials The second category is \"\"residential energy property costs.\"\" It includes: •Electric heat pumps •Electric heat pump water heaters •Central air conditioning systems •Natural gas, propane or oil waterheaters •Stoves that use biomass fuel •Natural gas, propane or oil furnaces •Natural gas, propane or oil hot water boilers •Advanced circulating fans for natural gas, propane or oil furnaces\"",
"title": ""
},
{
"docid": "303659",
"text": "The short answer is yes, electrical vehicles make logistical sense. The batteries aren't quite where they should be to really push the market, but the lifecycles are high enough, and the batteries themselves can be recycled. There are two major advantages that electric has over oil. The first is that electricity is abundant and can come from many sources. This means that a car can be running on power from coal, wind, solar, hydro-electric, or any other source of electricity. This also means that the cost per mile driven is generally lower than the cost of a gas driven car. Another big advantage is the national security it offers. If electric were to really enter the consumer market in a big way, the dependency on countries in the Middle East and Africa would be lessened. It would also ease some of the competition between nations like China and the United States over natural resources. Of course their are problems with electric cars as well, and they aren't even close to replacing gas for use in heavy machinery.",
"title": ""
},
{
"docid": "445139",
"text": "Please be honest when you cite figures. A more complete picture is this: Yes, 30% of new generating capacity (over last 5 years) has been wind However, only 4% of the US power grid is supplied by wind Meanwhile: 34% of US power generated is from natural gas 42% of total generating capacity is natural gas Natural gas is an easy replacement for coal. Natural gas is just as affordable, reliable, and scalable, while releasing fewer pollutants into the air. As coal plants continue to shut down, natural gas plants are expected to be built to replace them. Wind farm production is theorized to remain relatively consistent (rate of construction will be minimally affected by coal plant decommissions). Renewables all have cost, reliability, and scalability shortcomings. They are not an appropriate replacement for consistent sources (natural gas, coal, nuclear) until there is a reliable way to store the energy they produce. For now, renewable sources are far better served as supplements to others sources of electricity. It is natural gas pushing coal out, with renewables playing a small role at the margins. https://www.eia.gov/todayinenergy/detail.php?id=29732 https://www.eia.gov/todayinenergy/detail.php?id=30112 (These are both genuinely good. Not exciting, but good.)",
"title": ""
},
{
"docid": "347919",
"text": "Point being, the problem hasn't been fixed. The deficit went from enormous in 2009 to simply large today. It's never going to be paid back. The main issue to consider is that today the United States is the third largest oil producer in the world and the largest natural gas producer, thanks to hydraulic fracturing most of this surge happened during the Obama administration, spurred on by relatively high energy prices. [Without the fracking boom, the US economy would still be considered in a recession:](http://economics21.org/commentary/oil-and-gas-boom-propels-gdp) >Without the $300-$400 billion yearly increase in output from oil and gas production, economy growth would still be negative. Manhattan Institute senior fellow Mark Mills shows the extent these industries have contributed to U.S. growth in his new report, “Where the Jobs are: Small Businesses Unleash Energy Employment Boom.” The US manufacturing sector also benefits from this indirectly, as low energy costs thanks to suddenly abundant natural gas keeps domestic production affordable. Without the fracking boom, the US economy would be in a European type situation. [In fact, European companies move their manufacturing capacity to the US, citing low American gas prices.](http://www.ibtimes.com/natural-gas-boom-attracting-manufacturing-us-overseas-take-advantage-cheaper-fuel-1582512) The problem with all of this is that we know that fracking is not sustainable. It depends on very high oil prices, which consumers simply can't afford to continue paying. Without oil prices rising, the industry is forced to enter further and further into debt. Part of the reason oil prices are so high in the first place right now is because of speculative traders, who expect oil prices to rise higher in the future, which is unlikely to happen. When Obama claimed that there is 100 years worth of natural gas in the US, he was wrong. If he really believes that story himself, it's going to lead him to take bad decisions, by basing an economy on hypothetical cheap energy that won't be there in the future. The GDP contribution by the fracking industry is going to evaporate, at which point you're left with a massive debt you can't pay back.",
"title": ""
},
{
"docid": "519675",
"text": "There are a few ways you can go about paying this off quickly (and safely): You could start paying $386 monthly (ie, double what you're paying now). You'll pay less interest in the long run because they can only charge you for the amount outstanding. Remember, 6.8% of $12k is more than 6.8% of $6k. However, your plan sounds more sensible. Say you get to $6k paid off and $6k saved, you're able to pay off what's left and that's almost $200 a month you'll have extra. Although what I like about this is - if you become ill, lose your job, or whatever, then you're still able make the $193 payments, PLUS you'll have money saved for day-to-day expenses (food, water, gas, electricity, etc.) long enough to see yourself through. PS. They may charge you a settlement fee because if you pay early then they miss out on money... but check your contract with them first. Hope this helps!",
"title": ""
},
{
"docid": "419475",
"text": "First thing, ask your real estate agent who should have been involved in writing the contract, and can explain your options regarding the contingency. That being said... The inspection report is the decision point. For every issue/problem mentioned you have decide: Ignore; have the seller fix; have the seller give you money to fix; have the seller drop the price; or walk away. Minor things you can have the seller fix. They need to be done, but they can be done by the seller. Expensive things that are difficult to estimate the price in advance should also be done by the seller. The difficultly estimating the cost to repair will make it risky for you to negotiate a price break. Getting a credit of $1,000 when it ends up costing you $20,000 is something you want to avoid. For items that you want to do the fix yourself you want money at closing to do them, or ask for a price break. Items in this category include replacing an appliance. You can take the money and get exactly the one you want, or let the seller of the house buy one that has the least options and won't match the color. Buyers also take this option when they were going to renovate soon anyway. Walking away. This happens when there is a large expensive issue that is hard to fix. Or a very large list of mid-size problems. Issues in this category can include foundation cracks, major electrical problems, extensive leaks, mold. It can also include beautifully constructed additions that aren't up to code and were done without permits and inspections. Which category is your Radon in? You need to ask your agent, and read the inspection report. The agent can explain your options, and how likely the seller will be to agree. They can also tell you how likely you are to not lose the deposit if you do walk away.",
"title": ""
},
{
"docid": "538258",
"text": "well there are many papers on power spot price prediction, for example. It depends on what level of methodology you would like to use. Linear regression is one of the basic steps, then you can continue with more advanced options. I'm a phd student studying modelling the energy price (electricity, gas, oil) as stochastic process. Regarding to your questions: 1. mildly speaking, it's really hard, due to its random nature! (http://www.dataversity.net/is-there-such-a-thing-as-predictive-analytics/) 2. well, i would ask what kind of measure of success you mean? what level of predicted interval one could find successful enough? 3. would you like me to send you some of the math-based papers on? 4. as i know, the method is to fully capture all main characteristics of the price. If it's daily power price, then these are mean-reversion effect, high volatility, spike, seasonality (weekly, monthly, yearly). Would you tell me what kind of method you're using? Maybe we can discuss some shared ideas? Anna",
"title": ""
},
{
"docid": "546091",
"text": "Agreed, it'll be faster. Let's do a little math. Tesla is trying to hit 500k units in 2018. They want 1m in 2020. If Tesla can do 1m in 2020, how many EVs can *ALL* other western auto manufacturers build in 2020 (GM + Nissan + VW + Daimler + etc)? I'd take a swing at 2-3m. What about Chinese auto manufacturers? Probably 3m more, since EVs are a focus there? So if you count that up, it's 7-8m EVs in 2020, which is 10% of worldwide new car sales. This can all be accomplished in the $35k+ market. This also provides the volume to drive down battery and electronics costs to hit $30k and then $25k price points later in the 2020's. So if we're at 10% by 2020, I'd be shocked if we didn't have 50-75% EVs of new car sales by 2030. 20-50% growth over 10 years adds up quickly. The oil price crash of 2014 was caused by a 2% imbalance between supply and demand. So this predicts crashes in the price of oil and oil company stocks in the early 2020's. There's likely also political unrest in oil producing countries, as their economies start having revenue shortfalls. Given the friendliness of EVs to demand response, I'd think we'd just keep building intermittent renewables. When the wind blows and sun shines, EVs charge (and turn off otherwise) This will increase electricity demand, but put pressure on expensive and dirty coal and natural gas. All of this drives down the cost of electric driving, and CO2 emissions.",
"title": ""
},
{
"docid": "349544",
"text": "\"Make a list of all your expenses. I use an Excel spreadsheet but you can do it on the back of a napkin if you prefer. List fixed expenses, like rent, loan payments, insurance, etc. I include giving to church and charity as fixed expenses, but of course that's up to you. List regular but not fixed expenses, like food, heat and electricity, gas, etc. Come up with reasonable average or typical values for these. Keep records for at least a few months so you're not just guessing. (Though remember that some will vary with the season: presumably you spend a lot more on heat in the winter than in the summer, etc.) You should budget to put something into savings and retirement. If you're young and just starting out, it's easy to decide to postpone retirement savings. But the sooner you start, the more the money will add up. Even if you can't put away a lot, try to put away SOMETHING. And if you budget for it, you should just get used to not having this money to play with. Then total all this up and compare to your income. If the total is more than your income, you have a problem! You need to find a way to cut some expenses. I won't go any further with that thought -- that's another subject. Hopefully you have some money left over after paying all the regular expenses. That's what you have to play with for entertainment and other non-essentials. Make a schedule for paying your bills. I get paid twice a month, and so I pay most of my bills when I get a paycheck. I have some bills that I allocate to the first check of the month and some to the second, for others, whatever bills came in since my last check, I pay with the current check. I have it arranged so each check is big enough to pay all the bills that come from that check. If you can't do that, if you'll have a surplus from one check and a shortage from the next, then be sure to put money aside from the surplus check to cover the bills you'll pay at the next pay period. Always pay your bills before you spend money on entertainment. Always have a plan to pay your bills. Don't say, \"\"oh, I'll come up with the money somehow\"\". If you have debt -- student loans, car loans, etc -- have a plan to pay it off. One of the most common traps people fall into is saying, \"\"I really need to get out of debt. And I'm going to start paying off my debt. Next month, because this month I really want to buy this way cool toy.\"\" They put off getting out of debt until they have frittered away huge amounts of money on interest. Or worse, they keep accumulating new debt until they can't even pay the interest.\"",
"title": ""
},
{
"docid": "385028",
"text": "\"This is the best tl;dr I could make, [original](https://about.bnef.com/blog/henbest-energy-2040-faster-shift-clean-dynamic-distributed/) reduced by 94%. (I'm a bot) ***** > Onshore wind costs fall fast, and offshore falls faster. > Around $6 trillion of new investment in wind and solar power between now and 2040 will reshape the world&#039;s electricity markets as we move from a system where coal, gas and oil-fired power plants make up over 60% of capacity, to one where solar and wind are the two largest categories, and where fossil fuels make-up less than a third. > In Germany, new onshore wind and solar already appear to be cost-competitive with new coal and gas; in China today, coal is the lowest-cost, new-build electricity generation, but in 2019, onshore wind gets cheaper, then PV follows two years later; in the U.S., cheap natural gas makes it the lowest-cost source of new electricity right now, but by 2022-23 PV and wind both begin to beat it; and in India, new solar PV starts to look cheaper than new coal, across the country, from 2020. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/6kchsc/energy_to_2040_faster_shift_to_clean_dynamic/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~155602 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **wind**^#1 **New**^#2 **solar**^#3 **coal**^#4 **Gas**^#5\"",
"title": ""
},
{
"docid": "205697",
"text": "I'm waiting to get a tesla. My reason is that I hate getting and paying for gas. I use a lot of it for my commute. Would I like to save the world? Yes. But I want an electric car for no other reason than to stop pulling into a gas station.",
"title": ""
},
{
"docid": "588153",
"text": "A derivative is a financial instrument of a special kind, the kind “whose price depends on, or is derived from, another asset”. This definition is from John Hull, Options, Futures and Other Derivatives – a book definitely worth to own if you are curious about this, you can easily find old copies for a few dollars. The first point is that a derivative is a financial instrument, like credits, or insurances, the second point is that its price depends closely from the price of something else, the mentioned asset. In most cases derivatives can be understood as financial insurances against some risk bound to the asset. In the sequel I give a small list of derivatives and highlight the assets and the risk they can be bound to. And first, let me point out that the definition is (marginally) wrong because some derivatives depend on things which are not assets, nor do they have a price, like temperature, sunlight, or even your own life in the case of mortgages. But before going in this list, let me go through the remaining points of your question. What is the basic idea and concept behind a derivative? As already noted, in most cases, a derivative can be understood as a financial insurance compensating from a risk of some sort. In a classical insurance contract, one party of the contract is an insurance company, but in the broader case of a derivative, that counterparty can be pretty anything: an insurance, a bank, a government, a large company, and most probably market makers. How is it really used, and how does this deviate from the first point? Briefly, how does is it affecting people, and how is it causing problems? An important point with derivatives is that it can be arbitrarily complicated to compute their prices. Actually what is hidden in the attempt of giving a definition for derivatives, is that they are products whose price Y is a measurable function of one or several random variables X_1, X_2, … X_n on which we can use the theory of arbitrage pricing to get hints on the actual price Y of the asset – this is what the depends on means in technical terms. In the most favorable case, we obtain an easy formula linking Y to the X_is which tells us what is the price of our financial instrument. But in practice, it can be very difficult, if at all possible, to determine a price for derivatives. This has two implications: Persons possessing sophisticated techniques to compute the price of derivatives have a strategic advantage on derivatives market, in comparison to less advanced actors on the market. Organisation owning assets they cannot price cannot compute their bilan anymore, so that they cannot know for sure their financial situation. They are somehow playing roulette. But wait, if derivatives are insurances they should help to mitigate some financial risk, which precisely means that they should help their owners to more accurately see their financial situation! How is this not a contradiction? Some persons with sophisticated techniques to compute the price of derivatives are actually selling complicated derivatives to less knowledgeable persons. For instance, many communes in France and Germany have contracted credits whose reimbursements have a fixed interest part, like in a classical credit, and a variable interest part whose rate is computed against a complicated formula involving the value of the Swiss frank at each quarter starting from the inception of the credit. (So, for a 25 years running credit of theis type, the price Y of the credit at its inception depends on 100 Xs, which are the uncertain prices for the Swiss frank each quarter of the 25 next years.) Some of these communes can be quite small, with 5.000 inhabitants, and needless to say, do not have the required expertise to analyse the risks bound to such instruments, which in that special case led the court call the credit a swindling and to cancel the credit. But what chain of events leads a 5.000 inhabitants city in France to own a credit whose reimbursements depends on the Swiss frank? After the credit crunch in 2007 and the fall of Lehman Brothers in 2008, it has begun to be very hard to organise funding, which basically means to conclude credits running long in time on large amounts of money. So, the municipality needs a 25 years credit of 10.000.000 EUROS and goes to its communal bank. The communal bank has hundreds or thousands of municipalities looking for credits and needs itself a financing. So the communal bank goes to one of the five largest financial institutions in the world, which insists on selling a huge credit whose reimbursements have a variable part depending on hundred of values the Swiss frank will have in the 25 next years. Since the the big bank has better computation techniques than the small bank it makes a big profit. Since the small bank has no idea, how to compute the correct price of the credit it bought, it cuts this in pieces and sell it in the same form to the various communes it works with. If we were to attribute this kind of intentions to the largest five banks, we could ask about the possibility that they designed the credit to take advantage of the primitive evaluation methods of the small bank. We could also ask if they organised a cartel to force communal banks to buy their bermudean snowballs. And we could also ask, if they are so influent that they eventually can manipulate the Swiss frank to secure an even higher profit. But I will not go into this. To the best of my understanding, the subprime crisis is a play along the same plot, with different actors, but I know this latter subject only by what I could read in French newspapers. So much for the “How is it causing problems?” part. What is some of the terminology in relation to derivatives (and there meanings of course)? Answering this question is basically the purpose of the 7 first chapters of the book by Hull, along with deriving some important mathematical principles. And I will not copy these seven chapters here! How would someone get started dealing in derivatives (I'm playing a realistic stock market simulation, so it doesn't matter if your answer to this costs me money)? If you ask the question, I understand that you are not a professional, so that your are actually trying to become the one that has money and zero knowledge in the play I outlined above. I would recommand not doing this. That said, if you have a good mathematical background and can program well, once you are confindent with the books of Hull and Joshi, you can have fun implementing various market models and implementing trading strategies. Once you are confident with this, you can also read the articles on quantitative finance on arXiv.org. And once you are done with this, you can decide for yourself if you want to play the same market as the guys writing these articles. (And yes, even for the simplest options, they have better models than you have and will systematically outperform you in the long run, even if some random successes will give you the feeling that you do well and could do better.) (indeed, I've made it a personal goal to somehow lose every last cent of my money) You know your weapons! :) Two parties agree today on a price for one to deliver a commodity to the other at some future instant. This is a classical future contract, it can be modified in every imaginable way, usually by embedding options. For instance one party could have the option to choose between different delivery points or delivery days. Two parties write today a contract allowing the one party to buy at some future time a commodity to the the second party. The price is written today, as part of the contract. (There is the corresponding option entitling the owner to sell something.) Unlike the future contract, only one party can be obliged to do something, the other jas a right but no obligation. If you buy and option, your are buying some sort of insurance against a change of price on some asset. This is the most familiar to anybody. Credits can come in many different flavours, especially the formula to compute interests, or also embed options. Common options are early settlement options or restructuration options. While this is not completely inutitive, the credit works like an insurance. This is most easily understood from the side of the organisation lending the money, that speculates that the ratio of creanciers going bankrupt will be low enough for her to make profit, just like a fire insurance company speculates that the ratio of fire accidents will be low enough for her to make a profit. This is like a mortgage on a financial institution. Two parties agree that one will recive an upfront today and give a compensation to the second one if some third party defaults. Here this is an explicit insurance against the unfortuante event, where a creancier goes bankrupt. One finds here more or less standard options on electricity. But electricity have delicious particularities as it can practically not be stored, and fallout is also (usually) avoided. As for classical options, these are insurances against price moves. A swap is like two complementary credits on the same amount of money, so that it ends up in the two parties not actually exchanging the credit nominal and only paying interest one to the other — which makes only sense if these interests are computed with different formulas. Typical example are fixed rate vs. EURIBOR on some given maturity, which we interpret as an insurance against fluctuations of the EURIBOR, or a fixed rate vs. the exchange ratio between two currencies, which we interpret as an insurance against the two currencies decorrelating. Swaps are the richest and the most generic category of financial derivatives. The off-the-counter market features very imaginative, very customised insurance products. The most basic form is the insurance against drought, but you can image different dangers, and once you have it you can put it in options, in a swap, etc. For instance, a restaurant with a terrasse could enter in a weather insurance, paying each year a fixed amount of money and becoming in return an amount of money based on the amount of rainy day in a year. Actually, this list is virtually without limits!",
"title": ""
},
{
"docid": "465801",
"text": "I concur with pretty much what everyone else said. Let me break it down in a concrete plan of action. First, though, note that at least the minimum payments for the credit cards needs to be on this list of fixed expenses. Also, you have $868 remaining in a normal month -- food could be $500 or more easily for a family, so find out how much! Adding in just those 2 things, and you're already at your max. And there are other expenses in life. Ok, cutting from the top: DirectTv -- gone. Pure luxury, and between netflix, hulu and your internet connection (hook your computer to the tv), there's no need for it. $80 savings. Cell phones -- you're already moving in the right direction, but not far enough. In a financial crunch why does your stay-at-home wife have a cell? Especially when she could just as easily use Google Voice for free? Both plans gone, replaced by one of the prepaids @$45. $105 savings, total $186 savings. 529 plans -- Of course you want to save for your kids college, but it doesn't help them for you to drown financially. Gone until your credit card debit is too. $50 savings, $236 total. Ok, we're already up to $236/month in savings just cutting items you don't need. That probably gets you back into the black, but why stop there? Trimming expenses Electric -- ok, I know it's summer, but can you cut this back? Is the thermostat set as high as you can comfortably bear? Are you diligent in turning of lights, especially incandescent? Do you turn off your computer when you're not using it? See if you can get the Electric down by 10%. That's $20/month savings. Doesn't seem like much, but it adds up. Gas -- same with gas. Do you have gas hot water? If so, cut shower length. Saves on water too. Food -- this one you didn't list. But as I said, you could be spending $500 or $600 a month easily for a family. Do you guys plan meals, and thus plan shopping trips? If not, do it. You'll be surprised how much you can save. Either way, 10% reduction should be doable. That's $50/month. If you don't plan now, 20% is within reach -- that's $100/month. Ok, that may have added as much as $130 or so. If so, you're now up to $366/month savings. That's like a 15% raise. Simply cutting, however, is only half the plan. You want to improve your situation, so you can get the Directtv back (assuming you'll even want it at that point), and the wife's cell phone, for starters. To do that, you've got to nail down that debt. I figure you've got minimum $567.23/month in debt payments. That's not including your mortgage, and including an assumed $80/month minimum credit card payments. You pay over 21% of your take-home to short term and consumer debt! Yea, that's why you're hurting. Here's what you do In both cases, apply the extra payments entirely to one balance at a time. Pick either the smallest balance (psychologically best because you quickly see a loan & it's payment dissappear), or the highest interest (mathematically the best). Roll each regular payment that's paid off into the extra debt payments. You didn't list total debt balances, but you did say you had $4000 in credit card debt. Applying an extra $250/month to debt (out of that $366 savings), plus two extra paychecks of $1300 each, is $5600/year paid off. In under a year, you could have those credit cards paid off, and likely that window loan too. Start the 529s again, but keep going paying down the rest. When you have the car paid off, bring back the wife's cell (you and I both know that's going to be #1 on the list :) ), then finish off those student loans. Then bask in the extra $567/month - 21% of your income - you'll have in sweet, sweet green cash!",
"title": ""
},
{
"docid": "123291",
"text": "Just looking at CONED, [here is gas](https://www.coned.com/_external/cerates/documents/average_monthly_gas_bills.pdf) and [here is electric](https://www.coned.com/-/media/files/coned/documents/accountandbilling/about-your-bill-rates/average_monthly_electric_bills.pdf). You'll have to forgive me -- when it comes to NY, I'm more familiar with gas and with residential rates, so what I said doesn't hold true across the board for electric commercial customers. For residential electric, starting in 2009, delivery started outpacing commodity charges; by 2015 (not sure why they haven't posted 2016 data yet), $29 worth of electricity cost you $49 in delivery charges. For residential gas, the flip occurred in 2010 and was much more significant -- in 2016, a customer whose bill is just over $100 paid $75 for delivery and $25 for the actual gas (part of that is that gas prices are low, part of it is that delivery costs have gone up nearly 50%). Each utility is different, so the [gas info is here](http://www3.dps.ny.gov/W/PSCWeb.nsf/All/85297E80413DBEDB852581A6006261BE?OpenDocument) and the [electric info is here](http://www3.dps.ny.gov/W/PSCWeb.nsf/ArticlesByTitle/0B9E6D4CE48E09EE852578570055E27B?OpenDocument) if you're interested. I'm not sure about primers -- I haven't really looked for them -- but I know that many companies and brokers do have some materials on their websites. For electricity in particular, I'm much more familiar with Texas than New York, but a lot of the principles are the same: look at your bills and make sure you understand all the charges and what your usage/demand is (especially over the course of a year), look up the [utility tariff](http://www3.dps.ny.gov/W/PSCWeb.nsf/ArticlesByTitle/1ABA5E2E4E08F72585257687006F3AB1?OpenDocument), and make sure everything lines up. I harp on demand charges (a charge based on your peak energy usage during any set interval of time -- 15 minutes in TX, not sure about NY) because that's where commercial customers can get stuck paying really high charges.",
"title": ""
},
{
"docid": "262491",
"text": ">Oil is important because without it US can't go to war That's may be a reason but its far from the main one. Without oil the whole economy shuts down instantly. People can't get to work or stores to buy stuff. We can't run diesel peaker plants for electricity demand as easily either (although that's changed some due to natural gas). We use so much god damn oil that if supply is cut off for a day or two, everything stops. While grain is very important, that doesn't happen with food commodities. We actually grow so much extra food that we turn a lot into oil. If food was short, we'd stop doing that (I hope). Lastly, we scrutinize it in the media because our main supply is external. A lot comes from Canada sure, but the middle east is a major component of our supply. If those lines are cut off, prices surge. That *used* to hurt us bad because wed have to buy from more expensive sources (offshore, south america, anywhere else really). Now, small bumps in price are helping the US economy because of shale gas production in PA and Ohio. So oil is a very political commodity on the global stage. Look at Venezuela right now with low oil prices cutting off demand for their more costly oil. TLDR Oil is the feedstock for our economy and its a scarce resource.",
"title": ""
},
{
"docid": "254196",
"text": "When the first gas cars were made 100 years ago, they were toys for the rich You can't go from zero to cheap mass market instantly It's not a conspiracy, it's the nature of the business The only way to introduce a new product like an electric car is to target the buyer who is not primarily concerned with cost Later, as experience is gained, costs will come down I remember the first CD recorder It cost $15,000 and the disks were $30 each Now, you can get a CD/DVD recorder for $30",
"title": ""
},
{
"docid": "570071",
"text": "\"As advised you need to budget, but there are a few simple things you can do to make it easier. Work out how much your fixed bills are every month, for example, council tax, gas and electric, mortgage and rent etc. On pay-day, move an amount of cash equal to this into another bank account when you get paid. It's easier if this other account, let's call it a bills account, can pay the bills automatically via direct debits, you can then forget about it. Now your budget should tell you how much you spend on things that are more variable, food, fuel, travel etc. Again on pay-day, move an amount of cash aside to cover this (plus a small buffer amount) into another account. Whatever is now left in your main account is yours to spend or save as you see fit. You just need to make sure you are sticking to your budget and it's as easy as that. If you cannot pay direct debits from the other accounts you just need to move the money over to cover them when they need paying. Most banks will let you set up extra accounts so you can mvoe the money easily using internet banking or by a monthly standing order. If they won't let you have several \"\"current\"\" accounts you can use savings accounts but will need to manually move the money around as the bills are due. If you get all your direct debits to debit on pay-day, that makes it even easier. If you are struggling for money then prioritise paying off debt first and prioritise the debt with the highest interest rate.\"",
"title": ""
},
{
"docid": "167748",
"text": "\"How will making energy cheaper help? The issue is that average earnings have barely moved since the 70's, inflation has sky-rocketed for necessities and for assets. My dad was making the same as I am now when he bought their first home for $40,000. My smaller place cost me $300,000+. That isn't fucking sustainable. Natural gas, gasoline, electricity, those are all tiny slices of pie in comparison to food and shelter. Then the American government makes all these shitty chess-play moves that they think will stimulate the economy but they don't take into account that civilians aren't entities that behave like ideal statistical models. They don't fucking understand that people are concerned about the viability of their futures. The whole thing is nose-diving into the ground. Read the the book \"\"The Death of Money\"\" by James Rickards, America is fucked and the politicians don't care because they will be financially OK and will pass the buck on to the next generation to deal with.\"",
"title": ""
},
{
"docid": "89015",
"text": "A 25% variance in price, in most markets, isn't so crazy as to require it be some sort of terrible scam, but that doesn't mean much else. It could be the inclusion of floor plans that are carefully designed to add square footage at minimum cost and thus reduce the average cost per square foot without actually being cheaper otherwise, less insulation, thinner walls, cheap piping, minimized wiring, or they are just efficient and competitive. As you pointed out they don't have gas, so that's certainly one way you know they cut costs - no gas lines to install! As the article from NAHB: Cost of Constructing A Home points out, though, what this figure includes can vary. Does it include the finished lot? If so then a smaller lot would mean lower square footage building price - because the land is smaller and cheaper, not the house! Is any kind of financing quoted in the price? Compare also change-plan costs, any penalties for delays in construction, grade of materials, floor plans, customization costs, fees or premiums to pick colors/floors/counters/cabinets/fixtures, and so on. What about central cooling and heating - are they quoting an electric furnace? How does electrical heating in your area compare to the cost of gas heat? (relative pricing of electric and gas vary widely by region and climate) In short: often square footage price isn't the whole story of what it would cost to construct a home. Ensure you are comparing everything that's important to you and you are getting a full quote, not comparing small isolate sales-pitch figures with no clear details. If it turns out the price is 25% lower than other builders in your area and they give you what you are wanting, and you have the good sense to have a qualified home inspector and/or structural engineer inspect the home thoroughly before you take possession, then you might just have found a good builder! I'd encourage you to personally visit some of their past construction work, such as houses they build 2-10 years ago and ensure they are in the sort of condition you'd expect.",
"title": ""
},
{
"docid": "393206",
"text": "In the short term, this question is pretty simple: Are occasional use grid-scale natural gas plants economically viable compared to distributed gas generators? Home solar is an amazingly good deal now. Economically, the question isn't whether it'll take over most home power generation, it's how fast that will happen. Currently - at least where I live - the grid is still a good deal for backup power. If that changes, then people will stop using it. You can get a gas generator to cover a normal sized home installed for ~$4000. In places with piped gas, the price for running the generator looks comparable to grid power per kWh. So no, I wouldn't pay triple the price for grid power or buy a ton of extra storage. I'd get a natural gas generator and handle solar downtime locally.",
"title": ""
},
{
"docid": "183340",
"text": "What happened - affluence. No mortgage - one grandfather built his own house the other lived in a sod hut. No running water, no electricity, no natural gas/coal/oil heating. No car, no insurance, no gasoline They grew much of their own food. If you want it - it's all yours. Go for it.",
"title": ""
},
{
"docid": "377112",
"text": "For example: do I need a realtor, or can I do their job myself? In general in the United States the real estate agent fee is paid by the seller of the property. Their agent will be more than happy keep the entire fee if they don't have to split it with your agent. If you don't have an agent you will be missing somebody who can help you find the property that meets your needs. They can also help explain what the different parts of the contract mean and give you advice regarding making an offer. Do I need to pay for an inspection, or am I likely to save enough money from skipping it to cover potential problems that they would have caught? Inspections are optional. Though the amount you are risking is the entire value of the purchase. If the property has a problem in the foundation, or the septic system, or the plumbing or electrical the cost to fix the issue could render the purchase not worth doing. If you discover the problem a year later and you have to repair the house and have to find temporary housing for a few months, you will regret skipping the inspection. What are some of the ways I can cut expenses on closing costs? Is there any low-hanging fruit? You need to do your homework. When you are ready to purchase a property take good look at the good faith estimate and look at each item. Ask them what the expense covers. Push back against those that seem optional or excessive. Keep in mind that moving the closing date from the end of a month to the start of the next month only changes the timing those charges, it doesn't really save you money. Rolling the costs into the loan sound easy but you have to think about. It means that you will be paying interest on those charges for the life of the loan. It is good that you are starting to think about all the costs.",
"title": ""
},
{
"docid": "495463",
"text": "Startup costs are amazingly high. Running fiber to individual houses takes a lot of labor. Another problem you don't hear too much about is the legal side. I don't mean carriers fighting cities, etc. I'm a lawyer and there's a complex legal side when it comes to easements. An easement is a way to allow others access to your real property, or land. This is a complex subject, so I'll skim it a little. You can have an easement for a variety of reasons, one of them would be utilities. The gas, water and electric companies usually have an easement to fix/repair on a property. So if a storm knocks over a power pole, they can go onto the property to fix it without trespassing or needing special permission. You can also have an easement if, for example, you own a piece of land that is blocked by another piece of land from access to a road. You can have an easement granting you a driveway across the land that blocks you. There are many more examples and lots and lots of rules for easements, but you get the picture. When you set up a big fiber network, you are going to need easements to run it around and to be able to go onto properties to fix it. This is complex, takes a long time, money is often exchanged for easements, and they have to be recorded with the county. This takes a lot of time and money. That's not all. You usually have to go through permitting with the city and then you have to figure out where to run it. Can you use utility poles? Maybe the existing poles won't work and you'll have to install new ones. If you want to underground it, you're going to have to do all the permitting and easements, then you're going to have to look into shutting down streets to work, you're going to have to find all the underground sewer, water, gas, and other utility lines so you don't accidentally cut into them, there will be environmental regulations, and you're going to have to resurface/restore where you were digging. And I've probably left a few things out. This stuff is complex, expensive and takes a long time. A company like Google can afford it because they can lay out cash for a few years before it starts generating revenue. Personally, I think the federal government needs to get involved. The feds were involved in electrification and running telephone service. I don't think this is any different. It also would help the federal government, as well as state, county and city governments - they all need communication networks, too. I would build an agency like the old WPA or CCC to deploy fiber across America. It would take several years, but this is one of those government projects that would produce results, just like how electrification did.",
"title": ""
},
{
"docid": "154611",
"text": "\"In layman's terms, oil on the commodities market has a \"\"spot price\"\" and a \"\"future price\"\". The spot price is what the last guy paid to buy a barrel of oil right now (and thus a pretty good indicator of what you'll have to pay). The futures price is what the last guy paid for a \"\"futures contract\"\", where they agreed to buy a barrel of oil for $X at some point in the future. Futures contracts are a form of hedging; a futures contract is usually sold at a price somewhere between the current spot price and the true expected future spot price; the buyer saves money versus paying the spot price, while the seller still makes a profit. But, the buyer of a futures contract is basically betting that the spot price as of delivery will be higher, while the seller is betting it will be lower. Futures contracts are available for a wide variety of acceptable future dates, and form a curve when plotted on a graph that will trend in one direction or the other. Now, as Chad said, oil companies basically get their cut no matter what. Oil stocks are generally a good long-term bet. As far as the best short-term time to buy in to an oil stock, look for very short windows when the spot and near-future price of gasoline is trending downward but oil is still on the uptick. During those times, the oil companies are paying their existing (high) contracts for oil, but when the spot price is low it affects futures prices, which will affect the oil companies' margins. Day traders will see that, squawk \"\"the sky is falling\"\" and sell off, driving the price down temporarily. That's when you buy in. Pretty much the only other time an oil stock is a guaranteed win is when the entire market takes a swan dive and then bottoms out. Oil has such a built-in demand, for the foreseeable future, that regardless of how bad it gets you WILL make money on an oil stock. So, when the entire market's in a panic and everyone's heading for gold, T-debt etc, buy the major oil stocks across the spectrum. Even if one stock tanks, chances are really good that another company will see that and offer a buyout, jacking the bought company's stock (which you then sell and reinvest the cash into the buying company, which will have taken a hit on the news due to the huge drop in working capital). Of course, the one thing to watch for in the headlines is any news that renewables have become much more attractive than oil. You wait; in the next few decades some enterprising individual will invent a super-efficient solar cell that provides all the power a real, practical car will ever need, and that is simultaneously integrated into wind farms making oil/gas plants passe. When that happens oil will be a thing of the past.\"",
"title": ""
},
{
"docid": "229533",
"text": "Electric Power is Everywhere Present In Unlimited Quantities, It Can Drive The World's Machinery Without The Need Of Coal, Oil, Gas Or Any Other Fuel If you remember, the first time information like this leaked out, the inventor was shut down pretty fast. Therefore, after we get the Nicola Tesla Secret out, we've got no control over what happens next. But, we're willing to take a risk here. We're releasing this secret because this technology has been around far too long and can help far too many people save money while the power companies continue to ROB people during a poor economy.",
"title": ""
},
{
"docid": "21764",
"text": "The amount stated is the total amount of money the customer will be paying to the company. How much profit that will translate into is dependent on the type of contract. Some types of contracts: Cost plus fixed fee: they are paid what it costs to complete the contract plus a fee on top of that. That fee represents their profits. The costs will include salary, benefits, overhead, equipment, supplies. Firm fixed price: They perform the service, and they get paid a fixed amount. If their costs are higher than they forecast, then they may lose money. If they can be more efficient than they forecast, then they make more money. Time and materials: They are paid for completing each sub-task based on the number of hours it takes to complete each sub task, plus materials. This is used to hire a company to maintain a fleet of trucks. If the trucks are used a lot they will need more standard maintenance, plus additional repairs based on the type of use. They pay X for labor and Y for materials for an oil change, but A for labor and B for materials for a complete engine rebuild. There are many variations on these themes. Some put the risk on the customer, some on the company. How and when the company is paid is based on the terms of the contract. Some pay X% a month, others pay based on meeting milestones. Some pay based on the number of tasks completed in each time period. Some contracts run for a specific period of time, others have an initial period plus option years. The article may or may not specify if the quoted amount is the minimum amount of the contract or the maximum amount. The impact on the stock price is much more complex. Much more needs to be known about the structure of the contract, and who will be providing the service to determine if there will be profits. Some companies will bid to lose money, if it will serve as a bridge to another contract or to fill a gap that will allow them to delay layoffs.",
"title": ""
}
] |
9571
|
How are unmarketable market orders (other side of the order book is empty) matched with incoming orders? [duplicate]
|
[
{
"docid": "99757",
"text": "I don't have all the answers. On a illiquid stock, such situations do arise and there are specific mechanisms used by exchanges to match the order. It is generally not advisable to use market order on illiquid stock. There are lots of different variations here. I guess this comes down to specifications for individual exchanges, but I'm wondering if there's a standard here or a way to approach it from basic rules that clears up all these situations. There are quite a few variations and different treatments. Market order that are placed when the market is closed or just around market opening are traded at Market Open price that each exchange has a formulae to calculate. In the process Market Buy are matched to Market Sell at the Exchange calculated price. Not all order get matched and there could be spill over's. These are then matched to limit orders. Is this determined based on which sell order came first, or based on which would result in the best deal for the incoming buyer? Generally Market orders have highest priority of execution.",
"title": ""
}
] |
[
{
"docid": "56315",
"text": "Based on my research while asking How are unmarketable market orders (other side of the order book is empty) matched with incoming orders? and the one answer there, it seems like there are a few things for certain: All of this of course depends on the exact algorithm specified by the given exchange - I don't think there's a standard here.",
"title": ""
},
{
"docid": "470635",
"text": "\"Your logic breaks down because you assume that you are the only market participant on your side of the book and that the participant on the other side of the book has entered a market order. Here's what mostly happens: Large banks and brokerages trading with their own money (we call it proprietary or \"\"prop\"\" trading) will have a number of limit (and other, more exotic) orders sitting on both sides of the trading book waiting to buy or sell at a price that they feel is advantageous. Some of these orders will have sat on the book for many months if not years. These alone are likely to prevent your limit orders executing as they are older so will be hit first even if they aren't at a better price. On more liquid stocks there will also be a number of participants entering market orders on both sides of the book whose orders are matched up before limit orders are matched with any market orders. This means that pairing of market orders, at a better price, will prevent your limit order executing. In many markets high frequency traders looking for arbitrage opportunities (for example) will enter a few thousand orders a minute, some of these will be limit orders just off touch, others will be market orders to be immediately executed. The likelihood that your limit order, being as it is posited way off touch, is hit with all those traders about is minimal. On less liquid stocks there are market makers (large institutional traders) who effectively set the bid and offer prices by being willing to provide liquidity and fill the market orders at a temporary loss to themselves and will, in most cases, have limit orders set to provide this liquidity that will be close to touch. They are paid to do this by the exchange and inter-dealer brokers through their fees structure. They will fill the market orders that would hit your limit if they think that it would provide more liquidity in such a way that it fulfils their obligations. Only if there are no other participants looking to trade on the instrument at a better price than your limit (which, of course they can see unless you enter it into a dark pool) AND there is a market order on the opposite side of the book will your limit order be instantaneously be hit, executed, and move the market price.\"",
"title": ""
},
{
"docid": "208907",
"text": "That is mostly true, in most situations when there are more buy orders than sell orders (higher buy volume orders than sell volume orders), the price will generally move upwards and vice versa, when there are more sell orders than buy orders (higher sell volume orders than buy volume orders), the price will generally move downwards. Note that this does not always happen, but usually it does. You are also correct that for a trade to take place a buyer has to be matched with a seller (or the buy volume matched with the sell volume). But not all orders get executed as trades. Say there are 50 buy orders in the order book with a total volume of 100,000 shares and the highest buy order is currently at $10.00. On the other side there are only 10 sell orders in the order book with total volume of 10,000 shares and the lowest sell order is currently $10.05. At the moment there won't be a trade unless a new buyer or seller enters the market to match the opposing side, or an existing order gets amended upper or lower to match the opposing side. With more demand than supply in the order books what will be the most likely direction that this stock moves in? Most likely the price will move upwards. If a new buyer sees the price moving higher and then looks at the market depth, they would most likely place an order closer to the lowest sell order than the current highest buy order, say $10.01, to be first in line in case a market sell order is placed on the market. As new buy orders enter the market it drives the price higher and higher until the buy orders dry up.",
"title": ""
},
{
"docid": "555226",
"text": "\"I've alway thought that it was strange, but the \"\"price\"\" that gets quoted on a stock exchange is just the price of the last transaction. The irony of this definition of price is that there may not actually be any more shares available on the market at that price. It's also strange to me that the price isn't adjusted at all for the size of the transaction. A transaction of just 1 share will post a new price even if just seconds earlier 100,000 shares traded for a different price. (Ok, unrealistic example, but you get my point.) I've always believed this is an odd way to describe the price. Anyway, my diatribe here is supposed to illustrate the point that the fluctuations you see in price don't really reflect changing valuations by the stock-owning public. Each post in the exchange maintains a book of orders, with unmatched buy orders on one side and unmatched sell orders on the other side. If you go to your broker and tell him, \"\"fill my order for 50,000 shares at market price\"\", then the broker won't fill you 50,000 shares at .20. Instead, he'll buy the 50 @ .22, then 80 @ .23, then 100 @ .30, etc. Because your order is so large compared to the unmatched orders, your market order will get matched a bunch of the unmatched orders on the sell side, and each match will notch the posted price up a bit. If instead you asked the broker, \"\"open a limit order to buy 50000 shares at .20\"\", then the exchange will add your order to the book: In this case, your order likely won't get filled at all, since nobody at the moment wants to sell at .20 and historically speaking it's unlikely that such a seller will suddenly appear. Filling large orders is actually a common problem for institutional investors: http://www.businessweek.com/magazine/content/05_16/b3929113_mz020.htm http://www.cis.upenn.edu/~mkearns/papers/vwap.pdf (Written by a professor I had in school!)\"",
"title": ""
},
{
"docid": "538915",
"text": "\"Market price is just the bid or offer price of the last sell or buy order in the market. The price that you actually receive or pay will be the price that the person buying the stock off you or selling it to you will accept. If there are no other participants in the market to make up the other side of your order (i.e. to buy off you if you are selling or to sell to you if you are buying) the exchange pays large banks to be \"\"market makers\"\"; they fulfil your order using stocks that they don't want to either buy or sell just so that you get your order filled. When you place an order outside of market hours the order is kept on the broker's order books until the market reopens and then, at market opening time there is an opening \"\"auction\"\" at which orders are matched to opposing orders (i.e. each buy order will be matched with a sell) at a price determined by auction. You will not know what price the order was filled at until it has been filled. If you want to guarantee a price you can do so by placing a limit order that says not to pay more than a certain price for any unit of the stock.\"",
"title": ""
},
{
"docid": "31933",
"text": "The Limit Order are matched based on amount and time. The orders are listed Highest to Lowest on the Buy Side. The orders are listed Lowest to Highest on the Sell Side. If there are 2 Sell orders for same amount the order which is first in time [fractions of milliseconds] is first. The about is the example as to how the orders would look like on any exchange. Now the highest price the buyer is ready to pay is 20.21 and the lowest price a seller is ready to sell for is 20.25. Hence there is no trade. Now if a new Buy order comes in at 20.25, it matches with the sell and the deal is made. If a new Buy order comes in at 20.30, it still matches at 20.25. Similarly if a Sell order come in at 20.21, it matches and a deal is made. If a Sell order come in at 20.11, it still matches 20.21. Incase of market order, with the above example if there is a Buy order, it would match with the lowest sell order at 20.25, if there is not enough quantity , it would match the remaining quantity to the next highest at 20.31 and continue down. Similarly if there is a Sell market order, the it would match to the maximum a seller is ready to buy, ie 20.21, if there is not sufficient buy quantity at 20.21, it will match with next for 20.19 If say there are new buy order at 20.22 and sell orders at 20.24, these will sit first the the above queue to be matched. In your above example the Lowest Sell order was at 20.10 at time t1 and hence any buy order after time t1 for amount 20.10 or greater would match to this and the price would be 20.10. However if the Buy order was first ie at t1 there was a buy order for 20.21 and then at time later than t1, there is a sell order for say 20.10 [amount less than or equal to 20.21] it would match for 20.21. Essentially the market looks at who was the first to sell at lower price or who was the first to buy at higher price and then decide the trade. Edit [To Clarify xyz]: Say if there is an Sell order at $10 Qty 100. There is a buyer who is willing to pay Max $20 and is looking for Qty 500. Your key assumption that the Buyer does not know the current SELL price of $10 is incorrect. Now there are multiple things, the Buyer knows the lowest Sell order is at $10, he can put a matching Buy order at $10 Qty 100, and say $11 Qty 100 etc. This is painful. Second, lets say he puts a Buy order at $10 Qty 100, by the time the order hits the system someone else has put the trade at $10 and his order is fulfilled. So this buyer has to keep looking at booking and keep making adjustments, if its a large order, it would be extremely difficult and frustrating for this Buyer. Hence the logic of giving preference. The later Buy order says ... The Max I can pay is $20, match eveything at the current price and get the required shares.",
"title": ""
},
{
"docid": "306783",
"text": "This sometimes happens to me. It depends on how liquid the option is. Normally what I see happening is that the order book mutates itself around my order. I interpret this to mean that the order book is primarily market makers. They see a retail investor (me) come in and, since they don't have any interest in this illiquid option, they back off. Some other retail investor (or whatever) steps in with a market order, and we get matched up. I get a fill because I become the market maker for a brief while. On highly liquid options, buy limits at the bid tend to get swallowed because the market makers are working the spread. With very small orders (a contract or two) on very liquid options, I've had luck getting quick fills in the middle of the spread, which I attribute to MM's rebalancing their holdings on the cheap, although sometimes I like to think there's some other anal-retentive like me out there that hates to see such a lopsided book. :) I haven't noticed any particular tendency for this to happen more with puts or calls, or with buy vs sell transactions. For a while I had a suspicion that this was happening with strikes where IV didn't match IV of other strikes, but I never cared enough to chase it down as it was a minor part of my overall P/L.",
"title": ""
},
{
"docid": "189005",
"text": "Please refer to this question to understand the basics of how an order is matched. How do exchanges match limit orders? Now most of the times even Block orders follow the same matching criteria. I think you are assuming that for every large buy order there is a matching large sell order. This is not true. So on the Buy side at various point in times there were Buy Orders, with Single order more than 10,000 shares. On the sell side to fulfil these orders there may or may not be a single order of 10,000. More often there will be quite a few smaller orders or 500, 1000 or whatever amount that are present in the queue based on the amount & time sort order or even partially matching out of a sell order of 10,000 ... Similarly when there is a large sell order of more than 10,000 , these may not have got filled in by a large buy order but by smaller buy orders etc ... So if you average out the amounts on the buy side and the sell side there would definately be a difference. The analysis of this difference is as indicated in your question, buy price is more than sell price and hence people are bullish ...",
"title": ""
},
{
"docid": "164008",
"text": "The everyday investor buys at the ask and sells at the bid but the market maker does the opposite This is misleading; it has nothing to do with being either an investor or a market maker. It is dependent on the type of order that is submitted. When a market trades at the ask, this means that a buy market order has interacted with a sell limit order at the limit price. When a market trades at the bid, this means that a sell market order has interacted with a buy limit order at the limit price. An ordinary investor can do exactly the same as a market maker and submit limit orders. Furthermore, they can sit on both sides of the bid and ask exactly as a market maker does. In the days before high frequency trading this was quite common (an example being Daytek, whose traders were notorious for stepping in front of the designated market maker's bid/ask on the Island ECN). An order executes ONLY when both bid and ask meet. (bid = ask) This is completely incorrect. A transaction occurs when an active (marketable) order is matched with a passive (limit book) order. If the passive order is a sell limit then the trade has occurred at the ask, and if it is a buy limit the trade has occurred at the bid. The active orders are not bids and asks. The only exception to this would be if the bid and ask have become crossed. When a seller steps in, he does so with an ask that's lower than the stock's current ask Almost correct; he does so with an order that's lower than the stock's current ask. If it's a marketable order it will fill the front queued best bid, and if it's a limit order his becomes the new ask price. A trade does not need to occur at this price for it to become the ask. This is wrong, market makers are the opposite party to you so the prices are the other way around for them. This is wrong. There is no distinction between the market maker and yourself or any other member of the public (beside the fact that designated market makers on some exchanges are obliged to post both a bid and ask at all times). You can open an account with any broker and do exactly the same as a market maker does (although with nothing like the speed that a high frequency market-making firm can, hence likely making you uncompetitive in this arena). The prices a market maker sees and the types of orders that they are able to use to realize them are exactly the same as for any other trader.",
"title": ""
},
{
"docid": "148440",
"text": "\"The ex indicator is meant to be a help for market participants. On the ex-day orders will go into a different order book, the ex order book, which at the start of the ex day will be totally empty, i.e. no orders from the non-ex day book have been copied over. Why does this help? Well imagine you had a long-standing buy order in the book, well below the current price, and now the share price halves due to a 2-for-1 split, would you want to see your order executed? If so, your order should have gone into the ex-book which is only active on the ex-day (and orders in the ex book are usually copied over to the normal book on the day after the ex-day but this is exchange-specific). Think of it as an additional safety net to tell the exchange: \"\"I know what I'm doing: I want to buy this stock totally overpriced after the 2-for-1 split\"\". Now some exchanges and/or some securities (mostly derivatives) linked with the security in question don't have this notion of ex or the ex-book, and they will tell you by \"\"will not be quoted ex\"\" or \"\"the ex indicator is missing\"\". In your case (SNE) it is a sponsored ADR, the ex-date was Mar 28 2016, one day before the ex date of the Japanese original. According to my understanding of NYSE rules, there is no specific rule for or against omitting the ex-indicator. It seems to be a decision on a case by case basis. Looking through the dividends of other Japanese ADRs I drew the conclusion none of them have an ex-book and so all of them are announced as: \"\"Will not be quoted ex by the exchange\"\". Again, this is based on my observations.\"",
"title": ""
},
{
"docid": "525231",
"text": "\"There are two distinct questions that may be of interest to you. Both questions are relevant for funds that need to buy or sell large orders that you are talking about. The answer depends on your order type and the current market state such as the level 2 order book. Suppose there are no iceberg or hidden orders and the order book (image courtesy of this question) currently is: An unlimited (\"\"at market\"\") buy order for 12,000 shares gets filled immediately: it gets 1,100 shares at 180.03 (1,[email protected]), 9,700 at 180.04 and 1,200 at 180.05. After this order, the lowest ask price becomes 180.05 and the highest bid is obviously still 180.02 (because the previous order was a 'market order'). A limited buy order for 12,000 shares with a price limit of 180.04 gets the first two fills just like the market order: 1,100 shares at 180.03 and 9,700 at 180.04. However, the remainder of the order will establish a new bid price level for 1,200 shares at 180.04. It is possible to enter an unlimited buy order that exhausts the book. However, such a trade would often be considered a mis-trade and either (i) be cancelled by the broker, (ii) be cancelled or undone by the exchange, or (iii) hit the maximum price move a stock is allowed per day (\"\"limit up\"\"). Funds and banks often have to buy or sell large quantities, just like you have described. However they usually do not punch through order book levels as I described before. Instead they would spread out the order over time and buy a smaller quantity several times throughout the day. Simple algorithms attempt to get a price close to the time-weighted average price (TWAP) or volume-weighted average price (VWAP) and would buy a smaller amount every N minutes. Despite splitting the order into smaller pieces the price usually moves against the trader for many reasons. There are many models to estimate the market impact of an order before executing it and many brokers have their own model, for example Deutsche Bank. There is considerable research on \"\"market impact\"\" if you are interested. I understand the general principal that when significant buy orders comes in relative to the sell orders price goes up and when a significant sell order comes in relative to buy orders it goes down. I consider this statement wrong or at least misleading. First, stocks can jump in price without or with very little volume. Consider a company that releases a negative earnings surprise over night. On the next day the stock may open 20% lower without any orders having matched for any price in between. The price moved because the perception of the stocks value changed, not because of buy or sell pressure. Second, buy and sell pressure have an effect on the price because of the underlying reason, and not necessarily/only because of the mechanics of the market. Assume you were prepared to sell HyperNanoTech stock, but suddenly there's a lot of buzz and your colleagues are talking about buying it. Would you still sell it for the same price? I wouldn't. I would try to find out how much they are prepared to buy it for. In other words, buy pressure can be the consequence of successful marketing of the stock and the marketing buzz is what changes the price.\"",
"title": ""
},
{
"docid": "413132",
"text": "The order book looks fine, if it were a liquid market. However, a bid that matches with an ask will always be met on a first come first serve basis. There's no other way to do it. Most traders don't like doing that because they want to try to get a lower price. HFT don't have to worry about meeting the ask because they're just going to pass that cost on to the guy on the hook. By the time the HFT makes the buy they already know the guy wants to buy at 70.00 They did not know that at the time they placed the buy order. If the buy order from the HFT hasn't been cancelled it means they already found someone. How? By testing the market with sell orders at the same time they were sending buy orders. They keep a little bit of stock in reserve to perform these tests.",
"title": ""
},
{
"docid": "147573",
"text": "\"Yes there are huge number of parts in the chain. Entire careers can be made out of handling clearing and settlement (back office) work for banks, exchanges, and trading houses. Even more so in the old days when this had to be done by hand, but obviously now everything is electronic. I can provide some insight into your questions, at least on the trading side. Brokers in many cases have their own brokers or their own trading operations. They will have their own order entry and risk control systems, so that is all proprietary, but it usually doesn't involve more than send buy/sell Y shares of name X to venue Z at price P with extra instructions A,B,C,D,E. Eventually an order will make its way to a direct market participant who sends an electronic order directly to an exchange. Note that when you say market, you should be referring to such \"\"exchanges\"\". In the US these are the NYSE, NASDAQ, and so on. When you are talking about futures there is the CME, CBOT, and so on. In Europe there is the EUREX and so on. The \"\"market\"\" refers to all these exchanges together which all have their own order mechanisms and matching engines. In many cases exchanges will route orders to other exchanges depending on the specific country's trading rules. Exchanges compete with each other by fee and liquidity offerings, which are shouldered directly by market participants. Another detail is that each market participant has its own clearing firm, which has prior credit lines established with the market participant and a central clearing house. Like you said as soon as an order is matched, the exchange where the order takes place hands the trade over to the clearing house where the trade is then settled between the clearing firms representing either side of the trade. Clearing disputes happen at this step.\"",
"title": ""
},
{
"docid": "467852",
"text": "It is possible to figure out the next price. Just not for Joe Average. A stock exchange has a orderbook. This has two sides. One side has alle the buyers, how many shares they want, and what they are willing to pay. The other side has all the sellers, how many shares they got, and what price they are willing to accept. If any buyers and sellers match up, their orders are executed, money and shares are exchanged, everyone is happy. So the current asking price (the price you have to pay, to get some shares) is currently 12.46$. Let's say you want 6000 shares, for any price. The orderbook now looks like this: Your order is executed, you get 6000 shares for a total of 74,761$ (5900 * 12,46 + 100 * 12,47$). The order book now looks like this: The new asking price is 12.47$. Congrats, you knew the price in advance. Of course this is simplified, there are millions of entries on both sides, thousands of trades happen every millisecond and you'll have to pay the stock exchange a lot of money to give you all this information in real time. That's what high frequency traders are doing. They use highly specialised computer systems to exploit differences in stock exchanges all over the world. It's called arbitage. They have to be faster than the other guy. This race has gone on for a few years now, so that the limiting factor starts to become the speed of light. YOU are not going to benefit, or else you would not be asking questions on PERSONAL finance :)",
"title": ""
},
{
"docid": "261082",
"text": "\"That article, like almost any article written by a non-expert and quoting only \"\"research\"\" from lobbying groups, hugely misses the point. The vast majority of orders that end up being cancelled are cancelled as a standard part of exchanges' official market-maker programs. Each exchange wants you and me to know that it has liquidity -- that when we go to buy or sell some stock, there will be someone waiting on the other side of the trade. So the exchange pays (via lowered fees or even rebates) hundreds of registered market makers to constantly have orders resting in each product's order book within a few ticks of the current NBBO or the last trade price. That way, if everyone else should suddenly disappear from the market, you and I will still be able to trade our shares for a price somewhat close to the last trade price. But market makers who are simply acting in this \"\"backstop\"\" role don't actually want to have their orders filled, because those orders will almost always lose them money. So as prices rise and fall (as much as tens of times per second), the market makers need to cancel their resting orders (so they don't get filled) and add new ones at new prices (so they meet their obligations to the exchange). And because the number of orders resting in any given product's order book is vastly larger than the number of actual trades that take place in any given time period, naturally the number of cancellations is also going to hugely outweigh the number of actual trades. As much as 97% to 3% (or even more). But that's completely fine! You and I don't have to care about any of that. We almost never need the market makers to be there to trade with us. They're only there as a backstop. There's almost always plenty of organic liquidity for us to trade against. Only in the rare case where liquidity completely dries up do we really care that the registered market makers are there. And in those cases (ideally) the market makers can't cancel their orders (depending on how well the exchange has set up its market maker program). So, to answer your question, the effect of standard order cancellation on a stock is essentially none. If you were to visualize the resting orders in a product's book as prices moved up and down, you would essentially see a Gaussian distribution with mean at the last trade price, and it would move up and down with the price. That \"\"movement\"\" is accomplished by cancellations followed by new orders. P.S. As always, keep in mind that your and my orders almost never actually make it to a real stock exchange anymore. Nowadays they are almost always sent to brokers' and big banks' internal dark pools. And in there you and I have no idea what shenanigans are going on. As just one example, dark pools allow their operators and (for a fee) other institutional participants access to a feature called last look that allows them to cancel their resting order as late as after your order has been matched against it! :( Regarding the question in your comment ... If Alice is sending only bona fide orders (that is, only placing an order at time T if, given all the information she has at time T, she truly wants and intends for it to be filled) then her cancellation at a later time actually adds to the effectiveness of and public perception of the market as a tool for price discovery (which is its ultimate purpose). [In the following example imagine that there are no such things as trading fees or commissions or taxes.] Let's say Alice offers to buy AAPL at $99.99 when the rest of the market is trading it for $100.00. By doing so she is casting her vote that the \"\"fair value\"\" of a share of AAPL is between $99.99 and $100.00. After all, if she thought the fair value of a share of AAPL was higher -- say, between $100.00 and $100.01 -- then she should be willing to pay $100.00 (because that's below fair value) and she should expect that other people in the market will not soon decide to sell to her at $99.99. If some time later Alice does decide that the fair value of AAPL is between $100.00 and $100.01 then she should definitely cancel her order at $99.99, for exactly the reason discussed above. She probably won't get filled at $99.99, and by sitting there stubbornly she's missing out (potentially forever) on the possibility to make a profit. Through the simple act of cancelling her $99.99 order, Alice is once again casting a vote that she no longer thinks that's AAPL's fair value. She is (very slightly) altering the collective opinion of the entire market as to what a share of AAPL is worth. And if her cancellation then frees her up to place another order closer to her perceived fair value (say, at $100.00), then that's another vote for her honest optinion about AAPL's price. Since the whole goal of the market is to get a bunch of particpants to figure out the fair value of some financial instrument (or commodity, or smart phone, or advertising time, etc.), cancellations of honest votes from the past in order to replace them with new, better-informed honest votes in the present can only be a good thing for the market's effectiveness and perceived effectiveness. It's only when participants start sending non-honest votes (non bona fide orders) that things start to go off the rails. That's what @DumbCoder was referring to in his comment on your original question.\"",
"title": ""
},
{
"docid": "114319",
"text": "It's done by Opening Auction (http://www.advfn.com/Help/the-opening-auction-68.html): The Opening Auction Between 07.50 and a random time between 08.00 and 08.00.30, there will be called an auction period during which time, limit and market orders are entered and deleted on the order book. No order execution takes place during this period so it is possible that the order book will become crossed. This means that some buy and sell orders may be at the same price and some buy orders may be at higher prices than some sell orders. At the end of the random start period, the order book is frozen temporarily and an order matching algorithm is run. This calculates the price at which the maximum volume of shares in each security can be traded. All orders that can be executed at this price will be filled automatically, subject to price and priorities. No additional orders can be added or deleted until the auction matching process has been completed. The opening price for each stock will be either a 'UT' price or, in the event that there are no transactions resulting form the auction, then the first 'AT' trade will be used.",
"title": ""
},
{
"docid": "352965",
"text": "You can do FOK on both market and limit orders. Normal market orders will partial fill if you want more shares than are being offered, or if someone pulled their order before you get there and now there are fewer shares than you placed a trade for. With a FOK limit order not at the BBO you are shooting in the dark for a quick match, most of the time it does not fill. This is a commonly used order type for UHFT arbitrage. Some exchanges will not attempt to cross it for a match if its price is not at, or better than the market price. When the FOK limit order is at the BBO it is essentially a FOK market order. FYI: Sometimes you have a minimum quantity to fill option, so you can let the order sit on the book until it fills or you cancel.",
"title": ""
},
{
"docid": "251100",
"text": "In order to see whether you can buy or sell some given quantity of a stock at the current bid price, you need a counterparty (a buyer) who is willing to buy the number of stocks you are wishing to offload. To see whether such a counterparty exists, you can look at the stock's order book, or level two feed. The order book shows all the people who have placed buy or sell orders, the price they are willing to pay, and the quantity they demand at that price. Here is the order book from earlier this morning for the British pharmaceutical company, GlaxoSmithKline PLC. Let's start by looking at the left-hand blue part of the book, beneath the yellow strip. This is called the Buy side. The book is sorted with the highest price at the top, because this is the best price that a seller can presently obtain. If several buyers bid at the same price, then the oldest entry on the book takes precedence. You can see we have five buyers each willing to pay 1543.0 p (that's 1543 British pence, or £15.43) per share. Therefore the current bid price for this instrument is 1543.0. The first buyer wants 175 shares, the next, 300, and so on. The total volume that is demanded at 1543.0p is 2435 shares. This information is summarized on the yellow strip: 5 buyers, total volume of 2435, at 1543.0. These are all buyers who want to buy right now and the exchange will make the trade happen immediately if you put in a sell order for 1543.0 p or less. If you want to sell 2435 shares or fewer, you are good to go. The important thing to note is that once you sell these bidders a total of 2435 shares, then their orders are fulfilled and they will be removed from the order book. At this point, the next bidder is promoted up the book; but his price is 1542.5, 0.5 p lower than before. Absent any further changes to the order book, the bid price will decrease to 1542.5 p. This makes sense because you are selling a lot of shares so you'd expect the market price to be depressed. This information will be disseminated to the level one feed and the level one graph of the stock price will be updated. Thus if you have more than 2435 shares to sell, you cannot expect to execute your order at the bid price in one go. Of course, the more shares you are trying to get rid of, the further down the buy side you will have to go. In reality for a highly liquid stock as this, the order book receives many amendments per second and it is unlikely that your trade would make much difference. On the right hand side of the display you can see the recent trades: these are the times the trades were done (or notified to the exchange), the price of the trade, the volume and the trade type (AT means automatic trade). GlaxoSmithKline is a highly liquid stock with many willing buyers and sellers. But some stocks are less liquid. In order to enable traders to find a counterparty at short notice, exchanges often require less liquid stocks to have market makers. A market maker places buy and sell orders simultaneously, with a spread between the two prices so that they can profit from each transaction. For instance Diurnal Group PLC has had no trades today and no quotes. It has a more complicated order book, enabling both ordinary buyers and sellers to list if they wish, but market makers are separated out at the top. Here you can see that three market makers are providing liquidity on this stock, Peel Hunt (PEEL), Numis (NUMS) and Winterflood (WINS). They have a very unpalatable spread of over 5% between their bid and offer prices. Further in each case the sum total that they are willing to trade is 3000 shares. If you have more than three thousand Dirunal Group shares to sell, you would have to wait for the market makers to come back with a new quote after you'd sold the first 3000.",
"title": ""
},
{
"docid": "450515",
"text": "\"Market orders do not get priority over limit orders. Time is the only factor that matters in price/time order matching when the order price is the same. For example, suppose the current best available offer for AAPL is $100.01 and the best available bid is $100.00. Now a limit buy for $100.01 and a market buy arrive at around the same instant. The matching engine can only receive one order at a time, no matter how close together they arrive. Let's say that by chance the limit buy arrives first. The engine will check if there's a matching sell at $100.01 and indeed there is and a trade occurs. This all happens in an instant before the matching engine ever sees the market buy. Then it moves on to the market buy and processes it accordingly. On the other hand, let's say that by chance the market buy arrives first. The engine will match it with the best available sell (at $100.01) and a trade occurs. This all happens in an instant before the matching engine ever sees the limit buy. Then it moves on to the limit buy and processes it accordingly. So there's never a comparison between the two orders or their \"\"priorities\"\" because they never exist in the system at the same time. The first one to arrive is processed first; the second one to arrive is processed second.\"",
"title": ""
},
{
"docid": "546493",
"text": "\"You're confusing a specific visual representation of the top bid & ask orders selected from the order book with the actual \"\"top of the book\"\". \"\"Top\"\" in the sense of the \"\"top of the book\"\" is a ranking (by order of \"\"best\"\", different for bids vs. asks) and not meant to be strictly a visual positioning on a page or screen. The data in the visual representation comes from the top of the order book (the best bids, and the best asks), but that visual representation is choosing to present it in a specific way. Think of the \"\"book\"\" as the model, the abstract collection of outstanding bid and ask order data. When people talk about the \"\"top of the book\"\", they're talking about the best bids (higher being better), and the best asks (lower being better). The visual representation above is but one possible way to render a tip-of-the-iceberg view of the best orders in the \"\"book\"\". The advantage of that particular visual representation is that one can see the asks & bids converging towards the center. The spread is visible as the difference between the two middle elements – being the lowest row in the blue \"\"Asks\"\" area, and the highest row in the green \"\"Bids\"\" area. The up-arrow they had included in the \"\"Asks\"\" area was perhaps meant to provide a clue about how the data was sorted contrary to expectations of descending order of \"\"bestness\"\", and/or to imply there is further depth to the book data in the indicated direction. If the bids & asks had been oriented side-by-side instead, they might have chosen to represent it as below, re-arranging the rows in the \"\"Asks\"\" in the opposite order (i.e. in the order you had expected) so that the \"\"bests\"\" are both in the top row:\"",
"title": ""
},
{
"docid": "163905",
"text": "\"The simple answer is, there are many ways for trades to take place. Some systems use order-matching software that employs proprietary algorithms for deciding the order of processing, others use FIFO structures, and so on. Some brokerages may fill customer orders out of their own accounts (which happens more frequently than you might imagine), and others put their orders into the system for the market makers to handle. There's no easy all-encompassing answer to your question, but it's still a good one to ask. By the way, asking if the market is \"\"fair\"\" is a bit naive, because fairness depends on what side of the trade you came out on! (grin) If your limit order didn't get filled and you missed out on an opportunity, that's always going to seem unfair, right?\"",
"title": ""
},
{
"docid": "203573",
"text": "But how does the quantity matching happen? For example, if I want to buy 1000 shares at $100, but there is only one seller to sell 10 shares at $100, what happens then? This depends on the type of order you've placed. If you placed a fill-or-kill order, your order to buy or sell a certain number of shares is routed to the trading floor for immediate execution. If the order cannot be immediately filled, it is cancelled (killed) automatically. Note that the order must be filled in its entirety. Partial fills are not allowed. In your example, your buy order wouldn't be filled because it couldn't be matched to a sell order of the same volume. This is similar to an all-or-none order, which is an order that contains A condition instructing the broker to fill the order completely or not at all. If there is insufficient supply to meet the quantity requested by the order then it is canceled at the close of the market. In this case, if your order wasn't matched to an order of the same volume by the time the market closes, it's cancelled. If you simply placed a market/limit order, and (in the case of the limit order), part of your order was matched to another order with the right price, that part of your order will be filled, while the rest will remained unfilled.",
"title": ""
},
{
"docid": "63909",
"text": "\"In the first situation you describe, any intelligent routing algo will send a 1000 lot order to the lit exchange in step 1. Then you get filled 1000@$10. After the fill occurs, the matching engine tells everyone what happened. If the order book consists of 100 orders of 1 lot @ $10, and you place a \"\"buy 100 lots\"\" order, here is what happens: 1. The matching engine receives your order. 2. The matching engine matches your order against the 100 individual orders on the book. 3. The matching engine broadcasts 100 trade notifications. No one has any opportunity to cancel their orders since they only hear of the fill after it happened. The only way someone would have the opportunity to cancel is if there was 500 lots on one exchange and 500 on another. Then someone might observe a trade on exchange #1 and cancel their sell order on exchange #2 in response.\"",
"title": ""
},
{
"docid": "434596",
"text": "In general stock markets are very similar to that, however, you can also put in limit orders to say that you will only buy or sell at a given price. These sit in the market for a specified length of time and will be executed when an order arrives that matches the price (or better). Traders who set limit orders are called liquidity (or price) makers as they provide liquidity (i.e. volume to be traded) to be filled later. If there is no counterparty (i.e. buyer to your seller) in the market, a market maker; a large bank or brokerage who is licensed and regulated to do so, will fill your order at some price. That price is based on how much volume (i.e. trading) there is in that stock on average. This is called average daily volume (ADV) and is calculated over varying periods of time; we use ADV30 which is the 30 day average. You can always sell stocks for whatever price you like privately but a market order does not allow you to set your price (you are a price taker) therefore that kind of order will always fill at a market price. As mentioned above limit orders will not fill until the price is hit but will stay on book as long as they aren't filled, expired or cancelled.",
"title": ""
},
{
"docid": "599523",
"text": "\"I'm not sure the term actually has a clear meaning. We can think of \"\"what does this mean\"\" in two ways: its broad semantic/metaphorical meaning, and its mechanical \"\"what actual variables in the market represent this quantity\"\". Net buying/selling have a clear meaning in the former sense by analogy to the basic concept of supply and demand in equilibrium markets. It's not as clear what their meaning should be in the latter sense. Roughly, as the top comment notes, you could say that a price decrease is because of net selling at the previous price level, while a price rise is driven by net buying at the previous price level. But in terms of actual market mechanics, the only way prices move is by matching of a buyer and a seller, so every market transaction inherently represents an instantaneous balance across the bid/ask spread. So then we could think about the notion of orders. Actual transactions only occur in balance, but there is a whole book of standing orders at various prices. So maybe we could use some measure of the volume at various price levels in each of the bid/ask books to decide some notion of net buying/selling. But again, actual transactions occur only when matched across the spread. If a significant order volume is added on one side or the other, but at a price far away from the bid/offer - far enough that an actual trade at that price is unlikely to occur - should that be included in the notion of net buying/selling? Presumably there is some price distance from the bid/offer where the orders don't matter for net buying/selling. I'm sure you'd find a lot of buyers for BRK.A at $1, but that's completely irrelevant to the notion of net buying/selling in BRK.A. Maybe the closest thing I can think of in terms of actual market mechanics is the comparative total volumes during the period that would still have been executed if forced to execute at the end of period price. Assuming that traders' valuations are fixed through the period in question, and trading occurs on the basis of fundamentals (which I know isn't a good assumption in practice, but the impact of price history upon future price is too complex for this analysis), we have two cases. If price falls, we can assume all buyers who executed above the last price in the period would have happily bought at the last price (saving money), while all sellers who executed below the last price in the period would also be happy to sell for more. The former will be larger than the latter. If the price rises, the reverse is true.\"",
"title": ""
},
{
"docid": "286328",
"text": "\"If there are no limit orders on the opposite side of the book when your market order gets its turn for execution, it should be rejected by the market. A market order should generally not \"\"sit on the book\"\" like your question suggests waiting for another order to arrive. Thus, the situation that you describe should not happen in an ordinary market that is operating in an orderly fashion. This is not to say that your order cannot \"\"sit\"\" for a while in a queue - If there is heavy volume, orders will be executed in order, so your your market order may have to wait for orders entered ahead of it to be processed. But once its turn comes up, that's it. There are some related points to consider: I should caution that my answer is biased a bit to US stock markets, whereas you asked about currency markets. I believe the same basic principles apply, but I'd be swayed by someone with evidence to the contrary. I'd also note that currency tends to be more liquid than stock, so I think it's less likely that this situation would come up. Maybe possible for a \"\"weak\"\" currency or a currency that experiences a sudden crisis of some sort.\"",
"title": ""
},
{
"docid": "317365",
"text": "\"Most of the time* you're selling to other investors, not back to the company. The stock market is a collection of bid (buy offers) and asks (sell offers). When you sell your stock as a retail investor at the \"\"market\"\" price you're essentially just meeting whatever standing bid offers are on the market. For very liquid stocks (e.g. Apple), you can pretty much always get the displayed price because so many stocks are being traded. However during periods of very high volatility or for low-volume stocks, the quoted price may not be indicative of what you actually pay. As an example, let's say you have 5 stocks you're trying to sell and the bid-side order book is 2 stocks for $105, 2 for $100, and 5 for $95. In this scenario the quoted price will be $105 (the best bid price), but if you accept market price you'll settle 2 for 105, 2 for 100, and 1 for 95. After your sell order goes through, the new quoted price will be $95. For high volume stocks, there will usually be so many orders near the midpoint price ($105, in this case) that you won't see any price slippage for small orders. You can also post limit orders, which are essentially open orders waiting to be filled like in the above example. They ensure you get the price you want, but you have no way to guarantee they'll be filled or not. Edit: as a cool example, check out the bitcoin GDAX on coinbase for a live example of what the order book looks like for stocks. You'll see that the price of bitcoin will drift towards whichever direction has the less dense order book (e.g. price drifts upwards when there are far more bids than asks.)\"",
"title": ""
},
{
"docid": "122996",
"text": "\"I can think of the following situations in which one could see a trade occur between the visible best bid & offer: 1) on a public exchange, people have posted hidden limit orders with either bid prices above the best visible bid or offers below the best visible offer, and incoming orders have executed against this hidden liquidity[1]; 2) some orders may have been matched in dark pools which offer \"\"mid-point matching\"\" where buy and sell orders are matched using the mid-point of the best available publicly posted bid and offer as the reference price, and which executed trades are then reported to the public markets; or 3) some internalising broker has traded off exchange directly with a client and is now reporting the trade to the public as is often required. Now how exactly any of the above situations indicates that a \"\"trend is about to come to an end\"\", I do not know. [1] Exchanges often match orders on a price/visibility/time basis, whereby the orders are prioritised by price (better prices get to trade first), then by visibility (visible orders get to trade first) then by time (first come, first serve).\"",
"title": ""
},
{
"docid": "63403",
"text": "\"People must simply be willing to match your orders if they know about it. You can sniff orders out if you can see them or predict them. For instance, you can look at an order book and decide who you want to get filled at, especially if you are looking at different quotes from different exchanges. So you can get a \"\"better\"\" fill just by looking at what someone is willing to pay to enter/exit their order as well as what exchange they placed their order through, and send an order to that specific exchange to match them. You (or a program) can just watch the level 2's and place an order as soon as you see one you like. The orders on the level2's do not reveal ALL interested market participants. Also many brokers have difficulty updating options quotes. Finally, options & market volatility can inflate or decrease the price of options by large percentages very quickly.\"",
"title": ""
},
{
"docid": "28604",
"text": "\"The current stock price you're referring to is actually the price of the last trade. It is a historical price – but during market hours, that's usually mere seconds ago for very liquid stocks. Whereas, the bid and ask are the best potential prices that buyers and sellers are willing to transact at: the bid for the buying side, and the ask for the selling side. But, think of the bid and ask prices you see as \"\"tip of the iceberg\"\" prices. That is: The \"\"Bid: 13.20 x200\"\" is an indication that there are potential buyers bidding $13.20 for up to 200 shares. Their bids are the highest currently bid; and there are others in line behind with lower bid prices. So the \"\"bid\"\" you're seeing is actually the best bid price at that moment. If you entered a \"\"market\"\" order to sell more than 200 shares, part of your order would likely be filled at a lower price. The \"\"Ask: 13.27 x1,000\"\" is an indication that there are potential sellers asking $13.27 for up to 1000 shares. Their ask prices are the lowest currently asked; and there are others in line behind with higher ask prices. So the \"\"ask\"\" you're seeing is the best asking price at that moment. If you entered a \"\"market\"\" order to buy more than 1000 shares, part of your order would likely be filled at a higher price. A transaction takes place when either a potential buyer is willing to pay the asking price, or a potential seller is willing to accept the bid price, or else they meet in the middle if both buyers and sellers change their orders. Note: There are primarily two kinds of stock exchanges. The one I just described is a typical order-driven matched bargain market, and perhaps the kind you're referring to. The other kind is a quote-driven over-the-counter market where there is a market-maker, as JohnFx already mentioned. In those cases, the spread between the bid & ask goes to the market maker as compensation for making a market in a stock. For a liquid stock that is easy for the market maker to turn around and buy/sell to somebody else, the spread is small (narrow). For illiquid stocks that are harder to deal in, the spread is larger (wide) to compensate the market-maker having to potentially carry the stock in inventory for some period of time, during which there's a risk to him if it moves in the wrong direction. Finally ... if you wanted to buy 1000 shares, you could enter a market order, in which case as described above you'll pay $13.27. If you wanted to buy your shares at no more than $13.22 instead, i.e. the so-called \"\"current\"\" price, then you would enter a limit order for 1000 shares at $13.22. And more to the point, your order would become the new highest-bid price (until somebody else accepts your bid for their shares.) Of course, there's no guarantee that with a limit order that you will get filled; your order could expire at the end of the day if nobody accepts your bid.\"",
"title": ""
}
] |
PLAIN-1383
|
hydrogen sulfide
|
[
{
"docid": "MED-1188",
"text": "One hundred and eighteen missionaries working on 75 mission stations or hospitals in 24 sub-Saharan African countries provided information about their medical practice in the preceding year of 1981. Details were collected of the total number of patients seen and admitted during the year, and the number of cases of bloody diarrhoea, typhoid and inflammatory bowel disease. Over 1 million outpatients and about 190,000 inpatients were treated. These included 12,859 cases of bloody diarrhoea, of whom 1,914 had typhoid. Twenty-two cases of inflammatory bowel disease were also reported. Histological support was least available in West Africa and only 25% of hospitals had access to this facility. Nevertheless, the frequency with which inflammatory bowel disease in sub-Saharan Africa is difficult and limited by access to diagnostic facilities. It is likely to be some time before reliable estimates of the incidence and prevalence of Crohn's disease and ulcerative colitis in the rural African population can be made.",
"title": "Inflammatory bowel disease in rural sub-Saharan Africa: rarity of diagnosis in patients attending mission hospitals."
},
{
"docid": "MED-1421",
"text": "BACKGROUND: Hydrogen sulfide is a luminally acting, bacterially derived cell poison that has been implicated in ulcerative colitis. Sulfide generation in the colon is probably driven by dietary components such as sulfur-containing amino acids (SAAs) and inorganic sulfur (eg, sulfite). OBJECTIVE: We assessed the contribution of SAAs from meat to sulfide production by intestinal bacteria with use of both a model culture system in vitro and an in vivo human feeding study. DESIGN: Five healthy men were housed in a metabolic suite and fed a sequence of 5 diets for 10 d each. Meat intake ranged from 0 g/d with a vegetarian diet to 600 g/d with a high-meat diet. Fecal sulfide and urinary sulfate were measured in samples collected on days 9 and 10 of each diet period. Additionally, 5 or 10 g bovine serum albumin or casein/L was added to batch cultures inoculated with feces from 4 healthy volunteers. Concentrations of sulfide, ammonia, and Lowry-reactive substances were measured over 48 h. RESULTS: Mean (+/-SEM) fecal sulfide concentrations ranged from 0.22 +/- 0.02 mmol/kg with the 0-g/d diet to 3.38 +/- 0.31 mmol/kg with the 600-g/d diet and were significantly related to meat intake (P: < 0.001). Sulfide formation in fecal batch cultures supplemented with both bovine serum albumin and casein correlated with protein digestion, as measured by the disappearance of Lowry-reactive substances and the appearance of ammonia. CONCLUSION: Dietary protein from meat is an important substrate for sulfide generation by bacteria in the human large intestine.",
"title": "Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans."
},
{
"docid": "MED-1419",
"text": "To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon adenocarcinoma cell line HT29 clone 19a as a target. The fluorescence and length of the tails of the comet images reflects the degree of DNA damage in single cells. The mean DNA damage, expressed as the ratio of tail intensity (fluorescence in the tail) to total intensity of the comet after incubation with faecal water from volunteers consuming diet 1 was about twice as high as for diet 2. The susceptibility of the cells incubated with faecal water to DNA damage caused by additional hydrogen peroxide treatment showed no significant differences between the two diets. Generation of oxidized pyrimidine and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer.",
"title": "A diet high in fat and meat but low in dietary fibre increases the genotoxic potential of 'faecal water'."
},
{
"docid": "MED-1186",
"text": "We investigated the effect of resistant starch (RS) on markers of colonic protein metabolism. Eleven subjects participated in a randomized crossover study in which they consumed either high-RS (39 +/- 3 g/d, -chi +/- SEM) or low-RS (5 +/- 0.4 g/d) diets for 3 wk. All other macronutrients were kept constant. During the high-RS diet daily excretion of fecal nitrogen increased from 1.84 +/- 0.15 to 2.86 +/- 0.42 g/d (P < 0.01) and excretion of fecal phenols fell from 9.2 +/- 1.4 to 5.3 +/- 0.8 mg/d (P < 0.01). Fecal concentrations of ammonia decreased from 397 +/- 33 to 278 +/- 49 microgram/g (P < 0.01) and phenols decreased from 69 +/- 8 to 39 +/- 10 microgram/g (P < 0.001). Daily output of urinary ammonia, urea, phenols, and total nitrogen did not change significantly, but pH decreased from 6.4 +/- 0.1 to 6.2 +/- 0.1 (P < 0.05) during the high-RS period. These results suggest that RS significantly attenuates the accumulation of potentially harmful byproducts of protein fermentation in the human colon.",
"title": "Resistant starch lowers fecal concentrations of ammonia and phenols in humans."
},
{
"docid": "MED-1185",
"text": "Endogenous sulfite is generated as a consequence of the body's normal processing of sulfur-containing amino acids. Sulfites occur as a consequence of fermentation and also occur naturally in a number of foods and beverages. As food additives, sulfiting agents were first used in 1664 and approved in the United States as long ago as the 1800s. With such long experience with their use, it is easy to understand why these substances have been regarded as safe. They are currently used for a variety of preservative properties, including controlling microbial growth, preventing browning and spoilage, and bleaching some foods. It is estimated that up to 500,000 (< .05% of the population) sulfite-sensitive individuals live in the United States. Sulfite sensitivity occurs most often in asthmatic adults--predominantly women; it is uncommonly reported in preschool children. Adverse reactions to sulfites in nonasthmatics are extremely rare. Asthmatics who are steroid-dependent or who have a higher degree of airway hyperreactivity may be at greater risk of experiencing a reaction to sulfite-containing foods. Even within this limited population, sulfite sensitivity reactions vary widely, ranging from no reaction to severe. The majority of reactions are mild. These manifestations may include dermatologic, respiratory, or gastrointestinal signs and symptoms. Severe nonspecific signs and symptoms occur less commonly. Broncho-constriction is the most common sensitivity response in asthmatics. The precise mechanisms of the sensitivity responses have not been completely elucidated. Inhalation of sulfur dioxide (SO2) generated in the stomach following ingestion of sulfite-containing foods or beverages, a deficiency in a mitochondrial enzyme, and an IgE-mediated immune response have all been implicated.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Sulfite sensitivity: significance in human health."
},
{
"docid": "MED-5204",
"text": "It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Relevance of protein fermentation to gut health."
},
{
"docid": "MED-4342",
"text": "OBJECTIVES: Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. METHODS: The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. RESULTS: Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. CONCLUSIONS: High protein intake is associated with an increased risk of incident IBD in French middle-aged women.",
"title": "Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study."
},
{
"docid": "MED-1426",
"text": "BACKGROUND: To evaluate the influence of increased dietary protein intake on bacterial colonic metabolism in healthy volunteers. METHODS: Short chain fatty acids, ammonia, and volatile organic compounds in faecal samples, and phenols in the urine of five volunteers were measured after one week of basal nutrient intake and and after one week of a diet supplemented with a protein rich food (Fortimel; Nutricia, Zoetermeer, The Netherlands). Paired t tests and factor analysis were used for statistical analysis. RESULTS: Total energy and resistant carbohydrate intake remained unchanged in each study period. The percentage energy intake delivered as dietary protein, increased significantly (from 15.4% to 23.8%; p = 0.007) during supplement intake. A significant increase in faecal ammonia (p = 0.002), faecal valeric acid (p = 0.02), and urinary p-cresol (p = 0.04) was noted during supplementary protein intake. A total of 120 different volatile compounds were isolated from the faecal samples of which 10 increased significantly during dietary protein supplementation. The change in volatile pattern, especially for S containing metabolites, was clearly shown by a factor analysis model which made a distinction between the two dietary regimens for all volunteers. CONCLUSION: An increase in dietary protein leads to altered products formation by colonic metabolism, mainly reflected by an increase in faecal ammonia, faecal volatile S substances, and urinary p-cresol.",
"title": "Influence of dietary protein supplements on the formation of bacterial metabolites in the colon."
},
{
"docid": "MED-1425",
"text": "We examined the correlation between the incidence of Crohn disease and dietary change in a relatively homogeneous Japanese population. The incidence and daily intake of each dietary component were compared annually from 1966 to 1985. The univariate analysis showed that the increased incidence of Crohn disease was strongly (P < 0.001) correlated with increased dietary intake of total fat (r = 0.919). animal fat (r = 0.880), n-6 polyunsaturated fatty acids (r = 0.883), animal protein (r = 0.908), milk protein (r = 0.924), and the ratio of n-6 to n-3 fatty acid intake (r = 0.792). It was less correlated with intake of total protein (r = 0.482, P < 0.05), was not correlated with intake of fish protein (r = 0.055, P > 0.1), and was inversely correlated with intake of vegetable protein (r = -0.941, P < 0.001). The multivariate analysis showed that increased intake of animal protein was the strongest independent factor with a weaker second factor, an increased ration of n-6 to n-3 polyunsaturated fatty acids. The present study in association with reported clinical studies suggests that increased dietary intake of animal protein and n-6 polyunsaturated fatty acids with less n-3 polyunsaturated fatty acids may contribute to the development of Crohn disease.",
"title": "Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the inc..."
},
{
"docid": "MED-1582",
"text": "Background & Aims Increased intake of dietary fiber has been proposed to reduce risk of inflammatory bowel diseases (Crohn’s disease [CD], ulcerative colitis [UC]). However, few prospective studies have examined associations between long-term intake of dietary fiber and risk of incident CD or UC. Methods We collected and analyzed data from 170,776 women, followed over 26 y, who participated in the Nurses’ Health Study, followed for 3,317,425 person-y. Dietary information was prospectively ascertained via administration of a validated semi-quantitative food frequency questionnaire every 4 y. Self-reported CD and UC were confirmed through review of medical records. Cox proportional hazards models, adjusting for potential confounders, were used to calculate hazard ratios (HRs). Results We confirmed 269 incident cases of CD (incidence 8/100,000 person-y) and 338 cases of UC (incidence 10/100,000 person-y). Compared to the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval [CI], 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% CI 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC. Conclusion Based on data from the Nurses’ Health Study, long-term intake of dietary fiber, particularly from fruit, is associated with lower risk of CD but not UC. Further studies are needed to determine the mechanisms that mediate this association.",
"title": "A Prospective Study of Long-term Intake of Dietary Fiber and Risk of Crohn’s Disease and Ulcerative Colitis"
},
{
"docid": "MED-1420",
"text": "PURPOSE OF REVIEW: To highlight mechanisms whereby diet affects colonic function and disease patterns. RECENT FINDINGS: Topical nutrients are preferentially used by the gut mucosa to maintain structure and function. With the colon, topical nutrients are generated by the colonic microbiota to maintain mucosal health. Most importantly, short chain fatty acids control proliferation and differentiation, thereby reducing colon cancer risk. In patients with massive loss of small intestine, short chain fatty acid production supports survival by releasing up to 1000 kcal energy/day. Human studies show that the microbiota synthesizes a large pool of utilizable folate which may support survival in impoverished populations. Unfortunately, the microbiota may also elaborate toxic products from food residues such as genotoxic hydrogen sulfide by sulfur-reducing bacteria in response to a high-meat diet. The employment of culture-free techniques based on 16S regions of DNA has revealed that our colons harbor over 800 bacterial species and 7000 different strains. Evidence suggests that the diet directly influences the diversity of the microbiota, providing the link between diet, colonic disease, and colon cancer. The microbiota, however, can determine the efficiency of food absorption and risk of obesity. SUMMARY: Our investigations have focused on a small number of bacterial species: characterization of microbiota and its metabolism can be expected to provide the key to colonic health and disease.",
"title": "Nutrition and colonic health: the critical role of the microbiota."
},
{
"docid": "MED-1184",
"text": "It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3-5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.",
"title": "Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerativ..."
},
{
"docid": "MED-1187",
"text": "Background and aims: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. Methods: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. Results: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3–7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1–12.9)), protein (OR 3.00 (95% CI 1.25–7.19)), and alcohol (OR 2.71 (95% CI 1.1–6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19–6.4)) or sulphate (OR 2.6 (95% CI 1.08–6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. Conclusions: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.",
"title": "Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study"
},
{
"docid": "MED-3964",
"text": "BACKGROUND: A better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses. AIM: To review current knowledge on dietary risk factors for inflammatory bowel disease. METHODS: The PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease. RESULTS: Established non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case-control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate). CONCLUSIONS: A diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.",
"title": "Diet and risk of inflammatory bowel disease."
},
{
"docid": "MED-1581",
"text": "Crohn's disease is a life-long idiopathic inflammatory disease which affects the entire gastrointestinal tract and occasionally extra-intestinal organs. CD is thought to result from complex interactions between environmental factors, the gut microbes, and the genetic background and the immune system of the host. In the last decades research on these pathogenetic components, and especially on mucosal immunity, has led to the development of biologic agents and therapeutic strategies that have improved dramatically the treatment of CD but we are still far away from curing the disease. If there is a treatment for CD that will probably evolve through methodical steps towards integrating research on all the components involved in the pathogenesis of CD. This holistic and global approach may aid at unravelling the mysteries of CD and developing novel agents and therapeutic strategies which by targeting multiple pathogenetic pathways and at different stages of disease may lead hopefully to cure. Copyright © 2014 Elsevier Ltd. All rights reserved.",
"title": "When can we cure Crohn's?"
},
{
"docid": "MED-1418",
"text": "Hydrogen sulfide (H(2)S) is produced by indigenous sulfate-reducing bacteria in the large intestine and represents an environmental insult to the colonic epithelium. Clinical studies have linked the presence of either sulfate-reducing bacteria or H(2)S in the colon with chronic disorders such as ulcerative colitis and colorectal cancer, although at this point, the evidence is circumstantial and underlying mechanisms remain undefined. We showed previously that sulfide at concentrations similar to those found in the human colon induced genomic DNA damage in mammalian cells. The present study addressed the nature of the DNA damage by determining if sulfide is directly genotoxic or if genotoxicity requires cellular metabolism. We also questioned if sulfide genotoxicity is mediated by free radicals and if DNA base oxidation is involved. Naked nuclei from untreated Chinese hamster ovary cells were treated with sulfide; DNA damage was induced by concentrations as low as 1 micromol/L. This damage was effectively quenched by cotreatment with butylhydroxyanisole. Furthermore, sulfide treatment increased the number of oxidized bases recognized by formamidopyrimidine [fapy]-DNA glycosylase. These results confirm the genotoxicity of sulfide and strongly implicate that this genotoxicity is mediated by free radicals. These observations highlight the possible role of sulfide as an environmental insult that, given a predisposing genetic background, may lead to genomic instability or the cumulative mutations characteristic of colorectal cancer.",
"title": "Hydrogen sulfide induces direct radical-associated DNA damage."
}
] |
[
{
"docid": "MED-723",
"text": "OBJECTIVE: A variety of charcoal-containing devices are purported to minimize problems with odoriferous rectal gas; however, the evidence supporting the efficacy of these products is virtually all anecdotal. We objectively evaluated the ability of these devices to adsorb two malodorous, sulfide gases (hydrogen sulfide and methylmercaptan) instilled at the anus. METHODS: Via a tube, 100 ml of nitrogen containing 40 ppm of sulfide gases and 0.5% H(2) was instilled at the anus of six healthy volunteers who wore gas impermeable Mylar pantaloons over their garments. Since H(2) is not adsorbed by charcoal, the fraction of the sulfide gases removed could be determined from the concentration ratio of sulfide gas: H(2) in the pantaloon space relative to the ratio in instilled gas. RESULTS: Measurements with no device in place showed that subjects' garments removed 22.0 +/- 5.3% of the sulfide gases, and results obtained with each device were corrected for this removal. The only product that adsorbed virtually all of the sulfide gases was briefs constructed from an activated carbon fiber fabric. Pads worn inside the underwear removed 55-77% of the sulfide gases. Most cushions were relatively ineffective, adsorbing about 20% of the gases. CONCLUSIONS: The ability of charcoal-containing devices to adsorb odoriferous rectal gases is limited by incomplete exposure of the activated carbon to the gases. Briefs made from carbon fiber are highly effective; pads are less effective, removing 55-77% of the odor; cushions are relatively ineffective.",
"title": "Effectiveness of devices purported to reduce flatus odor."
},
{
"docid": "MED-1417",
"text": "Background: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis. Objective: To examine the hypothesis that the influence of diet on colon cancer risk is mediated by the microbiota through their metabolites, we measured differences in colonic microbes and their metabolites in African Americans with a high risk and in rural native Africans with a low risk of colon cancer. Design: Fresh fecal samples were collected from 12 healthy African Americans aged 50–65 y and from 12 age- and sex-matched native Africans. Microbiomes were analyzed with 16S ribosomal RNA gene pyrosequencing together with quantitative polymerase chain reaction of the major fermentative, butyrate-producing, and bile acid–deconjugating bacteria. Fecal short-chain fatty acids were measured by gas chromatography and bile acids by liquid chromatography–mass spectrometry. Results: Microbial composition was fundamentally different, with a predominance of Prevotella in native Africans (enterotype 2) and of Bacteroides in African Americans (enterotype 1). Total bacteria and major butyrate-producing groups were significantly more abundant in fecal samples from native Africans. Microbial genes encoding for secondary bile acid production were more abundant in African Americans, whereas those encoding for methanogenesis and hydrogen sulfide production were higher in native Africans. Fecal secondary bile acid concentrations were higher in African Americans, whereas short-chain fatty acids were higher in native Africans. Conclusion: Our results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids.",
"title": "Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans"
},
{
"docid": "MED-3282",
"text": "BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.",
"title": "Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment."
},
{
"docid": "MED-855",
"text": "Hydrogen peroxide is an oxidising agent that is used in a number of household products, including general-purpose disinfectants, chlorine-free bleaches, fabric stain removers, contact lens disinfectants and hair dyes, and it is a component of some tooth whitening products. In industry, the principal use of hydrogen peroxide is as a bleaching agent in the manufacture of paper and pulp. Hydrogen peroxide has been employed medicinally for wound irrigation and for the sterilisation of ophthalmic and endoscopic instruments. Hydrogen peroxide causes toxicity via three main mechanisms: corrosive damage, oxygen gas formation and lipid peroxidation. Concentrated hydrogen peroxide is caustic and exposure may result in local tissue damage. Ingestion of concentrated (>35%) hydrogen peroxide can also result in the generation of substantial volumes of oxygen. Where the amount of oxygen evolved exceeds its maximum solubility in blood, venous or arterial gas embolism may occur. The mechanism of CNS damage is thought to be arterial gas embolisation with subsequent brain infarction. Rapid generation of oxygen in closed body cavities can also cause mechanical distension and there is potential for the rupture of the hollow viscus secondary to oxygen liberation. In addition, intravascular foaming following absorption can seriously impede right ventricular output and produce complete loss of cardiac output. Hydrogen peroxide can also exert a direct cytotoxic effect via lipid peroxidation. Ingestion of hydrogen peroxide may cause irritation of the gastrointestinal tract with nausea, vomiting, haematemesis and foaming at the mouth; the foam may obstruct the respiratory tract or result in pulmonary aspiration. Painful gastric distension and belching may be caused by the liberation of large volumes of oxygen in the stomach. Blistering of the mucosae and oropharyngeal burns are common following ingestion of concentrated solutions, and laryngospasm and haemorrhagic gastritis have been reported. Sinus tachycardia, lethargy, confusion, coma, convulsions, stridor, sub-epiglottic narrowing, apnoea, cyanosis and cardiorespiratory arrest may ensue within minutes of ingestion. Oxygen gas embolism may produce multiple cerebral infarctions. Although most inhalational exposures cause little more than coughing and transient dyspnoea, inhalation of highly concentrated solutions of hydrogen peroxide can cause severe irritation and inflammation of mucous membranes, with coughing and dyspnoea. Shock, coma and convulsions may ensue and pulmonary oedema may occur up to 24-72 hours post exposure. Severe toxicity has resulted from the use of hydrogen peroxide solutions to irrigate wounds within closed body cavities or under pressure as oxygen gas embolism has resulted. Inflammation, blistering and severe skin damage may follow dermal contact. Ocular exposure to 3% solutions may cause immediate stinging, irritation, lacrimation and blurred vision, but severe injury is unlikely. Exposure to more concentrated hydrogen peroxide solutions (>10%) may result in ulceration or perforation of the cornea. Gut decontamination is not indicated following ingestion, due to the rapid decomposition of hydrogen peroxide by catalase to oxygen and water. If gastric distension is painful, a gastric tube should be passed to release gas. Early aggressive airway management is critical in patients who have ingested concentrated hydrogen peroxide, as respiratory failure and arrest appear to be the proximate cause of death. Endoscopy should be considered if there is persistent vomiting, haematemesis, significant oral burns, severe abdominal pain, dysphagia or stridor. Corticosteroids in high dosage have been recommended if laryngeal and pulmonary oedema supervene, but their value is unproven. Endotracheal intubation, or rarely, tracheostomy may be required for life-threatening laryngeal oedema. Contaminated skin should be washed with copious amounts of water. Skin lesions should be treated as thermal burns; surgery may be required for deep burns. In the case of eye exposure, the affected eye(s) shod eye(s) should be irrigated immediately and thoroughly with water or 0.9% saline for at least 10-15 minutes. Instillation of a local anaesthetic may reduce discomfort and assist more thorough decontamination.",
"title": "Hydrogen peroxide poisoning."
},
{
"docid": "MED-717",
"text": "OBJECTIVE: Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. DESIGN: Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. SUBJECTS/SETTING: The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. INTERVENTION: Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. MAIN OUTCOME MEASURES: Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. STATISTICAL ANALYSES: Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. RESULTS: More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. CONCLUSIONS: Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with gastrointestinal dysfunction. Because breath hydrogen peaks occurred at 90 to 114 minutes and were highly correlated with 180-minute breath hydrogen AUC, the use of peak hydrogen measures may be considered to shorten the duration of the exam.",
"title": "Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults."
},
{
"docid": "MED-854",
"text": "INTRODUCTION: Ingestion of a small amount of concentrated hydrogen peroxide can cause cerebral air gas embolism (CAGE). Hyperbaric oxygen therapy (HBOT) is the standard of care in the treatment of CAGE. We report a case of CAGE after accidental ingestion of 33%hydrogen peroxide treated with HBOT resulting in reversal of both the clinical and radiologic abnormalities. CASE REPORT: A 48 year-old male took two sips of 33% hydrogen peroxide. A short time later, he developed hematemesis, left sided hemiplegia, confusion, and left homonymous hemianopsia. Initial laboratory studies, chest x-ray, and brain CT were normal. MRI demonstrated areas of restricted diffusion and T2 hyper intensities in multiple vascular territories consistent with ischemia due to CAGE. Eighteen hours after arrival, the patient underwent HBOT at 3 atmospheres absolute (ATA) for 30 minutes and 2.5 ATA for 60 minutes with clinical improvement. Follow-up MRI at six months demonstrated resolution of the hyper intensities. DISCUSSION: A search of MEDLINE from 1950 to present revealed only two cases of CAGE from ingestion of concentrated hydrogen peroxide treated with HBOT. Both cases, similar to ours, had complete resolution of symptoms. Of the seven reported cases of CAGE from hydrogen peroxide that did not undergo HBOT, only in one patient was there a report of symptom resolution. CONCLUSION: Ingestion of even a small amount of concentrated hydrogen peroxide can result in cerebral air gas embolism. Hyperbaric oxygen therapy may be of benefit in reversing the symptoms and preventing permanent neurological impairment.",
"title": "Cerebral air gas embolism from concentrated hydrogen peroxide ingestion."
},
{
"docid": "MED-853",
"text": "OBJECTIVE: To present a child who developed gastric ulcers and duodenal erosions after ingestion of hydrogen peroxide 3% and delineate the epidemiology, medical outcomes, and toxicity of exposures to this agent managed by a poison control center. METHODS: A retrospective chart review of exposures to hydrogen peroxide 3% reported to the Long Island Regional Poison Control Center from January 1992 to April 1995 was conducted. Data extracted included age, route of exposure, amount of agent, symptoms, therapy, and medical outcome. RESULTS: There were 670 exposures to hydrogen peroxide 3% of 81,126 total exposures reported during the 40 months. Most exposures were by oral route (77%), occurred in children < 17 years old (67%), and were asymptomatic (85.6%). All but one exposure resulted in a benign outcome. One child, who presented with bloody emesis, developed multiple gastric ulcers and duodenal erosions after ingestion of hydrogen peroxide 2-4 oz. CONCLUSIONS: Exposure to hydrogen peroxide 3% is usually benign, however, severe gastric injury may occur following small ingestions in children. Patients who report persistent vomiting or bloody emesis require medical evaluation and consideration of endoscopy to evaluate gastrointestinal injury.",
"title": "Hydrogen peroxide 3% exposures."
},
{
"docid": "MED-4499",
"text": "Fourier transform infrared (FT-IR) spectroscopy and Raman spectroscopy were used to study the cell injury and inactivation of Campylobacter jejuni from exposure to antioxidants from garlic. C. jejuni was treated with various concentrations of garlic concentrate and garlic-derived organosulfur compounds in growth media and saline at 4, 22, and 35°C. The antimicrobial activities of the diallyl sulfides increased with the number of sulfur atoms (diallyl sulfide < diallyl disulfide < diallyl trisulfide). FT-IR spectroscopy confirmed that organosulfur compounds are responsible for the substantial antimicrobial activity of garlic, much greater than those of garlic phenolic compounds, as indicated by changes in the spectral features of proteins, lipids, and polysaccharides in the bacterial cell membranes. Confocal Raman microscopy (532-nm-gold-particle substrate) and Raman mapping of a single bacterium confirmed the intracellular uptake of sulfur and phenolic components. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to verify cell damage. Principal-component analysis (PCA), discriminant function analysis (DFA), and soft independent modeling of class analogs (SIMCA) were performed, and results were cross validated to differentiate bacteria based upon the degree of cell injury. Partial least-squares regression (PLSR) was employed to quantify and predict actual numbers of healthy and injured bacterial cells remaining following treatment. PLSR-based loading plots were investigated to further verify the changes in the cell membrane of C. jejuni treated with organosulfur compounds. We demonstrated that bacterial injury and inactivation could be accurately investigated by complementary infrared and Raman spectroscopies using a chemical-based, “whole-organism fingerprint” with the aid of chemometrics and electron microscopy.",
"title": "Investigating Antibacterial Effects of Garlic (Allium sativum) Concentrate and Garlic-Derived Organosulfur Compounds on Campylobacter jejuni by Using Fourier Transform Infrared Spectroscopy, Raman Spectroscopy, and Electron Microscopy"
},
{
"docid": "MED-4055",
"text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.",
"title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells."
},
{
"docid": "MED-718",
"text": "OBJECTIVE: To determine the relation of gas passage and abdominal bloating to the production of gas in the colon. DESIGN: Randomized, double-blind, crossover study of gaseous symptoms during a 1-week period. SETTING: A Veterans Affairs medical center. PARTICIPANTS: 25 healthy medical center employees. INTERVENTION: Participants' diets were supplemented with either a placebo (10 g of lactulose, a nonabsorbable sugar), psyllium (a fermentable fiber), or methylcellulose (a nonfermentable fiber). MEASUREMENTS: All participants were polled for gaseous symptoms (including number of gas passages, impression of increased rectal gas, and abdominal bloating), and five were examined for breath hydrogen excretion. RESULTS: Participants passed gas 10 +/- 5.0 times per day (mean +/- SD) during the placebo period. A significant increase in gas passages (to 19 +/- 12 times per day) and a subjective impression of increased rectal gas were reported with lactulose but not with either of the two fiber preparations. Breath hydrogen excretion, an indicator of hydrogen production in the colon, did not increase after ingestion of either of the fibers. However, a statistically significant (P < 0.05) increase in feelings of abdominal bloating (which the participants perceived as excessive gas in the bowel) was reported with both fiber preparations and with lactulose. CONCLUSIONS: The physician should distinguish between excessive gas (which indicates excessive gas production) and feelings of bloating (which are usually unrelated to excessive gas production). Treatment of the former consists of limiting the supply of fermentable material to the colonic bacteria. Symptoms of bloating usually indicate the irritable bowel syndrome, and therapy should be directed accordingly.",
"title": "The relation of passage of gas an abdominal bloating to colonic gas production."
},
{
"docid": "MED-5198",
"text": "The incidence of colorectal cancer (CRC) is dramatically higher in African Americans (AAs) than in Native Africans (NAs) (60:100,000 vs. <1:100,000) and slightly higher than in Caucasian Americans (CAs). To explore whether the difference could be explained by interactions between diet and colonic bacterial flora, we compared randomly selected samples of healthy 50- to 65-y-old AAs (n = 17) with NAs (n = 18) and CAs (n = 17). Diet was measured by 3-d recall, and colonic metabolism by breath hydrogen and methane responses to oral lactulose. Fecal samples were cultured for 7-alpha dehydroxylating bacteria and Lactobacillus plantarum. Colonoscopic mucosal biopsies were taken to measure proliferation rates. In comparison with NAs, AAs consumed more (P < 0.01) protein (94 +/- 9.3 vs. 58 +/- 4.1 g/d) and fat (114 +/- 11.2 vs. 38 +/- 3.0 g/d), meat, saturated fat, and cholesterol. However, they also consumed more (P < 0.05) calcium, vitamin A, and vitamin C, and fiber intake was the same. Breath hydrogen was higher (P < 0.0001) and methane lower in AAs, and fecal colony counts of 7-alpha dehydroxylating bacteria were higher and of Lactobacilli were lower. Colonic crypt cell proliferation rates were dramatically higher in AAs (21.8 +/- 1.1% vs. 3.2 +/- 0.8% labeling, P < 0.0001). In conclusion, the higher CRC risk and mucosal proliferation rates in AAs than in NAs were associated with higher dietary intakes of animal products and higher colonic populations of potentially toxic hydrogen and secondary bile-salt-producing bacteria. This supports our hypothesis that CRC risk is determined by interactions between the external (dietary) and internal (bacterial) environments.",
"title": "Why do African Americans get more colon cancer than Native Africans?"
},
{
"docid": "MED-3598",
"text": "Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.",
"title": "A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD."
},
{
"docid": "MED-4253",
"text": "We investigated the glycemic index (GI) and the insulinemic index (II) of cake made from whole soy powder (SBC) and the suppressive effects of SBC on the postprandial blood glucose and insulin by other carbohydrate foods. Furthermore, breath hydrogen excretion was simultaneously investigated. Twenty subjects were given 114 g SBC, 144 g cooked paddy-rice, and 60 g SBC with 144 g cooked paddy-rice in random order using a within-subject, repeated-measures design. Blood and end-expiratory gas were collected at the indicated periods after ingestion. The GI and the II of SBC were 22+/-6 and 48+/-29, respectively. The elevation of blood glucose by cooked paddy-rice was significantly suppressed by the addition of 60 g SBC, although the insulin secretion did not decrease. Breath hydrogen excretion by the addition of SBC to 144 g cooked paddy-rice was not significantly increased in comparison with cooked paddy-rice alone. SBC was of low GI and low II, but the postprandial insulin secretion in response to cooked paddy-rice was not suppressed.",
"title": "Effects of cake made from whole soy powder on postprandial blood glucose and insulin levels in human subjects."
},
{
"docid": "MED-720",
"text": "Bloating, abdominal distention, and flatulence represent very frequent complaints in functional disorders but their pathophysiology and treatment are largely unknown. Patients frequently associate these symptoms with excessive intestinal gas and the reduction of gas production may represent an effective strategy. The aim was to evaluate the effect of alpha-galactosidase administration, in a randomized double-blind placebo-controlled protocol, on intestinal gas production and gas-related symptoms after a challenge test meal in healthy volunteers. Eight healthy volunteers ingested 300 or 1200 GalU of alpha-galactosidase or placebo during a test meal containing 420 g of cooked beans. Breath hydrogen excretion and occurrence of bloating, abdominal pain, discomfort, flatulence, and diarrhea were measured for 8 hr. The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence. A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score. Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.",
"title": "The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms."
},
{
"docid": "MED-4526",
"text": "The sap of Croton lechleri Muell.-Arg (Euphorbiaceae), called Dragon's blood, is used in folk medicine as a cicatrizant, anti-inflammatory and to treat cancer. In this research, the antioxidant activity of Croton lechleri sap was evaluated against the yeast Saccharomyces cerevisiae and against maize plantlets treated with the oxidative agents apomorphine and hydrogen peroxide. The mutagenic activity of the sap was also analyzed using the Salmonella/microsome assay (Salmonella typhimurium TA97a, TA98, TA100, TA102, TA1535) and in cells of the yeast Saccharomyces cerevisiae. The results showed that Croton lechleri sap possesses significant antioxidant activity against the oxidative damages induced by apomorphine in Saccharomyces cerevisiae under all the conditions studied. However, in the case of hydrogen peroxide, antioxidant activity of the sap was detected only in cells in the stationary phase of growth. The sap was also able to protect cells of the maize plantlets from the toxic effect of apomorphine. This sap showed mutagenic activity for strain TA1535 of Salmonella typhimurium in the presence of metabolic activation and a weak mutagenic activity for strain TA98. These strains detect base pair substitutions and frameshift mutations, respectively. Mutagenicity was also observed in a haploid Saccharomyces cerevisiae strain XV185-14c for the lys1-1, his1-7 locus-specific reversion and hom3-10 frameshift mutations.",
"title": "Mutagenic and antioxidant activities of Croton lechleri sap in biological systems."
},
{
"docid": "MED-918",
"text": "Consumption of a large amount of dietary fructose induces gastrointestinal intolerance, and glucose has been known as an enhancer of fructose absorption. Erythritol is a nonglycemic sugar alcohol, and it has been suggested that erythritol is absorbed paracellularly. It was hypothesized that paracellular absorption of erythritol could also enhance paracellular absorption of fructose in healthy adults. This is one of the proposed pathways for how additional glucose enhances the absorption of fructose. Thirty-seven nondiabetic, healthy adults participated in a randomized, double-masked, controlled crossover study. After an overnight fast, participants consumed beverages containing either 50 g fructose and 50 g glucose, 50 g fructose and 33.3 g erythritol (an equimolar concentration of fructose), or 50 g fructose alone. Breath hydrogen response was determined for 8 hours postprandially. Gastrointestinal intolerance symptoms and the number and consistency of bowel movements were recorded for 24 hours postprandially. The breath hydrogen area under the curve (AUC) of the fructose and erythritol beverage was 2 times the AUC of the fructose beverage and 8.75 times the AUC of the fructose and glucose beverage (P < .001, respectively). Compared with fructose and glucose beverage and fructose alone, frequency of watery stools increased (P < .05) and gastrointestinal tolerance worsened (P < .05) when participants consumed fructose and erythritol. These data suggest that coingestion of equimolar concentrations of fructose and erythritol increased carbohydrate malabsorption. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Combination of erythritol and fructose increases gastrointestinal symptoms in healthy adults."
},
{
"docid": "MED-4869",
"text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.",
"title": "Evaluation of certain food additives."
},
{
"docid": "MED-1158",
"text": "The efficiencies of acidic solutions (radish, citric acid, ascorbic acid, acetic acid and hydrogen peroxide), neutral solutions (sodium chloride) and alkaline solution (sodium carbonate) as well as tap water in the elimination of organochlorine and organophosphorus pesticides from naturally contaminated potatoes were examined. The results indicated that acidic solutions were more effective than neutral and alkaline solutions in the elimination of the organochlorine compounds under investigation, Radish solutions eliminated pesticides completely, except o,p'-DDE (73.1% loss), followed by citric and ascorbic acid solutions. On the other hand, organophosphorus pesticides (pirimphos methyl, malathion and profenofos) were eliminated more by acidic, neutral and alkaline solutions than by organochlorines. The percentage of removal ranged from 98.5 to 100% for pirimphos methyl, 87.9 to 100% for malathion and 100% for profenofos.",
"title": "Behaviour of some organophosphorus and organochlorine pesticides in potatoes during soaking in different solutions."
},
{
"docid": "MED-3217",
"text": "To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.",
"title": "Age and systemic acid-base equilibrium: analysis of published data."
},
{
"docid": "MED-3582",
"text": "Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or \"lente\" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.",
"title": "Slow release dietary carbohydrate improves second meal tolerance."
},
{
"docid": "MED-5037",
"text": "Phenolic ingredients of an aqueous carob extract are well characterized and consist of mainly gallic acid (GA). In order to assess possible chemopreventive mechanisms of carob, which can be used as a cacao substitute, effects on expression of genes related to stress response and drug metabolism were studied using human colon cell lines of different transformation state (LT97 and HT29). Stress-related genes, namely catalase (CAT) and superoxide dismutase (SOD2), were induced by carob extract and GA in LT97 adenoma, but not in HT29 carcinoma cells. Although corresponding protein products and enzyme activities were not elevated, pretreatment with carob extract and GA for 24 h reduced DNA damage in cells challenged with hydrogen peroxide (H(2)O(2)). In conclusion, carob extract and its major phenolic ingredient GA modulate gene expression and protect colon adenoma cells from genotoxic impact of H(2)O(2). Upregulation of stress-response genes could not be related to functional consequences.",
"title": "Does an extract of carob (Ceratonia siliqua L.) have chemopreventive potential related to oxidative stress and drug metabolism in human colon cells?"
},
{
"docid": "MED-4125",
"text": "Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.",
"title": "Human gut microbiota does not ferment erythritol."
},
{
"docid": "MED-4124",
"text": "OBJECTIVE: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.g., by the diet. Erythritol, a simple polyol, could be such a compound. It is orally available, well tolerated, and its chemical structure resembles that of mannitol, a well-known hydroxyl radical (HO*) scavenger. METHODS: We studied the antioxidant properties of erythritol in vitro and subsequently determined its antioxidant activity and its vasoprotective effect in the streptozotocin diabetic rat. RESULTS: Erythritol was shown to be an excellent HO* radical scavenger and an inhibitor of 2,2'-azobis-2-amidinopropane dihydrochloride-induced hemolysis but inert toward superoxide radicals. High-performance liquid chromatographic and electron spin resonance spectroscopy studies showed that the reaction of erythritol with hydroxyl radicals resulted in the formation of erythrose and erythrulose by abstraction of a carbon-bound hydrogen atom. In the streptozotocin diabetic rat, erythritol displayed an endothelium-protective effect and, in accordance with the in vitro experiments, erythrose was found in the urine of erythritol-consuming rats. CONCLUSION: Erythritol acts as an antioxidant in vivo and may help protect against hyperglycemia-induced vascular damage. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Erythritol is a sweet antioxidant."
},
{
"docid": "MED-5263",
"text": "High postprandial serum lipid concentrations are associated with increased oxidative stress which, in turn, increases the risk of atherosclerosis. Epidemiological studies correlate lower incidence of cardiovascular disease with adherence to the Mediterranean diet. The aim of this study was to evaluate changes in inflammatory (TXB(2) and LTB(4)) and oxidative stress markers (urinary hydrogen peroxide levels and serum antioxidant capacity), in addition to classic lipid parameters, after a fat-rich meal administered to 12 normolipemic, healthy subjects. Following a Latin square design, subjects were divided into three groups, each one receiving a different kind of oil (extra virgin olive oil; EVOO, olive oil; OO or corn oil; CO, together with 150g of potatoes), with 2-week washout periods between treatments. Blood samples were drawn at baseline and after 1, 2, and 6h after the meal. A significant decrease in inflammatory markers, namely TXB(2) and LTB(4), after 2 and 6h after EVOO (but not OO or CO) consumption and a concomitant increase of serum antioxidant capacity were recorded. These data reinforce the notion that the Mediterranean diet reduces the incidence of coronary heart disease partially due to the protective role of its phenolic components, including those of extra virgin olive oil.",
"title": "Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil."
},
{
"docid": "MED-5059",
"text": "This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives: branching glycosyltransferase from Rhodothermus obamensis expressed in Bacillus subtilis, cassia gum, cyclamic acid and its salts (dietary exposure assessment), cyclotetraglucose and cyclotetraglucose syrup, ferrous ammonium phosphate, glycerol ester of gum rosin, glycerol ester of tall oil rosin, lycopene from all sources, lycopene extract from tomato, mineral oil (low and medium viscosity) class II and class III, octenyl succinic acid modified gum arabic, sodium hydrogen sulfate and sucrose oligoesters type I and type II. Specifications for the following food additives were revised: diacetyltartaric acid and fatty acid esters of glycerol, ethyl lauroyl arginate, glycerol ester of wood rosin, nisin preparation, nitrous oxide, pectins, starch sodium octenyl succinate, tannic acid, titanium dioxide and triethyl citrate. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.",
"title": "Evaluation of certain food additives. Seventy-first report of the Joint FAO/WHO Expert Committee on Food Additives."
},
{
"docid": "MED-5064",
"text": "To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.",
"title": "Consumption of Brussels sprouts protects peripheral human lymphocytes against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative ..."
},
{
"docid": "MED-4222",
"text": "Life span extending mutations in growth signaling pathways protect against age-dependent DNA damage in yeast and decrease insulin resistance and cancer in mice. To test their effect in humans, we monitored for 22 years Ecuadorian subjects with mutations in the growth hormone receptor gene leading to severe growth hormone receptor (GHR) and IGF-I deficiencies and combined this information with surveys to identify the cause and age of death for subjects who died before this period. The individuals with GHR deficiency (GHRD) exhibited only one non-lethal malignancy and no cases of diabetes, in contrast to 17% cancer and 5% diabetes prevalence in the controls. A possible explanation for the very low incidence of cancer may be revealed by in vitro studies: serum from GHRD subjects reduced DNA breaks but increased apoptosis in human mammary epithelial cells (HMECs) treated with hydrogen peroxide. We also observed reduced insulin concentrations (1.4 μU/ml vs. 4.4μU/ml in unaffected relatives) and a very low homoeostasis model assessment of insulin resistance (HOMA-IR) index (0.34 vs. 0.96 in unaffected relatives) in GHRD individuals, indicating increased insulin sensitivity, which could explain the absence of diabetes in these subjects. Incubation of HMECs with GHRD serum also resulted in reduced expression of RAS, PKA and TOR, and up-regulation of SOD2, changes that promote cellular protection and life span extension in model organisms. These results provide evidence for a role of evolutionarily conserved pathways in promoting aging and diseases in humans and identify a candidate drug target for healthy life span extension.",
"title": "Growth Hormone Receptor Deficiency is Associated With a Major Reduction in Pro-aging Signaling, Cancer and Diabetes in Humans"
},
{
"docid": "MED-4299",
"text": "The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.",
"title": "Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention."
},
{
"docid": "MED-4524",
"text": "This review summarizes the multifaceted aspects of antioxidants and the basic kinetic models of inhibited autoxidation and analyzes the chemical principles of antioxidant capacity assays. Depending upon the reactions involved, these assays can roughly be classified into two types: assays based on hydrogen atom transfer (HAT) reactions and assays based on electron transfer (ET). The majority of HAT-based assays apply a competitive reaction scheme, in which antioxidant and substrate compete for thermally generated peroxyl radicals through the decomposition of azo compounds. These assays include inhibition of induced low-density lipoprotein autoxidation, oxygen radical absorbance capacity (ORAC), total radical trapping antioxidant parameter (TRAP), and crocin bleaching assays. ET-based assays measure the capacity of an antioxidant in the reduction of an oxidant, which changes color when reduced. The degree of color change is correlated with the sample's antioxidant concentrations. ET-based assays include the total phenols assay by Folin-Ciocalteu reagent (FCR), Trolox equivalence antioxidant capacity (TEAC), ferric ion reducing antioxidant power (FRAP), \"total antioxidant potential\" assay using a Cu(II) complex as an oxidant, and DPPH. In addition, other assays intended to measure a sample's scavenging capacity of biologically relevant oxidants such as singlet oxygen, superoxide anion, peroxynitrite, and hydroxyl radical are also summarized. On the basis of this analysis, it is suggested that the total phenols assay by FCR be used to quantify an antioxidant's reducing capacity and the ORAC assay to quantify peroxyl radical scavenging capacity. To comprehensively study different aspects of antioxidants, validated and specific assays are needed in addition to these two commonly accepted assays.",
"title": "The chemistry behind antioxidant capacity assays."
},
{
"docid": "MED-2021",
"text": "AIM: To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms. METHODS: We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years. RESULTS: One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died. CONCLUSION: In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.",
"title": "Celiac disease: Management of persistent symptoms in patients on a gluten-free diet"
}
] |
1224
|
Calculating the cost of waiting longer for money
|
[
{
"docid": "76049",
"text": "The cost of an extra 30 days is $1459.80",
"title": ""
},
{
"docid": "94630",
"text": "This looks correct to me, for simple interest. If you are dealing with compound interest, the formula would be: So, A = 500000(1+0.036/365)^(30), or 501,481.57, or an interest of 1481.57, assuming the 3.6% is the annual nominal interest rate and it is compounded daily. Note that you are ignoring the depreciation and also ignoring the percentage of customers who will forfeit their debt in the 30 - 60 day period.",
"title": ""
}
] |
[
{
"docid": "290647",
"text": "If you're looking for a purely financial answer (ignoring the social/environmental aspects) there are a few different ways you can look at it. For these types of improvements the simplest is a payback calculation. How long would it take you to recoup the initial costs? For example, if the entire installation cost $5,000 (including any tax credits), and you save $100 per month (I'm making both numbers up), you'll pay back your investment in 50 months, or about 4 years. (Note that if you borrow money to do the improvement, then your payback period is longer because you're reducing the amount that you're saving each month by paying interest.) If you're deciding between different uses for the money (like investing, or paying down other debt) then you can look at the return that you're getting. Using the same example, you are spending $5,000 and getting $100 per month back, for a 24% annual return ($1,200 / $5,000), which is better than you can get on almost anything but a 401(k) match (meaning don't stop your 401(k) contributions to do this either). The decision on whether or wait or not then becomes - will the price drop faster than the amount of savings you will realize. So if you will save $100 per month in your electric bill, is the price of the complete installation going down by more than $100 each month? If not, you'd be better off buying now and start paying back the investment sooner.",
"title": ""
},
{
"docid": "584479",
"text": "I'm a bit skeptical of some of the views the author states, in particular: > The likelihood of executing a trade at the best price depends on the length of the queue to buy or sell and the incentives to trade. Longer queues lead to longer delays to execute a trade. Delays typically lead to worse outcomes. Quite simply, it makes no sense to wait on a longer line to receive a worse execution. Why would this be the case? If anything, I'd think that forcing through too many orders at once risks price slippage created by excess supply or demand. He argues that waiting in queue may impair price performance, but I'd think that possible favourable or adverse shifts in the price will average to zero over time. If this is the case and they do average to zero, then I think funds are doing the savvy thing by putting relatively small, low-priority trades in to the flow at a rate that saves the most money on average. I can see why day traders may not be too thrilled with this, but that is such a small slice of the mutual fund/brokerage clientele. In the broader picture, funds and brokerages are being squeezed so tightly on expense ratios that I'd think any cost saving/rebates they do get probably filter back to customers in the form of reduced fees. Take Robinhood as an example: they use their trading rebates to provide an extremely low cost trading platform for retail investors. That hardly seems unfair to me. Any traders care to comment? This is all just speculation on my part and I've not looked at any time series data yet.",
"title": ""
},
{
"docid": "463992",
"text": "As far as the money goes, it all comes down to the terms. What is going to cost you the least? Look for hidden fees and costs with the store credit. You will need to read the fine print of the credit agreement some automatically sign you up for a service that will cost you extra money every month. Compare what the costs are going to be over the term you will pay it off. A good calculator to help you figure this out is http://www.amortization-calc.com/ It is designed with larger loans but works for smaller loans too. Realize that you will have to add fees and finance charges into the total loan amount to get a good comparison. ** Unless you NEED a computer you should wait until you can afford to pay for it. Charging these types of expenses tends to lead down to a pit of debt that is hard to get out of. Wanting a computer really bad is not the same as a need.",
"title": ""
},
{
"docid": "228079",
"text": "I know this can be confusing because you tend to think of money being worth the face value. So let's eliminate that for the sake of an example that will be easier to understand. Let's say your friend loaned you rock worth $10 today. He expects you to pay him back an identical rock whenever you can. Now let's also assume that historically the price of rocks tends to go down every year. At some point you will need to buy a rock to pay your friend back. Because they keep getting cheaper, it costs less to buy the payback rock the longer you wait. Replace a dollar with a rock in the example and you have your answer. This is known as the time value of money. In reality, this is priced into the loan (via the interest rate) because the lender very much understands the math going on here. Also, it is more complicated because the longer you delay payment the more interest you pay (pebbles if you will) so it doesn't usually work to your advantage unless they underpriced the loan's interest rate.",
"title": ""
},
{
"docid": "171642",
"text": "\"You asked for simple, and I promise you this is... it just looks a bit math-heavy to start with because we have to handle a couple of different scenarios. Bear with me :) I find the best way to deal with these kinds of questions is to put together a \"\"Total cost\"\" for each option, for a sensible amount of time, and see what the difference is. We'll include the current cost for both options, plus the subsequent costs for 12 months: I find that more useful than a straight \"\"which is more expensive right now\"\" because it includes the potential costs of the next upgrade, and any changes to the plan. Let's throw some numbers together for the next 12 months (if your current plan is longer than 12 months, read the note at the bottom first) First, write down the cost of these things **The above assume that you have two options if you take the repair option (and only one option if you use the buy-out option). The two options we're assuming here are that you can either: If you'd choose the same new plan regardless of whether you take the $100 or $150 option, there's no need to include both options: to simplify things you can just use the same numbers for both b/c and Pu/Py and the calculation below will still work. When you've found and written down the above, just do the sums below to find your two total costs over 12 months. Nothing fancy, just plug the numbers above into the equation. eg if Pe (eBay value of the phone) is $80, replace Pe with 80. Don't forget to do the parts in brackets first! That's your total cost for both options for the next year. Note: I'm assuming that your plan ends within the next 12 months. If not, just replace 12 in the above calculations with another term! You can also do this if you want to find out the price difference over a longer period (noting that if you upgrade to the same plan regardless of choice, you'll get the same answer for any period longer than your current contract)\"",
"title": ""
},
{
"docid": "311642",
"text": "Emergency funds, car funds etc tend to have to be accessible quickly (which tends to rule out CDs unless you have the patience to work something like a monthly CD ladder, an I don't) and you'll want your principal protected. The latter pretty much rules out any proper investment (ETFs, mutual funds, stock market directly, Elbonian dirt futures etc). It's basically a risk-vs-return calculation. Not much risk, not much return but at least you're not losing from a nominal standpoint). Another consideration is that you normally aren't able to decide freely if and when you want to pull money out of an emergency fund. If it is an emergency, waiting three weeks to see if the stock market goes up a little further isn't an option so you might end up having to take a hit that would be irrelevant if you were investing long term but might hurt badly because you're left with no choice. I'd stick that sort of money into a money market account and either add to it if necessary to keep up with inflation or make sure that my non-retirement investments over and above these funds are performing well, as those will and should become a far bigger part of your wealth in the longer run.",
"title": ""
},
{
"docid": "489479",
"text": "When evaluating a refinance, you need to figure out the payback time. Refinancing costs money in closing costs. The payback time is the time it takes to recover the closing costs with the amount of money you are saving in interest. For example, if the closing costs are $2,000, your payback time is 2 years if it takes 2 years to save that amount in interest with the new interest rate vs. the old one. To estimate this, look at the difference in interest rate between your mortgage and the new one, and your mortgage balance. For example, let's say that you have $100,000 left on your mortgage, and the new rate is 1% lower than your current rate. In one year, you will save roughly $1,000 in interest. If your closing costs are $2,000, then your payback time is somewhere around 2 years. If you plan on staying in this house longer than the payback time, then it is beneficial to refinance. There are mortgage refinance calculators online that will calculate payback time more precisely. One thing to watch out for: when you refinance, if you expand the term of your mortgage, you might end up paying more interest over the long term, even though your rate is less and your monthly payment is less. For example, let's say you currently have 8 years left on a 15-year mortgage. If you refinance to a new 15-year mortgage, your monthly payment will go down, but if you only pay the new minimum payment for the next 15 years, you could end up paying more in interest than if you had just continued with your old mortgage for the next 8 years. To avoid this, refinance to a new mortgage with a term close to what you have left on your current mortgage. If you can't do that, continue paying whatever your current monthly payment is after you refinance, and you'll pay your new mortgage early and save on interest.",
"title": ""
},
{
"docid": "60088",
"text": "When evaluating a refinance, it all comes down to the payback. Refinancing costs money in closing costs. There are different reasons for refinancing, and they all have different methods for calculating payback. One reason to finance is to get a lower interest rate. When determining the payback time, you calculate how long it would take to recover your closing costs with the amount you save in interest. For example, if the closing costs are $2,000, your payback time is 2 years if it takes 2 years to save that amount in interest with the new interest rate vs. the old one. The longer you hold the mortgage after you refinance, the more money you save in interest with the new rate. Generally, it doesn't pay to refinance to a lower rate right before you sell, because you aren't holding the mortgage long enough to see the interest savings. You seem to be 3 years away from selling, so you might be able to see some savings here in the next three years. A second reason people refinance is to lower their monthly payment if they are having trouble paying it. I see you are considering switching from a 15 year to a 30 year; is one of your goals to reduce your monthly payment? By refinancing to a 30 year, you'll be paying a lot of interest in your first few years of payments, extending the payback time of your lower interest rate. A third reason people refinance is to pull cash out of their equity. This applies to you as well. Since you are planning on using it to remodel the home you are trying to sell, you have to ask yourself if the renovations you are planning will payoff in the increased sale price of your home. Often, renovations don't increase the value of their home as much as they cost. You do renovations because you will enjoy living in the renovated home, and you get some of your money back when you sell. But sometimes you can increase the value of your home by enough to cover the cost of the renovation. Talk to a real estate agent in your area to get their advice on how much the renovations you are talking about will increase the value of your home.",
"title": ""
},
{
"docid": "435825",
"text": "Things are generally fine. A credit balance is not a horrible thing. The argument against maintaining a credit balance is that you are essentially loaning the credit card issuer money at 0% interest. You probably have alternative investments that would pay better interest, so it's usually better to park your money there. All that said, it's unlikely that the interest on whatever balance you have is enough to be more than pennies. The way that a credit card works, you run up a balance in one period. Then there is a grace period. If you don't pay off the balance during the grace period, they start charging you interest. You also may have a minimum payment to make. If you don't make that payment, they'll charge you a late fee. The typical period to rack up charges is from the first to the last day of a month. The typical grace period is through the 20th or 25th of the next month. Your card may be different. So check the documentation (user agreement) for your card if you want the real data. It sounds like you paid off some purchases while you were still in the period where you rack up charges. While those purchases were posted to the account, they may not be counted in the balance calculation. If your credit balance exactly matches the payment you made, that's probably what happened. It's also possible that you overpaid the balance. If your credit balance is just a small amount, that's probably what happened. If you really want to be sure, you should call the credit card issuer and ask them. At best we can tell you how it normally works. Since this is your first month, you could just wait for your first bill and respond to that. So long as you pay off the entire balance shown there by the deadline, everything should be fine. Don't wait until the last day to pay. It's usually best to pay a week or so early so as to leave time for the mail to deliver the check and for them to process it. You can wait longer for an online payment, but a few business days early to give you a chance to handle potential problems is still good.",
"title": ""
},
{
"docid": "75522",
"text": "\"Imagine two restaurants. One has prices 15% higher than the other, and the owner pays this 15% to his wait staff in the form of higher wages. The other has lower prices, but the average customer gifts 15% to their waiter. Clearly, in the first restaurant, the 15% the wait staff receives is taxable income. It is traditional salary. What legitimate, economic justification is their for treating the second restaurant any differently? Imagine a grocery store in a small town that offered long-time customers a \"\"pay nothing\"\" option but made it clear that they'd be subject to social ostracism and no longer welcome in the store if they didn't gift 85% of the usual cost of the items. The customers would save on sales tax and the grocer would argue that all that money was gifts, not income. Of course this doesn't work. The IRS, and the laws, don't care very much about what you call things. They care about the underlying economic reality. If the money was part of the payment for the services rendered, regardless of how it was delivered, what the parties called it, or whether the obligation to pay was legal or social, it's still a payment for the service and it's still taxable. You would have to be able to argue to the IRS that it really was a gift and wasn't any form of payment for the service received. Otherwise, it's just a scheme to evade taxes.\"",
"title": ""
},
{
"docid": "30250",
"text": "\"This is really two questions about yield and contents. Content As others have noted, an annuity is a contractual obligation, not a portfolio contained within an investment product per se. The primary difference between whether an annuity is fixed or variable is what the issuer is guaranteeing and how much risk/reward you are sharing in. Generally speaking, the holdings of an issuer are influenced by the average \"\"duration\"\" of the payments. However, you can ascertain the assets that \"\"back\"\" that promise by looking at, for example, the holdings of a large insurance or securities firm. That is why issuers are generally rated as to their financial strength and ability to meet their obligations. A number of the market failures you mentioned were in part caused by the failure of these ratings to represent the true financial strength of the firm. Yield As to the second question of how they can offer a competitive rate, there are at least several reasons (I am assuming an immediate annuity) : 1) Return/Depletion of Principal The 7% you are being quoted is the percent of your principal that will be returned to you each year, not the rate of return being earned by the issuer. If you invest $100 in the market personally and get a 5% return, you have $105. However, the annuity's issuer is also returning part of your principal to you each year in your payment, as they don't return your principal when you eventually die. Because of this, they can offer you more each year than they really make in the market. What makes a Ponzi scheme different is that they are also paying out your principal (usually to others), but lie to you by telling you it's still in your account. :) 2) The Time Value of Money A promise to pay you $500 tomorrow costs less than $500 today A fixed annuity promises to pay you a certain amount of money each year. This can be represented as a rate of return calculated based on how much you have to pay to get that annual payment, but it is important to remember that the first payment will be worth substantially more in real purchasing power than the last payment you get. The longer you live, the less your fixed payment is worth in real terms due to inflation! In short, the rate of return has to be discounted for inflation, it is not a \"\"real\"\" rate of return. In other words, if you give me $500 today and I promise to pay you $100 for the next 5 years, I am making money not only because I can invest the money between now and then, but also because $100 will be worth less five years from now than it is today. With annuities, if you want your payment to rise in step with inflation, you have to pay more for that (a LOT more!). These are the two main reasons - here are a few smaller ones: 3) A very long Time Horizon If the stock market or another asset class is performing well/poorly, the issuer can often afford to wait much longer to buy or sell than an individual, and can take better advantage of historical highs and lows over the long term. 4) \"\"Big Boy\"\" investing A large, financially sound issuer can afford to take risks that an individual cannot, such as in very large or illiquid assets, such as a private company (a la Warren Buffet). 5) Efficiencies of scale Institutional investors have a number of legal advantages over individuals, which I won't discuss in detail here. However, they exist. Large issuers are also often in related business (insurance, mutual funds) such that they can deal in large volumes and form an internal clearinghouse (i.e. if I want to buy Facebook and you want to sell it, they can just move the stock around without doing any trading), with the result that their costs of trading are lower than those of an individual. Hope that helps!\"",
"title": ""
},
{
"docid": "491567",
"text": "Ignore sunk costs and look to future returns. Although it feels like a loss to exit an investment from a loss position, from a financial standpoint you should ignore the purchase price. If your money could be better invested somewhere else, then move it there. You shouldn't look at it as though you'll be more financially secure because you waited longer for the stock to reach the purchase price. That's psychological, not financial. Some portion of your invested wealth is stuck in this particular stock. If it would take three months for the stock to get back to purchase price but only two months for an alternate investment to reach that same level, then obviously faster growth is better. Your goal is greater wealth, not arbitrarily returning certain investments to their purchase price. Investments are just instrumental. You want more wealth. If an investment is not performing, then ignore purchase price and sunken costs. Look at the reasonable expectations about an investment going forward.",
"title": ""
},
{
"docid": "523461",
"text": "My question is, how income tax is calculated for partial redemption. Same as normal. The redemption should always be treated as FIFO. Say you are buying 10 units every month [I know the units maybe in fraction and price would be different every month and you are investing fixed amount]. After say 9 months you have 90 units. Now when you sell say 45 units, you are actually selling 10 units from first 4 months and 5 units from 5th month. So calculate the price at which you purchased these units. This becomes your cost. Now when you sell, you know the price. So subtract the sell price from cost price. This is your taxable income. Short term capital gains is taxed as per your tax bracket. So add this taxable income to your other income and calculate taxes accordingly. You have to pay tax in advance and not wait till year end. You can do this online as well.",
"title": ""
},
{
"docid": "476068",
"text": "\"I doubt you will get an answer equal to \"\"You can't save when you have debt\"\". Because most mortgages are for decades, very few people would be able to save for retirement if they had to wait to be mortgage free. The difficulty in saving occurs when the interest rate is very high (18% or more) and the interest is not deductible. Such as with credit cards. The minimum payment for your mortgage is 30% of your income. If that doesn't include taxes and homeowners insurance in the 30%, then for the United States that would be considered too large. While the general plan to pay down the mortgage is a good idea, make sure that you are able to handle the minimum payments before starting to increase the payments. Try the minimum for a year or two before getting aggressive The calculation is based on the interest rate of the mortgage, the interest rate of the savings account, and the potential tax deduction of the mortgage and the tax rate on the earned interest. Putting extra money into a mortgage, but missing out on matching retirement money would also have to be figured into the calculation. Make sure you do save for retirement , kids education, and emergencies. Unless your country has a complex system where the money can flow in and out of the mortgage, then once you put extra money into the mortgage you can't get it back when the car dies. The nice thing about putting extra money into a mortgage is that you can do it either in an organized way, or only when you feel comfortable. So it is not urgent for you to commit to a plan immediately. One thing to avoid is a plan that charges you a fee to add extra money, or charges a fee to switch to a bi-weekly mortgage. While your ideas is good, these plans should never cost any money to start, and may be a scam if a 3rd party gets between you and the lender.\"",
"title": ""
},
{
"docid": "503981",
"text": "\"Before the prevalence of electronic trading, trading stocks was very costly, dropping from ~15c in the late 1970s to less than a nickel per share today. Exchange fees for liquidity takers are ~0.3c per share, currently. When orders were negotiated exclusively by humans, stocks used to be quoted in fractions rather than decimal, such as $50 1/2 instead of something more precise like $50.02. That necessary ease of negotiation for humans to rapidly trade extended to trade size as well. Traders preferred to handle orders in \"\"round lots\"\", 100 shares, for ease of calculation of the total cost of the trade, so 100 shares at $50 1/2 would have a total cost of $5,050. The time for a human to calculate an \"\"odd lot\"\" of 72 shares at $50.02 would take much longer so would cost more per share, and these costs were passed on to the client. These issues have been negated by electronic trading and simply no longer exist except for obsolete brokerages. There are cost advantages for extremely large trades, well above 100 shares per trade. Brokerage fees today run the gamut: they can be as insignificant as what Interactive Brokers charges to as high as a full service broker that could charge hundreds of USD for a few thousand USD trade. With full service brokerages, the charges are frequently mystifying and quoted at the time a trade is requested. With discount brokerages, there is usually a fee per trade and a fee per share or contract. Interactive Brokers will charge a fee per share or option only and will even refund parts of the liquidity rebates exchanges provide, as close as possible to having a seat on an exchange. Even if a trader does not meet Interactive Brokers' minimum trading requirement, the monthly fee is so low that it is possible that a buy and hold investor could benefit from the de minimis trade fees. It should be noted that liquidity providing hidden orders are typically not rebated but are at least discounted. The core costs of all trades are the exchange fees which are per share or contract. Over the long run, costs charged by brokers will be in excess of charges by exchanges, and Interactive Brokers' fee schedule shows that it can be reduced to a simple markup over exchange fees. Exchanges sometimes have a fee schedule with lower charges for larger trades, but these are out of reach of the average individual.\"",
"title": ""
},
{
"docid": "329920",
"text": "Unfortunately, the thieves don't have to be all that sophisticated to make the money unrecoverable. What they typically do is open a phony bank account in the name of the victim. They receive the refund into the fraudulent account, and they immediately withdraw it. By the time anyone notices that the refund was fraudulent, the thief is long gone, and there is no money in the account to reclaim. It's not just the IRS who gets ripped off this way, by the way. Thieves use a similar technique to cash stolen credit cards. The thief will open a phony merchant account and a phony bank account in the victim's name. They will run the stolen cards on the merchant account and deposit the proceeds in the phony account. They are able to withdraw the funds before the fraudulent charges are noticed and reversed, and the processing company that the merchant account was opened with ends up eating the loss (or passing it along to their legitimate customers in the form of higher rates). Preventing this kind of fraud has costs. There are monetary costs associated with putting antifraud measures in place, and there are costs to the customers in the form of having to wait longer for their financial transactions to go through. Basically, everyone involved (the banks, the IRS, etc.) has to balance the losses against with the costs of preventing them. When fraud is rare, it's cheaper for them to eat the loss than to prevent it. If fraud starts to become more common you will see the institutions involved put into place additional checks to prevent improper transfers. Tax return fraud has become common enough that the IRS has instituted prevention measures such as requiring information from previous year tax returns in order to receive your refund. If that doesn't curb the problem, then they will probably add more measures, and perhaps they will slow down the payment process. However, they probably won't ever get the fraud losses down to zero because that would mean both angering taxpayers by delaying refunds and spending more money on fraud prevention than they save in avoided losses.",
"title": ""
},
{
"docid": "41023",
"text": "\"So this has been bugging me for a while, because I am facing a similar dilemma and I don't think anyone gave a clear answer. I bought a 2012 kia soul in 2012. 36 months financing at 300/mo. Will be done with my car loan in 2015. I plan on keeping it, while saving the same amount of money 300/mo until I buy my next car. But, I also have an option of trading it in for the the next car. Question: should I trade it in in 2015. should I keep it for 2 years more? 3 years more, before I buy the next car? What makes most financial sense and savings. I tried to dig up some data on edmunds - the trade-in value and \"\"true cost to own\"\" calculator. The make and model of my car started in 2010, so I do not have historical data, as well as \"\"cost to own\"\" calculator only spans 5 years. So - this is what I came up with: Where numbers in blue are totally made up/because I don't have the data for it. Granted, the trade-in values for the \"\"future\"\" years are guesstimated - based on Kia Soul's trade-in values from previous years (2010, 2011, 2012) But, this is handy, and as it gets closer to 2015 and beyond, I can re-plug in the data where it is available and have a better understanding of the trade-in vs keep it longer decision. Hope this helps. If the analysis is totally off the rocker, please let me know - i'll adjust it/delete it. Thank you\"",
"title": ""
},
{
"docid": "544020",
"text": "When the inflation rate increases, this tends to push up interest rates because of supply and demand: If the interest rate is less than the inflation rate, then putting your money in the bank means that you are losing value every day that it is there. So there's an incentive to withdraw your money and spend it now. If, say, I'm planning to buy a car, and my savings are declining in real value, then if I buy a car today I can get a better car than if I wait until tomorrow. When interest rates are high compared to inflation, the reverse is true. My savings are increasing in value, so the longer I leave my money in the bank the more it's worth. If I wait until tomorrow to buy a car I can get a better car than I would be able to buy today. Also, people find alternative places to keep their savings. If a savings account will result in me losing value every day my money is there, then maybe I'll put the money in the stock market or buy gold or whatever. So for the banks to continue to get enough money to make loans, they have to increase the interest rates they pay to lure customers back to the bank. There is no reason per se for rising interest rates to consumers to directly cause an increase in the inflation rate. Inflation is caused by the money supply growing faster than the amount of goods and services produced. Interest rates are a cost. If interest rates go up, people will borrow less money and spend it on other things, but that has no direct effect on the total money supply. Except ... you may note I put a bunch of qualifiers in that paragraph. In the United States, the Federal Reserve loans money to banks. It creates this money out of thin air. So when the interest that the Federal Reserve charges to the banks is low, the banks will borrow more from the Feds. As this money is created on the spot, this adds to the money supply, and thus contributes to inflation. So if interest rates to consumers are low, this encourages people to borrow more money from the banks, which encourages the banks to borrow more from the Feds, which increases the money supply, which increases inflation. I don't know much about how it works in other countries, but I think it's similar in most nations.",
"title": ""
},
{
"docid": "382381",
"text": "\"You are thinking about it this way: \"\"The longer I wait to exericse, the more knowledge and information I'll have, thus the more confidence I can have that I'll be able to sell at a profit, minimizing risk. If I exercise early and still have to wait, there may never be a chance I can sell at a profit, and I'll have lost the money I paid to exercise and any tax I had to pay when I exercised.\"\" All of that is true. But if you exercise early: The fair market value of the stock will probably be lower, so you may pay less income tax when you exercise. (This depends on your tax situation. Currently, ISO exercises affect your AMT.) If the company goes through a phase where the value is unusually high, you'll be able to sell and still get the tax benefits because you exercised earlier. You avoid the nightmare scenario where you leave the company (voluntarily or not) and can't afford to exercise your options because of the tax implications. In many realistic cases, exercising earlier means less risk. Imagine if you're working at a company that is privately held and you expect to be there for another year or so. You are very optimistic about the company, but not sure when it will IPO or get acquired and that may be several years off. The fair market value of the stock is low now, but may be much higher in a year. In this case, it makes a lot of sense to exercise now. The cost is low because the fair market value is low so it won't result in a huge tax bill. And then when you leave in a year, you won't have to choose between forfeiting your options or borrowing money to pay the much higher taxes due to exercise them then.\"",
"title": ""
},
{
"docid": "423625",
"text": "\"I would suggest you pay quarterly. Or, if you prefer, do the extra withholding. Don't wait until the end of the year. My experience is that of having a day job with freelance work on the side. I've spent a few years just freelancing, and I paid quarterly as requested to avoid the penalties. Now that I have a good day job again, my freelancing is just a small part of my income, and so I end up with a net return and no longer have to pay quarterly. You shouldn't wait until the end of the year to pay. This is assuming your wife is bringing in a decent income. The only scenario where you would want to wait is if her income is only a small amount (such as my wife's plans for an Etsy store). To the IRS, it doesn't really make a difference whether you withhold extra or pay quarterly. Of those two choices, my preference is to pay quarterly - it's easy to set up calendar reminders on the quarterly payment dates, which are always the same. I did the same as bstpierre when estimating my payments: just take last year's tax (for the business) and divide by 4 (adjusting for any obvious situational differences). That's usually close enough. Paying quarterly instead of via withholding means you get to hold on to your money (on average) for 6 weeks longer. Granted, that doesn't mean much with today's interest rates, but it's something. You may prefer the simpler accounting for withholding, though - you can \"\"set and forget\"\".\"",
"title": ""
},
{
"docid": "104328",
"text": "That makes sense doesn't it? Longer wait times? Won't that be the result of covering everyone? So yes, wait times are a concern. Is that your number 1 concern? More than money or how effective the system is? You will pay almost double to wait a month less for treatment(life threatening cases still get treated as fast as they do in the US if not faster), or to see a doctor two hours sooner? You will pay more for a system that gives you less? The quality of care is not dog shit. I don't know where you get this from. https://www.forbes.com/sites/danmunro/2014/06/16/u-s-healthcare-ranked-dead-last-compared-to-10-other-countries/#45cf82b6576f You will find this pattern in all other legitimate studies you look at. Your dog shit claim applies to the US more than anyone. Its amazing how willing Americans are to swallow the lie that changing their healthcare system will make it worse. That the free market is the answer. Reality does not reflect that and seeing as this is the economics subreddit, I think it should be very easy for people to come up with reasons why healthcare does not behave like selling widgets. Now, not all those systems are fully socialized. There are free market elements, for example, Germany and Switzerland are similar to Obamacare, however there is more robust regulations in those systems that help to keep costs down and quality up. The UK does have Universal Healthcare(all of them have a universal system actually, but the UK has single payer which is what I think you meant), and it goes pretty well. Even the Canadian system for all its flaws has better survival rates compared to American treatments, and at a much lower cost. Ask any Canadian if they would prefer the American system, or even if they would prefer to go back to pre-universal coverage days and any sane one would not....and Canada has the next worse system. Its marginally better than the American system, but at a much lower cost. What you think is ideal isn't based on any real research I suspect. Its based on ideology. This is a real American problem(I think its safe to assume you are American by your claim that ~~universal coverage~~ single payer is dog shit) If you decide what priorities are most important, and then look at the systems that exist in the world and see which ones best meet your criteria for success, it won't be a pure free market system. Every developed nation had a pure free market system at some point and each one had to switch to a better system. Nobody has switched back. The most free market system in the developed world is not only the worst performing, but also the most expensive.......as economic theory can predict due to the unique nature of healthcare.",
"title": ""
},
{
"docid": "375997",
"text": "The first thing that strikes me is: Is this a time-limited offer? Because if you can expect the offer to still be valid in a few weeks, why not just wait that month (which will earn you the money) and buy the car then? The second thing you need to consider is obviously the risk that in the interim, there will be an actual emergency which would require the money that you no longer have. The third thing to consider is whether you need the car now. Do you require a car to get around and your current one is breaking down, perhaps even to the point that repairing it would cost you more than buying a new car and it is currently not safe to drive? If so, compare the cost of repairing to the cost of buying; if the difference is small, and the new car would be more likely to be reliable than the old car after spending the money, then it can make sense to buy a new car and perhaps sell the old one in its current condition to someone who likes to tinker. (Even if you only recover a few hundreds of dollars, that's still money that perhaps you wouldn't otherwise have.) The fourth thing I would consider, especially given the time frame involved, is: Can you get a loan to buy the new car? Even if the interest rate is high, one month's worth of interest expense won't set you back very far, and it will keep the money in your emergency fund for if there is an actual emergency in the weeks ahead. Doing so might be a better choice than to take the money out of the emergency fund, if you have the opportunity; save the emergency fund for when that opportunity does not exist. And of course, without knowing how much you earn, take care to not end up with a car that is no more reliable than what you have now. Without knowing how much you earn and what the car you have in mind would cost, it's hard to say anything for certain, but if the car you have in mind costs less than a month's worth of net pay for you, consider whether it's likely to be reliable. Maybe you are making an absolutely stellar pay and the car will be perfectly fine; but there's that risk. Running the car by a mechanic to have it briefly checked out before buying it may be a wise move, just to make sure that you don't end up with a large car repair expense in a few months when the transmission gives up, for example.",
"title": ""
},
{
"docid": "216494",
"text": "Exactly. A fundamental principle of economics is that purchases are only so valuable, and when the price increases beyond that value, they are no longer needed. If someone has calculated that these people will costs millions, while only returning thousands, there is clearly no point in hiring them. It is exactly like considering private jet in the millions, when thousands of dollars of commercial airfare would do. There is no real reason to own the jet either. It is still fun to dream about owning a private jet. You might remark about buying one if they were cheaper. But, realistically, it is not needed given the costs. It is also fun to dream about growing your business, and tell others that you would grow your business with cheaper people, but it's not needed given the costs.",
"title": ""
},
{
"docid": "516444",
"text": "\"I'd like to suggest a plan. First, I know you want to buy a house. I get that, and that is an awesome goal to work for. You need to really sit down and decide why you want a house. People often tell we that they want a house because they are throwing their money away renting. This is just not true. There is a cost of renting, that is true, but there is also a cost of owning. There are many things with a house that you will have to pay for that will add little or no equity/value. Now that equity is nice to have, but make no mistake under no circumstance does every dime you put into your house increase its value. This is a huge misconception. There is interest, fees, repairs, taxes, and a bunch of other stuff that you will spend money on that will not increase the value of your home. You will do no harm, waiting a bit, renting, and getting to a better place before you buy a house. With that out of the way, time for the plan. Note: I'm not saying wait to buy a house; I am saying think of these as steps in the large house buying plan. Get your current debt under control. Your credit score doesn't suck, but it's not good either. It's middle of the road. Your going to want that higher if you can, but more importantly than that, you want to get into a pattern of making debt then honoring it. The single best advise I can give you is what my wife and I did. Get a credit card (you have one; don't get more) and then get into a habit of not spending more on that credit card than you actually have in the bank. If you have $50 in the bank, only spend that on your credit card. Then pay it in full, 100%, every payday (twice a month). This will improve your score quite a bit, and will, in time, get you in the habit of buying only what you can afford. Unless there has been an emergency, you should not be spending more on credit than you actually have. Your car loan needs to get under control. I'm not going to tell you to pay it off completely, but see point 2. Your car debt should not be more than you have in the bank. This, again is a credit building step. If you have 7.5k in the bank and own 7.5k on your car, your ability to get a loan will improve greatly. Start envelope budgeting. There are many systems out there, but I like YNAB a lot. It can totally turn your situation around in just a few months. It will also allow you to see your \"\"house fund\"\" growing. Breaking Point So far this sounds like a long wait, but it's not. It also sounds like I am saying to wait to actually buy a house, and I'm not. I am not saying get your debt to 0, nor do I think you should wait that long. The idea is that you get your debt under control and build a nice solid set of habits to keep it under control. A look at your finances at this point Now, at this point you still have debt, but your credit cards are at 0 and have been, every payday for a few months. Your car loan still exists, but you have money in the bank to cover this debt, and you could pay it off. It would eat your nest egg, but you could. You also have 15k set aside, just for the house. As you take longer looking for that perfect house, that number keeps growing. Your bank account now has over $25,000 in it. That's a good feeling on its own, and if you stick with your plan, buy your house and put down $15k, you still have plenty of wiggle room between credit cards that are not maxed out, and a $7.5k \"\"padding\"\" in case the roof falls in. Again it sounds like I'm saying wait. But I'm not, I'm saying plan better. All of these goals are very doable inside one year, a rough year to be sure, but doable. If you want to do it comfortably, then take two years. In that time you're looking, searching and learning.\"",
"title": ""
},
{
"docid": "348510",
"text": "Have you tried complaining to the Real Estate Institute in your state, and if that doesn't work try taking them to Fair Trading. I know from doing some work for real estates that getting money from them is like getting blood from a stone, but you just need to keep bugging them, talk to the manager or director, and tell them you have been waiting too long for your money, give them a deadline (not more than 3 business days) and tell them if you have not received the money by then you will make a complaint to the Real Estate Institute and take them to Fair Trading. Sometimes you have to go to the person who owns/ runs the business as the workers usually don't care, especially when it is extra work for them and they get no reward for doing it (plus the longer the Real Estate don't pay you the longer they earn interest on your money).",
"title": ""
},
{
"docid": "399751",
"text": "\"Gold is not an investment. Gold is a form of money. It and silver have been used as money much longer than paper. Paper money is a relatively recent invention (less than 350 years old) with a horrible track record of preserving wealth. When I exchange my paper US dollars for gold I'm exchanging one form of money for another. US dollars, or US Federal Reserve Notes to be more precise, can be printed ad nauseam by one bank that is totally private and is never audited. Keeping all of your savings in US dollars is ignoring history, it is believing the US Federal Reserve has your best interest in mind, it is hoping that somehow things will be different this time, it is believing that the US dollar will somehow magically be the first fiat currency to last a person's lifetime. TIPS may seem like a good hedge against inflation. However, the government offering TIPS is also the same government that is calculating the inflation rate used to adjust TIPS. What a great deal. If you do some research you discover that the method for calculating the consumer price index is always \"\"modified\"\" since it is always found to over estimate inflation. It is never found to under estimate inflation. Imagine that. Here is a chart showing the inflation rate as if it were calculated the same way as it was calculated in 1980. Buying any government debt is also a way to guarantee you or your children will be taxed in the future since the government will have to obtain the money from someone to pay back bonds. It's like voting for future taxes.\"",
"title": ""
},
{
"docid": "529032",
"text": "Adding to webdevduck's answer: Before you calculate your profits, you can pay money tax-free into a pension fund for the company director (that is you). Then if you pay yourself dividends, if you made lots of profit you don't have to pay it all as dividends. You can take some where the taxes are low, and then pay more money in later years. What you must NOT do is just take the money. The company may be yours, but the money isn't. It has to be paid as salary or dividend. (You can give the company director a loan, but that loan has to be repaid. Especially if a limited company goes bankrupt, the creditors would insist that loans from the company are repaid). After a bit more checking, here's the optimal approach, perfectly legal, expected and ethical: You pay yourself a salary of £676 per month. That's the point where you get all the advantages of national insurance without having to pay; above that you would have to pay 13.8% employers NI contributions and 12% employee's NI contributions, so for £100 salary the company has to pay £113.80 and you receive £88.00. Below £676 you pay nothing. You deduct the salary from your revenue, then you deduct all the deductible business costs (be wise in what you try to deduct), then you pay whatever you want into a pension fund. Well, up to I think £25,000 per year. The rest is profit. The company pays 19% corporation tax on profits. Then you pay yourself dividends. Any dividends until your income is £11,500 per year are tax free. Then the next £5,000 per year are tax free. Then any dividends until income + dividends = £45,000 per year is taxed at 7.5%. It's illegal to pay so much in dividends that the company can't pay its bills. Above £45,000 you decide if you want your money now and pay more tax, or wait and get it tax free. Every pound of dividend above £45,000 a year you pay 32.5% tax, but there is nobody forcing you to take the money. You can wait until business is bad, or you want a loooong holiday, or you retire. So at that time you will stay below £45,000 per year and pay only 7.5% tax.",
"title": ""
},
{
"docid": "590453",
"text": "If you're into math, do this thought experiment: Consider the outcome X of a random walk process (a stock doesn't behave this way, but for understanding the question you asked, this is useful): On the first day, X=some integer X1. On each subsequent day, X goes up or down by 1 with probability 1/2. Let's think of buying a call option on X. A European option with a strike price of S that expires on day N, if held until that day and then exercised if profitable, would yield a value Y = min(X[N]-S, 0). This has an expected value E[Y] that you could actually calculate. (should be related to the binomial distribution, but my probability & statistics hat isn't working too well today) The market value V[k] of that option on day #k, where 1 < k < N, should be V[k] = E[Y]|X[k], which you can also actually calculate. On day #N, V[N] = Y. (the value is known) An American option, if held until day #k and then exercised if profitable, would yield a value Y[k] = min(X[k]-S, 0). For the moment, forget about selling the option on the market. (so, the choices are either exercise it on some day #k, or letting it expire) Let's say it's day k=N-1. If X[N-1] >= S+1 (in the money), then you have two choices: exercise today, or exercise tomorrow if profitable. The expected value is the same. (Both are equal to X[N-1]-S). So you might as well exercise it and make use of your money elsewhere. If X[N-1] <= S-1 (out of the money), the expected value is 0, whether you exercise today, when you know it's worthless, or if you wait until tomorrow, when the best case is if X[N-1]=S-1 and X[N] goes up to S, so the option is still worthless. But if X[N-1] = S (at the money), here's where it gets interesting. If you exercise today, it's worth 0. If wait until tomorrow, there's a 1/2 chance it's worth 0 (X[N]=S-1), and a 1/2 chance it's worth 1 (X[N]=S+1). Aha! So the expected value is 1/2. Therefore you should wait until tomorrow. Now let's say it's day k=N-2. Similar situation, but more choices: If X[N-2] >= S+2, you can either sell it today, in which case you know the value = X[N-2]-S, or you can wait until tomorrow, when the expected value is also X[N-2]-S. Again, you might as well exercise it now. If X[N-2] <= S-2, you know the option is worthless. If X[N-2] = S-1, it's worth 0 today, whereas if you wait until tomorrow, it's either worth an expected value of 1/2 if it goes up (X[N-1]=S), or 0 if it goes down, for a net expected value of 1/4, so you should wait. If X[N-2] = S, it's worth 0 today, whereas tomorrow it's either worth an expected value of 1 if it goes up, or 0 if it goes down -> net expected value of 1/2, so you should wait. If X[N-2] = S+1, it's worth 1 today, whereas tomorrow it's either worth an expected value of 2 if it goes up, or 1/2 if it goes down (X[N-1]=S) -> net expected value of 1.25, so you should wait. If it's day k=N-3, and X[N-3] >= S+3 then E[Y] = X[N-3]-S and you should exercise it now; or if X[N-3] <= S-3 then E[Y]=0. But if X[N-3] = S+2 then there's an expected value E[Y] of (3+1.25)/2 = 2.125 if you wait until tomorrow, vs. exercising it now with a value of 2; if X[N-3] = S+1 then E[Y] = (2+0.5)/2 = 1.25, vs. exercise value of 1; if X[N-3] = S then E[Y] = (1+0.5)/2 = 0.75 vs. exercise value of 0; if X[N-3] = S-1 then E[Y] = (0.5 + 0)/2 = 0.25, vs. exercise value of 0; if X[N-3] = S-2 then E[Y] = (0.25 + 0)/2 = 0.125, vs. exercise value of 0. (In all 5 cases, wait until tomorrow.) You can keep this up; the recursion formula is E[Y]|X[k]=S+d = {(E[Y]|X[k+1]=S+d+1)/2 + (E[Y]|X[k+1]=S+d-1) for N-k > d > -(N-k), when you should wait and see} or {0 for d <= -(N-k), when it doesn't matter and the option is worthless} or {d for d >= N-k, when you should exercise the option now}. The market value of the option on day #k should be the same as the expected value to someone who can either exercise it or wait. It should be possible to show that the expected value of an American option on X is greater than the expected value of a European option on X. The intuitive reason is that if the option is in the money by a large enough amount that it is not possible to be out of the money, the option should be exercised early (or sold), something a European option doesn't allow, whereas if it is nearly at the money, the option should be held, whereas if it is out of the money by a large enough amount that it is not possible to be in the money, the option is definitely worthless. As far as real securities go, they're not random walks (or at least, the probabilities are time-varying and more complex), but there should be analogous situations. And if there's ever a high probability a stock will go down, it's time to exercise/sell an in-the-money American option, whereas you can't do that with a European option. edit: ...what do you know: the computation I gave above for the random walk isn't too different conceptually from the Binomial options pricing model.",
"title": ""
},
{
"docid": "235014",
"text": "\"There are two parts to the hack you describe. One is moving to a high-cost, high-pay country to work, and the other is moving to a low-cost, low-pay country to retire. As Dilip mentioned in a comment, the first part is not so easy in many cases. You can't just take a plane to the USA and start making big bucks immediately. In the first place, it's illegal to work without special visa permissions. Even if you manage to secure that permission (or take the risk of trying to work illegally), there's no guarantee you'll get a job, let alone a high-paying one. The same is true in most other high-paying countries. As for the second part, that takes considerable willpower as well. After spending X years getting used to a country, investing time and money, you must then have the resolve to uproot your life a second time and move to another country. For the most part, countries are expensive for a reason. Even if you in principle reject the cost-benefit tradeoffs of a particular country, it can be difficult to give up some of those benefits when the time comes (e.g., trains running on time, reliable electricity, donut shops, or whatever). You might \"\"get soft\"\" or become co-opted by the rich-country rat race and find it difficult to extricate yourself. All of these problems are compounded if, as in many cases, you happened to start a family while in the expensive country. At the least, moving would require uprooting not just you but your family. Also, quality of education is often one of the main reasons people immigrate permanently to expensive countries. Even a person who personally would prefer to retire to a cheaper country may be unwilling to transplant their children into that country's education system. (Of course, they could wait until the children are self-supporting, but that makes the wait longer, and may result in them living far away from their children, which they may not want.) As JoeTaxpayer notes, the same reasons may work on smaller levels, even within a country. In theory it's perfectly possible to power through a brief, lucrative career in Silicon Valley and then retire to Idaho, but it doesn't seem to happen as often as the plain numbers might suggest. A simple way to put it might be that the kind of person who would be happy living in a cheap environment often cannot or will not endure a lengthy \"\"tour of duty\"\" in an expensive environment. Either you like the expensive environment and stay, or you leave, not as a planned lifehack, but because you realize you don't like it.\"",
"title": ""
},
{
"docid": "224251",
"text": "\"The dirty secret of finance is that a lot of front office work is also boring. Get used to it. The moments when money pours magically from the phone and gushes unstoppably from your Bloomberg are brief and fleeting, and are punctuated by long months when you do little but scrub data, build models and systems, foster client relationships with people you don't especially like, and spend god-knows-how-long in mind-numbing internal meetings. You want to stab yourself now? Just wait. \"\"My department generates nothing because it's all compliance.\"\" <- Don't be this guy, it's not a commendable or mature attitude. Compliance and back office are not sexy areas, but without them guess what? Your trades won't settle and you'll end up in prison. They frequently work longer hours than front office, always get paid less than front office, and they've been told by better guys than you that they are nothing but a cost base. They also have long memories and a vindictive sense of retribution, especially for condescending front office twats who look down on them...\"",
"title": ""
}
] |
79
|
Active caspase-11 protein promotes pyroptosis.
|
[
{
"docid": "5099266",
"text": "Inflammasomes are multiprotein complexes that include members of the NLR (nucleotide-binding domain leucine-rich repeat containing) family and caspase-1. Once bacterial molecules are sensed within the macrophage, the inflammasome is assembled, mediating the activation of caspase-1. Caspase-11 mediates caspase-1 activation in response to lipopolysaccharide and bacterial toxins, and yet its role during bacterial infection is unknown. Here, we demonstrated that caspase-11 was dispensable for caspase-1 activation in response to Legionella, Salmonella, Francisella, and Listeria. We also determined that active mouse caspase-11 was required for restriction of L. pneumophila infection. Similarly, human caspase-4 and caspase-5, homologs of mouse caspase-11, cooperated to restrict L. pneumophila infection in human macrophages. Caspase-11 promoted the fusion of the L. pneumophila vacuole with lysosomes by modulating actin polymerization through cofilin. However, caspase-11 was dispensable for the fusion of lysosomes with phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference in the trafficking of phagosomes according to their cargo.",
"title": "Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization."
}
] |
[
{
"docid": "4407455",
"text": "Inflammatory caspases (caspase-1, -4, -5 and -11) are critical for innate defences. Caspase-1 is activated by ligands of various canonical inflammasomes, and caspase-4, -5 and -11 directly recognize bacterial lipopolysaccharide, both of which trigger pyroptosis. Despite the crucial role in immunity and endotoxic shock, the mechanism for pyroptosis induction by inflammatory caspases is unknown. Here we identify gasdermin D (Gsdmd) by genome-wide clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 nuclease screens of caspase-11- and caspase-1-mediated pyroptosis in mouse bone marrow macrophages. GSDMD-deficient cells resisted the induction of pyroptosis by cytosolic lipopolysaccharide and known canonical inflammasome ligands. Interleukin-1β release was also diminished in Gsdmd−/− cells, despite intact processing by caspase-1. Caspase-1 and caspase-4/5/11 specifically cleaved the linker between the amino-terminal gasdermin-N and carboxy-terminal gasdermin-C domains in GSDMD, which was required and sufficient for pyroptosis. The cleavage released the intramolecular inhibition on the gasdermin-N domain that showed intrinsic pyroptosis-inducing activity. Other gasdermin family members were not cleaved by inflammatory caspases but shared the autoinhibition; gain-of-function mutations in Gsdma3 that cause alopecia and skin defects disrupted the autoinhibition, allowing its gasdermin-N domain to trigger pyroptosis. These findings offer insight into inflammasome-mediated immunity/diseases and also change our understanding of pyroptosis and programmed necrosis.",
"title": "Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death"
},
{
"docid": "6000423",
"text": "Despite genetic heterogeneity, myelodysplastic syndromes (MDSs) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDSs is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem and progenitor cells (HSPCs) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of interleukin-1β (IL-1β) and IL-18, and pyroptotic cell death. Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPCs and bone marrow plasma. Further, like somatic gene mutations, S100A9-induced signaling activates NADPH oxidase (NOX), increasing levels of reactive oxygen species (ROS) that initiate cation influx, cell swelling, and β-catenin activation. Notably, knockdown of NLRP3 or caspase-1, neutralization of S100A9, and pharmacologic inhibition of NLRP3 or NOX suppress pyroptosis, ROS generation, and nuclear β-catenin in MDSs and are sufficient to restore effective hematopoiesis. Thus, alarmins and founder gene mutations in MDSs license a common redox-sensitive inflammasome circuit, which suggests new avenues for therapeutic intervention.",
"title": "The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype."
},
{
"docid": "11837657",
"text": "Mycobacterium tuberculosis (Mtb) infects lung macrophages, which instead of killing the pathogen can be manipulated by the bacilli, creating an environment suitable for intracellular replication and spread to adjacent cells. The role of host cell death during Mtb infection is debated because the bacilli have been shown to be both anti-apoptotic, keeping the host cell alive to avoid the antimicrobial effects of apoptosis, and pro-necrotic, killing the host macrophage to allow infection of neighboring cells. Since mycobacteria activate the NLRP3 inflammasome in macrophages, we investigated whether Mtb could induce one of the recently described inflammasome-linked cell death modes pyroptosis and pyronecrosis. These are mediated through caspase-1 and cathepsin-B, respectively. Human monocyte-derived macrophages were infected with virulent (H37Rv) Mtb at a multiplicity of infection (MOI) of 1 or 10. The higher MOI resulted in strongly enhanced release of IL-1β, while a low MOI gave no IL-1β response. The infected macrophages were collected and cell viability in terms of the integrity of DNA, mitochondria and the plasma membrane was determined. We found that infection with H37Rv at MOI 10, but not MOI 1, over two days led to extensive DNA fragmentation, loss of mitochondrial membrane potential, loss of plasma membrane integrity, and HMGB1 release. Although we observed plasma membrane permeabilization and IL-1β release from infected cells, the cell death induced by Mtb was not dependent on caspase-1 or cathepsin B. It was, however, dependent on mycobacterial expression of ESAT-6. We conclude that as virulent Mtb reaches a threshold number of bacilli inside the human macrophage, ESAT-6-dependent necrosis occurs, activating caspase-1 in the process.",
"title": "Human Macrophages Infected with a High Burden of ESAT-6-Expressing M. tuberculosis Undergo Caspase-1- and Cathepsin B-Independent Necrosis"
},
{
"docid": "34469966",
"text": "Interleukin-1β (IL-1β) is a cytokine whose bioactivity is controlled by activation of the inflammasome. However, in response to lipopolysaccharide, human monocytes secrete IL-1β independently of classical inflammasome stimuli. Here, we report that this constituted a species-specific response that is not observed in the murine system. Indeed, in human monocytes, lipopolysaccharide triggered an \"alternative inflammasome\" that relied on NLRP3-ASC-caspase-1 signaling, yet was devoid of any classical inflammasome characteristics including pyroptosome formation, pyroptosis induction, and K(+) efflux dependency. Genetic dissection of the underlying signaling pathway in a monocyte transdifferentiation system revealed that alternative inflammasome activation was propagated by TLR4-TRIF-RIPK1-FADD-CASP8 signaling upstream of NLRP3. Importantly, involvement of this signaling cascade was limited to alternative inflammasome activation and did not extend to classical NLRP3 activation. Because alternative inflammasome activation embraces both sensitivity and promiscuity of TLR4, we propose a pivotal role for this signaling cascade in TLR4-driven, IL-1β-mediated immune responses and immunopathology in humans.",
"title": "Human Monocytes Engage an Alternative Inflammasome Pathway."
},
{
"docid": "4345315",
"text": "Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle–Wells syndrome and neonatal-onset multiple-system inflammatory disease. Cryopyrin (also called Nalp3), the product of CIAS1, is a member of the NOD-LRR protein family that has been linked to the activation of intracellular host defence signalling pathways. Cryopyrin forms a multi-protein complex termed ‘the inflammasome’, which contains the apoptosis-associated speck-like protein (ASC) and caspase-1, and promotes caspase-1 activation and processing of pro-interleukin (IL)-1β (ref. 4). Here we show the effect of cryopyrin deficiency on inflammasome function and immune responses. Cryopyrin and ASC are essential for caspase-1 activation and IL-1β and IL-18 production in response to bacterial RNA and the imidazoquinoline compounds R837 and R848. In contrast, secretion of tumour-necrosis factor-α and IL-6, as well as activation of NF-κB and mitogen-activated protein kinases (MAPKs) were unaffected by cryopyrin deficiency. Furthermore, we show that Toll-like receptors and cryopyrin control the secretion of IL-1β and IL-18 through different intracellular pathways. These results reveal a critical role for cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1, and provide insights regarding the pathogenesis of autoinflammatory syndromes.",
"title": "Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3"
},
{
"docid": "15414628",
"text": "Legionella pneumophila, the causative agent of Legionnaires' pneumonia, resides in a distinct vacuole structure called Legionella-containing vacuole (LCV). The LCV resists fusion with the lysosome and permits efficient bacterial replication in host macrophages, which requires a Dot/Icm type IVB secretion system. Dot/Icm-translocated effector SdhA is critical for L. pneumophila intracellular growth and functions to prevent host cell death. Here, we show that the absence of SdhA resulted in elevated caspase-1 activation and IL-1β secretion as well as macrophage pyroptosis during Legionella infection. These inflammasome activation phenotypes were independent of the established flagellin-NAIP5-NLRC4 axis, but relied on the DNA-sensing AIM2 inflammasome. We further demonstrate that Legionella DNA was released into macrophage cytosol, and this effect was significantly exaggerated by the absence of SdhA. SdhA bears a functional Golgi-targeting GRIP domain that is required for preventing AIM2 inflammasome activation. Ectopically expressed SdhA formed a unique ring-shape membrane structure, further indicating a role in membrane trafficking and maintaining LCV membrane integrity. Our data together suggest a possible link, mediated by the function of SdhA, between LCV trafficking/maturation and suppression of host innate immune detection.",
"title": "Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking."
},
{
"docid": "34439544",
"text": "The BCL-2 (B cell CLL/Lymphoma) family is comprised of approximately twenty proteins that collaborate to either maintain cell survival or initiate apoptosis(1). Following cellular stress (e.g., DNA damage), the pro-apoptotic BCL-2 family effectors BAK (BCL-2 antagonistic killer 1) and/or BAX (BCL-2 associated X protein) become activated and compromise the integrity of the outer mitochondrial membrane (OMM), though the process referred to as mitochondrial outer membrane permeabilization (MOMP)(1). After MOMP occurs, pro-apoptotic proteins (e.g., cytochrome c) gain access to the cytoplasm, promote caspase activation, and apoptosis rapidly ensues(2). In order for BAK/BAX to induce MOMP, they require transient interactions with members of another pro-apoptotic subset of the BCL-2 family, the BCL-2 homology domain 3 (BH3)-only proteins, such as BID (BH3-interacting domain agonist)(3-6). Anti-apoptotic BCL-2 family proteins (e.g., BCL-2 related gene, long isoform, BCL-xL; myeloid cell leukemia 1, MCL-1) regulate cellular survival by tightly controlling the interactions between BAK/BAX and the BH3-only proteins capable of directly inducing BAK/BAX activation(7,8). In addition, anti-apoptotic BCL-2 protein availability is also dictated by sensitizer/de-repressor BH3-only proteins, such as BAD (BCL-2 antagonist of cell death) or PUMA (p53 upregulated modulator of apoptosis), which bind and inhibit anti-apoptotic members(7,9). As most of the anti-apoptotic BCL-2 repertoire is localized to the OMM, the cellular decision to maintain survival or induce MOMP is dictated by multiple BCL-2 family interactions at this membrane. Large unilamellar vesicles (LUVs) are a biochemical model to explore relationships between BCL-2 family interactions and membrane permeabilization(10). LUVs are comprised of defined lipids that are assembled in ratios identified in lipid composition studies from solvent extracted Xenopus mitochondria (46.5% phosphatidylcholine, 28.5% phosphatidylethanoloamine, 9% phosphatidylinositol, 9% phosphatidylserine, and 7% cardiolipin)(10). This is a convenient model system to directly explore BCL-2 family function because the protein and lipid components are completely defined and tractable, which is not always the case with primary mitochondria. While cardiolipin is not usually this high throughout the OMM, this model does faithfully mimic the OMM to promote BCL-2 family function. Furthermore, a more recent modification of the above protocol allows for kinetic analyses of protein interactions and real-time measurements of membrane permeabilization, which is based on LUVs containing a polyanionic dye (ANTS: 8-aminonaphthalene-1,3,6-trisulfonic acid) and cationic quencher (DPX: p-xylene-bis-pyridinium bromide)(11). As the LUVs permeabilize, ANTS and DPX diffuse apart, and a gain in fluorescence is detected. Here, commonly used recombinant BCL-2 family protein combinations and controls using the LUVs containing ANTS/DPX are described.",
"title": "Examining BCL-2 family function with large unilamellar vesicles."
},
{
"docid": "6767271",
"text": "Although adjuvants are critical vaccine components, their modes of action are poorly understood. In this study, we investigated the mechanisms by which the heat-killed mycobacteria in CFA promote Th17 CD4(+) T cell responses. We found that IL-17 secretion by CD4(+) T cells following CFA immunization requires MyD88 and IL-1β/IL-1R signaling. Through measurement of Ag-specific responses after adoptive transfer of OTII cells, we confirmed that MyD88-dependent signaling controls Th17 differentiation rather than simply production of IL-17. Additional experiments showed that CFA-induced Th17 differentiation involves IL-1β processing by the inflammasome, as mice lacking caspase-1, ASC, or NLRP3 exhibit partially defective responses after immunization. Biochemical fractionation studies further revealed that peptidoglycan is the major component of heat-killed mycobacteria responsible for inflammasome activation. By assaying Il1b transcripts in the injection site skin of CFA-immunized mice, we found that signaling through the adaptor molecule caspase activation and recruitment domain 9 (CARD9) plays a major role in triggering pro-IL-1β expression. Moreover, we demonstrated that recognition of the mycobacterial glycolipid trehalose dimycolate (cord factor) by the C-type lectin receptor mincle partially explains this CARD9 requirement. Importantly, purified peptidoglycan and cord factor administered in mineral oil synergized to recapitulate the Th17-promoting activity of CFA, and, as expected, this response was diminished in caspase-1- and CARD9-deficient mice. Taken together, these findings suggest a general strategy for the rational design of Th17-skewing adjuvants by combining agonists of the CARD9 pathway with inflammasome activators.",
"title": "Cord factor and peptidoglycan recapitulate the Th17-promoting adjuvant activity of mycobacteria through mincle/CARD9 signaling and the inflammasome."
},
{
"docid": "40312663",
"text": "Inflammasome-mediated IL-1beta production is central to the innate immune defects that give rise to certain autoinflammatory diseases and may also be associated with the generation of IL-17-producing CD4(+) T (Th17) cells that mediate autoimmunity. However, the role of the inflammasome in driving adaptive immunity to infection has not been addressed. In this article, we demonstrate that inflammasome-mediated IL-1beta plays a critical role in promoting Ag-specific Th17 cells and in generating protective immunity against Bordetella pertussis infection. Using a murine respiratory challenge model, we demonstrated that the course of B. pertussis infection was significantly exacerbated in IL-1R type I-defective (IL-1RI(-/-)) mice. We found that adenylate cyclase toxin (CyaA), a key virulence factor secreted by B. pertussis, induced robust IL-1beta production by dendritic cells through activation of caspase-1 and the NALP3-containing inflammasome complex. Using mutant toxins, we demonstrate that CyaA-mediated activation of caspase-1 was not dependent on adenylate cyclase enzyme activity but was dependent on the pore-forming capacity of CyaA. In addition, CyaA promoted the induction of Ag-specific Th17 cells in wild-type but not IL-1RI(-/-) mice. Furthermore, the bacterial load was enhanced in IL-17-defective mice. Our findings demonstrate that CyaA, a virulence factor from B. pertussis, promotes innate IL-1beta production via activation of the NALP3 inflammasome and, thereby, polarizes T cell responses toward the Th17 subtype. In addition to its known role in subverting host immunity, our findings suggest that CyaA can promote IL-1beta-mediated Th17 cells, which promote clearance of the bacteria from the respiratory tract.",
"title": "Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis."
},
{
"docid": "24185667",
"text": "The stress-activated kinase JNK mediates key cellular responses to oxidative stress. Here we show that DAP kinase (DAPk), a cell death promoting Ser/Thr protein kinase, plays a main role in oxidative stress-induced JNK signaling. We identify protein kinase D (PKD) as a novel substrate of DAPk and demonstrate that DAPk physically interacts with PKD in response to oxidative stress. We further show that DAPk activates PKD in cells and that induction of JNK phosphorylation by ectopically expressed DAPk can be attenuated by knocking down PKD expression or by inhibiting its catalytic activity. Moreover, knockdown of DAPk expression caused a marked reduction in JNK activation under oxidative stress, indicating that DAPk is indispensable for the activation of JNK signaling under these conditions. Finally, DAPk is shown to be required for cell death under oxidative stress in a process that displays the characteristics of caspase-independent necrotic cell death. Taken together, these findings establish a major role for DAPk and its specific interaction with PKD in regulating the JNK signaling network under oxidative stress.",
"title": "DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress"
},
{
"docid": "7681810",
"text": "Mitotic spindle assembly is mediated by two processes: a centrosomal and a chromosomal pathway. RanGTP regulates the latter process by releasing microtubule-associated proteins from inhibitory complexes. NuSAP, a microtubule- and DNA-binding protein, is a target of RanGTP and promotes the formation of microtubules near chromosomes. However, the contribution of NuSAP to cell proliferation in vivo is unknown. Here, we demonstrate that the expression of NuSAP highly correlates with cell proliferation during embryogenesis and adult life, making it a reliable marker of proliferating cells. Additionally, we show that NuSAP deficiency in mice leads to early embryonic lethality. Spindle assembly in NuSAP-deficient cells is highly inefficient and chromosomes remain dispersed in the mitotic cytoplasm. As a result of sustained spindle checkpoint activity, the cells are unable to progress through mitosis, eventually leading to caspase activation and apoptotic cell death. Together, our findings demonstrate that NuSAP is essential for proliferation of embryonic cells and, simultaneously, they underscore the importance of chromatin-induced spindle assembly.",
"title": "NuSAP is essential for chromatin-induced spindle formation during early embryogenesis."
},
{
"docid": "16863359",
"text": "Inflammasomes are multiprotein complexes that link pathogen recognition and cellular stress to the processing of the proinflammatory cytokine interleukin-1β (IL-1β). Whereas inflammasome-mediated activation is heavily studied in hematopoietic macrophages and dendritic cells, much less is known about microglia, resident tissue macrophages of the brain that originate from a distinct progenitor. To directly compare inflammasome-mediated activation in different types of macrophages, we isolated primary microglia and hematopoietic macrophages from adult, healthy rhesus macaques. We analyzed the expression profile of NOD (nucleotide-binding oligomerization domain)-like receptors, adaptor proteins, and caspases and characterized inflammasome activation and regulation in detail. We here demonstrate that primary microglia can respond to the same innate stimuli as hematopoietic macrophages. However, microglial responses are more persistent due to lack of negative regulation on pro-IL-1β expression. In addition, we show that while caspase 1, 4, and 5 activation is pivotal for inflammasome-induced IL-1β secretion by hematopoietic macrophages, microglial secretion of IL-1β is only partially dependent on these inflammatory caspases. These results identify key cell type-specific differences that may aid the development of strategies to modulate innate immune responses in the brain.",
"title": "Inflammasome-induced IL-1β secretion in microglia is characterized by delayed kinetics and is only partially dependent on inflammatory caspases."
},
{
"docid": "56528795",
"text": "Liver is a vital organ with many important functions, and the maintenance of normal hepatic function is necessary for health. As an essential mechanism for maintaining cellular homeostasis, autophagy plays an important role in ensuring normal organ function. Studies have indicated that the degeneration of hepatic function is associated with autophagic deficiency in aging liver. However, the underlying mechanisms still remain unclear. The serine protease Omi/HtrA2 belongs to the HtrA family and promotes apoptosis through either the caspase-dependent or caspase-independent pathway. Mice lacking Omi/HtrA2 exhibited progeria symptoms (premature aging), which were similar to the characteristics of autophagic insufficiency. In this study, we demonstrated that both the protein level of Omi/HtrA2 in liver and hepatic function were reduced as rats aged, and there was a positive correlation between them. Furthermore, several autophagy-related proteins (LC3II/I, Beclin-1 and LAMP2) in rat liver were decreased significantly with the increasing of age. Finally, inhibition of Omi/HtrA2 resulted in reduced autophagy and hepatic dysfunction. In conclusion, these results suggest that Omi/HtrA2 participates in age-related autophagic deficiency in rat liver. This study may offer a novel insight into the mechanism involved in liver aging.",
"title": "Omi/HtrA2 Participates in Age-Related Autophagic Deficiency in Rat Liver"
},
{
"docid": "23985464",
"text": "Wild-type p53 has recently been shown to repress transcription from several cellular and viral promoters. Since p53 mutations are the most frequently reported genetic defects in human cancers, it becomes important to study the effects of mutations of p53 on promoter functions. We, therefore, have studied the effects of wild-type and mutant human p53 on the human proliferating-cell nuclear antigen (PCNA) promoter and on several viral promoters, including the herpes simplex virus type 1 UL9 promoter, the human cytomegalovirus major immediate-early promoter-enhancer, and the long terminal repeat promoters of Rous sarcoma virus and human T-cell lymphotropic virus type I. HeLa cells were cotransfected with a wild-type or mutant p53 expression vector and a plasmid containing a chloramphenicol acetyltransferase reporter gene under viral (or cellular) promoter control. As expected, expression of the wild-type p53 inhibited promoter function. Expression of a p53 with a mutation at any one of the four amino acid positions 175, 248, 273, or 281, however, correlated with a significant increase of the PCNA promoter activity (2- to 11-fold). The viral promoters were also activated, although to a somewhat lesser extent. We also showed that activation by a mutant p53 requires a minimal promoter containing a lone TATA box. A more significant increase (25-fold) in activation occurs when the promoter contains a binding site for the activating transcription factor or cyclic AMP response element-binding protein. Using Saos-2 cells that do not express p53, we showed that activation by a mutant p53 was a direct enhancement. The mutant forms of p53 used in this study are found in various cancer cells. The activation of PCNA by mutant p53s may indicate a way to increase cell proliferation by the mutant p53s. Thus, our data indicate a possible functional role for the mutants of p53 found in cancer cells in activating several important loci, including PCNA.",
"title": "Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells."
},
{
"docid": "25251625",
"text": "The use of caspase inhibitors has revealed the existence of alternative backup cell death programs for apoptosis. The broad-spectrum caspase inhibitor zVAD-fmk modulates the three major types of cell death. Addition of zVAD-fmk blocks apoptotic cell death, sensitizes cells to necrotic cell death, and induces autophagic cell death. Several studies have shown a crucial role for the kinase RIP1 and the adenosine nucleotide translocator (ANT)-cyclophilin D (CypD) complex in necrotic cell death. The underlying mechanism of zVAD-fmk-mediated sensitization to necrotic cell death involves the inhibition of caspase-8-mediated proteolysis of RIP1 and disturbance of the ANT-CypD interaction. RIP1 is also involved in autophagic cell death. Caspase inhibitors and knockdown studies have revealed negative roles for catalase and caspase-8 in autophagic cell death. The positive role of RIP1 and the negative role of caspase-8 in both necrotic and autophagic cell death suggest that the pathways of these two types of cell death are interconnected. Necrotic cell death represents a rapid cellular response involving mitochondrial reactive oxygen species (ROS) production, decreased adenosine triphosphate concentration, and other cellular insults, whereas autophagic cell death first starts as a survival attempt by cleaning up ROS-damaged mitochondria. However, when this process occurs in excess, autophagy itself becomes cytotoxic and eventually leads to autophagic cell death. A better understanding of the molecular mechanisms of these alternative cell death pathways may provide therapeutic tools to combat cell death associated with neurodegenerative diseases, ischemia-reperfusion pathologies, and infectious diseases, and may also facilitate the development of alternative cytotoxic strategies in cancer treatment.",
"title": "Caspase inhibitors promote alternative cell death pathways."
},
{
"docid": "27460509",
"text": "Cardiac myocyte apoptosis has been demonstrated in end-stage failing human hearts. The therapeutic utility of blocking apoptosis in congestive heart failure (CHF) has not been elucidated. This study investigated the role of caspase activation in cardiac contractility and sarcomere organization in the development of CHF. In a rabbit model of heart failure obtained by rapid ventricular pacing, we demonstrate, using in vivo transcoronary adenovirus-mediated gene delivery of the potent caspase inhibitor p35, that caspase activation is associated with a reduction in contractile force of failing myocytes by destroying sarcomeric structure. In this animal model gene transfer of p35 prevented the rise in caspase 3 activity and DNA-histone formation. Genetically manipulated hearts expressing p35 had a significant improvement in left ventricular pressure rise (+dp/dt), decreased end-diastolic chamber pressure (LVEDP), and the development of heart failure was delayed. To better understand this benefit, we examined the effects of caspase 3 on cardiomyocyte dysfunction in vitro. Microinjection of activated caspase 3 into the cytoplasm of intact myocytes induced sarcomeric disorganization and reduced contractility of the cells. These results demonstrate a direct impact of caspases on cardiac function and may lead to novel therapeutic strategies via antiapoptotic regimens.",
"title": "Blocking caspase-activated apoptosis improves contractility in failing myocardium."
},
{
"docid": "13583521",
"text": "According to dogma, initiator caspases are activated through proximity-induced homodimerization, but some studies infer that during apoptosis caspase-9 may instead form a holoenzyme with the Apaf-1 apoptosome. Using several biochemical approaches, including a novel site-specific crosslinking technique, we provide the first direct evidence that procaspase-9 homodimerizes within the apoptosome, markedly increasing its avidity for the complex and inducing selective intramolecular cleavage at Asp-315. Remarkably, however, procaspase-9 could also bind via its small subunit to the NOD domain in Apaf-1, resulting in the formation of a heterodimer that more efficiently activated procaspase-3. Following cleavage, the intersubunit linker (and associated conformational changes) in caspase-9-p35/p12 inhibited its ability to form homo- and heterodimers, but feedback cleavage by caspase-3 at Asp-330 removed the linker entirely and partially restored activity to caspase-9-p35/p10. Thus, the apoptosome mediates the formation of caspase-9 homo- and heterodimers, both of which are impacted by cleavage and contribute to its overall function.",
"title": "The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities"
},
{
"docid": "25677651",
"text": "Microbe-macrophage interactions play a central role in the pathogenesis of many infections. The ability of some bacterial pathogens to induce macrophage apoptosis has been suggested to contribute to their ability to elude innate immune responses and successfully colonize the host. Here, we provide evidence that activation of liver X receptors (LXRs) and retinoid X receptors (RXRs) inhibits apoptotic responses of macrophages to macrophage colony-stimulating factor (M-CSF) withdrawal and several inducers of apoptosis. In addition, combined activation of LXR and RXR protected macrophages from apoptosis caused by infection with Bacillus anthracis, Escherichia coli, and Salmonella typhimurium. Expression-profiling studies demonstrated that LXR and RXR agonists induced the expression of antiapoptotic regulators, including AIM/CT2, Bcl-X(L), and Birc1a. Conversely, LXR and RXR agonists inhibited expression of proapoptotic regulators and effectors, including caspases 1, 4/11, 7, and 12; Fas ligand; and Dnase1l3. The combination of LXR and RXR agonists was more effective than either agonist alone at inhibiting apoptosis in response to various inducers of apoptosis, and it acted synergistically to induce expression of AIM/CT2. Inhibition of AIM/CT2 expression in response to LXR/RXR agonists partially reversed their antiapoptotic effects. These findings reveal unexpected roles of LXRs and RXRs in the control of macrophage survival and raise the possibility that LXR/RXR agonists may be exploited to enhance innate immunity to bacterial pathogens that induce apoptotic programs as a strategy for evading host responses.",
"title": "Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis."
},
{
"docid": "11921405",
"text": "The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium-invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in ∼100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1α/β and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections.",
"title": "Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa."
},
{
"docid": "10852047",
"text": "We recently developed a class of novel antitumor agents that elicit a potent growth-inhibitory response in many tumor cells cultured in vitro. WK175, a member of this class, was chosen as a model compound that showed strong in vitro efficacy. WK175 interferes with the intracellular steady-state level of NAD(+), resulting in a decreased cellular NAD(+) concentration. We found that WK175 induces apoptotic cell death without any DNA-damaging effect. The apoptotic death signaling pathway initiated by WK175 was examined in detail: mitochondrial membrane potential, cytochrome c release, caspase 3 activation, caspase 3 and poly(ADP-ribose) polymerase cleavage, and the appearance of a sub-G(1) cell cycle population were determined in time course studies in THP-1 (a human monocytic leukemia cell line) cells. We found activation of this cascade after 24 h of treatment with 10 nM WK175. Induction of apoptosis was prevented by bongkrekic acid, Z-Asp-Glu-Val-Asp-fluoromethylketone, and Z-Leu-Glu-His-Asp-fluoromethylketone, inhibitors of the mitochondrial permeability transition and of caspase 3 and 9, respectively, but not by Ac-Tyr-Val-Ala-Asp-CHO, a specific caspase 1 inhibitor, suggesting the involvement of the permeability transition pore, caspase 3, and caspase 9 in the WK175-induced apoptotic cascade. These results imply that decreased NAD(+) concentration initiates the apoptotic cascade, resulting in the antitumor effect of WK175.",
"title": "WK175, a novel antitumor agent, decreases the intracellular nicotinamide adenine dinucleotide concentration and induces the apoptotic cascade in human leukemia cells."
},
{
"docid": "5386514",
"text": "The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-γ (IFN-γ)–producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X7 purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing for the secretion of interleukin-1β (IL-1β). The priming of IFN-γ–producing CD8+ T cells by dying tumor cells fails in the absence of a functional IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3−/−) or caspase-1–deficient (Casp-1−/−) mice unless exogenous IL-1β is provided. Accordingly, anticancer chemotherapy turned out to be inefficient against tumors established in purinergic receptor P2rx7−/− or Nlrp3−/− or Casp1−/− hosts. Anthracycline-treated individuals with breast cancer carrying a loss-of-function allele of P2RX7 developed metastatic disease more rapidly than individuals bearing the normal allele. These results indicate that the NLRP3 inflammasome links the innate and adaptive immune responses against dying tumor cells.",
"title": "Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors"
},
{
"docid": "33387953",
"text": "Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signaling. Multiple mutations in GNB1 affect the protein interface that binds Gα subunits as well as downstream effectors and disrupt Gα interactions with the Gβγ dimer. Different mutations in Gβ proteins clustered partly on the basis of lineage; for example, all 11 GNB1 K57 mutations were in myeloid neoplasms, and seven of eight GNB1 I80 mutations were in B cell neoplasms. Expression of patient-derived GNB1 variants in Cdkn2a-deficient mouse bone marrow followed by transplantation resulted in either myeloid or B cell malignancies. In vivo treatment with the dual PI3K-mTOR inhibitor BEZ235 suppressed GNB1-induced signaling and markedly increased survival. In several human tumors, mutations in the gene encoding GNB1 co-occurred with oncogenic kinase alterations, including the BCR-ABL fusion protein, the V617F substitution in JAK2 and the V600K substitution in BRAF. Coexpression of patient-derived GNB1 variants with these mutant kinases resulted in inhibitor resistance in each context. Thus, GNB1 and GNB2 alterations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling.",
"title": "Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance"
},
{
"docid": "17755060",
"text": "Tumor cells have high-energetic and anabolic needs and are known to adapt their metabolism to be able to survive and keep proliferating under conditions of nutrient stress. We show that PKCζ deficiency promotes the plasticity necessary for cancer cells to reprogram their metabolism to utilize glutamine through the serine biosynthetic pathway in the absence of glucose. PKCζ represses the expression of two key enzymes of the pathway, PHGDH and PSAT1, and phosphorylates PHGDH at key residues to inhibit its enzymatic activity. Interestingly, the loss of PKCζ in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, whereas patients with low levels of PKCζ have a poor prognosis. Furthermore, PKCζ and caspase-3 activities are correlated with PHGDH levels in human intestinal tumors. Taken together, this demonstrates that PKCζ is a critical metabolic tumor suppressor in mouse and human cancer.",
"title": "Control of Nutrient Stress-Induced Metabolic Reprogramming by PKCζ in Tumorigenesis"
},
{
"docid": "9197092",
"text": "Dietary polyphenols have been associated with reduced risk of chronic diseases, but the precise molecular mechanisms of protection remain unclear. This work was aimed at studying the effect of (-)-epicatechin (EC) and chlorogenic acid (CGA) on the regulation of apoptotic and survival/proliferation pathways in a human hepatoma cell line (HepG2). EC or CGA treatment for 18 h had a slight effect on cell viability and decreased reactive oxygen species formation, and EC alone promoted cell proliferation, whereas CGA increased glutathione levels. Phenols neither induced the caspase cascade for apoptosis nor affected expression levels of Bcl-xL or Bax. A sustained activation of the major survival signals AKT/PI-3-kinase and ERK was shown in EC-treated cells, rather than in CGA-exposed cells. These data suggest that EC and CGA have no effect on apoptosis and enhance the intrinsic cellular tolerance against oxidative insults either by activating survival/proliferation pathways or by increasing antioxidant potential in HepG2.",
"title": "Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line."
},
{
"docid": "15419873",
"text": "Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that detects viral RNA and elicits an antiviral immune response. Two N-terminal caspase activation and recruitment domains (CARDs) transmit the signal, and the regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to discriminate pathogenic from self-RNA. However, the function of the DExH box helicase domain that is also required for activity is less clear. Using single-molecule protein-induced fluorescence enhancement, we discovered a robust adenosine 5'-triphosphate-powered dsRNA translocation activity of RIG-I. The CARDs dramatically suppress translocation in the absence of 5'-triphosphate, and the activation by 5'-triphosphate triggers RIG-I to translocate preferentially on dsRNA in cis. This functional integration of two RNA molecular patterns may provide a means to specifically sense and counteract replicating viruses.",
"title": "Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA."
},
{
"docid": "22116439",
"text": "Tau aggregation and amyloid β protein (Aβ) deposition are the main causes of Alzheimer's disease (AD). Peroxisome proliferator-activated receptor γ (PPARγ) activation modulates Aβ production. To test whether the PPARγ agonist pioglitazone (PIO) is also effective in preventing tau aggregation in AD, we used a cellular model in which wild-type tau protein (4R0N) is overexpressed (M1C cells) (Hamano et al., 2012) as well as primary neuronal cultures. PIO reduced both phosphorylated and total tau levels, and inactivated glycogen synthase kinase 3β, a major tau kinase, associated with activation of Akt. In addition, PIO decreased cleaved caspase3 and C-terminal truncated tau species by caspase, which is expected to decrease tau aggregation. A fractionation study showed that PIO reduced high molecular-weight (120 kDa), oligomeric tau species in Tris Insoluble, sarkosyl-soluble fractions. Tau decrease was reversed by adding GW9662, a PPARγ antagonist. Together, our current results support the idea that PPARγ agonists may be useful therapeutic agents for AD.",
"title": "Pioglitazone prevents tau oligomerization."
},
{
"docid": "14530534",
"text": "Chromatin insulators are DNA elements that regulate the level of gene expression either by preventing gene silencing through the maintenance of heterochromatin boundaries or by preventing gene activation by blocking interactions between enhancers and promoters. CCCTC-binding factor (CTCF), a ubiquitously expressed 11-zinc-finger DNA-binding protein, is the only protein implicated in the establishment of insulators in vertebrates. While CTCF has been implicated in diverse regulatory functions, CTCF has only been studied in a limited number of cell types across human genome. Thus, it is not clear whether the identified cell type-specific differences in CTCF-binding sites are functionally significant. Here, we identify and characterize cell type-specific and ubiquitous CTCF-binding sites in the human genome across 38 cell types designated by the Encyclopedia of DNA Elements (ENCODE) consortium. These cell type-specific and ubiquitous CTCF-binding sites show uniquely versatile transcriptional functions and characteristic chromatin features. In addition, we confirm the insulator barrier function of CTCF-binding and explore the novel function of CTCF in DNA replication. These results represent a critical step toward the comprehensive and systematic understanding of CTCF-dependent insulators and their versatile roles in the human genome.",
"title": "Comprehensive Identification and Annotation of Cell Type-Specific and Ubiquitous CTCF-Binding Sites in the Human Genome"
},
{
"docid": "26887439",
"text": "To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library targeting approximately 4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin) significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G(2)-M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin protein.",
"title": "Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells."
},
{
"docid": "2543135",
"text": "Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. Recently, it has been shown that autophagy can induce cells to die; however, the mechanism of the autophagic cell death program is unclear. We now show that caspase inhibition leading to cell death by means of autophagy involves reactive oxygen species (ROS) accumulation, membrane lipid oxidation, and loss of plasma membrane integrity. Inhibition of autophagy by chemical compounds or knocking down the expression of key autophagy proteins such as ATG7, ATG8, and receptor interacting protein (RIP) blocks ROS accumulation and cell death. The cause of abnormal ROS accumulation is the selective autophagic degradation of the major enzymatic ROS scavenger, catalase. Caspase inhibition directly induces catalase degradation and ROS accumulation, which can be blocked by autophagy inhibitors. These findings unveil a molecular mechanism for the role of autophagy in cell death and provide insight into the complex relationship between ROS and nonapoptotic programmed cell death.",
"title": "Autophagic programmed cell death by selective catalase degradation."
},
{
"docid": "17231273",
"text": "Energy deficiency and dysfunction of the Na+, K+-ATPase are common consequences of many pathological insults. The nature and mechanism of cell injury induced by impaired Na+, K+-ATPase, however, are not well defined. We used cultured cortical neurons to examine the hypothesis that blocking the Na+, K+-ATPase induces apoptosis by depleting cellular K+ and, concurrently, induces necrotic injury in the same cells by increasing intracellular Ca2+ and Na+. The Na+, K+-ATPase inhibitor ouabain induced concentration-dependent neuronal death. Ouabain triggered transient neuronal cell swelling followed by cell shrinkage, accompanied by intracellular Ca2+ and Na+ increase, K+ decrease, cytochrome c release, caspase-3 activation, and DNA laddering. Electron microscopy revealed the coexistence of ultrastructural features of both apoptosis and necrosis in individual cells. The caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD-FMK) blocked >50% of ouabain-induced neuronal death. Potassium channel blockers or high K+ medium, but not Ca2+ channel blockade, prevented cytochrome c release, caspase activation, and DNA damage. Blocking of K+, Ca2+, or Na+ channels or high K+ medium each attenuated the ouabain-induced cell death; combined inhibition of K+ channels and Ca2+ or Na+ channels resulted in additional protection. Moreover, coapplication of Z-VAD-FMK and nifedipine produced virtually complete neuroprotection. These results suggest that the neuronal death associated with Na+, K+-pump failure consists of concurrent apoptotic and necrotic components, mediated by intracellular depletion of K+ and accumulation of Ca2+ and Na+, respectively. The ouabain-induced hybrid death may represent a distinct form of cell death related to the brain injury of inadequate energy supply and disrupted ion homeostasis.",
"title": "Ionic mechanism of ouabain-induced concurrent apoptosis and necrosis in individual cultured cortical neurons"
}
] |
193468
|
Return to Paradise is a film released before 2000.
|
[
{
"docid": "Return_to_Paradise_(1998_film)",
"text": "Return to Paradise is a 1998 American drama-thriller film directed by Joseph Ruben , written by Wesley Strick and Bruce Robinson , and starring Vince Vaughn , Anne Heche , and Joaquin Phoenix . Return to Paradise is a remake of the 1989 French film Force majeure . The film had its premiere on August 10 , 1998 , and was released to theaters on August 14 , 1998 .",
"title": ""
}
] |
[
{
"docid": "Return_to_Paradise_(1953_film)",
"text": "Return to Paradise is a Technicolor South Seas drama film released by United Artists in 1953 . The film was directed by Mark Robson and starred Gary Cooper , Barry Jones and Roberta Haynes . It was based on a short story , Mr. Morgan , by James Michener in his short story collection Return to Paradise , his sequel to Tales of the South Pacific . It was filmed on location in Matautu , Western Samoa ( present-day Samoa ) .",
"title": ""
},
{
"docid": "Panic_in_Paradise",
"text": "Panic in Paradise can refer to : Panic in Paradise ( album ) , an album by `` X-Dream '' released in 2000 Panic in Paradise ( film ) , a 1960 Danish film",
"title": ""
},
{
"docid": "Another_Day_in_Paradise_(disambiguation)",
"text": "`` Another Day in Paradise '' is the name of a Phil Collins song released in 1989 . Another Day in Paradise may also refer to : Another Day in Paradise ( album ) , a 1994 album by Strung Out Another Day in Paradise ( novel ) , a 1997 novel by Eddie Little Another Day in Paradise ( film ) , a 1998 film based on the Eddie Little novel Another Day in Paradise , a 2001 book by Jim Toomey Another Day in Paradise , a 2006 CD by Lee Richards Another Day in Paradise ( Belly album ) , a 2016 hip-hop album by rapper Belly Another Day in Paradise , a 2008 companion documentary to the TV series Carrier Just Another Day in Paradise , a 1982 album and song by Bertie Higgins Just Another Day in Paradise ( Phil Vassar song ) , a 2000 song by Phil Vassar",
"title": ""
},
{
"docid": "Return_to_Me",
"text": "Return to Me is a 2000 American romantic comedy-drama film directed by Bonnie Hunt and starring David Duchovny and Minnie Driver . It was filmed in Chicago , Illinois and was released on April 7 , 2000 by Metro-Goldwyn-Mayer . It was Carroll O'Connor 's final film before his death the following year .",
"title": ""
},
{
"docid": "Le_Mamea_Matatumua_Ata",
"text": "Le Mamea Matatumua Ata , OBE , was one of the framers of the Constitution of Samoa . He held senior positions under the New Zealand Trusteeship of Samoa and in the Independent State of Samoa . He held the high chief ( matai ) title Le Mamea from Matautu , Lefaga and the orator title Matatumua from Faleasi'u . For his work , he was honoured as an Officer of The Most Excellent Order of the British Empire ( OBE ) . He also played the role of Tonga in Return to Paradise ( 1953 film ) a South Seas drama film starring Gary Cooper released by United Artists in 1953 . Return to Paradise was filmed on location in Matautu , Lefaga .",
"title": ""
},
{
"docid": "Paradise_(2013_film)",
"text": "Paradise ( also known as Lamb of God ) is an American comedy-drama film written and directed by Diablo Cody , in her directorial debut . It stars Julianne Hough , Russell Brand , Octavia Spencer , Holly Hunter , Iliza Shlesinger and Kathleen Rose Perkins and was released October 18 , 2013 . The title is a take on the fact that while many tourists visit the Las Vegas Strip they are actually spending most of their time in the town of Paradise rather than in the actual city of Las Vegas . This was the last film by Mandate Pictures before it was shut down .",
"title": ""
},
{
"docid": "Extended_Versions_(Styx_album)",
"text": "Styx - Extended Versions : The Encore Collection is a compilation of live tracks recorded by the band Styx . The album was released in 2000 , but each track on the album had been released as part of Styx 's 1997 double live album Return to Paradise '' .",
"title": ""
},
{
"docid": "Paradise_Found",
"text": "Paradise Found may refer to : Paradise Found ( film ) , 2003 biographical film Paradise Found ( musical ) , 2010 London musical Paradise Found , song from Up ( film score ) Paradise Found , 1979 song by Amii Stewart on the album Paradise Bird Paradise Found/Luck Before You Leap , episode of Iggy Arbuckle",
"title": ""
},
{
"docid": "100_Years_(film)",
"text": "100 Years : The Movie You Will Never See is an upcoming film written by and starring John Malkovich and directed by Robert Rodriguez . 100 Years is due to be released on 18 November 2115 . Malkovich and Rodriguez announced in November 2015 that they had teamed with Louis XIII Cognac , owned by Rémy Martin , to create a film inspired by the hundred years it takes to make a bottle of Louis XIII . Although the film 's plot remains a complete secret , on 18 November 2015 , Malkovich and Rodriguez released three teaser trailers . None showed footage from the film , but instead imagine three possible futures , from a dystopia wasteland to a technological paradise . Pending release , the film is being kept in a high-tech safe in bulletproof glass that will open automatically on 18 November 2115 , the day of the film 's premiere . One thousand guests from around the world , including Malkovich and Rodriguez , have received an invitation to the premiere , which they can hand down to their descendants . The safe in which 100 Years is kept was showcased at the 2016 Cannes Film Festival and various other cities before being returned to Cognac , France and the Louis XIII cellars .",
"title": ""
},
{
"docid": "Shangri-La_(The_Blackeyed_Susans_album)",
"text": "Shangri-La is the sixth and most recent studio album by The Blackeyed Susans , released in July 2003 . After initial writing sessions in mid-1999 , recording of the album was scheduled for 2000 . It was postponed when the band 's then record company , Mds , was bought by Festival Records . The band eventually returned to the project in 2002 , after their covers album Dedicated to the Ones We Love . It was released on their own label , Teardrop , the following year . The title of the album Shangri-La , refers to an illusory island paradise , a lost utopia that exists only in imagination and metaphor an apt name considering it was almost abandoned as an impossible project . In an interview Phil Kakulas commented `` It was named before , back when I still had all faith that it would be released , '' Kakulas begins , `` but it seems almost prophetic in that we did almost lose it . The name ` Shangri-La ' seems to sum up a lot of what the album is about . The songs seem to deal with what happiness might be and where you might find happiness . Also I 've been listening to a lot of the Shangri-Las , the girl group , and I like that seedy neon lights appeal . My vision of Shangri-La is much more like Vegas or something like that . It 's a fools paradise . '' Shangri-La was nominated for ` Best Adult Contemporary Album ' at the 2003 ARIA Awards , missing out to John Farnham 's The Last Time .",
"title": ""
},
{
"docid": "Return_to_Paradise_(1935_film)",
"text": "Return to Paradise ( French : Retour au paradis ) is a 1935 French film directed by Serge de Poligny and starring Claude Dauphin , Mary Morgan and Marcel André . The film 's sets were designed by Pierre Schild .",
"title": ""
},
{
"docid": "Vince_Vaughn",
"text": "Vincent Anthony Vaughn ( born March 28 , 1970 ) is an American actor , producer , screenwriter , activist , and comedian . Vaughn began acting in the late 1980s , appearing in minor television roles before attaining wider recognition with the 1996 comedy-drama film Swingers . He has appeared in a number of films in the 1990s , including the sports film Rudy ( 1993 ) , the sci-fi adventure dinosaur film The Lost World : Jurassic Park ( 1997 ) , and the drama-thriller Return to Paradise ( 1998 ) . In the 2000s , he acted in several comedies , including Old School ( 2003 ) , Dodgeball : A True Underdog Story ( 2004 ) , Wedding Crashers ( 2005 ) , The Break-Up ( 2006 ) , and Fred Claus ( 2007 ) . He continued his comedic roles in the 2010s with The Dilemma ( 2011 ) , The Watch ( 2012 ) , and The Internship ( 2013 ) . In 2015 , he starred as Frank Semyon in the second season of the HBO anthology crime drama television series True Detective alongside Colin Farrell , Taylor Kitsch and Rachel McAdams .",
"title": ""
},
{
"docid": "The_Paradise_Motel",
"text": "The Paradise Motel are an independent Australian rock band which formed in Hobart in 1994 . They relocated to Melbourne and issued two albums on Mushroom Records , Still Life ( 28 August 1996 ) and Flight Paths ( 4 June 1998 ) before moving to the United Kingdom where they released a third , Reworkings ( 27 February 1999 ) , before disbanding in early 2000 . The group reformed in January 2008 in Melbourne and issued more albums , Australian Ghost Story ( 11 June 2010 ) , I Still Hear Your Voice at Night ( 29 January 2011 ) and Oh Boy ( 2 September 2013 ) .",
"title": ""
},
{
"docid": "Squatta's_Paradise",
"text": "Squatta 's Paradise is the second extended play released by the American ska punk/anarcho punk band Choking Victim . The E.P. was recorded in April , 1996 and released later that same year . `` Squatta 's Paradise '' was later released in CD format in 2000 , along with `` Crack Rock Steady '' as the `` Crack Rock Steady/Squatta 's Paradise '' compilation .",
"title": ""
},
{
"docid": "Return_to_Paradise_(Randy_Stonehill_album)",
"text": "Return to Paradise is an album by Randy Stonehill , released in 1989 , on Myrrh Records . The title is a reference to Stonehill 's earlier album , Welcome to Paradise . This album was listed at No. 76 in the 2001 book , CCM Presents : The 100 Greatest Albums in Christian Music .",
"title": ""
},
{
"docid": "Gangsta's_Paradise_(album)",
"text": "Gangsta 's Paradise is the second studio album by rapper Coolio , released on November 21 , 1995 . It is Coolio 's best-selling album , with over three million copies sold in the United States . The album produced three singles , which became hits : the title track ( which was first used in the 1995 film Dangerous Minds , released before Coolio 's album ) , `` 1 , 2 , 3 , 4 ( Sumpin ' New ) '' , and `` Too Hot '' .",
"title": ""
},
{
"docid": "Death_in_Paradise_(TV_series)",
"text": "Death in Paradise is a British-French crime comedy-drama television series created by Robert Thorogood , starring Ben Miller ( series 1 -- 3 ) , Kris Marshall ( series 3 -- 6 ) & Ardal O'Hanlon ( series 6 -- present ) . The programme is a joint UK and French production filmed on the French Caribbean island of Guadeloupe and broadcast on BBC One in the United Kingdom and France 2 in France . Death in Paradise has enjoyed high ratings , leading to repeated renewals . A sixth series began broadcasting on 5 January 2017 and aired its finale on 23 February , with the subsequent DVD release occurring three days later on 27 February 2017 . The series will return in 2018 for a seventh series .",
"title": ""
},
{
"docid": "Rockin'_the_Paradise",
"text": "`` A.D. 1928 / Rockin ' the Paradise '' is the fourth single release from Styx 's 1981 triple-platinum album Paradise Theatre . It was released to rock stations as defined by Billboard Magazine . `` A.D. 1928 '' is a short , piano-based song by Dennis DeYoung , set to the same melody as `` The Best of Times '' , that segues into the song `` Rockin ' the Paradise '' . This and the preceding track would serve as the opening songs of not only the Paradise Theater album but also its subsequent tour and the 1996 Return to Paradise reunion tour . Tommy Shaw played the guitar solo on the studio version , but subsequent live versions include a second guitar solo from James Young towards the end . A video for the song was the tenth to air on MTV when it debuted in the U.S. on August 1 , 1981 .",
"title": ""
},
{
"docid": "Batman_Beyond:_Return_of_the_Joker",
"text": "Batman Beyond : Return of the Joker ( also known as Batman of the Future : Return of the Joker in Europe and Australia ) is a 2000 American direct-to-video animated film featuring the comic book superhero Batman and his archenemy , the Joker . It is set in the continuity of the animated series Batman Beyond , in which Bruce Wayne has retired from crime fighting , giving the mantle of Batman to high-school student Terry McGinnis , and serves as a sequel to both Batman : The Animated Series and The New Batman Adventures . As in the TV series , Will Friedle and Kevin Conroy star as Terry McGinnis and Bruce Wayne , respectively . Mark Hamill , who played the Joker opposite Conroy in Batman : The Animated Series and The New Batman Adventures , reprises his role . Before its release , the film was heavily edited to remove scenes of extreme violence , and some dialogue was altered , thus creating the `` Not-Rated '' version of the film . The original version was subsequently released on DVD following an online petition to have the original version released . It received a PG-13 rating from the Motion Picture Association of America ( MPAA ) for violence , the first animated Batman film and from Warner Bros. . Family Entertainment to do so . Mephisto Odyssey and Static-X contributed the song `` Crash ( The Humble Brothers Remix ) '' on the film 's soundtrack , along with a music video directed by Len Wiseman featured on the DVD .",
"title": ""
},
{
"docid": "Steve_Sekely",
"text": "Steve Sekely ( 1899-1979 ) was a Hungarian film director . Born Székely István , he was known by several names , based on his changing professional and immigration status , including Stefan Szekely . He directed films in Hungarian , German , and English . He worked as a newspaper journalist in Germany , before returning to Hungary in the early 1930s . He directed one of the most famous classic Hungarian films , the frequently revived comedy Hyppolit , a lakáj ( 1931 ) . That film was remade in 2000 and the original was later digitally restored and released on DVD . Sekely left pre-war Hungary , fleeing growing Fascism and laws restricting rights and professional opportunities for Jews . He worked in Hollywood for much of his subsequent career , directing mostly B movies and early episodic TV , although he directed his best-known English language film , the cult science fiction thriller The Day of the Triffids in the UK and returned to Hungary to direct his final film , The Girl Who Liked Purple Flowers , which was released in 1973 .",
"title": ""
},
{
"docid": "Pamela_Gordon_(actress)",
"text": "Pamela Gordon Wedner ( stage name Pamela Gordon , 8 April 1937 -- 21 September 2003 ) was an American film and stage actress . She was born in Pittsburgh , Pennsylvania . Her films included Frances ( 1982 ) , Weird Science , Another Day in Paradise ( 1998 ) and Chuck & Buck ( 2000 ) . She was acting in Harvey at the Laguna Playhouse six weeks before she died , aged 66 .",
"title": ""
},
{
"docid": "Paradise,_Texas_(film)",
"text": "Paradise , Texas is a 2006 family drama film directed by Lorraine Senna and starring Timothy Bottoms , Ben Estus , and Meredith Baxter . Premiering at the 2006 WorldFest Film Festival , Paradise , Texas received a Gold Remi Award . After a limited theatrical release , the film was made available on DVD in October 2006 .",
"title": ""
},
{
"docid": "Paradise_(1926_film)",
"text": "Paradise is a lost 1926 silent escapist-romance directed by Irvin Willat and released by First National Pictures . The film stars Milton Sills and Betty Bronson . Based on a popular novel , Paradise , by Cosmo Hamilton and John Russell . One of Sills most successful films .",
"title": ""
},
{
"docid": "Kimberley_Joseph",
"text": "Kimberley Joseph ( born August 30 , 1973 ) is a Canadian Australian actress who is based in the United States . Joseph was born in Canada , brought up on the Gold Coast in Australia and educated in Switzerland . After returning to Australia , she began a degree at Bond University but dropped out at the age of 19 when she was cast in the soap opera Paradise Beach . She had no formal acting training but appeared in the soap for the 18 months it was produced . After Paradise Beach ended , she had casual work on Hey Hey It 's Saturday before co-hosting the popular Seven Network series Gladiators . After two series of Gladiators , Joseph was eager to return to acting , so took the role of villain Joanne Brennan in Home and Away from 1995 to 1996 . In 1999 , she moved to the United States to study acting at the Atlantic Theater Company in New York City , then spent 18 months unsuccessfully auditioning for roles in Los Angeles . In 2001 , she was cast as Jo Ellison in the British television series Cold Feet . She appeared in the fourth and fifth series and returned to Australia two days after filming the final episode in 2002 . In 2004 , she appeared in a major recurring role as Dr. Grace Connelly in six episodes of the Australian soap opera All Saints . She returned to America after filming All Saints , where she got a small role as flight attendant Cindy Chandler in the pilot episode of Lost . The role was supposed to be a one-off in the pilot but a producer liked Joseph and the character , so brought her back for a recurring role in the second , third and sixth seasons . Away from acting , Joseph has been involved in efforts to highlight the effects of Soviet nuclear testing in Kazakhstan , including directing a short film .",
"title": ""
},
{
"docid": "Merlin:_The_Return",
"text": "Merlin : The Return is a 2000 British fantasy film written , produced , and directed by Paul Matthews . The film stars Rik Mayall , Patrick Bergin , Craig Sheffer , Adrian Paul , Julie Hartley , and Tia Carrere . The film is about chronicles the story of Merlin and King Arthur . The film was released in the United Kingdom on 22 December 2000 .",
"title": ""
},
{
"docid": "Paradise_(Styx_song)",
"text": "`` Paradise '' is the only single release from Styx 's 1997 live double album Return to Paradise . The song was originally written and recorded by Dennis DeYoung for his musical The Hunchback of Notre Dame . The song was re-recorded by Styx for inclusion as one of three new studio tracks on the live album . It was released only to radio stations and not commercially , charting at # 27 on the Billboard Adult Contemporary chart . It is , to date , the last Styx song to chart on the AC chart . At the same time , the track `` On My Way '' was also released to radio stations , but it failed to chart .",
"title": ""
},
{
"docid": "Return_to_Paradise_(Styx_album)",
"text": "Return to Paradise is a live album by Styx , released in 1997 . It features songs from their successful reunion tour with Tommy Shaw , but without John Panozzo , who died in July 1996 . It includes three new studio tracks , including `` Dear John '' , which Shaw wrote as a tribute to Panozzo .",
"title": ""
},
{
"docid": "Dream_Walkin'",
"text": "Dream Walkin ' is the fourth studio album from American country music artist Toby Keith . His last studio album for Mercury Records before signing with Dreamworks Records , it was certified gold by the RIAA for sales of 500,000 copies . The tracks `` We Were in Love '' , `` I 'm So Happy I Ca n't Stop Crying '' , `` Dream Walkin ' '' , and `` Double Wide Paradise '' were all released as singles . Respectively , these reached # 2 , # 2 , # 5 , and # 40 on the Hot Country Songs charts , making this the first studio album of Keith 's career not to produce any Number One hits . `` I 'm So Happy I Ca n't Stop Crying '' was originally recorded by British rock artist Sting on his 1997 album Mercury Falling , from which it was released as a single . The version featured here is a duet with Sting , and is Sting 's only entry on the country music charts . `` Jacky Don Tucker ( Play by the Rules , Miss All the Fun ) '' was later included in the soundtrack to the 2006 film Broken Bridges , which was also Keith 's debut as an actor . It was earlier included in the 2000 movie The Dukes of Hazzard : Hazzard in Hollywood ! A music video was filmed for `` Tired '' , although it was not released as a single .",
"title": ""
},
{
"docid": "Paradise_Lost_3:_Purgatory",
"text": "Paradise Lost 3 : Purgatory is a 2011 documentary film and sequel to the films Paradise Lost : The Child Murders at Robin Hood Hills and Paradise Lost 2 : Revelations . The three films chronicle the arrest , 18-year imprisonment , and eventual release of Damien Echols , Jason Baldwin , and Jessie Misskelley , otherwise known as the West Memphis Three . The films , directed by Joe Berlinger and Bruce Sinofsky , are considered to play a substantial role in generating publicity , awareness , and support for the innocence of the West Memphis 3 . It aired on HBO on January 12 , 2012 . The film was also nominated for a Primetime Emmy Award for Exceptional Merit in Documentary Filmmaking ( 2012 ) , and for an Academy Award for Best Documentary Feature .",
"title": ""
},
{
"docid": "Another_Day_in_Paradise_(film)",
"text": "Another Day in Paradise is a 1998 drama film directed by Larry Clark , and released by Trimark Pictures . It is based on the novel Another Day in Paradise written by Eddie Little . The movie won the Grand Prix award at the 1999 Festival du Film Policier de Cognac . The film starred James Woods , Melanie Griffith , Vincent Kartheiser and Natasha Gregson Wagner . Previously both Woods and Griffith had worked together in the 1975 film Night Moves and the 1990 TV film Women and Men : Stories of Seduction .",
"title": ""
}
] |
472
|
Glucose restriction to 0.05% reduces RLS (replicative life span) by 20-40% in S. cerevisiae.
|
[
{
"docid": "4414481",
"text": "Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals. We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide). In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals.",
"title": "Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration"
},
{
"docid": "7185591",
"text": "Calorie restriction slows aging and increases life span in many organisms. In yeast, a mechanistic explanation has been proposed whereby calorie restriction slows aging by activating Sir2. Here we report the identification of a Sir2-independent pathway responsible for a majority of the longevity benefit associated with calorie restriction. Deletion of FOB1 and overexpression of SIR2 have been previously found to increase life span by reducing the levels of toxic rDNA circles in aged mother cells. We find that combining calorie restriction with either of these genetic interventions dramatically enhances longevity, resulting in the longest-lived yeast strain reported thus far. Further, calorie restriction results in a greater life span extension in cells lacking both Sir2 and Fob1 than in cells where Sir2 is present. These findings indicate that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes.",
"title": "Sir2-Independent Life Span Extension by Calorie Restriction in Yeast"
},
{
"docid": "26330861",
"text": "Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.",
"title": "Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae."
}
] |
[
{
"docid": "1754001",
"text": "The sirtuins are a phylogenetically conserved family of NAD(+) -dependent protein deacetylases that consume one molecule of NAD(+) for every deacetylated lysine side chain. Their requirement for NAD(+) potentially makes them prone to regulation by fluctuations in NAD(+) or biosynthesis intermediates, thus linking them to cellular metabolism. The Sir2 protein from Saccharomyces cerevisiae is the founding sirtuin family member and has been well characterized as a histone deacetylase that functions in transcriptional silencing of heterochromatin domains and as a pro-longevity factor for replicative life span (RLS), defined as the number of times a mother cell divides (buds) before senescing. Deleting SIR2 shortens RLS, while increased gene dosage causes extension. Furthermore, Sir2 has been implicated in mediating the beneficial effects of caloric restriction (CR) on life span, not only in yeast, but also in higher eukaryotes. While this paradigm has had its share of disagreements and debate, it has also helped rapidly drive the aging research field forward. S. cerevisiae has four additional sirtuins, Hst1, Hst2, Hst3, and Hst4. This review discusses the function of Sir2 and the Hst homologs in replicative aging and chronological aging, and also addresses how the sirtuins are regulated in response to environmental stresses such as CR.",
"title": "Yeast sirtuins and the regulation of aging."
},
{
"docid": "4463811",
"text": "Dietary energy restriction has been a widely used means of experimentally extending mammalian life span. We report here that lifelong reduction in the concentration of a single dietary component, the essential amino acid L-methionine, from 0.86 to 0.17% of the diet results in a 30% longer life span of male Fischer 344 rats. Methionine restriction completely abolished growth, although food intake was actually greater on a body weight basis. Studies of energy consumption in early life indicated that the energy intake of 0.17% methionine-fed animals was near normal for animals of their size, although consumption per animal was below that of the much larger 0.86% methionine-fed rats. Increasing the energy intake of rats fed 0.17% methionine failed to increase their rate of growth, whereas restricting 0.85% methionine-fed rats to the food intake of 0.17% methionine-fed animals did not materially reduce growth, indicating that food restriction was not a factor in life span extension in these experiments. The biochemically well-defined pathways of methionine metabolism and utilization offer the potential for uncovering the precise mechanism(s) underlying this specific dietary restriction-related extension of life span.",
"title": "Low methionine ingestion by rats extends life span."
},
{
"docid": "11527822",
"text": "The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA. Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. A possible role of the conserved SIR2 in mammalian aging is discussed.",
"title": "The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13"
},
{
"docid": "6106004",
"text": "Publisher Summary The budding yeast Saccharomyces cerevisiae ( S. cerevisiae ) divides asymmetrically. In vegetative growth, yeast cells reproduce by budding, and the position where the bud forms ultimately determines the plane of cell division. This chapter describes the detailed procedures for the separation and isolation of mothers and daughters. These protocols have been used by investigators studying aging, bud site selection, and other aspects of asymmetric cell division. The chapter describes the procedures for performing life span analysis by micromanipulation and the steps for the large-scale collection of old cells. At the beginning and the end of a life span, it can be difficult to distinguish mothers from daughters. At most points in the life span, daughter cells are smaller than the mothers that produced them. In addition, mother cells will generally bud a second time before their daughter cells form their first bud. One method for effective isolation of virgin daughter cells from mother cells, but not for recovery of old mothers, is called a “baby machine. ” Mother cells are attached to a membrane and allowed to divide. Daughter cells from these attached cells are eluted continuously by washing the membrane.",
"title": "Separation of mother and daughter cells."
},
{
"docid": "23017040",
"text": "Reduced dietary methionine intake (0.17% methionine, MR) and calorie restriction (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are unclear, both regimens feature lower body weight and reductions in adiposity. Reduced fat deposition in CR is linked to preservation of insulin responsiveness in older animals. These studies examine the relationship between insulin responsiveness and visceral fat in MR and test whether, despite lower food intake observed in MR animals, decreased visceral fat accretion and preservation of insulin sensitivity is not secondary to CR. Accordingly, rats pair fed (pf) control diet (0.86% methinone, CF) to match the food intake of MR for 80 weeks exhibit insulin, glucose, and leptin levels similar to control-fed animals and comparable amounts of visceral fat. Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF. In a separate cohort, insulin responses of older MR animals as measured by oral glucose challenge are similar to young animals. Longitudinal assessments of MR and CF through 112 weeks of age reveal that MR prevents age-associated increases in serum lipids. By 16 weeks, MR animals show a 40% reduction in insulin-like growth factor-1 (IGF-1) that is sustained throughout life; CF IGF-1 levels decline much later, beginning at 112 weeks. Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction.",
"title": "Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction."
},
{
"docid": "19460822",
"text": "When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.",
"title": "Extending healthy life span--from yeast to humans."
},
{
"docid": "23664875",
"text": "Termination of replication forks at the natural termini of the rDNA of Saccharomyces cerevisiae is controlled in a sequence-specific and polar mode by the interaction of the Fob1p replication terminator protein with the tandem Ter sites located in the nontranscribed spacers. Here we show, by both 2D gel analyses and chromatin immunoprecipitations (ChIP), that there exists a second level of global control mediated by the intra-S-phase checkpoint protein complex of Tof1p and Csm3p that protect stalled forks at Ter sites against the activity of the Rrm3p helicase (\"sweepase\"). The sweepase tends to release arrested forks presumably by the transient displacement of the Ter-bound Fob1p. Consistent with this mechanism, very few replication forks were arrested at the natural replication termini in the absence of the two checkpoint proteins. In the absence of the Rrm3p helicase, there was a slight enhancement of fork arrest at the Ter sites. Simultaneous deletions of the TOF1 (or CSM3), and the RRM3 genes restored fork arrest by removing both the fork-releasing and fork-protection activities. Other genes such as MRC1, WSS1, and PSY2 that are also involved in the MRC1 checkpoint pathway were not involved in this global control. This observation suggests that Tof1p-Csm3p function differently from MRC1 and the other above-mentioned genes. This mechanism is not restricted to the natural Ter sites but was also observed at fork arrest caused by the meeting of a replication fork with transcription approaching from the opposite direction.",
"title": "The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae."
},
{
"docid": "23601616",
"text": "Objective:Consumption of high-fat diet exerts adverse effects on learning and memory formation, which is linked to impaired hippocampal function. Activation of glucagon-like peptide-1 (GLP-1) signalling ameliorates detrimental effects of obesity-diabetes on cognitive function; however, mechanisms underlying these beneficial actions remain unclear. This study examined effects of daily subcutaneous treatment with GLP-1 mimetic, Liraglutide, on synaptic plasticity, hippocampal gene expression and metabolic control in adult obese diabetic (ob/ob) mice. Results:Long-term potentiation (LTP) induced by area CA1 was completely abolished in ob/ob mice compared with lean controls. Deleterious effects on LTP were rescued (P<0.001) with Liraglutide. Indeed, Liraglutide-treated mice exhibited superior LTP profile compared with lean controls (P<0.01). Expression of hippocampal brain-derived neurotropic factor and neurotrophic tyrosine kinase receptor-type 2 were not significantly different, but synaptophysin and Mash1 were decreased in ob/ob mice. Treatment with Liraglutide over 21 days increased expression of Mash1 in ob/ob mice (2.0-fold; P<0.01). These changes were associated with significantly reduced plasma glucose (21% reduction; P<0.05) and markedly improved plasma insulin concentrations (2.1- to 3.3-fold; P<0.05 to P<0.01). Liraglutide also significantly reduced the glycaemic excursion following an intraperitonal glucose load (area under curve (AUC) values: 22%; P<0.05) and markedly enhanced the insulin response to glucose (AUC values: 1.6-fold; P<0.05). O2 consumption, CO2 production, respiratory exchange ratio and energy expenditure were not altered by Liraglutide therapy. On day 21, accumulated food intake (32% reduction; P<0.05) and number of feeding bouts (32% reduction; P<0.05) were significantly reduced but simple energy restriction was not responsible for the beneficial actions of Liraglutide. Conclusion:Liraglutide elicits beneficial effects on metabolic control and synaptic plasticity in mice with severe obesity and insulin resistance mediated in part through increased expression of Mash1 believed to improve hippocampal neurogenesis and cell survival.",
"title": "Liraglutide improves hippocampal synaptic plasticity associated with increased expression of Mash1 in ob/ob mice"
},
{
"docid": "15975146",
"text": "The fungal pathogen, Cryptococcus neoformans, has been shown to undergo replicative aging. Old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. As a consequence of this age-associated resilience, old cells accumulate during chronic infection. Based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the host and affect its virulence. SIR2 is a well-conserved histone deacetylase, and a pivotal target for the development of anti-aging drugs. We tested its effect on C. neoformans' replicative lifespan (RLS). First, a mutant C. neoformans strain (sir2Δ) was generated, and confirmed a predicted shortened RLS in sir2Δ cells consistent with its known role in aging. Next, RLS analysis showed that treatment of C. neoformans with Sir2p-agonists resulted in a significantly prolonged RLS, whereas treatment with a Sir2p-antagonist shortened RLS. RLS modulating effects were dependent on SIR2 and not observed in sir2Δ cells. Because SIR2 loss resulted in a slightly impaired fitness, effects of genetic RLS modulation on virulence could not be compared with wild type cells. Instead we chose to chemically modulate RLS, and investigated the effect of Sir2p modulating drugs on C. neoformans cells in a Galleria mellonella infection model. Consistent with our hypothesis that shifts in the generational age of the infecting yeast population alters its vulnerability to host cells, we observed decreased virulence of C. neoformans in the Galleria host when RLS was prolonged by treatment with Sir2p agonists. In contrast, treatment with a Sir2p antagonist, which shortens RLS enhanced virulence in Galleria. In addition, combination of Sir2p agonists with antifungal therapy enhanced the antifungal's effect. Importantly, no difference in virulence was observed with drug treatment when sir2Δ cells were used for infection, which confirmed target specificity and ruled out non-specific effects of the drugs on the Galleria host. Thus, this study suggests that RLS modulating drugs, such as Sir2p agonists, shift lifespan and vulnerability of the fungal population, and should be further investigated as a potential class of novel antifungal drug targets that can enhance antifungal efficacy.",
"title": "Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence"
},
{
"docid": "26596106",
"text": "In the yeast S. cerevisiae, ribosome assembly is linked to environmental conditions by the coordinate transcriptional regulation of genes required for ribosome biogenesis. In this study we show that two nonessential stress-responsive genes, YAR1 and LTV1, function in 40S subunit production. We provide genetic and biochemical evidence that Yar1, a small ankyrin-repeat protein, physically interacts with RpS3, a component of the 40S subunit, and with Ltv1, a protein recently identified as a substoichiometric component of a 43S preribosomal particle. We demonstrate that cells lacking YAR1 or LTV1 are hypersensitive to particular protein synthesis inhibitors and exhibit aberrant polysome profiles, with a reduced absolute number of 40S subunits and an excess of free 60S subunits. Surprisingly, both mutants are also hypersensitive to a variety of environmental stress conditions. Overexpression of RPS3 suppresses both the stress sensitivity and the ribosome biogenesis defect of Deltayar1 mutants, but does not suppress either defect in Deltaltv1 mutants. We propose that YAR1 and LTV1 play distinct, nonessential roles in 40S subunit production. The stress-sensitive phenotypes of strains lacking these genes reveal a hitherto unknown link between ribosome biogenesis factors and environmental stress sensitivity.",
"title": "Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae."
},
{
"docid": "14145440",
"text": "BACKGROUND DNA replication and mitosis are triggered by activation of kinase complexes, each made up of a cyclin and a cyclin-dependent kinase (Cdk). It had seemed possible that the association of Cdks with different classes of cyclins specifies whether S phase (replication) or M phase (mitosis) will occur. The recent finding that individual B-type cyclins (encoded by the genes CLB1-CLB6) can have functions in both processes in the budding yeast Saccharomyces cerevisiae casts doubt on this notion. RESULTS S. cerevisiae strains lacking C1b1-C1b4 undergo DNA replication once but fail to enter mitosis. We have isolated mutations in two genes, SIM1 and SIM2 (SIM2 is identical to SEC72), which allow such cells to undergo an extra round of DNA replication without mitosis. The Clb5 kinase, which promotes S phase, remains active during the G2-phase arrest of cells of the parental strain, but its activity declines rapidly in sim mutants. Increased expression of the CLB5 gene prevents re-replication. Thus, a cyclin B-kinase that promotes DNA replication in G1-phase cells can prevent re-replication in G2-phase cells. Inactivation of C1b kinases by expression of the specific C1b-Cdk1 inhibitor p40SIC1 is sufficient to induce a prereplicative state at origins of replication in cells blocked in G2/M phase by nocodazole. Re-activation of C1b-Cdk1 kinases induces a second round of DNA replication. CONCLUSIONS We propose that S-phase-promoting cyclin B--Cdk complexes prevent re-replication during S, G2 and M phases by inhibiting the transition of replication origins to a pre-replicative state. This model can explain both why origins 'fire' only once per S phase and why S phase is dependent on completion of the preceding M phase.",
"title": "S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state"
},
{
"docid": "6277638",
"text": "The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation. Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.",
"title": "Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster"
},
{
"docid": "14544564",
"text": "Sterol-sensing nuclear receptors and insulin-like growth factor signaling play evolutionarily conserved roles in the control of aging. In the nematode Caenorhabditis elegans, bile acid-like steroid hormones known as dafachronic acids (DAs) influence longevity by binding to and regulating the activity of the conserved nuclear receptor DAF-12, and the insulin receptor (InsR) ortholog DAF-2 controls life span by inhibiting the FoxO transcription factor DAF-16. How the DA/DAF-12 pathway interacts with DAF-2/InsR signaling to control life span is poorly understood. Here we specifically investigated the roles of liganded and unliganded DAF-12 in life span control in the context of reduced DAF-2/InsR signaling. In animals with reduced daf-2/InsR activity, mutations that either reduce DA biosynthesis or fully abrogate DAF-12 activity shorten life span, suggesting that liganded DAF-12 promotes longevity. In animals with reduced DAF-2/InsR activity induced by daf-2/InsR RNAi, both liganded and unliganded DAF-12 promote longevity. However, in daf-2/InsR mutants, liganded and unliganded DAF-12 act in opposition to control life span. Thus, multiple DAF-12 activities influence life span in distinct ways in contexts of reduced DAF-2/InsR signaling. Our findings establish new roles for a conserved steroid signaling pathway in life span control and elucidate interactions among DA biosynthetic pathways, DAF-12, and DAF-2/InsR signaling in aging.",
"title": "Influence of Steroid Hormone Signaling on Life Span Control by Caenorhabditis elegans Insulin-Like Signaling"
},
{
"docid": "6718824",
"text": "Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.",
"title": "Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat."
},
{
"docid": "13940200",
"text": "Genome-wide association studies are now identifying disease-associated chromosome regions. However, even after convincing replication, the localization of the causal variant(s) requires comprehensive resequencing, extensive genotyping and statistical analyses in large sample sets leading to targeted functional studies. Here, we have localized the type 1 diabetes (T1D) association in the interleukin 2 receptor alpha (IL2RA) gene region to two independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5′ regions of IL2RA and RBM17 (odds ratio = 2.04, 95% confidence interval = 1.70–2.45; P = 1.92 × 10−28; control frequency = 0.635). Furthermore, we have associated IL2RA T1D susceptibility genotypes with lower circulating levels of the biomarker, soluble IL-2RA (P = 6.28 × 10−28), suggesting that an inherited lower immune responsiveness predisposes to T1D.",
"title": "Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes"
},
{
"docid": "35345807",
"text": "Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD(+) concentration through the combined action of NAD(+) biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD(+) precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD(+) salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD(+) concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD(+). The INAM-induced increase in NAD(+) was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD(+) salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD(+). We also provide evidence suggesting that INAM influences the expression of multiple NAD(+) biosynthesis and salvage pathways to promote homeostasis during stationary phase.",
"title": "Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration."
},
{
"docid": "1576955",
"text": "Mutations in daf-2 and age-1 cause a dramatic increase in longevity as well as developmental arrest at the dauer diapause stage in Caenorhabditis elegans. daf-2 and age-1 encode components of an insulin-like signaling pathway. Both daf-2 and age-1 act at a similar point in the genetic epistasis pathway for dauer arrest and longevity and regulate the activity of the daf-16 gene. Mutations in daf-16 cause a dauer-defective phenotype and are epistatic to the diapause arrest and life span extension phenotypes of daf-2 and age-1 mutants. Here we show that mutations in this pathway also affect fertility and embryonic development. Weak daf-2 alleles, and maternally rescued age-1 alleles that cause life span extension but do not arrest at the dauer stage, also reduce fertility and viability. We find that age-1(hx546) has reduced both maternal and zygotic age-1 activity. daf-16 mutations suppress all of the daf-2 and age-1 phenotypes, including dauer arrest, life span extension, reduced fertility, and viability defects. These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. The regulation of fertility, life span, and metabolism by an insulin-like signaling pathway is similar to the endocrine regulation of metabolism and fertility by mammalian insulin signaling.",
"title": "An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans."
},
{
"docid": "26083387",
"text": "The Saccharomyces cerevisiae DNA helicase Rrm3p is needed for normal fork progression through >1000 discrete sites scattered throughout the genome. Here we show that replication of all yeast chromosomes was markedly delayed in rrm3 cells. Delayed replication was seen even in a region that lacks any predicted Rrm3p-dependent sites. Based on the pattern of replication intermediates in two-dimensional gels, the rate of fork movement in rrm3 cells appeared similar to wild-type except at known Rrm3p-dependent sites. These data suggest that although Rrm3p has a global role in DNA replication, its activity is needed only or primarily at specific, difficult-to-replicate sites. By the criterion of chromatin immunoprecipitation, Rrm3p was associated with both Rrm3p-dependent and -independent sites, and moved with the replication fork through both. In addition, Rrm3p interacted with Pol2p, the catalytic subunit of DNA polymerase epsilon, in vivo. Thus, rather than being recruited to its sites of action when replication forks stall at these sites, Rrm3p is likely a component of the replication fork apparatus.",
"title": "The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes."
},
{
"docid": "23918031",
"text": "The platelet precursor, the megakaryocyte, matures to a polyploid cell as a result of DNA replication in the absence of mitosis (endomitosis). The factors controlling endomitosis are accessible to analysis in our megakaryocytic cell line, MegT, generated by targeted expression of temperature-sensitive simian virus 40 large T antigen to megakaryocytes of transgenic mice. We aimed to define whether endomitosis consists of a continuous phase of DNA synthesis (S) or of S phases interrupted by gaps. Analysis of the cell cycle in MegT cells revealed that, upon inactivation of large T antigen, the cells shifted from a mitotic cell cycle to an endomitotic cell cycle consisting of S/Gap phases. The level of the G1/S cyclin, cyclin A, as well as of the G1 phase cyclin, cyclin D3, were elevated at the onset of DNA synthesis, either in MegT cells undergoing a mitotic cell cycle or during endomitosis. In contrast, the level of the mitotic cyclin, cyclin B1, cycled in cells displaying a mitotic cell cycle while not detectable during endomitosis. Comparable levels of the mitotic kinase protein, Cdc2, were detected during the mitotic cell cycle or during endomitosis; however, cyclin B1-dependent Cdc2 kinase activity was largely abolished in the polyploid cells. Fibroblasts immortalized with the same heat-labile oncogene do not display reduced levels of cyclin B1 upon shifting to high temperature nor do they become polyploid, indicating that reduced levels of cyclin B1 is a property of megakaryocytes and not of the T-antigen mutant. We conclude that cellular programming during endoreduplication in megakaryocytes is associated with reduced levels of cyclin B1.",
"title": "The cell cycle in polyploid megakaryocytes is associated with reduced activity of cyclin B1-dependent cdc2 kinase."
},
{
"docid": "344240",
"text": "Actions of protein products resulting from alternative splicing of the Igf1 gene have received increasing attention in recent years. However, the significance and functional relevance of these observations remain poorly defined. To address functions of IGF-I splice variants, we examined the impact of loss of IGF-IEa and IGF-IEb on the proliferation and differentiation of cultured mouse myoblasts. RNA interference-mediated reductions in total IGF-I, IGF-IEa alone, or IGF-IEb alone had no effect on cell viability in growth medium. However, cells deficient in total IGF-I or IGF-IEa alone proliferated significantly slower than control cells or cells deficient in IGF-IEb in serum-free media. Simultaneous loss of both or specific loss of either splice variant significantly inhibited myosin heavy chain (MyHC) immunoreactivity by 70-80% (P < 0.01) under differentiation conditions (48 h in 2% horse serum) as determined by Western immunoblotting. This loss in protein was associated with reduced MyHC isoform mRNAs, because reductions in total IGF-I or IGF-IEa mRNA significantly reduced MyHC mRNAs by approximately 50-75% (P < 0.05). Loss of IGF-IEb also reduced MyHC isoform mRNA significantly, with the exception of Myh7, but to a lesser degree (∼20-40%, P < 0.05). Provision of mature IGF-I, but not synthetic E peptides, restored Myh3 expression to control levels in cells deficient in IGF-IEa or IGF-IEb. Collectively, these data suggest that IGF-I splice variants may regulate myoblast differentiation through the actions of mature IGF-I and not the E peptides.",
"title": "Loss of IGF-IEa or IGF-IEb impairs myogenic differentiation."
},
{
"docid": "516867",
"text": "The unicellular eukaryotic organisms represent the popular model systems to understand aging in eukaryotes. Candida albicans, a polymorphic fungus, appears to be another distinctive unicellular aging model in addition to the budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe. The two types of Candida cells, yeast (blastospore) form and hyphal (filamentous) form, have similar replicative lifespan. Taking the advantage of morphologic changes, we are able to obtain cells of different ages. Old Candida cells tend to accumulate glycogen and oxidatively damaged proteins. Deletion of the SIR2 gene causes a decrease of lifespan, while insertion of an extra copy of SIR2 extends lifespan, indicating that like in S. cerevisiae, Sir2 regulates cellular aging in C. albicans. Interestingly, Sir2 deletion does not result in the accumulation of extra-chromosomal rDNA molecules, but influences the retention of oxidized proteins in mother cells, suggesting that the extra-chromosomal rDNA molecules may not be associated with cellular aging in C. albicans. This novel aging model, which allows efficient large-scale isolation of old cells, may facilitate biochemical characterizations and genomics/proteomics studies of cellular aging, and help to verify the aging pathways observed in other organisms including S. cerevisiae.",
"title": "Candida albicans, a distinctive fungal model for cellular aging study"
},
{
"docid": "9513785",
"text": "We previously reported that maternal protein restriction in rodents influenced the rate of growth in early life and ultimately affected longevity. Low birth weight caused by maternal protein restriction followed by catch-up growth (recuperated animals) was associated with shortened lifespan whereas protein restriction and slow growth during lactation (postnatal low protein: PLP animals) increased lifespan. We aim to explore the mechanistic basis by which these differences arise. Here we investigated effects of maternal diet on organ growth, metabolic parameters and the expression of insulin/IGF1 signalling proteins and Sirt1 in muscle of male mice at weaning. PLP mice which experienced protein restriction during lactation had lower fasting glucose (P = 0.038) and insulin levels (P = 0.046) suggesting improved insulin sensitivity. PLP mice had higher relative weights (adjusted by body weight) of brain (P = 0.0002) and thymus (P = 0.031) compared to controls suggesting that enhanced functional capacity of these two tissues is beneficial to longevity. They also had increased expression of insulin receptor substrate 1 (P = 0.021) and protein kinase C zeta (P = 0.046). Recuperated animals expressed decreased levels of many insulin signalling proteins including PI3 kinase subunits p85alpha (P = 0.018), p110beta (P = 0.048) and protein kinase C zeta (P = 0.006) which may predispose these animals to insulin resistance. Sirt1 protein expression was reduced in recuperated offspring. These observations suggest that maternal protein restriction can affect major metabolic pathways implicated in regulation of lifespan at a young age which may explain the impact of maternal diet on longevity.",
"title": "Maternal Protein Restriction Affects Postnatal Growth and the Expression of Key Proteins Involved in Lifespan Regulation in Mice"
},
{
"docid": "33960383",
"text": "Abstract Evidence obtained in the 1990's strongly supports the notion that glycaemic control is important not only in Type I (insulin-dependent), but also in Type II (non-insulin-dependent) diabetes mellitus. Although measurement of HbA1c is the standard for assessing the effect of glucose control in the occurrence and prevention of diabetic sequelae, more recent evidence indicates that other glucose parameters are also important. Postchallenge and postprandial hyperglycaemic peaks seem to be prospective determinants of vascular damage in early Type II diabetes. Currently, there is no overall accepted standard approach for the pharmacological management of Type II diabetes. The United Kingdom Prospective Diabetes Study has shown that reaching a near-normal glycaemic target is critically important and the pharmacotherapy of this progressive disease is difficult. Loss of endogenous insulin secretion has been substantiated to cause the progression of Type II diabetes in the United Kingdom Prospective Diabetes Study. Early insulinization, however, was not advantageous over other forms of therapy. The advent of polypharmacy in recent years has greatly strengthened the treatment of this disease. This synergy has been extended of late with the development of early-phase insulin secretion agents. Two such agents, nateglinide and repaglinide, can be used to reduce mealtime glucose excursions and HbA1c as monotherapy, and in combination with metformin; their antidiabetic potential is similar to the combination treatment with glibenclamide and metformin. Additional substantiation of their long-term effect on improving life expectancy and reducing diabetic complications in Type II diabetic patients is now required.",
"title": "The role of oral antidiabetic agents: why and when to use an early-phase insulin secretion agent in Type II diabetes mellitus"
},
{
"docid": "31407112",
"text": "The loss of the ability to deaminate l-serine severely impairs growth and cell division in Escherichia coli K-12. A strain from which the three genes (sdaA, sdaB, tdcG) coding for this organism's three l-serine deaminases had been deleted grows well in glucose minimal medium but, on subculture into minimal medium with glucose and casamino acids, it makes very large, abnormally shaped cells, many of which lyse. When inoculated into Luria-Bertani (LB) broth with or without glucose, it makes very long filaments. Provision of S-adenosylmethionine restores cell division in LB broth with glucose, and repairs much of the difficulty in growth in medium with casamino acids. We suggest that replication of E. coli is regulated by methylation, that an unusually high intracellular l-serine concentration, in the presence of other amino acids, starves the cell for S-adenosylmethionine and that it is the absence of S-adenosylmethionine and/or of C1-tetrahydrofolate derivatives that prevents normal cell division.",
"title": "Deficiency in l-serine deaminase results in abnormal growth and cell division of Escherichia coli K-12."
},
{
"docid": "26710772",
"text": "Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.",
"title": "Sympathetic activation during early pregnancy in humans."
},
{
"docid": "36606083",
"text": "Many fundamental aspects of DNA replication, such as the exact locations where DNA synthesis is initiated and terminated, how frequently origins are used, and how fork progression is influenced by transcription, are poorly understood. Via the deep sequencing of Okazaki fragments, we comprehensively document replication fork directionality throughout the S. cerevisiae genome, which permits the systematic analysis of initiation, origin efficiency, fork progression, and termination. We show that leading-strand initiation preferentially occurs within a nucleosome-free region at replication origins. Using a strain in which late origins can be induced to fire early, we show that replication termination is a largely passive phenomenon that does not rely on cis-acting sequences or replication fork pausing. The replication profile is predominantly determined by the kinetics of origin firing, allowing us to reconstruct chromosome-wide timing profiles from an asynchronous culture.",
"title": "Quantitative, genome-wide analysis of eukaryotic replication initiation and termination."
},
{
"docid": "39187170",
"text": "Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.",
"title": "Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity."
},
{
"docid": "24494539",
"text": "OBJECTIVE To observe the clinical effects of acupuncture combined with auricular point sticking based on the western medication for post stroke depression (PSD). METHODS Sixty patients with PSD were randomly assigned into an acupuncture plus auricular application group (a combination group) and a medication group, 30 cases in each one. 20 mg paroxetine hydrochloride was prescribed orally in the medication group, once a day for continuous 8 weeks. Based on the above treatment, 30-minute acupuncture was used in the combination group for 8 weeks at Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Yintang (GV 29), Shenmen (HT 7), Neiguan (PC 6), Taichong (LR 3), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Fenglong (ST 40), once the other day and three times a week. Auricular point sticking therapy for 8 weeks was applied at shenmen (TF4), pizhixia (AT4), xin (CO15), and gan (CO12), with pressing 3 times a day and once 3-5 days. The total score and each factor scores of Hamilton's depression scale (HAMD) were observed in the two groups before and after treatment, and Asberg's antidepressant side-effect rating scale (SERS) and clinical effect were evaluated. RESULTS After treatment, the total HAMD scores of the two groups decreased compared with those before treatment (both P<0.05), with better effect in the combination group (P<0.05). The scores of the combination group after treatment were lower than those in the medication group, including the anxiety/somatization factor, sleep disturbance factor, hopelessness factor (all P<0.05). The total effective rate of the combination group was 86.7% (26/30), which was better than 66.7% (20/30) of the medication group (P<0.05). The SERS score of the combination group was lower than that of the medication group (P<0.05). CONCLUSIONS Acupuncture combined with auricular point sticking can improve the clinical symptoms and are effective and safe for PSD.",
"title": "[Acupuncture combined with auricular point sticking therapy for post stroke depression:a randomized controlled trial]."
},
{
"docid": "3761017",
"text": "BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.",
"title": "Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion"
},
{
"docid": "40996863",
"text": "STUDY OBJECTIVE To review evidence on the association between restless legs syndrome (RLS) and attention-deficit/hyperactivity disorder (ADHD), to discuss the hypothetical mechanisms underlying this association, and to consider the potential interest for common pharmacologic treatments of RLS and ADHD when co-occurring. METHOD A PubMed search. RESULTS In clinical samples, up to 44% of subjects with ADHD have been found to have RLS or RLS symptoms, and up to 26% of subjects with RLS have been found to have ADHD or ADHD symptoms. Several mechanisms may explain this association. Sleep disruption associated with RLS might lead to inattentiveness, moodiness, and paradoxical overactivity. Diurnal manifestations of RLS, such as restlessness and inattention, might mimic ADHD symptoms. Alternatively, RLS might be comorbid with idiopathic ADHD. Subjects with RLS and a subset of subjects with ADHD might share a common dopamine dysfunction. Limited evidence suggests that some dopaminergic agents, such as levodopa/carbidopa, pergolide, and ropinirole, may be effective in children with RLS associated with ADHD symptoms. CONCLUSIONS Although still limited, evidence from clinical studies demonstrates an association between RLS and ADHD or ADHD symptoms. Further clinical studies using standard criteria and procedures are needed to better estimate the degree of association. Epidemiologic studies are required to assess the relationship between ADHD and RLS symptoms in nonclinical samples. Further investigations should address the mechanisms underlying the relationship between RLS and ADHD. Several dopaminergic agents seem to be promising treatment for RLS associated with ADHD symptoms. To date, however, the absence of randomized and blinded controlled studies does not allow evidence-based recommendations.",
"title": "Restless legs syndrome and attention-deficit/hyperactivity disorder: a review of the literature."
}
] |
150875
|
1996 was the year when Sophie Turner was born.
|
[
{
"docid": "Sophie_Turner",
"text": "Sophie Turner ( born 21 February 1996 ) is an English actress . Turner made her professional acting debut as Sansa Stark on the HBO fantasy television series Game of Thrones ( 2011 -- present ) , which brought her international recognition and critical praise . For her performance , she has received four nominations for Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Drama Series , as well as a Young Artist Award nomination for Best Supporting Young Actress in a TV Series . Turner has also starred in the television film The Thirteenth Tale ( 2013 ) and she made her feature film debut in Another Me ( 2013 ) . She has also starred in the action comedy Barely Lethal ( 2015 ) and played Jean Grey / Phoenix in the X-Men film series .",
"title": ""
}
] |
[
{
"docid": "Sophie_Turner_(disambiguation)",
"text": "Sophie Turner is an English actress . Sophie Turner may also refer to : Sophie Turner ( model ) ( born 1984 ) , Australian model and reality television personality Sophie Turner Laing ( born 1960 ) , British businesswoman",
"title": ""
},
{
"docid": "Sophie_Turner_(model)",
"text": "Sophie Turner ( born 30 April 1984 ) is an Australian model , reality television personality and lawyer who first came to prominence as a contestant on the Australian television series Search for a Supermodel .",
"title": ""
},
{
"docid": "Sophie_Turner_Laing",
"text": "Sophie Turner Laing ( born 7 September 1960 ) is a British businesswoman and media executive . She has been Chief Executive Officer of global content creator , producer and distributor Endemol Shine Group since December 2014 . Prior to taking up her current role , she held a number of senior positions at Sky in the UK , including Director of Movies and Managing Director of Content . She had previously worked for the BBC as Acting Director of Television and , along with Peter Orton , was a founder of HiT Entertainment .",
"title": ""
},
{
"docid": "Sophie_Falkiner",
"text": "Sophie Falkiner ( born 20 March 1974 , in Melbourne ) is an Australian television presenter . Sophie has previously presented an entertainment news series Confidential on Fox8 . She was also a presenter on The Great Outdoors and letter-turner on Wheel of Fortune . Falkiner 's big break on Wheel of Fortune came after completing a Bachelor of Media Studies ( majoring in journalism ) at Macquarie University . In addition to hosting Sydney Weekender , she also hosted Crown Australian Celebrity Poker Challenge . She also worked as a research assistant for Today Tonight . Sophie also works as a spokesmodel , having represented Berlei and Wonderbra in Australia and has appeared on the covers of various Australian magazines . She also featured in a series of ads for Neutrogena . Falkiner has appeared on Sunrise and filled in for Kerri-Anne Kennerley on Kerri-Anne . She was married to Tony Thomas and has one daughter Isabella Grace Thomas , born on 28 March 2005 and one son Jack Aston Thomas born on 28 January 2009 .",
"title": ""
},
{
"docid": "Neil_Turner_(Australian_politician)",
"text": "Neil John Turner ( 25 June 1934 -- 4 July 2011 ) was a National Party of Australia politician from Queensland . He served as the Minister of Transport and Speaker of the Legislative Assembly of Queensland . Turner was born in 1934 in Charleville . He served as the member for Warrego between 1974 and 1986 , and the member for Nicklin between 1990 and 1998 , when he lost his seat to independent Peter Wellington . He served as Speaker from 1996 until his 1998 defeat . On 4 July 2011 , Turner died at the age of 77 .",
"title": ""
},
{
"docid": "Turner_Program_Services",
"text": "Turner Program Services was the former syndication arm of Turner Broadcasting . It served the same purpose as Turner Entertainment 's distribution unit , with the exception that TPS was more involved in distributing television series rather than films . Founded in 1982 , the company was originally responsible for syndicating Turner-produced programs ( such as the syndicated game show Starcade ) as well as developing programming for TBS such as Night Tracks . TPS expanded its distribution into other networks ' series in the 1990s , syndicating series such as The Wonder Years ( which is now owned by 20th Television since 2011 ) . When Turner bought the rights to the Hanna-Barbera library of cartoons TPS became their distributor to local stations . One of the more notable series TPS was responsible for developing was Captain Planet and the Planeteers , which was a co-production with DiC Entertainment and centered on a character created by Turner Broadcasting founder Ted Turner . DiC and Turner combined on the development of the series while TPS was responsible for the distribution of the series , which aired on both TBS and in syndication . ( When the series ' sequel , The New Adventures of Captain Planet , debuted in 1993 , Turner Entertainment through Hanna-Barbera developed and produced the series on its own , and neither TPS nor DiC was involved . ) Also , earlier in 1986 , TPS , with the help of veteran anime translator Fred Ladd , produced a second English translation of the 1970s anime Science Ninja Team Gatchaman called G-Force : Guardians of Space , which would subsequently air on TBS ( 1986 ) and Cartoon Network ( 1995 -- 1997 ) . TPS also held partial distribution rights to G-Force ( along with King Features Entertainment ) until all rights to the series reverted to license holder Sandy Frank Entertainment in 2003 . Upon Time Warner 's purchase of Turner in 1996 , TPS was merged into Telepictures Productions and the combined entity became known as Telepictures Distribution , which is now part of Warner Bros. . Television Distribution ( Telepictures still exists as a production company ) . Category : Time Warner subsidiaries Category : Companies established in 1982 Category : Companies disestablished in 1996 Category : Television syndication distributors Category :1982 establishments in the United States",
"title": ""
},
{
"docid": "Dick_Turner",
"text": "Richard `` Dick '' Turner ( 19 August 1932 -- 16 June 2008 ) , a.k.a. `` Tosser '' , was a rugby league manager . Turner was born in 1932 and played in the Brisbane Rugby League competition for Brisbane Norths and Redcliffe . He also coached Redcliffe in 1968 and 1969 . Turner was the Queensland state rugby league team 's manager from 1982 until 1996 , when he stepped down to take a role in the `` Former Origin Greats '' ( FOGS ) organisation . He was also the Australian team manager on the 1986 Kangaroo Tour of Great Britain . He was also chairman of the South Queensland Crushers club during its entire existence from 1995 to 1997 . In 2008 , during his battle with illness he wrote a letter for the Queensland rugby league team which has been read to them for inspiration in subsequent State of Origin series . He died as chairman of FOGS on 16 June 2008 because of long-term illness . That year he won the `` Service to Sport Award '' at the Queensland Sport Awards . Actor Michael Caton inherited Turner 's ` cultural ambassador role with the Queensland rugby league team . During the 2009 State of Origin series , he was honoured outside Lang Park with a plaque .",
"title": ""
},
{
"docid": "Venues_of_the_1996_Summer_Olympics",
"text": "For the 1996 Summer Olympics , a total of twenty-nine sports venues were used . Several sports venues for the 1996 Olympics were built before the 1960s as college venues . The first professional teams in Atlanta came in 1966 , when Major League Baseball 's Atlanta Braves moved from Milwaukee and the NFL added the Atlanta Falcons as an expansion team . In 1968 , the NBA came to the city when the Atlanta Hawks arrived from St. Louis , and the NHL arrived four years later with the expansion Atlanta Flames . The Braves and Falcons shared Atlanta -- Fulton County Stadium from 1966 through 1991 , after which the Falcons moved into the Georgia Dome , playing at that stadium from 1992 through 2016 . The Braves would remain at the former stadium through the 1996 season . The Hawks initially played at Alexander Memorial Coliseum , now McCamish Pavilion , on the campus of Georgia Institute of Technology ( better known as Georgia Tech ) before the Omni Coliseum was completed in 1972 for both the Hawks and Flames . After the , the Flames left for their current home of Calgary . Bidding for the 1996 Games was held in 1990 . Seventy-five percent of the venues used for the 1996 Games were owned by the state of Georgia . One of the new venues , the Georgia International Horse Park , had organization issues for the modern pentathlon event that included the competitors being forced to sit under an oak tree during the riding part of the event . The Georgia World Congress Center hosted the dramatic weightlifting 64 kg event that involved national tensions between Greece and Turkey . After the Olympics , the Olympic Stadium , as intended from its construction , was converted into a baseball park known as Turner Field , which opened in 1997 . That same year , both Atlanta -- Fulton County Stadium and the Omni Coliseum were imploded within one week of one another . Philips Arena was built upon the former Omni 's footprint and opened in 1999 , while the area where Atlanta -- Fulton County Stadium stood is now a parking lot near Turner Field . The Braves vacated Turner Field after their 2016 season to move to a new ballpark , SunTrust Park , in Cobb County ; Georgia State University acquired Turner Field and its surrounding parking lots in January 2017 and is currently converting the former Olympic Stadium a second time into Georgia State Stadium to host their college football program .",
"title": ""
},
{
"docid": "Hayley_Turner",
"text": "Hayley Turner OBE ( born 3 January 1983 ) is a retired English professional jockey with 764 career wins . Turner is widely considered to be the first woman to achieve a sustained , day-in , day-out , successful career as a professional jockey in the UK . Hayley Turner 's success has seen an enormous increase in the number of female apprentice jockeys riding in the UK in the second decade of the 21st century . She became the first women to ride 100 UK Flat race winners during a calendar year , when winning on ` Mullitovermaurice ' at Wolverhampton on 30 December 2008 . In that year Turner rode in over 900 races in the UK - one of only five riders to achieve the milestone that year . On 31 August 2015 Turner announced that she would retire from riding at the end of the season . Among many plans she will join the horse racing broadcaster At The Races . In 2016 , it was announced that she will be a regular contributor to the new ITV Racing team when their 4-year deal as the new terrestrial home of British horse racing comes into effect on 1 January 2017 .",
"title": ""
},
{
"docid": "Phil_Turner_(footballer,_born_1962)",
"text": "Phil Turner ( born 12 February 1962 in Sheffield , England ) is a retired English footballer . Turner , a central midfielder , began his career at Lincoln City with whom he won promotion to the Third Division in 1981 under Colin Murphy , and formed midfield partnerships with Glenn Cockerill and then Neil Redfearn before joining Grimsby Town in 1986 . In May 1985 he was to witness a nightmare when 56 spectators were killed in a horrendous stand fire while playing Bradford City . A brief spell at Leicester City followed before he joined Notts County in 1989 . He would become a stalwart of the Magpies side , winning back-to-back promotions in 1990 and 1991 , and remained at the club until his retirement in 1996 .",
"title": ""
},
{
"docid": "Sophie_Gurney",
"text": "Sophie Jane Gurney ( née Raverat , first married name Pryor ; 20 December 1919 -- 10 June 2011 ) was an English artist , linked to many of the leading intellectual and cultural figures of the early 20th century . Gurney was born in 1919 , the younger daughter of the French painter Jacques Raverat and his English wife Gwen ( née Darwin ) . Through her mother she was a great-granddaughter of the naturalist Charles Darwin . Her father died in 1925 when she was only five years old , and she and her elder sister Elisabeth were temporarily taken into the care of her first cousin once removed Nora Barlow and her husband Alan . Sophie married the entomologist Mark Pryor in 1940 ; they had four children . Emily ( 1942 -- 2008 ) , William ( born 1945 ) , Lucy ( born 1948 ) and Nelly ( born 1952 ) , who married the film director/farmer Philip Trevelyan . Mark and Sophie Pryor were involved in a road traffic accident in 1967 , in which she was relatively unharmed but which left him with brain damage in a persistent vegetative state for almost three years until his death in 1970 , aged 51 . She also had to deal with her son William 's heroin addiction . She subsequently remarried Henry Charles Horton Gurney OBE ( 1913 -- 1997 , known as Charles ) , professor of mechanical engineering at the University of Hong Kong ( 1966-1973 ) , who had been Mark 's boss at RAE Farnborough . On his retirement , they moved to Totnes , Devon , where Sophie became a member of the 21 Group of artists .",
"title": ""
},
{
"docid": "James_Turner_(athlete)",
"text": "James Michael Turner ( born 22 May 1996 ) is an Australia Paralympic athlete and soccer player with cerebral palsy . He has represented Australia as part of the Australia Paralympic soccer team , the ParaRoos , and was its player of the year in 2013 . At the 2016 Summer Paralympics , he won the Men 's 800 m T36 in a world record time of 2:02.39 .",
"title": ""
},
{
"docid": "Sophie_Aguie",
"text": "Sophie Aguie ( born 31 December 1996 ) is an Ivorian professional footballer . She was part of the Ivorian squad for the 2015 FIFA Women 's World Cup .",
"title": ""
},
{
"docid": "Eric_Turner_(American_football)",
"text": "Eric Ray Turner ( September 20 , 1968 -- May 28 , 2000 ) was a safety who played for the Cleveland Browns , the Baltimore Ravens and the Oakland Raiders . He died of stomach cancer at the age of 31 , two weeks after claiming he was not gravely ill . He was buried at Ivy Lawn Memorial Park in Ventura , California . Turner attended Ventura High School and then played college football at UCLA where he was an All-American in 1990 . Nicknamed `` E-Rock '' by his teammates , Turner drew comparisons to former Bruins great Don Rogers . He was the 2nd overall pick in the 1991 NFL Draft -- the highest choice for a defensive back in football 's modern era ( technically the highest since Jerry Stovall in 1963 ) . Originally drafted by the Cleveland Browns , signed a four-year , $ 6 million contract , which included a $ 3.15 million signing bonus , making the first-year compensation a record for a National Football League rookie . After the Browns moved to Baltimore in 1996 , Turner played one more season for them . He made his second Pro Bowl and was second on the team with 112 tackles and tied for lead with five interceptions , although those numbers went largely unnoticed on a defense that allowed 441 points , third-highest in the league . Following the 1996 season Turner , who had the most expensive contract among all NFL safeties , was cut by the Ravens and became an unrestricted free agent for the first time in his six-year career . Turner signed a four-year , $ 6 million deal with the Raiders in 1997 . Turner recorded 30 interceptions in just 109 career games , including returns for touchdowns of 93 and 94 yards . In 2001 , he was named to the Ventura County Sports Hall of Fame . The football field at Ventura High School is named in his honor .",
"title": ""
},
{
"docid": "Sophie_Moressée-Pichot",
"text": "Sophie Moressée-Pichot ( born 3 April 1962 ) is a French fencer . She won a gold medal in the women 's team épée event at the 1996 Summer Olympics .",
"title": ""
},
{
"docid": "Peter_Orton",
"text": "Peter Charles Orton , CVO ( 17 June 1943 -- 5 December 2007 ) was a British media entrepreneur and television producer noted for his work in children 's television . He and businesswoman Sophie Turner Laing founded HiT Entertainment in 1989 . Orton led the company from 1989 to 2005 when he sold it to Apax . After HiT was sold to Apax in 2005 , he retired but kept close contacts with the entertainment world .",
"title": ""
},
{
"docid": "Sophie_Charlotte_Ducker",
"text": "Sophie Charlotte Ducker ( 9 April 1909 -- 20 May 2004 ) was a German-born Australian botanist . She was born Sophie Charlotte von Klemperer in Dresden . She studied at the Cheltenham Ladies ' College in England . She began the study of botany at the University of Geneva and the University of Stuttgart . She stopped her studies in 1931 when she married Johann Friedrich Ducker . The family left Germany at the outbreak of hostilities and moved to Tehran , Persia . In 1941 , they were forced to move again and settled in Australia . Ducker worked as a research assistant for Dr. Ethel Irene McLennan of the botany school at the University of Melbourne . She completed a BSc at the University in 1952 . In 1957 , she became a botany lecturer at the university and , in 1961 , a senior lecturer . She specialized in marine botany , especially algae . She retired in 1974 but continued to conduct research , present papers and lecture . After her retirement , she collaborated with Professor Bruce Knox at the University of Melbourne on pollination , particularly that of seagrasses . Ducker received a DSc from the University of Melbourne in 1978 . She also published biographies of early Australian botanists . In 1996 , she received the Australian and New Zealand Association for the Advancement of Science 's Mueller medal . Ducker died in Melbourne at the age of 95 .",
"title": ""
},
{
"docid": "Simon_Turner_(cricketer)",
"text": "Simon Jonathan Turner ( born 28 April 1960 ) played first-class and List A cricket for Somerset in 1984 and 1985 . He was born at Cuckfield , West Sussex . In first-class and List A cricket , Turner played as a left-handed lower-order batsman and wicketkeeper , acting as deputy to Trevor Gard in two spells -- the month of July 1984 and a week in June 1985 -- when Gard was injured . He made some useful runs in first-class matches with a highest score of 27 not out in the game against Glamorgan at Taunton in 1984 . He was less successful with the bat in one-day matches . Turner 's younger brother , Rob , was Somerset 's regular wicketkeeper for 15 years from 1991 to 2005 . Simon Turner played high-calibre club cricket for Weston-super-Mare Cricket Club for more than 20 years from 1978 , and his brother also played for the club . Turner has also played a handful of games for Axbridge cricket club in 2010 and 2011 . The latest game for Axbridge was 11 September 2011 vs Horrington scoring 30 not out from 38 balls .",
"title": ""
},
{
"docid": "Sophie_Taylor",
"text": "Sophie Taylor ( born 2 February 1996 ) is a former international swimmer who swam breaststroke . She won a gold medal for England in the women 's 100 metres breaststroke at the Commonwealth Games .",
"title": ""
},
{
"docid": "James_Turner",
"text": "James Turner may refer to : James Turner ( soldier ) ( 1615 -- circa 1686 ) , 17th-century Scottish general James Turner ( North Carolina politician ) ( 1766 -- 1824 ) , U.S. governor and senator James Turner , 1st Baron Netherthorpe ( 1908 -- 1980 ) , British peer James Turner ( athlete ) ( born 1996 ) , Australian Paralympic athlete James Turner ( active since 2004 ) , writer of the webcomic Beaver and Steve James Turner ( bishop ) ( 1829 -- 1893 ) , Australian Anglican bishop James Turner ( active 1930 -- 1947 ) in List of Swallows and Amazons characters James Turner ( historian ) ( born 1946 ) , American intellectual historian and professor James Turner ( illustrator ) ( active 2005 -- 2008 ) , Canadian writer and illustrator of graphic novels James Turner ( Maryland politician ) ( 1783 -- 1861 ) , U.S. congressman James Turner ( tennis ) ( born 1965 ) , British tennis player James Turner ( Worcestershire cricketer ) ( 1886 -- 1968 ) , English cricketer James Turner ( Nottinghamshire cricketer ) ( 1865 -- 1945 ) , English cricketer James Turner ( Canadian politician ) ( 1826 -- 1889 ) , Scottish-born merchant and political figure in Ontario , Canada James Alfred Turner ( 1850 -- 1908 ) , Australian painter James Aspinall Turner ( 1797 -- 1867 ) , British businessman , entomologist and Whig politician James M. Turner ( 1928 -- 1981 ) , American politician and criminal from New Jersey James Milton Turner ( 1840 -- 1915 ) , American ambassador to Liberia and assistant superintendent of Missouri schools James Smith Turner ( 1832 -- 1904 ) , Scottish dentist",
"title": ""
},
{
"docid": "Jeff_Turner",
"text": "Jeffrey Steven Turner ( born April 9 , 1962 ) is an American retired professional basketball player and broadcasting announcer . Turner played ten NBA seasons ( 1984 -- 1987 ; 1989 -- 1996 ) , spending time with the New Jersey Nets as well as the Orlando Magic . He ended his NBA career with 3,697 career points . Turner was a 6 ' 9 '' forward/center . After his career ended he spent nine years as a radio color commentator for the Magic . He then served as the head boys basketball coach at Lake Highland Preparatory School in Orlando , Florida from to 2005 to 2013 , where he compiled a 151-72 record and won the state title in 2013 . From 2011 to 2013 he was also a studio analyst for Magic games . In 2013 , Turner was named television color commentator for the Magic . Turner starred as a college player for Vanderbilt University . He was selected by the New Jersey Nets with the 17th pick of the 1984 NBA Draft . Turner was a member of the Gold Medal 1984 U.S. Olympic basketball team coached by Bobby Knight . The team included Michael Jordan , Patrick Ewing and Steve Alford . Turner also played for the US national team in the 1982 FIBA World Championship , winning the silver medal .",
"title": ""
},
{
"docid": "Sophie_Kamlish",
"text": "Sophie Kamlish ( born 20 August 1996 ) is a British Paralympic athlete who competes in sprint events in T44 events . She represented Great Britain at the 2012 Summer Paralympics and 2016 Summer Paralympics .",
"title": ""
},
{
"docid": "Anna_Jobarteh",
"text": "Anna Sophie Jobarteh ( born 3 April 1996 ) is an English actress , best known for playing the role of Ruth Kirby on the British television series Waterloo Road . She also played a role in thriller series Paradox in 2009 , when she played the role of Dionne Hudson . She starred as Christie in a show called Combat Kids on the CBBC Channel in 2010 .",
"title": ""
},
{
"docid": "Myles_Turner",
"text": "Myles Turner may refer to : Myles Turner ( basketball ) ( born 1996 ) , American player for the Indiana Pacers of the National Basketball Association Myles Turner ( park warden ) ( 1921 -- 1984 ) , warden of the Serengeti National Park in Tanzania from 1956 to 1972",
"title": ""
},
{
"docid": "Baby_(MacLachlan_novel)",
"text": "Baby is a 1995 novel by Patricia MacLachlan . It explores the themes of family and abandonment while offering a touching novel about a family who discovers a baby and has to care for it . With the baby , is a short note , explaining why the baby was left , and with brief information about her . It was also adapted into a 2000 made-for-TV movie directed by Robert Allan Ackerman and starring Farrah Fawcett , Keith Carradine , and Jean Stapleton . It was about Twelve-year-old Larkin lives with her mom and dad on an island year round . The story opens at the end of summer , as the last summer ferry carries the tourists away until the next summer . One little island `` guest '' is left behind at Larkin 's home . An almost year old baby , Sophie , has been left by her mother with a note attached telling the family that `` I will come back for her one day . '' Sophie becomes the catalyst which brings about healing in Larkin 's family . As the family takes in Sophie , they uncover the pain surrounding the loss of Larkin 's newborn brother , `` Baby , '' six months prior . Larkin 's parents never talk about him , never named him , and through their silence have isolated each other from themselves and from their daughter . The story unfolds beautifully as Larkin 's family cycles through fear of love , love for Sophie , then once again has to face loss again , when Sophie 's mother returns in the spring to claim her . During the story , Larkin discovers poetry and how words are `` wondrous '' and powerful , and through this power Larkin and her family find their way back from loss and pain . Baby speaks powerfully to foster care , too . Larkin 's grandmother , with foresight , has the following conversation with Larkin : `` This is not meant to be easy , '' she said , `` It is a very important thing to do , for Sophie and especially for your mother and father . But it will not be easy . Do you understand ? '' I understood . I did . I knew that what she meant was what Papa had said . Sophie was not ours . Someday she would go away . Another thing to miss . `` Why is it important ? '' I asked her ... `` It is important , Larkin , because we are giving Sophie something to take away with her when she goes . '' `` What ? '' asked Lalo -LSB- Larkin 's friend -RSB- . `` What will she take with her ? '' `` Us , '' said Byrd firmly . `` And what will we have when she 's gone ? '' I asked . Twelve years later , Sophie comes to visit the island , because Byrd had died . Larkin 's younger brother was named William . Category :1995 American novels Category : American novels adapted into films",
"title": ""
},
{
"docid": "Sophie_Wilcox",
"text": "Sophie Elizabeth Wilcox ( born 2 January 1975 in Croydon , London ) is an English actress who is most notable for appearing in the BBC miniseries adaptation of The Chronicles of Narnia as Lucy Pevensie when she was 13 years old . She appeared in The Lion , the Witch and the Wardrobe in 1988 , as well as its sequel Prince Caspian and the Voyage of the Dawn Treader in 1989 . After a decade-long absence from acting , Wilcox returned to the screen with a small role in the film Gangster Kittens .",
"title": ""
},
{
"docid": "Turner_Field",
"text": "Turner Field was a baseball park located in Atlanta , Georgia . From 1997 to 2016 , it served as the home ballpark to the Atlanta Braves of Major League Baseball ( MLB ) . Originally built as Centennial Olympic Stadium in 1996 to serve as the centerpiece of the 1996 Summer Olympics , the stadium was converted into a baseball park to serve as the new home of the team . The Braves moved less than one block from Atlanta -- Fulton County Stadium , which served as their home ballpark for 31 seasons from 1966 to 1996 . Opening during the Braves ' `` division dominance '' years , Turner Field hosted the NLDS a total of 11 times ( 1997 -- 2005 , 2010 , 2013 ) ; it also hosted the NLCS four times ( 1997 -- 1999 , 2001 ) , as well as one World Series ( 1999 ) , one NL Wild Card Game ( 2012 , the first in baseball history ) , and the 2000 Major League Baseball All-Star Game . The Braves played the final game at Turner Field on October 2 , 2016 , a 1 -- 0 win over the Detroit Tigers . The franchise allowed its lease on the facility to expire at the end of the calendar year . In 2017 , the team moved to the newly-constructed SunTrust Park , located in nearby Cobb County . The building is currently being reconfigured for the second time , with its infrastructure serving as the basis for the future Georgia State Stadium .",
"title": ""
},
{
"docid": "William_Styron",
"text": "William Clark Styron Jr. ( June 11 , 1925 -- November 1 , 2006 ) was an American novelist and essayist who won major literary awards for his work . Styron was best known for his novels , including : Lie Down in Darkness ( 1951 ) , his acclaimed first work , published at age 26 ; The Confessions of Nat Turner ( 1967 ) , narrated by Nat Turner , the leader of an 1831 Virginian slave revolt ; Sophie 's Choice ( 1979 ) , a story `` told through the eyes of a young aspiring writer from the South , about a Polish Catholic survivor of Auschwitz and her brilliant but psychotic Jewish lover in postwar Brooklyn '' . In 1985 , he suffered from his first serious bout with depression . When he emerged out from under this initial experience , Styron was able to write the memoir Darkness Visible '' ( 1990 ) , the work he became best known for during the last two decades of his life .",
"title": ""
},
{
"docid": "William_Ralph_Turner",
"text": "William Ralph Turner ( 20 April 1920 - 10 July 2013 ) was a painter from Manchester . William Ralph Turner was born in Chorlton-on-Medlock , Manchester in 1920 . A largely self taught painter and teacher he has become known as one of the last authentic Northern English industrial artists . Lowry was to visit Turner 's exhibitions at the Tib Lane gallery in the 1950s and 60s and the influence of L.S. Lowry can be seen in Turner 's work . For about 60 years Turner painted the North West and surrounding areas , often from memories and images obtained while indulging his passion for cycling long distances . A prolific painter , he painted thousands of pictures , including several hundred that featured the Stockport Viaduct . He was comissioned by Peter Burdett ( of The Pitcairn Gallery ) in the 1970s to paint Lyon in France and was represented by The Pitcairn until 1985 when the then owner , Wendy Levy , sold the gallery . In the 1980s he had exhibitions in Windsor and Eton and self organised shows in and around the Cheshire area and in 1989 he was featured in a major book about Northern Artists by the artist and critic Peter Davies . Turner was `` re-discovered '' by David Gunning , an art dealer from Todmorden , in 2000 , when Turner was 80 . Parkinson 's Disease eventually forced Turner to stop painting . In 2005 he was given a retrospective at Gallery Oldham with an accompanying book . An exhibition of Turner 's work took place at Clark Art in Hale , Cheshire , in 2010 .",
"title": ""
},
{
"docid": "Sophie_Wright",
"text": "Sophie Wright may refer to : Sophie Wright ( Emmerdale ) , fictional character on British TV show Emmerdale in 1996-97 Sophie B. Wright ( 1866 -- 1912 ) , New Orleans educator Sophie Wright ( chef ) , British chef",
"title": ""
}
] |
PLAIN-1324
|
hazelnut oil
|
[
{
"docid": "MED-4303",
"text": "Four out of eight 'healthier' oils-namely, almond oil, avocado oil, hazelnut oil and macadamia nut oil-studied were rich sources of monounsaturated fatty acids like olive oil. Grape seed oil, rice barn oil (marketed recently), toasted sesame oil and walnut oil contained high levels of essential fatty acids. The order of oxidative stability determined by Rancimat measuring of the induction period at four temperatures (90 degrees C, 100 degrees C, 110 degrees C, and 120 degrees C) was found to be macadamia oil > rice bran oil approximately toasted sesame oil > avocado oil > almond oil > hazelnut oil > grape seed oil > walnut oil. High-level monounsaturated fatty acid oils gave a linear relationship between 100 times the reciprocal of the induction period against the total unsaturated fatty acid content obtained as %C18:2 + 0.08 x C18:1 + 2.08 x %C18:3, while the polyunsaturated fatty acid oils gave an exponential relationship. In the case of rice bran and hazelnut oils, shelf-life prediction from the extrapolation of the Arrhenius plots and the Q(10) factors was compared well with that of storage time given by the oil producers. In the cases of the other oils (with an exception of macadamia nut oil), the predicted shelf-lives were significantly lower than that of the storage times; especially, walnut oil (very prone to oxidation) gave 15-20 times lower shelf-life than the best-before storage life.",
"title": "Oxidative stability and shelf-life evaluation of selected culinary oils."
}
] |
[
{
"docid": "MED-2384",
"text": "BACKGROUND: Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS: The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS: Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION: Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit. Copyright © 2013 National Lipid Association. All rights reserved.",
"title": "Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects."
},
{
"docid": "MED-4004",
"text": "Evidence suggests that monounsaturated and polyunsaturated fats facilitate greater absorption of carotenoids than saturated fats. However, the comparison of consuming a polyunsaturated fat source versus a saturated fat source on tomato carotenoid bioaccumulation has not been examined. The goal of this study was to determine the influence of coconut oil and safflower oil on tomato carotenoid tissue accumulation in Mongolian gerbils ( Meriones unguiculatus ) fed a 20% fat diet. Coconut oil feeding increased carotenoid concentrations among many compartments including total carotenoids in the serum (p = 0.0003), adrenal glandular phytoene (p = 0.04), hepatic phytofluene (p = 0.0001), testicular all-trans-lycopene (p = 0.01), and cis-lycopene (p = 0.006) in the prostate-seminal vesicle complex compared to safflower oil. Safflower oil-fed gerbils had greater splenic lycopene concentrations (p = 0.006) compared to coconut oil-fed gerbils. Coconut oil feeding increased serum cholesterol (p = 0.0001) and decreased hepatic cholesterol (p = 0.0003) compared to safflower oil. In summary, coconut oil enhanced tissue uptake of tomato carotenoids to a greater degree than safflower oil. These results may have been due to the large proportion of medium-chain fatty acids in coconut oil, which might have caused a shift in cholesterol flux to favor extrahepatic carotenoid tissue deposition.",
"title": "Coconut oil enhances tomato carotenoid tissue accumulation compared to safflower oil in the Mongolian gerbil ( Meriones unguiculatus )."
},
{
"docid": "MED-5085",
"text": "In this study, the adhesion factors examined were time between frying and coating, surface oil content, chip temperature, oil composition, NaCl size, NaCl shape, and electrostatic coating. Three different surface oil content potato chips, high, low, and no, were produced. Oils used were soybean, olive, corn, peanut, and coconut. After frying, chips were coated immediately, after 1 d, and after 1 mo. NaCl crystals of 5 different particle sizes (24.7, 123, 259, 291, and 388 microm) were coated both electrostatically and nonelectrostatically. Adhesion of cubic, dendritic, and flake crystals was examined. Chips were coated at different temperatures. Chips with high surface oil had the highest adhesion of salt, making surface oil content the most important factor. Decreasing chip temperature decreased surface oil and adhesion. Increasing time between frying and coating reduced adhesion for low surface oil chips, but did not affect high and no surface oil chips. Changing oil composition did not affect adhesion. Increasing salt size decreased adhesion. Salt size had a greater effect on chips with lower surface oil content. When there were significant differences, cubic crystals gave the best adhesion followed by flake crystals then dendritic crystals. For high and low surface oil chips, electrostatic coating did not change adhesion of small size crystals but decreased adhesion of large salts. For no surface oil content chips, electrostatic coating improved adhesion for small salt sizes but did not affect adhesion of large crystals.",
"title": "Factors dominating adhesion of NaCl onto potato chips."
},
{
"docid": "MED-927",
"text": "OBJECTIVE: To assess the effects of krill oil on blood lipids, specifically total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). METHODS: A multi-center, three-month, prospective, randomized study followed by a three-month, controlled follow-up of patients treated with 1 g and 1.5 g krill oil daily. Patients with hyperlipidemia able to maintain a healthy diet and with blood cholesterol levels between 194 and 348 mg per dL were eligible for enrollment in the trial. A sample size of 120 patients (30 patients per group) was randomly assigned to one of four groups. Group A received krill oil at a body mass index (BMI)-dependent daily dosage of 2-3 g daily. Patients in Group B were given 1-1.5 g krill oil daily, and Group C was given fish oil containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) per gram of oil at a dose of 3 g daily. Group D was given a placebo containing microcrystalline cellulose. The krill oil used in this study was Neptune Krill Oil, provided by Neptune Technologies and Bioresources, Laval, Quebec, Canada. OUTCOME MEASURES: Primary parameters tested (baseline and 90-day visit) were total blood cholesterol, triglycerides, LDL, HDL, and glucose. RESULTS: Krill oil 1-3 g per day (BMI-dependent) was found to be effective for the reduction of glucose, total cholesterol, triglycerides, LDL, and HDL, compared to both fish oil and placebo. CONCLUSIONS: The results of the present study demonstrate within high levels of confidence that krill oil is effective for the management of hyperlipidemia by significantly reducing total cholesterol, LDL, and triglycerides, and increasing HDL levels. At lower and equal doses, krill oil was significantly more effective than fish oil for the reduction of glucose, triglycerides, and LDL levels.",
"title": "Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia."
},
{
"docid": "MED-928",
"text": "Background Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared. Methods In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed. Results The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC0-72 h: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC0-72 h: 59.78 ± 36.75%*h) and EE (mean AUC0-72 h: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA. Conclusion Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.",
"title": "Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations - a comparative bioavailability study of fish oil vs. krill oil"
},
{
"docid": "MED-1390",
"text": "Background It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk. Methods We included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality. Results During follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil consumption, cardiovascular disease and mortality risk decreased by 10% and 7%, respectively. No significant associations were found for cancer and all-cause mortality. The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group. Conclusions Olive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk. Trial registration This study was registered at controlled-trials.com (http://www.controlled-trials.com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.",
"title": "Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study"
},
{
"docid": "MED-3668",
"text": "OBJECTIVE: Investigate the effects of lavender oil on the central nervous system, autonomic nervous system, and mood responses in humans after inhalation. MATERIAL AND METHOD: Twenty healthy volunteers participated in the experiments. The present study assessed autonomic parameters such as blood pressure, heart rate, respiratory rate, and skin temperature to determine the arousal level of the autonomic nervous system. In addition, subjects were asked to estimate their mood responses such as feeling pleasant or unpleasant, uncomfortable, sensuality, relaxation, or refreshing in order to assess subjective behavioral arousal. Finally, electroencephalogram (EEG) was recorded from 31 electrodes on the scalp according to the international 10 to 20 system, and EEG power spectra were calculated by Fast Fourier Transform (FFT). Data was analyzed by comparing the effects of lavender oil on physiological and mood states with sweet almond oil. These assessments were measured before and after using paired t-test statistical procedure. RESULTS: The results revealed that lavender oil caused significant decreases of blood pressure, heart rate, and skin temperature, which indicated a decrease of autonomic arousal. In terms of mood responses, the subjects in the lavender oil group categorized themselves as more active, fresher relaxed than subjects just inhaling base oil. Compared with base oil, lavender oil increased the power of theta (4-8 Hz) and alpha (8-13 Hz) brain activities. The topographic map showed obviously more scattering power in alpha range waves particularly in bilateral temporal and central area. CONCLUSION: The findings provided evidence the relaxing effect of inhaling lavender oil.",
"title": "The effects of lavender oil inhalation on emotional states, autonomic nervous system, and brain electrical activity."
},
{
"docid": "MED-2711",
"text": "Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.",
"title": "Accidental bullous phototoxic reactions to bergamot aromatherapy oil."
},
{
"docid": "MED-3659",
"text": "We report the annual results of patch testing with lavender oil for a 9-year period from 1990 to 1998 in Japan. Using Finn Chambers and Scanpor tape, we performed 2-day closed patch testing with lavender oil 20% pet. on the upper back of each patient suspected of having cosmetic contact dermatitis. We compared the frequency of positive patch tests to lavender oil each year with those to other fragrances. We diagnosed contact allergy when patch test reactions were + or <+ at 1 day after removal. The positivity rate of lavender oil was 3.7% (0-13.9%) during the 9-year period from 1990 to 1998. The positivity rate of lavender oil increased suddenly in 1997. Recently, in Japan, there has been a trend for aromatherapy using lavender oil. With this trend, placing dried lavender flowers in pillows, drawers, cabinets, or rooms has become a new fashion. We asked patients who showed a positive reaction to lavender oil about their use of dried lavender flowers. We confirmed the use of dried lavender flowers in 5 cases out of 11 positive cases in 1997 and 8 out of 15 positive cases in 1998. We concluded that the increase in patch test positivity rates to lavender oil in 1997 and 1998 was due to the above fashion, rather than due to fragrances in cosmetic products.",
"title": "Results of patch testing with lavender oil in Japan."
},
{
"docid": "MED-5268",
"text": "Olive oil is well known for its cardioprotective properties; however, epidemiological data showing that olive oil consumption reduces incident CHD events are still limited. Therefore, we studied the association between olive oil and CHD in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort study. The analysis included 40 142 participants (38 % male), free of CHD events at baseline, recruited from five EPIC-Spain centres from 1992 to 1996 and followed up until 2004. Baseline dietary and lifestyle information was collected using interview-administered questionnaires. Cox proportional regression models were used to assess the relationship between validated incident CHD events and olive oil intake (energy-adjusted quartiles and each 10 g/d per 8368 kJ (2000 kcal) increment), while adjusting for potential confounders. During a 10·4-year follow-up, 587 (79 % male) CHD events were recorded. Olive oil intake was negatively associated with CHD risk after excluding dietary mis-reporters (hazard ratio (HR) 0·93; 95 % CI 0·87, 1·00 for each 10 g/d per 8368 kJ (2000 kcal) and HR 0·78; 95 % CI 0·59, 1·03 for upper v. lower quartile). The inverse association between olive oil intake (per 10 g/d per 8368 kJ (2000 kcal)) and CHD was more pronounced in never smokers (11 % reduced CHD risk (P = 0·048)), in never/low alcohol drinkers (25 % reduced CHD risk (P < 0·001)) and in virgin olive oil consumers (14 % reduced CHD risk (P = 0·072)). In conclusion, olive oil consumption was related to a reduced risk of incident CHD events. This emphasises the need to conserve the traditional culinary use of olive oil within the Mediterranean diet to reduce the CHD burden.",
"title": "Olive oil intake and CHD in the European Prospective Investigation into Cancer and Nutrition Spanish cohort."
},
{
"docid": "MED-5269",
"text": "BACKGROUND AND AIM: Currently, more than 30% of the caloric intake in the Colombian population comes from vegetable oil consumption mainly by the ingestion of deep-fried foods. Recently, it has been reported that unsaturated fatty acid rich oils have a beneficial effect on the endothelial function. Nevertheless, it is well know that the deep-frying process alters the chemical composition of vegetable oils and can produce adverse effects in the endothelial function. OBJECTIVE: To evaluate the acute effect of the ingestion of large amounts of olive, soybean and palm oils, fresh and at two different deep-fry levels, on the glucose and lipid profiles and the endothelial function. METHODS AND RESULTS: Ten healthy young volunteers were included in the study. After performing a baseline evaluation of cardiovascular risk factors and drawing a fasting blood sample, subjects were exposed to a randomly assigned potato soup meal containing 60 mL of one of three different vegetable oils (olive, soybean and palm), either fresh or at one of two different deep-fry levels (10 and 20 fries, respectively). Flow-mediated vasodilation (FMD) was performed in fasting conditions and 3h after the intake of the oil rich meal. Furthermore, blood samples were taken at these stages for the lipid profiles and plasma glucose determinations. All the meals resulted in a similar acute endothelial impairment (FMD decrease of 32.1%, confidence interval [CI] 95%, 28.0-36.2) and postprandial increase in triglycerides (27.03%, CI 95%, 20.5-33.3), independently of the type of oil ingested (p=0.44) and regardless of its deep-fry level (p=0.62). No correlation was found between endothelial impairment and postprandial triglyceride increment (r=-0.22, p=0.09). CONCLUSIONS: No difference was found in the acute adverse effect of the ingestion of different vegetable oils on the endothelial function. All the vegetable oils, fresh and deep-fried, produced an increase in the triglyceride plasma levels in healthy subjects.",
"title": "Olive, soybean and palm oils intake have a similar acute detrimental effect over the endothelial function in healthy young subjects."
},
{
"docid": "MED-1833",
"text": "BACKGROUND: Cod liver oil is an important source of vitamin D, but also contains other fat-soluble components such as vitamin A. Before 1999, the cod liver oil formula in Norway contained a high concentration of vitamin A (1000 µg per 5 ml). High vitamin A status is associated with increased risks of several chronic diseases. OBJECTIVE: To investigate the association between cod liver oil intake and asthma development. METHODS: In the Nord-Trøndelag Health Study, a total of 25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006-2008. Current analysis based on 17 528 subjects who were free of asthma and had complete information on cod liver oil intake at baseline. Cod liver oil intake was defined as daily intake ≥ 1 month during the year prior to baseline. Incident asthma was reported as new-onset asthma during the 11-year follow-up. RESULTS: Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for ≥ 1 month over the past year. Cod liver oil intake was significantly associated with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment for age, sex, daily smoking, physical activity, education, socio-economic status, family history of asthma, and body mass index (BMI). The positive association was consistent across age (< 40/≥ 40 years), sex (men/women), family history of asthma (yes/no) and BMI subgroups (< 25/≥ 25 kg/m(2)). CONCLUSIONS: Intake of cod liver oil with high vitamin A content was significantly associated with increased incidence of adult-onset asthma.",
"title": "Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study."
},
{
"docid": "MED-4731",
"text": "BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.",
"title": "No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-..."
},
{
"docid": "MED-4000",
"text": "Coconut oil is a common edible oil in many countries, and there is mixed evidence for its effects on lipid profiles and cardiovascular disease risk. Here we examine the association between coconut oil consumption and lipid profiles in a cohort of 1,839 Filipino women (age 35–69 years) participating in the Cebu Longitudinal Health and Nutrition Survey, a community based study in Metropolitan Cebu City. Coconut oil intake was measured as individual coconut oil intake calculated using two 24-hour dietary recalls (9.54 ± 8.92 grams). Cholesterol profiles were measured in plasma samples collected after an overnight fast. Mean lipid values in this sample were total cholesterol (TC) (186.52 ± 38.86 mg/dL), high density lipoprotein cholesterol (HDL-c) (40.85 ± 10.30 mg/dL), low density lipoprotein cholesterol (LDL-c) (119.42 ± 33.21 mg/dL), triglycerides (130.75 ± 85.29 mg/dL) and the TC/HDL ratio (4.80 ± 1.41). Linear regression models were used to estimate the association between coconut oil intake and each plasma lipid outcome after adjusting for total energy intake, age, body mass index (BMI), number of pregnancies, education, menopausal status, household assets and urban residency. Dietary coconut oil intake was positively associated with HDL-c levels.",
"title": "Coconut oil predicts a beneficial lipid profile in pre-menopausal women in the Philippines"
},
{
"docid": "MED-839",
"text": "Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results.",
"title": "Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA."
},
{
"docid": "MED-2195",
"text": "The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®",
"title": "The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips."
},
{
"docid": "MED-3662",
"text": "Essential oils distilled from members of the genus Lavandula have been used both cosmetically and therapeutically for centuries with the most commonly used species being L. angustifolia, L. latifolia, L. stoechas and L. x intermedia. Although there is considerable anecdotal information about the biological activity of these oils much of this has not been substantiated by scientific or clinical evidence. Among the claims made for lavender oil are that is it antibacterial, antifungal, carminative (smooth muscle relaxing), sedative, antidepressive and effective for burns and insect bites. In this review we detail the current state of knowledge about the effect of lavender oils on psychological and physiological parameters and its use as an antimicrobial agent. Although the data are still inconclusive and often controversial, there does seem to be both scientific and clinical data that support the traditional uses of lavender. However, methodological and oil identification problems have severely hampered the evaluation of the therapeutic significance of much of the research on Lavandula spp. These issues need to be resolved before we have a true picture of the biological activities of lavender essential oil. Copyright 2002 John Wiley & Sons, Ltd.",
"title": "Biological activities of lavender essential oil."
},
{
"docid": "MED-1443",
"text": "SUMMARY BACKGROUND: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti-inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo. METHODS: 40 volunteers were enrolled in this monocentric,randomized,placebo-controlled double-blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV-B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place-bo.The effect of the test substances on the UV-induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non-irradiated skin. RESULTS: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV-induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent. CONCLUSIONS: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.",
"title": "Anti-inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test."
},
{
"docid": "MED-5095",
"text": "Docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for eye and brain development and ongoing visual, cognitive, and cardiovascular health. Unlike fish-sourced oils, the bioavailability of DHA from vegetarian-sourced (algal) oils has not been formally assessed. We assessed bioequivalence of DHA oils in capsules from two different algal strains versus bioavailability from an algal-DHA-fortified food. Our 28-day randomized, placebo-controlled, parallel group study compared bioavailability of (a) two different algal DHA oils in capsules (\"DHASCO-T\" and \"DHASCO-S\") at doses of 200, 600, and 1,000 mg DHA per day (n = 12 per group) and of (b) an algal-DHA-fortified food (n = 12). Bioequivalence was based on changes in plasma phospholipid and erythrocyte DHA levels. Effects on arachidonic acid (ARA), docosapentaenoic acid-n-6 (DPAn-6), and eicosapentaenoic acid (EPA) were also determined. Both DHASCO-T and DHASCO-S capsules produced equivalent DHA levels in plasma phospholipids and erythrocytes. DHA response was dose-dependent and linear over the dose range, plasma phospholipid DHA increased by 1.17, 2.28 and 3.03 g per 100 g fatty acid at 200, 600, and 1,000 mg dose, respectively. Snack bars fortified with DHASCO-S oil also delivered equivalent amounts of DHA on a DHA dose basis. Adverse event monitoring revealed an excellent safety and tolerability profile. Two different algal oil capsule supplements and an algal oil-fortified food represent bioequivalent and safe sources of DHA.",
"title": "Bioequivalence of Docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food."
},
{
"docid": "MED-5271",
"text": "OBJECTIVES: This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND: The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS: We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS: All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS: In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.",
"title": "The postprandial effect of components of the Mediterranean diet on endothelial function."
},
{
"docid": "MED-5274",
"text": "BACKGROUND: Olive oil polyphenols have been associated with several cardiovascular health benefits. This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure (BP) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension. METHODS: We conducted a double-blind, randomized, crossover dietary-intervention study. After a run-in period of 4 months (baseline values), two diets were used, one with polyphenol-rich olive oil (∼30 mg/day), the other with polyphenol-free olive oil. Each dietary period lasted 2 months with a 4-week washout between diets. Systolic and diastolic BP, serum or plasma biomarkers of endothelial function, oxidative stress, and inflammation, and ischemia-induced hyperemia in the forearm were measured. RESULTS: When compared to baseline values, only the polyphenol-rich olive oil diet led to a significant (P < 0.01) decrease of 7.91 mm Hg in systolic and 6.65 mm Hg of diastolic BP. A similar finding was found for serum asymmetric dimethylarginine (ADMA) (-0.09 ± 0.01 µmol/l, P < 0.01), oxidized low-density lipoprotein (ox-LDL) (-28.2 ± 28.5 µg/l, P < 0.01), and plasma C-reactive protein (CRP) (-1.9 ± 1.3 mg/l, P < 0.001). The polyphenol-rich olive oil diet also elicited an increase in plasma nitrites/nitrates (+4.7 ± 6.6 µmol/l, P < 0.001) and hyperemic area after ischemia (+345 ± 386 perfusion units (PU)/sec, P < 0.001). CONCLUSIONS: We concluded that the consumption of a diet containing polyphenol-rich olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension.",
"title": "Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension."
},
{
"docid": "MED-3864",
"text": "BACKGROUND: Skin sensitivity is a common problem in the Western population correlated with changes of skin properties like skin barrier function, hydration and skin physiology. Skin properties can be modulated by dietary fatty acids (FA), especially poly-unsaturated FA. The present study was performed to evaluate the effect of daily supplementation with flaxseed oil and safflowerseed oil on healthy volunteers with sensitive skin. METHODS: The study was designed as a randomized, double-blind 12-week intervention with 2 female treatment groups (n = 13). Plasma FA profile, skin sensitivity, skin hydration, transepidermal water loss (TEWL) and skin surface were evaluated on day 0, week 6 and week 12. RESULTS: Supplementation with flaxseed oil led to significant decreases in sensitivity (after nicotinate irritation), TEWL, skin roughness and scaling, while smoothness and hydration were increased. Concomitantly, the ratio of n-6/n-3 FA in plasma decreased. Upon supplementation with safflowerseed oil, only a significant improvement in skin roughness and hydration was observed; however, the effects were less pronounced and determined at a later point in time than with flaxseed oil. The plasma n-6/n-3 FA ratio increased. CONCLUSION: The data provide evidence that daily intake of flaxseed oil modulates skin condition. Copyright © 2010 S. Karger AG, Basel.",
"title": "Supplementation of flaxseed oil diminishes skin sensitivity and improves skin barrier function and condition."
},
{
"docid": "MED-1831",
"text": "In children, omega-3 polyunsaturated fatty acids (PUFAs) may elicit a suite of health benefits including enhancement of cognitive development. Subsequently, dietary supplements containing omega-3 PUFAs have become increasingly popular. Often, the largest source of beneficial PUFAs in these supplements is fish oil, which may contain significant levels of contaminants such as polychlorinated biphenyls (PCBs). The objectives of this study were to evaluate congener-specific PCB concentrations in 13 over-the-counter children's dietary supplements containing fish oils/powders and assess potential PCB exposures through ingestion of these products on a daily basis. Every supplement analysed contained PCBs, with a mean concentration of 9 ± 8 ng PCBs/g supplement. When following serving size suggestions, mean daily exposure values ranged from 2.5 to 50.3 ng PCBs/day. Daily exposures for children's supplements were significantly lower than those previously reported for adult supplements and may be explained, in part, by the variability in the amount of fish oil (and PUFA content) in a serving size. Based on this study, factors such as fish oil purification methods (e.g., molecular distillation) and the trophic level of the fish species used to make the fish oil cannot be used as indicators of PCB levels within children's supplements. Fish supplements may decrease or increase daily PCB exposure compared with ingestion of fresh fish. However, eating fish high in omega-3 PUFAs and low in PCBs may reduce PCB exposure compared with daily supplementation with fish oils for some products studied.",
"title": "Children's daily exposure to polychlorinated biphenyls from dietary supplements containing fish oils."
},
{
"docid": "MED-2412",
"text": "OBJECTIVE: To determine the effects of fish oil supplementation on lipid levels and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A comprehensive search of Medline, Embase, Lilacs, the Cochrane Clinical Trials Registry bibliographies of relevant papers, and expert input updated through September 1998 was undertaken. All randomized placebo-controlled trials were included in which fish oil supplementation was the only intervention in subjects with type 2 diabetes. Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. Eighteen trials including 823 subjects followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day The outcomes studied were glycemic control and lipid levels. RESULTS: Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil on lowering triglycerides (-0.56 mmol/l [95% CI -0.71 to -0.41]) and raising LDL cholesterol (0.21 mmol/l [0.02 to 0.41]). No statistically significant effect was observed for fasting glucose. HbA1c total cholesterol, or HDL cholesterol. The triglyceride-lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited hypertriglyceridemic subjects and used higher doses of fish oil. Heterogeneity was observed and explained by the recruitment of subjects with baseline hypertriglyceridemia in some studies. CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, raises LDL cholesterol, and has no statistically significant effect on glycemic control. Trials with hard clinical end points are needed.",
"title": "Fish oil supplementation in type 2 diabetes: a quantitative systematic review."
},
{
"docid": "MED-4943",
"text": "Fish and seal oil dietary supplements, marketed to be rich in omega-3 fatty acids, are frequently consumed by Canadians. Samples of these supplements (n = 30) were collected in Vancouver, Canada, between 2005 and 2007. All oil supplements were analyzed for polychlorinated biphenyls (PCBs) and organochlorine insecticides (OCs) and each sample was found to contain detectable residues. The highest SigmaPCB and SigmaDDT (1,1,1-trichloro-di-(4-chlorophenyl)ethane) concentrations (10400 ng/g and 3310 ng/g, respectively) were found in a shark oil sample while lowest levels were found in supplements prepared using mixed fish oils (anchovy, mackerel, and sardine) (0.711 ng SigmaPCB/g and 0.189 ng SigmaDDT/g). Mean SigmaPCB concentrations in oil supplements were 34.5, 24.2, 25.1, 95.3, 12.0, 5260, 321, and 519 ng/g in unidentified fish, mixed fish containing no salmon, mixed fish with salmon, salmon, vegetable with mixed fish, shark, menhaden (n = 1), and seal (n = 1), respectively. Maximum concentrations of the other OCs were generally observed in the seal oil. The hexachlorinated PCB congeners were the dominant contributors to SigmaPCB levels, while SigmaDDT was the greatest contributor to organochlorine levels. Intake estimates were made using maximum dosages on manufacturers' labels and results varied widely due to the large difference in residue concentrations obtained. Average SigmaPCB and SigmaDDT intakes were calculated to be 736 +/- 2840 ng/d and 304 +/- 948 ng/d, respectively.",
"title": "Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides."
},
{
"docid": "MED-1859",
"text": "Response surface methodology was used to investigate the effect and interactions of processing variables such as roselle extract (0.1-1.3%), soybean oil (5-20%) on physicochemical, textural and sensory properties of cooked pork patties. It was found that reduction in thickness, pH, L* and b* values decreased; however, water-holding capacity, reduction in diameter and a* values increased, respectively, as the amount of roselle increased. Soybean oil addition increased water-holding capacity, reduction in thickness, b* values of the patties. The hardness depended on the roselle and soybean oil added, as its linear effect was negative at p<0.01. The preference of color, tenderness, juiciness, and overall quality depend on the addition of roselle and soybean oil. The maximum overall quality score (5.42) was observed when 12.5 g of soybean oil and 0.7 g of roselle extract was added. The results of this optimization study would be useful for meat industry that tends to increase the product yield for patties using the optimum levels of ingredients by RSM. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Roselle (Hibiscus sabdariffa L.) and soybean oil effects on quality characteristics of pork patties studied by response surface methodology."
},
{
"docid": "MED-1523",
"text": "Peppermint oil is easily available as a constituent of medicines. A near fatal case due to ingestion of toxic dose of oral peppermint oil is being reported. The patient came in a comatosed state and was in shock. She was managed with mechanical ventilation and ionotropes. Her vital parameters reached normal within 8 hours and became conscious by 24 hours. The side effects of peppermint oil are considered to be mild but this case report warns that ingestion of oral toxic doses of peppermint oil could be dangerous.",
"title": "A near fatal case of high dose peppermint oil ingestion- Lessons learnt"
},
{
"docid": "MED-1373",
"text": "The endothelium is involved in many of the processes related to the development of atherosclerosis, which is considered an inflammatory disease. Actually, traditional risk factors for atherosclerosis predispose to endothelial dysfunction, which is manifested as an increase in the expression of specific cytokines and adhesion molecules. There are firm evidence supporting the beneficial effects of olive oil, the most genuine component of the Mediterranean diet. Although the effects of olive oil and other oleic acid-rich dietary oils on atherosclerosis and plasma lipids are well known, the roles of minor components have been less investigated. Minor components constitute only 1-2% of virgin olive oil (VOO) and are composed of hydrocarbons, polyphenols, tocopherols, sterols, triterpenoids and other components usually found in traces. Despite their low concentration, non-fatty acid constituents may be of importance because studies comparing monounsaturated dietary oils have reported different effects on cardiovascular disease. Most of these compounds have demonstrated antioxidant, anti-inflammatory and hypolipidemic properties. In this review, we summarize current knowledge on the effects of these compounds contained in VOO on vascular dysfunction and the mechanisms by which they modulate endothelial activity. Such mechanisms involve the release of nitric oxide, eicosanoids (prostaglandins and leukotrienes) and adhesion molecules, in most cases by activation of nuclear factor kappaB by reactive oxygen species.",
"title": "The role of virgin olive oil components in the modulation of endothelial function."
},
{
"docid": "MED-5263",
"text": "High postprandial serum lipid concentrations are associated with increased oxidative stress which, in turn, increases the risk of atherosclerosis. Epidemiological studies correlate lower incidence of cardiovascular disease with adherence to the Mediterranean diet. The aim of this study was to evaluate changes in inflammatory (TXB(2) and LTB(4)) and oxidative stress markers (urinary hydrogen peroxide levels and serum antioxidant capacity), in addition to classic lipid parameters, after a fat-rich meal administered to 12 normolipemic, healthy subjects. Following a Latin square design, subjects were divided into three groups, each one receiving a different kind of oil (extra virgin olive oil; EVOO, olive oil; OO or corn oil; CO, together with 150g of potatoes), with 2-week washout periods between treatments. Blood samples were drawn at baseline and after 1, 2, and 6h after the meal. A significant decrease in inflammatory markers, namely TXB(2) and LTB(4), after 2 and 6h after EVOO (but not OO or CO) consumption and a concomitant increase of serum antioxidant capacity were recorded. These data reinforce the notion that the Mediterranean diet reduces the incidence of coronary heart disease partially due to the protective role of its phenolic components, including those of extra virgin olive oil.",
"title": "Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil."
},
{
"docid": "MED-3666",
"text": "Most cases of male prepubertal gynecomastia are classified as idiopathic. We investigated possible causes of gynecomastia in three prepubertal boys who were otherwise healthy and had normal serum concentrations of endogenous steroids. In all three boys, gynecomastia coincided with the topical application of products that contained lavender and tea tree oils. Gynecomastia resolved in each patient shortly after the use of products containing these oils was discontinued. Furthermore, studies in human cell lines indicated that the two oils had estrogenic and antiandrogenic activities. We conclude that repeated topical exposure to lavender and tea tree oils probably caused prepubertal gynecomastia in these boys. 2007 Massachusetts Medical Society",
"title": "Prepubertal gynecomastia linked to lavender and tea tree oils."
}
] |
114687
|
Larry Buttrose's book Cafe Royale has also been published by another name.
|
[
{
"docid": "Larry_Buttrose",
"text": "Larry Philip Buttrose ( born 16 December 1952 ) is an Australian writer , journalist and academic . He is the ghostwriter of the Saroo Brierley memoir A Long Way Home ( adapted for the screen as the major international feature film Lion ) . He is also the author of the novels The Maze of the Muse and Sweet Sentence , and the travel books The King Neptune Day & Night Club , and Cafe Royale ( also published as The Blue Man ) . For the stage he co-wrote the hit musical Hot Shoe Shuffle , as well Kurtz , his stage adaptation of Heart of Darkness , and a stage adaptation of Don Quixote . For the screen he co-wrote the feature Gino and the feature documentary Movietone Memories , and is currently working on the screenplay for Hicks , about the life of Australian inmate in Guantanamo , David Hicks . He teaches Screenwriting at New York University 's Sydney campus at The Rocks .",
"title": ""
}
] |
[
{
"docid": "Buttrose",
"text": "Buttrose is a surname . Notable people with the surname include : Ita Buttrose ( born 1942 ) , Australian journalist and businesswoman Larry Buttrose ( born 1952 ) , Australian writer Stroma Buttrose ( born 1929 ) , Australian architect",
"title": ""
},
{
"docid": "Palpasa_Cafe",
"text": "Palpasa Cafe ( Nepali : पल्पसा क्याफे ) is a novel by Nepali author Narayan Wagle . It tells the story of an artist , Drishya , during the height of the Nepalese Civil War . The novel is partly a love story of Drishya and the first generation American Nepali , Palpasa , who has returned to the land of her parents after 9/11 . It is often called an anti-war novel , and describes the effects of the civil war on the Nepali countryside that Drishya travels to . The book has been a best-seller in Nepal , creating a sales record for a Nepali book of 25,000 copies in the first year . It was Wagle 's first book . Since its release , the book has received many honours including the highly prestigious literary award in Nepal , the Madan Puraskar . After Palpasa Cafe , Wagle has written another best-selling book , Mayur Times . The book was written originally in Nepali and was later translated into English and Korean . The book has sold over 52,000 copies as of July 2012 . Palpasa Cafe has officially became the first Nepali novel available in Kindle , it also comes in various portable and ebook formats like mobi and pdf .",
"title": ""
},
{
"docid": "Stroma_Buttrose",
"text": "Stroma Buttrose ( born 29 October 1929 ) is an Australian architect , who became the first female Planning Assistant in South Australia , joining the Town Planners Office in 1957 ( later called the State Planning office ) . Buttrose is considered to be a pioneering figure of women in architecture , as she was the first female Commissioner of the Planning Appeal Board , as well as being the author of numerous architectural publications , most notably City Planning in Australia in 1975 . Buttrose supervised the Gawler Land Use Survey , as well as the Willunga Land Use Survey , both areas covering approximately 100 by 40 kilometers . She was also instrumental in the production of the Development Plan for the Metropolitan Area of Adelaide , which was published in 1963 . in 1973 , Buttrose was the first woman to be appointed Commissioner of the Town Planning Appeal Board/Tribunal , which later became the Environment , Resources and Development Court .",
"title": ""
},
{
"docid": "Cafe_Royal_Cocktail_Book",
"text": "The Cafe Royal Cocktail Book is a collection of cocktail recipes compiled by William J. Tarling , published by the United Kingdom Bartenders Guild in 1937 . It contains a number of pioneering recipes , including the 20th Century and what later became the Margarita .",
"title": ""
},
{
"docid": "Larry_Hyman",
"text": "Larry M. Hyman ( born September 26 , 1947 in Los Angeles ) is Professor of Linguistics in the Department of Linguistics at the University of California at Berkeley . He is a specialist in phonology , and has particular interest in African languages . He received his B.S. , M.A , and Ph.D. degrees from the University of California at Los Angeles . He has received numerous grants for his research , mostly from the National Science Foundation , and has won several awards , both within and beyond the University . He has published many papers and contributed to many books . Hyman is editor or on the editorial board of many journals in his field , including Linguistic Inquiry , Journal of African Languages & Linguistics , Language , Natural Language and Linguistic Theory , Lingua Descriptive Series , Phonology ( Yearbook ) , Linguistic Typology and Africana Linguistica ( Musée royal de l'Afrique central ) . He has been Chair , Editorial Board , University of California Publications in Linguistics since 1999 . He has published over 120 peer-reviewed articles , many chapters in academic books , and numerous conference talks .",
"title": ""
},
{
"docid": "Break_the_Chains_(book)",
"text": "Break the Chains is a work of political non-fiction written by Scottish socialist and trade unionist Richie Venton and published in 2015 by the Scottish Socialist Party . In the book , Venton argues the case for an immediate # 10 an hour minimum wage , without discrimination ; a national maximum wage ; a shorter working week ; and strategies to `` unchain the unions '' . It has been compared favourably to The Establishment : And How They Get Away With It by Owen Jones . The book was launched in Bacchus Cafe Bar , Glasgow on Thursday 17 December 2015 . Another launch event was announced in Dundee . The Glasgow launch was livestreamed over the Internet .",
"title": ""
},
{
"docid": "Asian_Affairs",
"text": "Asian Affairs , the journal of the Royal Society for Asian Affairs , has been published continuously since 1914 ( originally as the Journal of the Central Asian Society , and from 1931 to 1969 as the Journal of the Royal Central Asian Society ) . It covers a range of social , political , and historical subjects linked to Asia . It also is a major source of book reviews . The Journal provides a forum at the interface between learned interest , scholarship , journalism and personal experience . There are also two magazines called Asian Affairs , one published for the past decade or so from Hong Kong , and another from Delhi .",
"title": ""
},
{
"docid": "Firestorm_Cafe_&_Books",
"text": "Firestorm Books & Coffee is a worker-owned and self-managed `` anti-capitalist business '' located in the `` West Asheville '' section of Asheville , North Carolina , USA . Named after the Firestorm , this infoshop operates with an eye on creating a sustainable , radical community event space . Firestorm Cafe & Books features a coffee bar , vegan food , free wireless internet , an extensive stock of books , and regular events ( such as film screenings , political and economic teach-ins , local and traveling musicians and community workshops ) . Firestorm Cafe & Books opened in May , 2008 , spearheaded by Co-Creators Libertie Valance and Neala Byrne ( aka Kila Donovan ) . Since opening , Firestorm has hosted economist Thomas Greco , gay activist Wayne Besen , the Beehive Collective , environmental scholar Kirkpatrick Sale , and benefits for the animal rights group Mercy for Animals . In May 2010 , Firestorm Cafe & Books was named the '' # 2 Best Slow Money Business in America '' by the Slow Money Alliance . In December 2011 , Firestorm was featured in a list of the `` 10 Coolest Independent Coffee Shops Across the US '' surveyed by Zagat , a U.S. publisher of popular restaurant guides . In January 2014 , the Firestorm Collective announced that they would be closing the downtown space and looking for a new location in West Asheville . Firestorm was closed from March 2014 to July 2015 . In July 2015 , the collective officially opened the new space on Haywood Road in West Asheville , under the name Firestorm Books & Coffee . The name change reflected the expanded focus on operating as a bookstore in addition to the cafe offerings .",
"title": ""
},
{
"docid": "Ita_Buttrose",
"text": "Ita Clare Buttrose AO OBE ( born 17 January 1942 ) is an Australian journalist , businesswoman , television personality and author . She was the founding editor of Cleo , a high-circulation magazine aimed at women aged 20 to 40 that was frank about sexuality ( and , in its infancy , featured nude male centrefolds ) and , later , as the editor of the more conventional Australian Women 's Weekly . She is the youngest person ever to be appointed editor of the Weekly , which was then , per capita , the largest-selling magazine in the world . Since 2013 , Buttrose has been a panelist on the Network Ten morning program Studio 10 .",
"title": ""
},
{
"docid": "Master_Point_Press",
"text": "Master Point Press is a Canadian book publishing company located in Toronto , Ontario , Canada . It grew out of Canadian Master Point magazine ( 1992 -- 1997 ) , which was published by Ray and Linda Lee . The company began publishing books in 1994 . While primarily interested in books on contract bridge , MPP also publishes books on other games and intellectual pursuits , such as chess . Notable bridge players whose works have been published by Master Point Press include Michael Rosenberg , Larry Cohen , Edwin Kantar , Terence Reese , Barbara Seagram , and David Bird . Master Point Press receives funding from the Government of Canada through the Book Publishing Industry Development Program ( BPIDP ) for their publishing activities . The company has been expanding its online presence with a blogging site , as well as Mastering Bridge , a resource for both bridge teachers and students .",
"title": ""
},
{
"docid": "Marc_Sorenson",
"text": "Dr. Marc Sorenson is a doctor of education with a background in health and fitness . He graduated from Brigham Young University in 1973 . He and his wife , Vicki , founded and developed National Institute of Fitness in 1974 . Dr. Sorenson and Vicki sold the resort to Franklin Quest ( now Franklin Covey ) corporation in 1994 . They are currently directors of another health resort called National Institute of Health and Fitness ( NIHF ) in Midway , Utah . Dr. Sorenson has published a scientific paper in the journal Dermatoendocrinology , on Vitamin D and erectile dysfunction ( ED ) , theorizing that lack of vitamin D or sunlight could be a contributor to ED . He was also co-author of a scientific paper on vitamin D and athletics , published in Science and Medicine in Exercise and Sports , and coauthored another paper in the Journal of Sexual Medicine regarding ED , chronic periodontitis and vitamin D. His book Megahealth was a selection of the Literary Guild , Doubleday Book Club and Doubleday Health Book Club . He has done meticulous and extensive research into hundreds of published papers on sunlight , vitamin D and health in order to write his current book , Vitamin D3 and Solar Power . The book has also been published in both the Czech Republic and Israel . He has written several other books , including an English vocabulary builder , `` I Want to have words with you ! '' He was also named a founding director of the Breast Cancer Natural Prevention Foundation ( BCNPF ) .",
"title": ""
},
{
"docid": "Brokeback_Mountain_(short_story)",
"text": "`` Brokeback Mountain '' is a short story by American author Annie Proulx . It was originally published in The New Yorker on October 13 , 1997 . The New Yorker won the National Magazine Award for Fiction for its publication of `` Brokeback Mountain '' in 1998 . Proulx won an O. Henry Award prize ( third place ) for her story in 1998 . The story was published in a slightly expanded version in Proulx 's 1999 collection of short stories , Close Range : Wyoming Stories . This collection was named a finalist for the 2000 Pulitzer Prize for Fiction . Screenwriters Larry McMurtry and Diana Ossana adapted the story for a film of the same name , released in 2005 . At that time , the short story and the screenplay were published together , along with essays by Proulx and the screenwriters , as Brokeback Mountain : Story to Screenplay . The story was also published separately in book form . This work has also been adapted as an opera by the same name , composed by Charles Wuorinen with a libretto in English by Proulx . It premiered at the Teatro Real in Madrid on January 28 , 2014 .",
"title": ""
},
{
"docid": "Lion_(2016_film)",
"text": "Lion is a 2016 biographical film directed by Garth Davis ( in his feature debut ) and written by Luke Davies , based on the non-fiction book A Long Way Home by Saroo Brierley with Larry Buttrose . The film stars Dev Patel , Rooney Mara , David Wenham and Nicole Kidman . The film , which had its world premiere at the Toronto International Film Festival on September 10 , 2016 , was given a limited release on November 25 , 2016 , by the Weinstein Company before opening generally on January 6 , 2017 . It was released in Australia on January 19 , 2017 and in the United Kingdom on January 20 , 2017 .",
"title": ""
},
{
"docid": "Gaia_(Marvel_Comics)",
"text": "Gaia , also known as the Guardian of the Universal Amalgamator , is a fictional comic book superhero appearing in American comic books published by Marvel Comics . The character has been depicted as possibly a mutant or extraterrestrial . Created by Larry Hama , she first appeared in Generation X # 37 .",
"title": ""
},
{
"docid": "Peter_Trower",
"text": "Peter Gerald Trower ( born 25 August 1930 ) is a Canadian poet and novelist . Trower was born in St Leonards-on-Sea , England , and came to Canada in 1940 . He worked for 22 years as a logger and has been writing professionally since 1971 . Peter has published three novels to date , more than ten books of poetry and numerous articles . One of his novels , Grogan 's Cafe ( novel ) , is in pre-production for a film In 1976 , Trower was the subject of a CBC documentary titled Between the Sky and the Splinters , after his 1974 book of poetry of the same name .",
"title": ""
},
{
"docid": "Lone_Star_Cafe",
"text": "The Lone Star Cafe was a cafe and club in New York City at 61 Fifth at the corner of Fifth Avenue and 13th Street , from 1976 to 1989 . The Texas-themed cafe opened in February 1976 and became the premier country music venue in New York and booked big names and especially acts from Texas , like Greezy Wheels , George Strait , Asleep at the Wheel and Roy Orbison . Willie Nelson , Kinky Friedman , Roy Orbison , Delbert McClinton , Freddy Fender , Lonnie Mack , Doug Sahm , Jerry Jeff Walker , and the Lost Gonzo Band were among Texas musicians who frequented the Lone Star Cafe . Joe Ely and Billy Joe Shaver also appeared at the cafe . The words from Shaver 's 1973 song `` Old Five and Dimers Like Me '' were displayed on a banner in the front of the cafe : `` Too Much Ai n't Enough . '' Other national acts played the cafe , including The Blues Brothers , Clifton Chenier , and James Brown , who recorded a live album there in 1985 . In the 1970s Texas political types in New York would visit the Lone Star Cafe , including Larry King , Ann Richards , Tommy Tune , Dan Rather , John Connally , Chet Flippo , Mark White and Linda Ellerbee . The cafe sported a unique 40-foot sculpture of a giant iguana created by artist Bob `` Daddy-O '' Wade on top of the building . Neighboring businesses did not appreciate the sculpture and sought to have it removed . Although a court battle determined that it was art , eventually it was removed . In 1983 with the support of Mayor Ed Koch , the Iguana was restored to the roof at a ceremony with Koch and then-Texas governor Mark White . The cafe was co-founded by Mort Cooperman and Bill McGivney , two ad executives at Wells Rich Greene Advertising . Bill McGivney left shortly afterwards and was replaced by Bill Dick . Both Bill Dick and Mort Cooperman appeared in Kinky Friedman 's book A Case of the Lone Star . Bill Dick was depicted as the owner and Mort Cooperman was the nefarious Detective Sergeant Mort Cooperman .",
"title": ""
},
{
"docid": "Naravadee",
"text": "Naravadee , the pen name of Pensri Kiengsiri ( born 1931 ) , is a Thai writer . Her name also appears as Narāwadī . She was born in Narathiwat Province and studied physiotherapy at the Royal Melbourne Hospital and Melbourne University . While working as a physiotherapist , she also began writing . She has published over thirty novels , several collections of short stories and a book of poetry in English Poems from Thailand . She has been president of the Writers ' Association of Thailand . Her novel Fā Klai Thalē Kwāng ( The Sea is Wide , The Sky is Near ) received a National Book Award in 1995 .",
"title": ""
},
{
"docid": "Sam_Coslow",
"text": "Sam Coslow ( December 27 , 1902 -- April 2 , 1982 ) was an American songwriter , singer , film producer , publisher , and market analyst . Coslow was born in New York City . He began writing songs as a teenager . He contributed songs to Broadway revues , formed the music publishing company Spier and Coslow with Larry Spier and made a number of recordings as a performer . With the explosion of film musicals in the late 1920s , Hollywood attracted a number of ambitious young songwriters and Coslow joined the exodus in 1929 . Coslow and his partner Larry Spier sold their publishing business to Paramount Pictures and Coslow became a Paramount songwriter . One of his first assignments for the studio was the score for the 1930 film The Virtuous Sin . He formed a successful partnership with composer Arthur Johnston and together they provided the scores for a number of films including Bing Crosby vehicles . Coslow became a film producer in the 1940s and won the Academy Award for Best Short Film for his production Heavenly Music in 1943 . He was married to actress Esther Muir from 1934 to 1948 , and they had a daughter Jacqueline Coslow , who also worked as an actress . In 1953 he married cabaret singer , Frances King , of Cafe Societie duo Noble & King . Sam and Frances remained married until his death in 1982 . Together they have a daughter , Cara Coslow who gained notoriety as Head of Casting for Carsey Werner Productions and the Producer of the television series Dante 's Cove . Cara is also an author of two books . During the 1960s Coslow 's work shifted from music and film to market analysis . During this time Coslow founded the publishing company Investor 's Press , which published investing books and the newsletter `` Indicator Digest . '' During the 1970s Coslow wrote two books , `` Cocktails for Two '' which focused on his musical career and `` Super Yields '' which focused on investing . He died in New York City .",
"title": ""
},
{
"docid": "Heron_Books",
"text": "Heron Books , Inc. is an assumed business name of Delphi Schools Inc. , under which the company publishes many paperback books for teachers , students , and home schoolers , as well as single-subject dictionaries for all grade levels . It is a trademark owned by Northwest Research , Inc. , which is another assumed business name of Delphi Schools Inc. . Heron Books has its headquarters on the property of The Delphian School in unincorporated Yamhill County , Oregon , near Sheridan . Several of Heron Books published works for students are based on the teachings of L. Ron Hubbard , the founder of Scientology . The Heron Basics Program is listed on the website of the Delphi Academy as their basis of instruction . Delphi Schools is a private school system licensed by Applied Scholastics , another Scientology-related entity . Two other publishers have been called Heron Books , both based in London . One published faux-leather classics in the late 1960s and early 1970s while the other published new fiction and nonfiction as an imprint of Quercus from 2011 to 2016 .",
"title": ""
},
{
"docid": "Maryam_Hooleh",
"text": "Maryam Hooleh ( born 1978 ) is an Iranian writer and poet . Maryam Hooleh , a young Iranian Kurd and one of the most gifted poets of her generation who now lives in Sweden , is one of these writers who -- for some time now -- have turned into thorns in the side of the Iranian regime . The profoundly uninhibited and confrontational style of Hooleh 's poetry has daringly exposed the crude disregard of the Islamic regime for human life . It has also drawn attention to the bodies of women , the most manifest objects of repression by the regime . At the same time , this confrontational style can provide ammunition for a damaging assault on the mullahs ' regime . Her works have usually dark and ironic atmosphere and abstract language where no signifier refers back to its usual signified ; her works are questioning religious and cultural taboos and criticize human condition in the postmodern world , and her poetry is usually labeled by postmodernism . Hooleh was born in Tehran . She began to write at an early age . At the age of seventeen , Hooleh travelled from Iran to Greece , illegally and on foot . It took 23 days to make the trip to Athens . She stayed one year and then returned to Iran . Mansoureh Saboori , an American director and filmmaker , made a documentary about her life , her poems and her trip to Greece which is called Another Birth . ( `` Another birth '' is also the name of a book written by Iranian poet Forugh Farrokhzad . ) Hooleh 's first book , The kite will never fly in my hands , was published in 1998 by Midland Graphic publishing in Chicago and her second book , In the Alleys of Athens , was published in 1999 by the Mir-Kasra publishing house in Tehran . In 2000 Hooleh was invited by The Iranian Women Studies Foundation to Sweden where her third book , Cursed Booth , was published by Baran publications . In 2003 she won a literary scholarship from Swedish PEN and moved to Sweden . Her fourth and fifth books , Contemporaneous leprosy and Hell INC , were published by Arzan publications in 2004 and her sixth book , The Sticky Dreams of a Banished Butterfly , was published over the net as a E-book and Audio Book . Her poetry has also been among the most selected works for translation in anthologies . Hooleh 's poems have been translated to English , Swedish , French , Kurdish , Turkish and some other languages , and she was one of the poets invited to the Struga Poetry Evnings in 2014 .",
"title": ""
},
{
"docid": "Dallas_Woodburn",
"text": "Dallas Woodburn is a writer , speaker , and literacy advocate . She is the author of two published books : There 's a Huge Pimple on My Nose and 3 a.m. . She is also the founder of Write On ! For Literacy , a non-profit organization dedicated to encouraging young people to read and write , such as another book that has been published called '' Dancing with The Pen '' . Her nonfiction has been published in numerous national publications , her short fiction has been nominated for a Pushcart Prize , and her plays have been produced in Los Angeles and New York City .",
"title": ""
},
{
"docid": "The_Vinyl_Cafe_Notebooks",
"text": "Vinyl Cafe Notebooks : a collection of essays from The Vinyl Cafe ( 2010 ) is Stuart McLean 's ninth book and each one has been a Canadian bestseller . McLean has sold over 1 million books in Canada . Unlike the other `` Vinyl Cafe '' books , these are not `` Dave and Morley stories '' . Selected from 15 years of radio-show archives and re-edited by the author , this eclectic essay collection provides a glimpse into the thoughtful mind at work behind The Vinyl Cafe . From meditations on peacekeeping to praise for the toothpick , The Vinyl Cafe Notebooks runs the gamut from considered argument to light-hearted opinion . Whether McLean is visiting a forgotten corner of the Canadian Shield , a big-city doughnut factory , or Sir John A. Macdonald 's gravesite , his observations are absorbing , unexpected , and original . With thought-provoking proposals about the world we live in and introductions to the people he meets in his extensive travels across our country , The Vinyl Cafe Notebooks is informed by McLean 's intimate relationship with Canada and Canadians . Yet the collection is also an intriguing look at the writer himself -- his past , his present , and his vision of the future . Sometimes funny , often wise , and always entertaining , The Vinyl Cafe Notebooks provides a wealth of reading pleasure that fans will return to again and again .",
"title": ""
},
{
"docid": "Lewis_Masonic",
"text": "Lewis Masonic is a British publishing company specialising in works on and for freemasonry . Originally called `` A Lewis '' , the name was a pseudonym for John Hogg , who was a Scottish Freemason from Edinburgh who was living in London . Founded in 1801 , it is the largest and oldest Masonic publisher in the World . Lewis Masonic is well known to English Freemasons , as Lewis produces many of the ritual books used by United Grand Lodge of England lodges and Holy Royal Arch Chapters . Originally the company focused on ritual books , minute books and other products for use in Lodges . Nowadays , Lewis Masonic is an imprint of Ian Allan Publishing ( having been acquired in 1973 ) , and has expanded its publishing to reach a broader audience . Lewis Masonic also publishes The Square , which is England 's longest-running Masonic magazine . The company takes its name from that of a lewis , which in freemasonry denotes a freemason brought into the fraternity by his father ; it also alludes to the lifting appliance of the same name which is an item most useful for both operative masons and speculative Masons . Lewis Masonic was named after these `` lewises '' because it was created to support Freemasonry as the other lewises support others , both actual and philosophical .",
"title": ""
},
{
"docid": "Marla_Streb",
"text": "Marla Streb ( born June 24 , 1965 ) is an American professional cyclist and was inducted in the mountain bike hall of fame in 2013 . She has won a World Cup downhill in 2005 ( Austria ) , twice won the Single Speed World Championship in 1999 and 2006 and also won the X-Games in 1999 . Streb has written and published two books , appeared on the cover of Outside Magazine , and has been featured on network television and movies such as the IMAX movie Top Speed . Marla is the founder and owner of Baltimore , MD 's first and only bicycle-cafe , called HandleBar Cafe . Streb also works as the PR and media liaison with the all-women 's professional trade team , The Clif Pro Team , and contracts as an LCI instructor with Bike Maryland , a non-profit cycling advocacy organization . She and her husband Mark Fitzgerald also own a natural-surface trail design company called Streb Trail Systems in Costa Rica .",
"title": ""
},
{
"docid": "Sten_Odenwald",
"text": "Sten Felix Odenwald ( born November 23 , 1952 ) is an American astronomer , author , and NASA scientist-educator . Odenwald has worked as part of the NASA Cosmic Background Explorer , Diffuse Infrared Background Experiment investigating the cosmic infrared background . He has published four books : The Astronomy Cafe , The 23rd Cycle , Patterns in the Void and Back to the Astronomy Cafe . He has also appeared in a number of TV and radio documentaries on astronomy and space weather . Since receiving his Ph.D. in astronomy from Harvard University in 1982 , he has been an astronomer in the Washington , D.C. area , primarily at NASA 's Goddard Spaceflight Center in Greenbelt , Maryland . Since 2000 , he has been actively involved in science and math education at NASA , and was a founding member of the Sun-Earth Connection Education Forum , among many other high-visibility NASA education projects involving space weather issues , archeoastronomy and the transits of Venus in 2004 and 2012 . He is currently the director of STEM Education at the National Institute of Aerospace .",
"title": ""
},
{
"docid": "Jorkens_Borrows_Another_Whiskey",
"text": "Jorkens Borrows Another Whiskey is a collection of fantasy short stories , narrated by Mr. Joseph Jorkens , by writer Lord Dunsany . It was first published in London by Michael Joseph in 1954 . It was the fifth collection of Dunsany 's Jorkens tales to be published . It has also been issued in combination with the sixth book , The Last Book of Jorkens , in the omnibus edition The Collected Jorkens , Volume Three , published by Night Shade Books in 2005 . The book collects thirty-four short pieces by Dunsany , and in one key story , Jorkens is joined in the story by his most common adversary , Terbut .",
"title": ""
},
{
"docid": "Larry_Sloan",
"text": "Lloyd Lawrence `` Larry '' Sloan ( 1922 -- October 14 , 2012 ) was an American publisher of Mad Libs and co-founder of the Los Angeles publishing company , Price Stern Sloan , which opened in the early 1960s . Sloan was born Lloyd Lawrence Solomon to Joseph Solomon and Freida Lewis Solomon in New York City in 1922 . His mother opened a clothing business and his father was a graduate of Columbia Law School 1908lawyer . Sloan and his parents moved to Los Angeles after his only sibling , Grenna Sloan , moved to California to pursue an acting career . Larry Sloan initially studied at the University of California , Los Angeles ( UCLA ) , but soon left college to enlist in the United States Army following the outbreak of World War II . He later attended Stanford University , where he studied Chinese language . He returned to Los Angeles after the war . Sloan became a columnist for the Hollywood Citizen News and a reporter for several magazines covering Hollywood 's entertainment and gossip industries . Sloan 's connections led to a career transition as a press agent and publicist representing Carol Channing , Mae West , and Elizabeth Taylor , among others . In 1958 , television writer Leonard B. Stern and comedian Roger Price launched Mad Libs , a word game book series which the duo had first invented in 1953 . Stern and Price had named the game `` Mad Libs '' after overhearing an argument between an actor and talent agent at a New York City restaurant . In the 1960s , Price and Stern partnered with Larry Sloan , a friend from high school , to found Price Stern Sloan , a publishing company based in Los Angeles which published Mad Libs . Sloan served as the company 's first CEO . Stern later noted in a 1994 Washington Post interview that Sloan `` eventually became the business man behind Mad Libs . '' The company headquartered on La Cienega Boulevard in West Hollywood . Under Sloan , Price Stern Sloan became the one of the largest publishing houses on the West Coast of the United States . In addition to releasing more than 70 editions of Mad Libs under Sloan , the company also published 150 softcover books under Sloan by 1973 . While simultaneously serving as CEO , Sloan also edited manuscripts submitted for publication . He personally edited a series of joke books called , World 's Worst Jokes . Sloan created and published the successful book , `` The VIP Desk Diary , after asking himself `` What would somebody 's desk diary look like if they were the richest man in the world ? '' Other successful titles , many of which were humorous , released under Sloan was How to Be a Jewish Mother , written by Dan Greenburg and first released in 1965 and Droodles , which was also created by Roger Price . Still , Mad Libs proved to be one of the company 's most successful products , with 110 million copies sold as of 2012 . Larry Sloan further launched Price Stern Sloan 's `` Wee Sing '' product line in the late 1970s . Sloan had found a handmade children 's book of the same name , which led to a successful line of books , videos , and audio releases , including Wee Sing Video Series and Wee Sing in Sillyville . Price Stern Sloan partner and Mad Libs co-creator Roger Price died in 1990 . In 1993 , Leonard Stern and Larry Sloan sold Price Stern Sloan to Putnam Berkley Group , which is now known as Penguin Group . Sloan and Stern later co-founded Tallfellow Press , a publishing company specializing in business books based in Beverly Hills . Sloan 's daughter , Claudia Sloan , continues to head Tallfellow , as of 2012 . Larry Sloan died from a brief illness at Cedars-Sinai Medical Center in Los Angeles on October 14 , 2012 , at the age of 89 . He was the last surviving founder of Price Stern Sloan , as Leonard Stern had died in 2011 . Sloan was survived by his wife of thirty-nine years , Eleanor ; five children - Claudia Sloan , Bonnie Smigel-Derin , Liz Fallert , Amy Harrison and Scott Harrison ; and six grandchildren . He had been a longtime resident of Malibu , California .",
"title": ""
},
{
"docid": "Johny_Pitts",
"text": "Johny Pitts is an English television presenter , writer and photographer from Firth Park , Sheffield . He is of mixed-race heritage ( his father is from New York and was in the '70s soul band The Fantastics , which was the subject of a 2015 BBC Radio 4 documentary written and presented by Pitts ) . Currently presenting Escape from Scorpion Island , Roar and All Over the Place , he also had stints on CD : UK hosting with Lauren Laverne and Myleene Klass and on Blue Peter and MTV . He is a keen musician and member of the Bare Knuckle Soul collective , who have supported the likes of Omar , the Pharcyde , Plantlife and Alice Russell and garnered acclaim from Giles Peterson , Zane Lowe and Trevor Nelson , as well as appearing on the Norman Jay Good Times 7 compilation . Pitts has written for Blues & Soul magazine , Straight No Chaser and The Observer , and won the Decibel Penguin Prize for new writers , with his short story `` Audience '' appearing in the anthology The Map of Me published by Penguin Books . He studied poetry under Debjani Chatterjee and has performed solo and alongside renowned poets John Agard and Valerie Bloom at venues such as the Albany Theatre , the Jazz Café , the Big Chill Festival , Notting Hill Arts Club and the Soho Theatre . Pitts recently collaborated with the novelist Caryl Phillips and Art Angel on a photographic essay exploring immigration and the River Thames for the BBC/Arts Council 's The Space , and founded the website www.afropean.com , which is part of the Guardian newspaper 's `` Africa Network '' , and the ENAR Foundation award-winning `` Afropean Culture '' page . His photography has been featured on The New York Times Lens Blog and the front covers of the Journal of Postcolonial Writing and Harvard University 's Transition Magazine A limited edition photo book was published by Cafe Royal Books He is a Fellow of the Royal Geographical Society .",
"title": ""
},
{
"docid": "Natasha_Larry",
"text": "Natasha Larry ( born December 11 , 1981 ) is the author of Grey Girl : A Memoir of Blackness . This book , published in January 2007 , is about the author 's move to the South and the subsequent culture shock she experienced . Further , her book explores the demands African Americans place on each other to be `` blacker , '' and what this concept of `` blackness '' really means . Her work has also appeared in publications such as Writing Edge and Escaping Elsewhere magazines . She has also appeared in the poetry anthology Coffee Break Poetry . Natasha Larry is a graduate of East Tennessee State University and resides in Huntsville , AL with her daughter , Jordan ( born 2/21/08 ) and her partner , Dave ( born 7/30/83 ) . She is currently working on a young adult paranormal/fantasy series , Darwin 's Children , the first novel of which will be published in 2011 by Penumbra . Her official site , NatashaLarry.com has plenty more information .",
"title": ""
},
{
"docid": "The_Schwa_Was_Here",
"text": "The Schwa Was Here is a young adult novel by Neal Shusterman , published by Dutton Penguin in 2004 . It is about an eighth-grader 's friendship with another student named Calvin Schwa , who goes almost completely unnoticed by the people around him . The book received critical acclaim upon its release , receiving a starred review from School Library Journal and a positive review from Booklist . It also received the 2005 Boston Globe/Horn Book Magazine award for fiction and poetry . The book has reportedly been optioned by The Disney Channel for a telefilm project . Shusterman , who worked with the channel on the project Pixel Perfect , was lined up to write the script for the project . This book has also been adapted into a three act play by Kory Howard , and was performed for the first time ever in February of 2017 , by the Manti High School Theatre Department .",
"title": ""
}
] |
PLAIN-2283
|
twin studies
|
[
{
"docid": "MED-4581",
"text": "We prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable-adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age.",
"title": "Fruit and vegetable consumption and cognitive decline in aging women."
},
{
"docid": "MED-4583",
"text": "Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.",
"title": "Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study."
},
{
"docid": "MED-4582",
"text": "Objective: Diet may be associated with risk of dementia and Alzheimer's disease (AD). We examined the association between fruit and vegetable consumption in midlife and risk for all types of dementia and AD. Methods: Participants were 3,779 members of the Swedish Twin Registry who completed a diet questionnaire approximately 30 years prior to cognitive screening and full clinical evaluation for dementia as part of the HARMONY study. Among the participants, 355 twins were diagnosed with dementia. Among these, 81 twin pairs were discordant for dementia (50 discordant for AD). Data were analyzed with logistic regression for the entire sample using generalized estimating equations to adjust for relatedness of twins, and with conditional logistic regression for the co-twin control design. Results: In fully-adjusted models, a medium or great proportion of fruits and vegetables in the diet, compared to no or small, was associated with a decreased risk of dementia and AD. This effect was observed among women and those with angina. Similar, but non-significant, odds ratios were found in the co-twin control analyses. Conclusion: Our findings suggest that higher fruit and vegetable consumption may reduce the risk of dementia, especially among women and those with angina pectoris in midlife.",
"title": "Midlife Fruit and Vegetable Consumption and Risk of Dementia in Later Life in Swedish Twins"
}
] |
[
{
"docid": "MED-1587",
"text": "OBJECTIVE: To evaluate the possible biochemical effect of diet and heredity on the rates of monozygotic and dizygotic twinning. STUDY DESIGN: In that insulin-like growth factor (IGF) has been found to be elevated in cows selected for their demonstrated increased twinning rate, the effect of agents that influence the level of IGF in women was examined. This was correlated with their prior history of singleton versus twin birthing. In particular, the effect of diets consisting of or excluding animal products that have elevated IGF content (e.g., milk) was considered. RESULTS: Vegan women, who exclude dairy products from their diets, have a twinning rate which is one-fifth that of vegetarians and omnivores. CONCLUSION: The results reported here support the proposed IGF model of dizygotic twinning. Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation.",
"title": "Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate."
},
{
"docid": "MED-4133",
"text": "BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.",
"title": "Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study."
},
{
"docid": "MED-5007",
"text": "Circulating adiponectin is emerging as an important link between obesity, type 2 diabetes, and cardiovascular disease (CVD). However, the spectrum of lifestyle factors that modulate the adiponectin concentration remains to be elucidated, particularly among women. We conducted a cross-sectional study of 877 female twin pairs from the TwinsUK adult twin registry. Using a co-twin design, we examined dietary and body composition influences on adiponectin by conducting matched, within-pair analyses to eliminate confounding. Following multivariable adjustment within-twin pairs, significant influences on adiponectin (log-transformed, percent change per SD of the dietary/body composition variable) were observed for nonstarch polysaccharides (3.25%; 95% CI: 0.06, 6.54; P < 0.05) and magnesium intake (3.80%; 95%CI: 0.17, 7.57; P < 0.05), with a trend toward an association for fruit and vegetable (F&V) intakes (2.55%; 95% CI: -0.26, 5.45; P = 0.08). These modest positive associations cannot be explained by confounding through other lifestyle factors shared by the twins. A significant relationship between adiponectin and 3 derived dietary patterns (F&V, dieting, traditional English), carbohydrate, protein, trans fat, and alcohol intake was also observed. Strong inverse associations with adiponectin were observed for BMI (-10.72%; 95% CI: -13.78, -7.55), total (-6.89%: 95% CI: -10.34, -3.30; P < 0.05), and central fat mass (-12.50%; 95% CI: -15.82, -9.05; P < 0.05); these relationships were significant both when twins were analyzed as individuals and when characteristics were contrasted within-twin pairs, suggesting a direct effect. We observed modest associations between dietary factors and adiponectin in female twins, independent of adiposity, and report strong inverse associations with body composition. These data reinforce the importance of weight maintenance and increasing consumption of diets rich in plant-based foods to prevent CVD and type 2 diabetes.",
"title": "Plasma adiponectin concentrations are associated with body composition and plant-based dietary factors in female twins."
},
{
"docid": "MED-1584",
"text": "Advances in assisted reproductive technology and increases in the proportion of maternities in older women have both contributed to the steep increase in the incidence of twin pregnancies since the 1980s. Maternal and perinatal complications are higher in twins than in singleton pregnancies. A significant proportion of perinatal mortality and morbidity among twins is due to the high incidence of preterm delivery and the added complication of twin-to-twin transfusion syndrome (TTTS) in monochorionic twins. Monochorionic twins also have a much higher rate of perinatal mortality than dichorionic twins, the greatest risk being before fetal viability (<24 weeks gestation). Early diagnosis of twins and their chorionicity, close fetal surveillance, particularly of monochorionic twins, and prompt therapeutic intervention in TTS are necessary to reduce perinatal mortality. Intrapartum management in the hospital setting with anaesthetic and neonatal facilities, as well as critical assessment of mode of delivery, have led to better outcomes. Ultrasonography is a valuable tool in the management of twin pregnancy. This chapter briefly summarises these topics, with a particular focus on recent literature.",
"title": "Obstetric complications of twin pregnancies."
},
{
"docid": "MED-1916",
"text": "BACKGROUND: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers. METHODS: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders. RESULTS: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P< .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03). CONCLUSIONS: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.",
"title": "The association between physical activity in leisure time and leukocyte telomere length."
},
{
"docid": "MED-1585",
"text": "As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Effects of twin gestation on maternal morbidity."
},
{
"docid": "MED-892",
"text": "Background: Evidence links dietary sodium to hypertension and cardiovascular disease (CVD), but investigation of its influence on cardiovascular function is limited. Objective: We examined the relation between habitual dietary sodium and coronary flow reserve (CFR), which is a measure of overall coronary vasodilator capacity and microvascular function. We hypothesized that increased sodium consumption is associated with lower CFR. Design: Habitual daily sodium intake for the previous 12 mo was measured in 286 male middle-aged twins (133 monozygotic and dizygotic pairs and 20 unpaired twins) by using the Willett food-frequency questionnaire. CFR was measured by positron emission tomography [N13]-ammonia, with quantitation of myocardial blood flow at rest and after adenosine stress. Mixed-effects regression analysis was used to assess the association between dietary sodium and CFR. Results: An increase in dietary sodium of 1000 mg/d was associated with a 10.0% lower CFR (95% CI: −17.0%, −2.5%) after adjustment for demographic, lifestyle, nutritional, and CVD risk factors (P = 0.01). Across quintiles of sodium consumption, dietary sodium was inversely associated with CFR (P-trend = 0.03), with the top quintile (>1456 mg/d) having a 20% lower CFR than the bottom quintile (<732 mg /d). This association also persisted within pairs: a 1000-mg/d difference in dietary sodium between brothers was associated with a 10.3% difference in CFR after adjustment for potential confounders (P = 0.02). Conclusions: Habitual dietary sodium is inversely associated with CFR independent of CVD risk factors and shared familial and genetic factors. Our study suggests a potential novel mechanism for the adverse effects of dietary sodium on the cardiovascular system. This trial was registered at clinicaltrials.gov as NCT00017836.",
"title": "Habitual dietary sodium intake is inversely associated with coronary flow reserve in middle-aged male twins"
},
{
"docid": "MED-1586",
"text": "Women with a multiple pregnancy face greater risks for themselves and their infants than women pregnant with one child. Pre-pregnancy care should focus on avoiding multiple pregnancy. Early prenatal care centres on determining chorionicity and screening for fetal anomalies, with later care focusing on the presentation, prediction and management of preterm birth, and intrauterine growth restriction. The optimal timing and mode of birth are the focus of current multicentre, randomised, controlled trials. However, the data from such trials on care for women with a multiple pregnancy are limited. Many areas of care require better-quality information, including when using assisted reproductive techniques, the optimal number of embryos to be transferred, care after the diagnosis of chorionicity, and the benefits of specialised multiple pregnancy clinics. Better-quality information is required to inform clinical practice for women with complications of multiple pregnancy, including monoamniotic twin pregnancy, treatment of twin-to-twin transfusion syndrome, and care following single intrauterine fetal death.",
"title": "Evidence-based care of women with a multiple pregnancy."
},
{
"docid": "MED-1588",
"text": "Multiple pregnancy rates remain high after assisted conception because of a misconceived assumption that transferring three or more embryos will maximize pregnancy rates. Maternal morbidity is sevenfold greater in multiple pregnancies than in singletons, perinatal mortality rates are fourfold higher for twins and sixfold higher for triplets, while cerebral palsy rates are 1-1.5% in twin and 7-8% in triplet pregnancies. Therefore, multiple pregnancies must be considered a serious adverse outcome of assisted reproductive techniques. Primary prevention of multiple pregnancies is the solution. The overwhelming evidence presented in this chapter demonstrates that limiting the embryo transfer in in vitro fertilization to two embryos would significantly reduce adverse maternal and perinatal outcomes by reducing the incidence of high order multiple pregnancies without reducing take-home-baby rates. Secondary prevention by multifetal pregnancy reduction is effective, but not acceptable to all patients. New developments in blastocyst culture, single embryo transfer, embryo cryopreservation and pre-implantation aneuploidy exclusion, should allow improvements in pregnancy rates without increasing multiple pregnancies.",
"title": "Reducing the incidence of twins and triplets."
},
{
"docid": "MED-1442",
"text": "We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h2 from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype–phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.",
"title": "Genetic Analysis of Chemosensory Traits in Human Twins"
},
{
"docid": "MED-1237",
"text": "It has become widely accepted that Type 2 diabetes is inevitably life-long, with irreversible and progressive beta cell damage. However, the restoration of normal glucose metabolism within days after bariatric surgery in the majority of people with Type 2 diabetes disproves this concept. There is now no doubt that this reversal of diabetes depends upon the sudden and profound decrease in food intake, and does not relate to any direct surgical effect. The Counterpoint study demonstrated that normal glucose levels and normal beta cell function could be restored by a very low calorie diet alone. Novel magnetic resonance methods were applied to measure intra-organ fat. The results showed two different time courses: a) resolution of hepatic insulin sensitivity within days along with a rapid fall in liver fat and normalisation of fasting glucose levels; and b) return of normal beta cell insulin secretion over weeks in step with a fall in pancreas fat. Now that it has been possible to observe the pathophysiological events during reversal of Type 2 diabetes, the reverse time course of events which determine the onset of the condition can be identified. The twin cycle hypothesis postulates that chronic calorie excess leads to accumulation of liver fat with eventual spill over into the pancreas. These self-reinforcing cycles between liver and pancreas eventually cause metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia. It is now clear that Type 2 diabetes is a reversible condition of intra-organ fat excess to which some people are more susceptible than others.",
"title": "Banting Memorial Lecture 2012 Reversing the twin cycles of Type 2 diabetes"
},
{
"docid": "MED-2848",
"text": "Type 1 diabetes is increasing rapidly in many parts of the Western world, most evidently in Scandinavia. A low concordance rate of insulin-dependent diabetes mellitus among monozygotic twins clearly indicates that genetic risk factors may be necessary, but are not sufficient for the disease to occur. The strongest genetic risk markers are located in the HLA region of chromosome 6, but these DNA specificities differ in different populations. Risk genes are indicated in other chromosomes of the human genome, suggesting a complex interaction between genes and environment as the cause of the disease. The pathogenesis of the disease is proposed to be autoimmune in nature and environmental risk factors may either initiate autoimmunity or accelerate an already ongoing beta-cell destruction. Risk factors disclosed by epidemiological studies that may accelerate the pathogenetic process are: a cold environment, a high growth rate, infections and stressful life events. Risk factors that may initiate the autoimmune process include early exposure to cow's milk proteins, nitrosamines or early foetal events such as blood group incompatibility or foetal viral infections. In conclusion, population-based epidemiological studies have helped to confirm proposed aetiological models that have arisen from experimental research. These epidemiological studies have also introduced important new findings that may reveal the complex aetiology of the disease and advance understanding closer to the ultimate goal of primary prevention.",
"title": "The aetiology of type 1 diabetes: an epidemiological perspective."
},
{
"docid": "MED-2089",
"text": "In this study, genotoxicity of two mouthwash products (chlorexidin, benzidamine-HCl) were investigated in the Drosophila Wing-Spot Test which makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. Induced mutations are detected as single mosaic spots on the wing blade of surviving adults that show either the multiple wing hairs or flare phenotype. Induced recombination leads to mwh and flr twin spots and also, to some extent, to mwh single spots. Recording of the frequency and the size of different spots is allowed for a quantitative determination of the mutagenic and recombinogenic effects. Trans-heterozygous third-instar larvae were treated at different concentrations of the mouthwash products. Chlorexidin exposure concentrations were 0.5, 1 and 2mg/ml. Benzidamine-HCl exposure concentrations were 0.38, 0.75 and 1.5mg/ml. In addition, the observed mutations were classified according to size and type of mutation per wing. Both chlorexidin and benzidamine-HCl were genotoxic in terms of total mutations per wing at the highest doses. Survival rates of flies used in the experiments were significantly lower than those of the control group, with both mouthwash products showing toxic effects on Drosophila melanogaster larvae. Copyright (c) 2010 Elsevier Ltd. All rights reserved.",
"title": "Genotoxicity of two mouthwash products in the Drosophila Wing-Spot Test."
},
{
"docid": "MED-1849",
"text": "The neuroanatomic specificity with which Alzheimer's disease (AD) progresses could provide clues to AD etiopathology. Magnetic resonance imaging studies of AD clinical progression have confirmed general conclusions from earlier studies of AD neuropathological progression wherein neurofibrillary tangle pathology was observed to spread along a well-defined sequence of corticocortical and corticosubcortical connections, preferentially affecting certain cell types, while sparing others. Identical and non-identical twin studies have consistently shown AD has mixed (environmental and genetic) etiopathogenesis. The decades-long prodromal phase over which AD develops suggests slow but progressive accumulation of a toxic or infective agent over time. Major environmental candidates are reviewed to assess which best fits the profile of an agent that slowly accrues in susceptible cell types of AD-vulnerable brain regions to toxic levels by old age, giving rise to AD neuropathology without rapid neuronal lysis. Chronic aluminum neurotoxicity best matches this profile. Many humans routinely ingest aluminum salts as additives contained in processed foods and alum-treated drinking water. The physical properties of aluminum and ferric iron ions are similar, allowing aluminum to use mechanisms evolved for iron to enter vulnerable neurons involved in AD progression, accumulate in those neurons, and cause neurofibrillary damage. The genetic component of AD etiopathogenesis apparently involves a susceptibility gene, yet to be identified, that increases aluminum absorption because AD and Down syndrome patients have higher than normal plasma, and brain, aluminum levels. This review describes evidence for aluminum involvement in AD neuropathology and the clinical progression of sporadic AD.",
"title": "Aluminum involvement in the progression of Alzheimer's disease."
},
{
"docid": "MED-1932",
"text": "There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.",
"title": "Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study"
},
{
"docid": "MED-1863",
"text": "IMPORTANCE Previous studies have suggested an association between vegetarian diets and lower blood pressure (BP), but the relationship is not well established. OBJECTIVE To conduct a systematic review and meta-analysis of controlled clinical trials and observational studies that have examined the association between vegetarian diets and BP. DATA SOURCES MEDLINE and Web of Science were searched for articles published in English from 1946 to October 2013 and from 1900 to November 2013, respectively. STUDY SELECTION All studies met the inclusion criteria of the use of (1) participants older than 20 years, (2) vegetarian diets as an exposure or intervention, (3) mean difference in BP as an outcome, and (4) a controlled trial or observational study design. In addition, none met the exclusion criteria of (1) use of twin participants, (2) use of multiple interventions, (3) reporting only categorical BP data, or (4) reliance on case series or case reports. DATA EXTRACTION AND SYNTHESIS Data collected included study design, baseline characteristics of the study population, dietary data, and outcomes. The data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Net differences in systolic and diastolic BP associated with the consumption of vegetarian diets were assessed. RESULTS Of the 258 studies identified, 7 clinical trials and 32 observational studies met the inclusion criteria. In the 7 controlled trials (a total of 311 participants; mean age, 44.5 years), consumption of vegetarian diets was associated with a reduction in mean systolic BP (-4.8 mm Hg; 95% CI, -6.6 to -3.1; P < .001; I2 = 0; P = .45 for heterogeneity) and diastolic BP (-2.2 mm Hg; 95% CI, -3.5 to -1.0; P < .001; I2 = 0; P = .43 for heterogeneity) compared with the consumption of omnivorous diets. In the 32 observational studies (a total of 21,604 participants; mean age, 46.6 years), consumption of vegetarian diets was associated with lower mean systolic BP (-6.9 mm Hg; 95% CI, -9.1 to -4.7; P < .001; I2 = 91.4; P < .001 for heterogeneity) and diastolic BP (-4.7 mm Hg; 95% CI, -6.3 to -3.1; P < .001; I2 = 92.6; P < .001 for heterogeneity) compared with the consumption of omnivorous diets. CONCLUSIONS AND RELEVANCE Consumption of vegetarian diets is associated with lower BP. Such diets could be a useful nonpharmacologic means for reducing BP.",
"title": "Vegetarian diets and blood pressure: a meta-analysis."
},
{
"docid": "MED-1656",
"text": "Background Low back pain (LBP) is common in children and adolescents, and it is becoming a public health concern. In recent years there has been a considerable increase in research studies that examine the prevalence of LBP in this population, but studies exhibit great variability in the prevalence rates reported. The purpose of this research was to examine, by means of a meta-analytic investigation, the prevalence rates of LBP in children and adolescents. Methods Studies were located from computerized databases (ISI Web of Knowledge, MedLine, PEDro, IME, LILACS, and CINAHL) and other sources. The search period extended to April 2011. To be included in the meta-analysis, studies had to report a prevalence rate (whether point, period or lifetime prevalence) of LBP in children and/or adolescents (≤ 18 years old). Two independent researchers coded the moderator variables of the studies, and extracted the prevalence rates. Separate meta-analyses were carried out for the different types of prevalence in order to avoid dependence problems. In each meta-analysis, a random-effects model was assumed to carry out the statistical analyses. Results A total of 59 articles fulfilled the selection criteria. The mean point prevalence obtained from 10 studies was 0.120 (95% CI: 0.09 and 0.159). The mean period prevalence at 12 months obtained from 13 studies was 0.336 (95% CI: 0.269 and 0.410), whereas the mean period prevalence at one week obtained from six studies was 0.177 (95% CI: 0.124 and 0.247). The mean lifetime prevalence obtained from 30 studies was 0.399 (95% CI: 0.342 and 0.459). Lifetime prevalence exhibited a positive, statistically significant relationship with the mean age of the participants in the samples and with the publication year of the studies. Conclusions The most recent studies showed higher prevalence rates than the oldest ones, and studies with a better methodology exhibited higher lifetime prevalence rates than studies that were methodologically poor. Future studies should report more information regarding the definition of LBP and there is a need to improve the methodological quality of studies.",
"title": "Prevalence of low back pain in children and adolescents: a meta-analysis"
},
{
"docid": "MED-2158",
"text": "Background Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case–control and cohort studies to investigate the association between coffee consumption and liver cancer. Methods We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case–control studies and seven cohort studies. Results The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42–0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I2 = 10.2%). The ORs were 0.50 (95% CI: 0.40–0.63) for case–control studies and 0.48 (95% CI: 0.38–0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25–0.56) in males and 0.60 (95% CI: 0.33–1.10) in females. The OR was 0.45 (95% CI: 0.36–0.56) in Asian studies and 0.57 (95% CI: 0.44–0.75) in European studies. The OR was 0.39 (95% CI: 0.28–0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46–0.66) after adjustment for a history of liver disease. Conclusions The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed.",
"title": "Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis"
},
{
"docid": "MED-5250",
"text": "Several prospective studies considered the relation between coffee consumption and mortality. Most studies, however, were underpowered to detect an association, since they included relatively few deaths. To obtain quantitative overall estimates, we combined all published data from prospective studies on the relation of coffee with mortality for all causes, all cancers, cardiovascular disease (CVD), coronary/ischemic heart disease (CHD/IHD) and stroke. A bibliography search, updated to January 2013, was carried out in PubMed and Embase to identify prospective observational studies providing quantitative estimates on mortality from all causes, cancer, CVD, CHD/IHD or stroke in relation to coffee consumption. A systematic review and meta-analysis was conducted to estimate overall relative risks (RR) and 95 % confidence intervals (CI) using random-effects models. The pooled RRs of all cause mortality for the study-specific highest versus low (≤1 cup/day) coffee drinking categories were 0.88 (95 % CI 0.84-0.93) based on all the 23 studies, and 0.87 (95 % CI 0.82-0.93) for the 19 smoking adjusting studies. The combined RRs for CVD mortality were 0.89 (95 % CI 0.77-1.02, 17 smoking adjusting studies) for the highest versus low drinking and 0.98 (95 % CI 0.95-1.00, 16 studies) for the increment of 1 cup/day. Compared with low drinking, the RRs for the highest consumption of coffee were 0.95 (95 % CI 0.78-1.15, 12 smoking adjusting studies) for CHD/IHD, 0.95 (95 % CI 0.70-1.29, 6 studies) for stroke, and 1.03 (95 % CI 0.97-1.10, 10 studies) for all cancers. This meta-analysis provides quantitative evidence that coffee intake is inversely related to all cause and, probably, CVD mortality.",
"title": "A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases."
},
{
"docid": "MED-5362",
"text": "BACKGROUND: Studies of single nutrients on depression have produced inconsistent results, and they have failed to consider the complex interactions between nutrients. An increasing number of studies in recent years are investigating the association of overall dietary patterns and depression. OBJECTIVE: This study aimed to systematically review current literature and conduct meta-analyses of studies addressing the association between dietary patterns and depression. DESIGN: Six electronic databases were searched for articles published up to August 2013 that examined the association of total diet and depression among adults. Only studies considered methodologically rigorous were included. Two independent reviewers completed study selection, quality rating, and data extraction. Effect sizes of eligible studies were pooled by using random-effects models. A summary of the findings was presented for studies that could not be meta-analyzed. RESULTS: A total of 21 studies were identified. Results from 13 observational studies were pooled. Two dietary patterns were identified. The healthy diet pattern was significantly associated with a reduced odds of depression (OR: 0.84; 95% CI: 0.76, 0.92; P < 0.001). No statistically significant association was observed between the Western diet and depression (OR: 1.17; 95% CI: 0.97, 1.68; P = 0.094); however, the studies were too few for a precise estimate of this effect. CONCLUSIONS: The results suggest that high intakes of fruit, vegetables, fish, and whole grains may be associated with a reduced depression risk. However, more high-quality randomized controlled trials and cohort studies are needed to confirm this finding, specifically the temporal sequence of this association.",
"title": "A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults."
},
{
"docid": "MED-946",
"text": "BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control. OBJECTIVES: The objective of this systematic review was to evaluate the efficacy of bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. SEARCH STRATEGY: Computer assisted structured searches of MEDLINE, EMBASE, The Cochrane library, CINAHL and PsychInfo were conducted for the years 1966-2009. An updated search in April 2011 identified 10 studies which will be considered for inclusion in a future update of this review. SELECTION CRITERIA: Randomized controlled trials comparing bulking agents, antispasmodics or antidepressants with a placebo treatment in patients with irritable bowel syndrome aged over 12 years were considered for inclusion. Only studies published as full papers were included. Studies were not excluded on the basis of language. The primary outcome had to include improvement of abdominal pain, global assessment or symptom score. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the selected studies. Risk Ratios (RR) and Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated. A proof of practice analysis was conducted including sub-group analyses for different types of bulking agents, spasmolytic agents or antidepressant medication. This was followed by a proof of principle analysis where only the studies with adequate allocation concealment were included. MAIN RESULTS: A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies; 186 patients; SMD 0.03; 95% CI -0.34 to 0.40; P = 0.87), global assessment (11 studies; 565 patients; RR 1.10; 95% CI 0.91 to 1.33; P = 0.32) or symptom score (3 studies; 126 patients SMD -0.00; 95% CI -0.43 to 0.43; P = 1.00). Subgroup analyses for insoluble and soluble fibres also showed no statistically significant benefit. Separate analysis of the studies with adequate concealment of allocation did not change these results. There was a beneficial effect for antispasmodics over placebo for improvement of abdominal pain (58% of antispasmodic patients improved compared to 46% of placebo; 13 studies; 1392 patients; RR 1.32; 95% CI 1.12 to 1.55; P < 0.001; NNT = 7), global assessment (57% of antispasmodic patients improved compared to 39% of placebo; 22 studies; 1983 patients; RR 1.49; 95% CI 1.25 to 1.77; P < 0.0001; NNT = 5) and symptom score (37% of antispasmodic patients improved compared to 22% of placebo; 4 studies; 586 patients; RR 1.86; 95% CI 1.26 to 2.76; P < 0.01; NNT = 3). Subgroup analyses for different types of antispasmodics found statistically significant benefits for cimteropium/ dicyclomine, peppermint oil, pinaverium and trimebutine. Separate analysis of the studies with adequate allocation concealment found a significant benefit for improvement of abdominal pain. There was a beneficial effect for antidepressants over placebo for improvement of abdominal pain (54% of antidepressants patients improved compared to 37% of placebo; 8 studies; 517 patients; RR 1.49; 95% CI 1.05 to 2.12; P = 0.03; NNT = 5), global assessment (59% of antidepressants patients improved compared to 39% of placebo; 11 studies; 750 patients; RR 1.57; 95% CI 1.23 to 2.00; P < 0.001; NNT = 4) and symptom score (53% of antidepressants patients improved compared to 26% of placebo; 3 studies; 159 patients; RR 1.99; 95% CI 1.32 to 2.99; P = 0.001; NNT = 4). Subgroup analyses showed a statistically significant benefit for selective serotonin releasing inhibitors (SSRIs) for improvement of global assessment and for tricyclic antidepressants (TCAs) for improvement of abdominal pain and symptom score. Separate analysis of studies with adequate allocation concealment found a significant benefit for improvement of symptom score and global assessment. Adverse events were not assessed as an outcome in this review. AUTHORS' CONCLUSIONS: There is no evidence that bulking agents are effective for treating IBS. There is evidence that antispasmodics are effective for the treatment of IBS. The individual subgroups which are effective include: cimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine. There is good evidence that antidepressants are effective for the treatment of IBS. The subgroup analyses for SSRIs and TCAs are unequivocal and their effectiveness may depend on the individual patient. Future research should use rigorous methodology and valid outcome measures.",
"title": "Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome."
},
{
"docid": "MED-2853",
"text": "Background Two criteria based on a 2 h 75 g OGTT are being used for the diagnosis of gestational diabetes (GDM), those recommended over the years by the World Health Organization (WHO), and those recently recommended by the International Association for Diabetes in Pregnancy Study Group (IADPSG), the latter generated in the HAPO study and based on pregnancy outcomes. Our aim is to systematically review the evidence for the associations between GDM (according to these criteria) and adverse outcomes. Methods We searched relevant studies in MEDLINE, EMBASE, LILACS, the Cochrane Library, CINHAL, WHO-Afro library, IMSEAR, EMCAT, IMEMR and WPRIM. We included cohort studies permitting the evaluation of GDM diagnosed by WHO and or IADPSG criteria against adverse maternal and perinatal outcomes in untreated women. Only studies with universal application of a 75 g OGTT were included. Relative risks (RRs) and their 95% confidence intervals (CI) were obtained for each study. We combined study results using a random-effects model. Inconsistency across studies was defined by an inconsistency index (I2) > 50%. Results Data were extracted from eight studies, totaling 44,829 women. Greater risk of adverse outcomes was observed for both diagnostic criteria. When using the WHO criteria, consistent associations were seen for macrosomia (RR = 1.81; 95%CI 1.47-2.22; p < 0.001); large for gestational age (RR = 1.53; 95%CI 1.39-1.69; p < 0.001); perinatal mortality (RR = 1.55; 95% CI 0.88-2.73; p = 0.13); preeclampsia (RR = 1.69; 95%CI 1.31-2.18; p < 0.001); and cesarean delivery (RR = 1.37;95%CI 1.24-1.51; p < 0.001). Less data were available for the IADPSG criteria, and associations were inconsistent across studies (I2 ≥ 73%). Magnitudes of RRs and their 95%CIs were 1.73 (1.28-2.35; p = 0.001) for large for gestational age; 1.71 (1.38-2.13; p < 0.001) for preeclampsia; and 1.23 (1.01-1.51; p = 0.04) for cesarean delivery. Excluding either the HAPO or the EBDG studies minimally altered these associations, but the RRs seen for the IADPSG criteria were reduced after excluding HAPO. Conclusions The WHO and the IADPSG criteria for GDM identified women at a small increased risk for adverse pregnancy outcomes. Associations were of similar magnitude for both criteria. However, high inconsistency was seen for those with the IADPSG criteria. Full evaluation of the latter in settings other than HAPO requires additional studies.",
"title": "Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria"
},
{
"docid": "MED-1176",
"text": "Many studies have investigated the neurodevelopmental effects of prenatal and early childhood exposures to organophosphate (OP) pesticides among children, but they have not been collectively evaluated. The aim of the present article is to synthesize reported evidence over the last decade on OP exposure and neurodevelopmental effects in children. The Data Sources were PubMed, Web of Science, EBSCO, SciVerse Scopus, SpringerLink, SciELO and DOAJ. The eligibility criteria considered were studies assessing exposure to OP pesticides and neurodevelopmental effects in children from birth to 18 years of age, published between 2002 and 2012 in English or Spanish. Twenty-seven articles met the eligibility criteria. Studies were rated for evidential consideration as high, intermediate, or low based upon the study design, number of participants, exposure measurement, and neurodevelopmental measures. All but one of the 27 studies evaluated showed some negative effects of pesticides on neurobehavioral development. A positive dose–response relationship between OP exposure and neurodevelopmental outcomes was found in all but one of the 12 studies that assessed dose–response. In the ten longitudinal studies that assessed prenatal exposure to OPs, cognitive deficits (related to working memory) were found in children at age 7 years, behavioral deficits (related to attention) seen mainly in toddlers, and motor deficits (abnormal reflexes) seen mainly in neonates. No meta-analysis was possible due to different measurements of exposure assessment and outcomes. Eleven studies (all longitudinal) were rated high, 14 studies were rated intermediate, and two studies were rated low. Evidence of neurological deficits associated with exposure to OP pesticides in children is growing. The studies reviewed collectively support the hypothesis that exposure to OP pesticides induces neurotoxic effects. Further research is needed to understand effects associated with exposure in critical windows of development.",
"title": "Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: A systematic review"
},
{
"docid": "MED-1343",
"text": "BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients. Copyright 2008 Massachusetts Medical Society.",
"title": "Selective publication of antidepressant trials and its influence on apparent efficacy."
},
{
"docid": "MED-4153",
"text": "CONTEXT: Emerging evidence suggests that sedentary behavior (i.e., time spent sitting) may be negatively associated with health. The aim of this study was to systematically review the evidence on associations between occupational sitting and health risks. EVIDENCE ACQUISITION: Studies were identified in March-April 2009 by literature searches in PubMed, PsycINFO, CENTRAL, CINAHL, EMBASE, and PEDro, with subsequent related-article searches in PubMed and citation searches in Web of Science. Identified studies were categorized by health outcome. Two independent reviewers assessed methodologic quality using a 15-item quality rating list (score range 0-15 points, higher score indicating better quality). Data on study design, study population, measures of occupational sitting, health risks, analyses, and results were extracted. EVIDENCE SYNTHESIS: 43 papers met the inclusion criteria (21% cross-sectional, 14% case-control, 65% prospective); they examined the associations between occupational sitting and BMI (n=12); cancer (n=17); cardiovascular disease (CVD, n=8); diabetes mellitus (DM, n=4); and mortality (n=6). The median study-quality score was 12 points. Half the cross-sectional studies showed a positive association between occupational sitting and BMI, but prospective studies failed to confirm a causal relationship. There was some case-control evidence for a positive association between occupational sitting and cancer; however, this was generally not supported by prospective studies. The majority of prospective studies found that occupational sitting was associated with a higher risk of DM and mortality. CONCLUSIONS: Limited evidence was found to support a positive relationship between occupational sitting and health risks. The heterogeneity of study designs, measures, and findings makes it difficult to draw definitive conclusions at this time. Copyright © 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.",
"title": "Occupational sitting and health risks: a systematic review."
},
{
"docid": "MED-950",
"text": "BACKGROUND: The association between consumption of multivitamins and breast cancer is inconsistent in epidemiologic studies. OBJECTIVE: To perform a meta-analysis of cohort and case-control studies to evaluate multivitamin intake and its relationship with breast cancer risk. METHODS: The published literature was systematically searched and reviewed using MEDLINE (1950 through July 2010), EMBASE (1980 through July 2010), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010 issue 1). Studies that included specific risk estimates were pooled using a random-effects model. The bias and quality of these studies were assessed with REVMAN statistical software (version 5.0) and the GRADE method of the Cochrane Collaboration. RESULTS: Eight of 27 studies that included 355,080 subjects were available for analysis. The total duration of multivitamin use in these trials ranged from 3 to 10 years. The frequency of current use in these studies ranged from 2 to 6 times/week. In analyses by duration of use 10 years or longer or 3 years or longer and by frequency 7 or more times/week that were reported in these studies, multivitamin use was not significantly associated with the risk of breast cancer. Only 1 recent Swedish cohort study concluded that multivitamin use is associated with an increased risk of breast cancer. The results of a meta-analysis that pooled data from 5 cohort studies and 3 case-control studies indicated that the overall multivariable relative risk and odds ratio were 0.10 (95% CI 0.60 to 1.63; p = 0.98) and 1.00 (95% CI 0.51 to 1.00; p = 1.00), respectively. The association was not statistically significant. CONCLUSIONS: Multivitamin use is likely not associated with a significant increased or decreased risk of breast cancer, but these results highlight the need for more case-control studies or randomized controlled clinical trials to further examine this relationship.",
"title": "Multivitamin supplement use and risk of breast cancer: a meta-analysis."
},
{
"docid": "MED-2771",
"text": "We have previously found a positive association between milk consumption and prostate cancer risk using meta-analysis to analyze published case-control studies. In the present study, further meta-analysis was conducted to estimate the summary relative risk (RR) between the consumption of milk and dairy products and prostate cancer from cohort studies published between 1966- 2006. We found 18 relevant articles and 13 independent studies were available for our analysis. The summary RR was 1.13 (95% confidence interval = 1.02-1.24) when comparing the highest with the lowest quantile of consumption. The summary RRs by study stratification showed a positive association. A dose-response relationship was identified when combining the studies that partitioned the consumption by quintiles. We also evaluated the effects of some limitations, such as dairy classification, prostate cancer stages and publication bias, in the present study. These findings, together with the previous study, suggest that the consumption of milk and dairy products increases the risk of prostate cancer. This is biologically plausible since milk contains considerable amounts of fat, hormones, and calcium that are associated with prostate cancer risk.",
"title": "Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies."
},
{
"docid": "MED-5036",
"text": "We evaluated long-term use of mobile phones and the risk for brain tumours in case-control studies published so far on this issue. We identified ten studies on glioma and meta-analysis yielded OR = 0.9, 95% CI = 0.8-1.1. Latency period of > or =10-years gave OR = 1.2, 95% CI = 0.8-1.9 based on six studies, for ipsilateral use (same side as tumour) OR = 2.0, 95% CI = 1.2-3.4 (four studies), but contralateral use did not increase the risk significantly, OR = 1.1, 95% CI = 0.6-2.0. Meta-analysis of nine studies on acoustic neuroma gave OR = 0.9, 95% CI = 0.7-1.1 increasing to OR = 1.3, 95% CI = 0.6-2.8 using > or =10-years latency period (four studies). Ipsilateral use gave OR = 2.4, 95% CI = 1.1-5.3 and contra-lateral OR = 1.2, 95% CI = 0.7-2.2 in the > or =10-years latency period group (three studies). Seven studies gave results for meningioma yielding overall OR = 0.8, 95% CI = 0.7-0.99. Using > or =10-years latency period OR = 1.3, 95% CI = 0.9-1.8 was calculated (four studies) increasing to OR = 1.7, 95% CI = 0.99-3.1 for ipsilateral use and OR = 1.0, 95% CI = 0.3-3.1 for contralateral use (two studies). We conclude that this meta-analysis gave a consistent pattern of an association between mobile phone use and ipsilateral glioma and acoustic neuroma using > or =10-years latency period.",
"title": "Meta-analysis of long-term mobile phone use and the association with brain tumours."
},
{
"docid": "MED-5323",
"text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Endocrine-disrupting chemicals and obesity development in humans: a review."
},
{
"docid": "MED-1400",
"text": "BACKGROUND: The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes. OBJECTIVE: We aimed to update our previous meta-analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status. DESIGN: We conducted a comprehensive literature search through electronic databases up to June 2010. RESULTS: The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality. CONCLUSION: This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases.",
"title": "Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis."
}
] |
202649
|
Aaron Carter is solely Canadian.
|
[
{
"docid": "Aaron_Carter",
"text": "Aaron Charles Carter ( born December 7 , 1987 ) is an American singer . He came to fame as a pop and hip hop singer in the late 1990s , establishing himself as a star among pre-teen and teenage audiences during the early 2000s with his four studio albums . Born in Tampa , Florida , Carter began performing at age seven and released his self-titled debut album in 1997 . His second album Aaron 's Party ( Come Get It ) ( 2000 ) sold three million copies in the United States , and Carter began making guest appearances on Nickelodeon and touring with the Backstreet Boys shortly after the record 's release . Carter 's next album , Oh Aaron , also went platinum , and the musician released his most recent studio album , Another Earthquake ! , in 2002 , followed by his 2003 Most Requested Hits collection . He has since appeared on Dancing With the Stars , the Broadway play The Fantasticks , and made several one-off performances . In 2014 , he announced that he would begin releasing new music and began by releasing a single featuring rapper Pat SoLo , `` Ooh Wee '' , which first became available as a free download with purchase on his web store . Carter released a single , Fool 's Gold , on April 1 , 2016 and an EP titled LøVë on February 10 , 2017 .",
"title": ""
}
] |
[
{
"docid": "Come_Get_It:_The_Very_Best_of_Aaron_Carter",
"text": "Come Get It : The Very Best of Aaron Carter is American teen pop singer Aaron Carter 's second compilation album , released in 2006 . The album received mixed reviews , with ChartAttack calling it inexplicable .",
"title": ""
},
{
"docid": "Aaron_Accetta",
"text": "Aaron Accetta is a New York -- based Multi-Platinum record producer , songwriter , and musician . He is currently co-owner of Dirty Canvas Music , a full scale music production company focused on artist development . The first artist signed to Dirty Canvas was Brooklyn based alt rock band American Authors in 2011 , who received a joint record deal with Island Records in 2012 . Subsequent acts signed to Dirty Canvas include Young Rising Sons in early 2014 , who received a joint record deal with Interscope records on June 17 , 2014 and The Karma Killers . Accetta has written and/or produced for such names as He is We , Forever The Sickest Kids , James Garfunkel , Brooke Hogan , Deborah Gibson , Jordan Knight , Rich Cronin , LFO , Keke Palmer , Aaron Carter , Nick Carter , and Jeff Timmons . Born and raised in Mt. Kisco , NY , a small town outside of New York City , Accetta began his music career at the early age of fourteen ; writing his first song on his Fender Stratocaster . By age sixteen , he started his first band called , The Fuse . After The Fuse parted ways , Accetta and lead vocalist , Dan Woods , put their efforts towards a new project : JBender , a melodic , hook-driven rock band produced by Sam Hollander . In February 2001 , the band signed a major recording contract with Columbia Records . The band was later dropped in 2002 . Accetta began focusing solely on his producing and songwriting career after the fall of JBender . In 2002 , he teamed up with pop artist , Mandy Ventrice , and began co-writing with the likes of Shep Goodman , Kenny Gioia , and Sam Hollander . In 2003 , Accetta was offered an in-house producer and songwriting position for Trans Continental Records based out of Orlando , FL . Shortly after , his credibility as a producer and songwriter grew tremendously ; earning him rave reviews in Billboard Magazine , and an RIAA Certified Gold Record commemorating the sales of his production on Aaron Carter 's single , Saturday Night .",
"title": ""
},
{
"docid": "Oh_Aaron",
"text": "Oh Aaron is American teen pop singer Aaron Carter 's third studio album , released in the summer of 2001 . The album features three collaborations with No Secrets and his older brother , Nick Carter . Although not as successful as his second album , it found success in the U.S. , peaking at # 7 and was certified Platinum by the RIAA making this Aaron 's second top 10 album and second platinum-selling album . This album was also his second album that was released under Jive Records . Oh Aaron was accompanied by a concert DVD of the same name , which was released on March 26 , 2002 , and included footage of his 2001 concert in Baton Rouge , Louisiana , as well as music videos and interviews . Play Along Toys also created an Aaron Carter action figure in conjunction with the album 's release .",
"title": ""
},
{
"docid": "2_Good_2_B_True",
"text": "2 Good 2 B True is American teen pop singer Aaron Carter 's third compilation album . The album primarily consists of songs that originally appeared on Aaron Carter 's last three studio albums . It was released in February 2006 , only one month after his previous compilation Come Get It : The Very Best of Aaron Carter .",
"title": ""
},
{
"docid": "House_of_Carters",
"text": "House of Carters ( previously known as The Carters ) is an American documentary/reality show on the E! cable network , and MuchMusic in Canada , about the lives of Backstreet Boy Nick Carter and his four siblings reuniting in Los Angeles ( while Carter was gearing up for the Backstreet Boys 6th studio album Unbreakable ) as they try to revive their careers as well as reconnect as a family . The series premiered on October 2 , 2006 . Eight episodes were ordered . The show stars Nick , B.J. , Aaron , Leslie and Angel Carter . The show was parodied on Saturday Night Live on October 21 , 2006 , with Andy Samberg as Aaron Carter and Jason Sudeikis as Nick Carter .",
"title": ""
},
{
"docid": "List_of_songs_recorded_by_Aaron_Carter",
"text": "The following is a list of released songs recorded and performed by Aaron Carter .",
"title": ""
},
{
"docid": "Aaron's_Party_(Come_Get_It)",
"text": "Aaron 's Party ( Come Get It ) is the second studio album by American pop singer Aaron Carter . It serves as the follow-up to his international debut album . Aaron 's Party was released in the fall of 2000 becoming the first album under Jive Records . This album was also certified 3 × Platinum by the RIAA for selling over 3 million copies in the United States making it Carter 's most successful album . The lead single `` Aaron 's Party ( Come Get It ) '' was featured on the 2000 compilation album Now That 's What I Call Music ! 5 .",
"title": ""
},
{
"docid": "Fool's_Gold_(Aaron_Carter_song)",
"text": "`` Fool 's Gold '' is a single by American pop musician Aaron Carter . It was released on April 1 , 2016 . Considered to be a comeback single , the song appeared on Carter 's extended play ( EP ) , LØVË . The song managed to make an appearance on the 2016 compilation album Now That 's What I Call Music ! 60",
"title": ""
},
{
"docid": "Jesse_Rath",
"text": "Jesse Rath ( born February 11 , 1989 ) is a Canadian film and television actor . He starred in the television series 18 to Life as Carter Boyd and as Ram on Aaron Stone . He was also on Syfy series , Defiance playing the role of Alak Tarr .",
"title": ""
},
{
"docid": "Aaron_Carter_discography",
"text": "This is a comprehensive listing of official releases by American pop singer Aaron Carter . He has sold more than 4 millions albums in the United States , and more than 10 million worldwide .",
"title": ""
},
{
"docid": "Now_or_Never_(Nick_Carter_album)",
"text": "Now or Never is the debut solo album by Nick Carter , best known as a member of the Backstreet Boys , released on October 29 , 2002 by Jive Records . The album debuted at # 17 in its first week on the Billboard 200 , selling some 70,000 copies during first week in U.S. . It fell out of the top 50 in its second week , but sold well enough to be certified Gold by the RIAA in December 2002 . Two singles were released from the album , neither of which had any impact on the US charts . The first single , `` Help Me '' , did reach # 9 on the Canadian Singles Chart . `` I Got You '' was a major hit in Europe and Southeast Asia . Aaron Carter gave sneak previews of three of the songs from the album on his album Another Earthquake .",
"title": ""
},
{
"docid": "Another_Earthquake!",
"text": "Another Earthquake ! is American teen pop singer Aaron Carter 's fourth studio album released in the fall of 2002 . The album made its chart debut at # 18 in the Billboard with 41,000 sold but plummet to # 41 ( 21,000 ) in its second week . This album was not as successful as Oh Aaron and became Aaron 's third overall and final studio album under the company of Jive Records . As of 2015 , Another Earthquake ! remains Carter 's last official studio album , although he continues to tour across the world .",
"title": ""
},
{
"docid": "Leslie_Carter",
"text": "Leslie Barbara Carter ( June 6 , 1986 -- January 31 , 2012 ) was an American pop singer best known as the sister of Backstreet Boys member Nick Carter and Aaron Carter .",
"title": ""
},
{
"docid": "Crazy_Little_Party_Girl",
"text": "`` Crazy Little Party Girl '' is the second single from Aaron Carter 's self-titled debut album , Aaron Carter . While failing to chart in the United States , the single found more success in European countries such as United Kingdom , Norway and Sweden , reaching the Top 10 in all three countries .",
"title": ""
},
{
"docid": "Crush_on_You_(The_Jets_song)",
"text": "`` Crush on You '' was the second single released in 1986 from the Jets ' critically and commercially successful debut album The Jets . It was also a successful single , reaching number three in the U.S. Jerry Knight and Aaron Zigman cowrote the hit single which put The Jets on the charts . In August 1997 , Aaron Carter released a cover of the song on his debut self-titled album , Aaron Carter . It reached the top ten in some countries worldwide , such as the UK and Australia in 1998 . In 2000 , Alan Braxe used a sample of `` Crush on You '' in his song `` Intro '' . In 2011 , the dubstep group Nero sampled the song and released it as a single on 16 October 2011 . It peaked in the top 40 on the UK Singles Chart .",
"title": ""
},
{
"docid": "Aaron_Carter_(album)",
"text": "Aaron Carter is the self-titled debut studio album by American pop singer Aaron Carter , brother of Backstreet Boys member Nick Carter . It was originally released in December 1997 in Europe and re-released the next year with a new song and a remix , as well as being released in the United States in the summer of 1998 . The original version of the album was also available as a limited edition including a poster and a pen that had written on the side , `` I Love Aaron '' , available in red , yellow , green or blue . The album reached the top 10 in some European countries , and reached number 12 in the United Kingdom . While it did not chart on the US Billboard 200 , it did manage to reach number 17 on the US Top Heatseekers chart , and sold more than 100,000 copies in the United States . Three singles were released from the album ; `` Crush on You '' , a cover of The Jets ' 1985 song , `` Crazy Little Party Girl '' , and `` I 'm Gon na Miss You Forever '' . Other songs were released as limited edition singles in some regions . `` Crush on You '' and `` Crazy Little Party Girl '' went top 10 and 20 respectively in Australia , while both went top 10 in the UK . All three singles went top 20 in Germany and Sweden , with `` I 'm Gon na Miss You Forever '' peaking at number 24 on the UK Singles Chart . `` Surfin ' U.S.A. '' , a cover of the 1963 song by The Beach Boys , was later included on the re-release edition of the album , and released separately as an EP , and went top 20 in the UK and Germany . When the album was first made available to purchase on iTunes , it strangely featured a Parental Advisory label next to the songs . This was changed to a `` clean '' label at a later date ; however , no `` explicit '' version exists , as none of the songs actually feature any profanity or suggestive themes , partly due to Carter 's age at the time ( he became ten years old six days after the album 's release ) ; and intended audience . The album sold more than 1 million copies worldwide .",
"title": ""
},
{
"docid": "Virginia_Carter",
"text": "Virginia Carter is a Canadian-born physicist and entertainment executive . Carter was born in Arvida , Quebec in 1936 . She studied math and physics at McGill University and graduated magna cum laude in 1958 . She then earned a master 's degree from the University of Southern California . She was hired by the Douglas Aircraft Corporation in 1962 . She then went to work for The Aerospace Corporation , where she was their sole female physicist . She stayed with Aerospace Corp. for nine years , conducting research on vacuum ultraviolet spectroscopy and high atmospheric conditions . Carter was a spokesperson for the women 's movement in the early 1970s and was president of the National Organization for Women 's Los Angeles chapter . She stepped down from the position after she was diagnosed with breast cancer . She also advocated for passage of the Equal Rights Amendment . Carter met Frances Lear through their common activism in the feminist movement . She introduced Carter to her husband , television producer Norman Lear . Starting in 1973 , she became director of creative affairs for him at Embassy Television . She worked on the sitcoms Maude and All in the Family . In 1976 she was promoted to vice president for creative affairs . Carter started a film division at Tandem and was the executive producer for the 1981 film The Wave . The film , based on The Third Wave experiment , won Peabody and Emmy Awards . After Tandem was sold to Coca Cola in the 1980s , Carter became president of J.O. Crystal , a firm that manufactures synthetic rubies . She retired from management of the firm in 2002 . She also worked with the Population Media Center .",
"title": ""
},
{
"docid": "Aaron's_Party:_The_Videos",
"text": "Aaron 's Party : The Videos is pop musician Aaron Carter 's first music video DVD with videos from his then-recent album , Aaron 's Party ( Come Get It ) . It was released in 2000 , the month after the release of the corresponding album . The video peaked at # 7 at US Billboard Top Music Video Charts . The DVD was certified Platinum by RIAA in December 1 , 2000 .",
"title": ""
},
{
"docid": "Oh_Aaron:_Live_in_Concert",
"text": "Oh Aaron : Live in Concert is the fourth DVD release by pop singer Aaron Carter , released in 2002 . It is his second live concert video . The video peaked at # 6 at US Billboard Top Music Video charts . The DVD was certified Gold by RIAA in May 1 , 2002 .",
"title": ""
},
{
"docid": "Aaron's_Party_(Come_Get_It)_(song)",
"text": "`` Aaron 's Party ( Come Get It ) '' is the first single from Aaron Carter 's second studio album , Aaron 's Party ( Come Get It ) . To date , it 's his most successful single in the United States , reaching # 35 on the Hot 100 , becoming his only Top 40 hit . On May 9th 2017 , American rapper Lymphatic T used `` Aaron 's Party '' to diss both Aaron and his small stature . It was also featured on the 2000 compilation album Now That 's What I Call Music ! 5 . The song is featured in the European Dancing Stage EuroMix 2 arcade .",
"title": ""
},
{
"docid": "Alex_Carter",
"text": "Alex Carter may refer to : Alex Carter ( American football ) ( born 1994 ) , American football cornerback Alex Carter ( British actor ) ( Hollyoaks and Emmerdale ; born 1982 ) Alex Carter ( Canadian actor ) ( born 1964 ) , Canadian television and film actor Alexander Carter ( 1909 -- 2002 ) , Canadian bishop Alexandra Carter ( born 1987 ) , Canadian voice actress Alexandra Carter ( politician ) , English politician",
"title": ""
},
{
"docid": "Aaron's_Party:_Live_in_Concert",
"text": "Aaron 's Party : Live in Concert is teen pop star Aaron Carter 's first concert DVD and third video release overall , released in 2001 . The video peaked at # 1 at US Billboard Top Music Video charts . The DVD was certified Platinum by RIAA in September 5 , 2001 .",
"title": ""
},
{
"docid": "Love_Shines",
"text": "Love Shines may refer to : Love Shines ( film ) , a 2010 documentary film about Canadian songwriter Ron Sexsmith Love Shines ( album ) , a 1983 album by American singer B. J. Thomas , `` Love Shines '' ( song ) , a 1992 song by Fleetwood Mac `` Love Shines ( A Song for My Daughters about God ) '' ( song ) , a 2006 song by Live `` Love Shines '' ( song ) , a 2011 song by Austin Stone Worship , written by Aaron Ivey , Philip Edsel , Matt Carter .",
"title": ""
},
{
"docid": "Nick_Carter_(musician)",
"text": "Nickolas Gene `` Nick '' Carter ( born January 28 , 1980 ) is an American singer , songwriter , actor , dancer , record producer , author and video director . He is best known as a member of the pop group the Backstreet Boys . As of 2015 , Carter has released three solo albums , Now or Never , I 'm Taking Off and All American during breaks between Backstreet Boys schedules , and a collaboration with Jordan Knight titled Nick & Knight . He has made occasional television appearances and starred in his own reality shows , House of Carters and I ( Heart ) Nick Carter . He gained fame in the mid 1990s and early 2000s as a teen idol . He is also the older and only brother of singer Aaron Carter .",
"title": ""
},
{
"docid": "Not_Too_Young,_Not_Too_Old",
"text": "`` Not Too Young , Not Too Old '' is a pop song from singer Aaron Carter 's third album , Oh Aaron . It 's his second song and single to feature vocals from his older brother , Nick .",
"title": ""
},
{
"docid": "Most_Requested_Hits",
"text": "Most Requested Hits is American teen pop singer Aaron Carter 's first compilation album and fourth overall album under Jive Records . The album did not make the top 50 and has only sold about 50,000 copies to date . The compilation included no tracks from Carter 's self-titled debut album , including one of Carter 's most successful singles worldwide , `` Crush on You '' .",
"title": ""
},
{
"docid": "Aaron_Kelly",
"text": "Aaron Kelly may refer to : Aaron Kelly ( singer ) ( born 1993 ) , American singer from Sonestown , Pennsylvania Aaron Kelly ( Canadian football ) ( born 1986 ) , Canadian football wide receiver Aaron Kelly ( Battlestar Galactica ) , a fictional character in the reimagined Battlestar Galactica TV program Aaron Kelly ( American football ) , played in 2008 Atlantic Coast Conference football season",
"title": ""
},
{
"docid": "Leave_It_Up_to_Me",
"text": "`` Leave It Up to Me '' is the lead single from the Jimmy Neutron : Boy Genius soundtrack recorded by teen star Aaron Carter . Carter performed two other songs along with this on the soundtrack , `` A.C. 's Alien Nation '' and `` Go Jimmy Jimmy '' .",
"title": ""
},
{
"docid": "Conversations_with_Other_Women",
"text": "Conversations with Other Women is a 2005 bittersweet romantic drama film directed by Hans Canosa , written by Gabrielle Zevin , starring Aaron Eckhart and Helena Bonham Carter . The film won Best Actress for Bonham Carter at the 2005 Tokyo International Film Festival .",
"title": ""
},
{
"docid": "That's_How_I_Beat_Shaq",
"text": "`` That 's How I Beat Shaq '' is a single from Aaron Carter 's second album , Aaron 's Party ( Come Get It ) . Released on February 6 , 2001 , the single features guest vocals from Shaquille O'Neal . The song was used in the trailer for Hey Arnold ! : The Movie .",
"title": ""
}
] |
4858
|
My Co-Signer is the Primary Account Holder for my Car Loan - Does this affect my credit?
|
[
{
"docid": "555099",
"text": "It sounds like your father got a loan and you are making the payments. If your name and SSN are not on the loan then you are not getting credit for making the payments your father is. So it will not affect your credit. If you are on the loan as a secondary borrower it will affect your credit but not substantially on the positive but could affect it substantially on the negative side. Since your father is named as the primary borrower you will probably need to talk with him about it first. If this is a mistake the 2 of you will need to work together with the bank to get it corrected. Since your father is currently listed first the bank is probably going to be unable(even if they are willing) to make a change to the loan now with out his explicit permission. In addition if the loan is in your fathers name, if it is a vehicle loan, then the car is most likely in your fathers name as well. Most states require that the primary signatory on a vehicle loan also be the primary owner on the title to the vehicle. If your fathers name is the primary name on the title then you would have to retitle the car to refinance in your name.",
"title": ""
}
] |
[
{
"docid": "267182",
"text": "\"I want to first state that I'm not an attorney and this is not a response that would be considered legal advice. I'm going to assume this was a loan was made in the USA. The OP didnt specify. A typical auto loan has a borrower and a co-borrower or \"\"cosigner\"\". The first signer on the contract is considered the \"\"primary\"\". As to your question about a primary being a co-borrower my answer would be no. Primary simply means first signer and you can't be a first signer and a co-borrower. Both borrower and co-borrower, unless the contract specifies different, are equally responsible for the auto loan regardless if you're a borrower or a co-borrower (primary or not primary). I'm not sure if there was a situation not specified that prompted the question. Just remember that when you add a co-borrower their positive and negative financials are handled equally as the borrower. So in some cases a co-borrower can make the loan not qualify. (I worked for an auto finance company for 16 years)\"",
"title": ""
},
{
"docid": "142876",
"text": "I am 17 and currently have a loan out for a car. My parents also have terrible credit, and because I knew this I was able to get around it. Your co-signer on your loan does not have to be your parent, at least in Wisconsin, I used my grandmother, who has excellent credit, as my cosigner. With my loan, we had made it so it doesn't hurt her credit if I don't get my payments in on time, maybe this is something for you to look into.",
"title": ""
},
{
"docid": "273759",
"text": "\"The wording of this question is very confusing because \"\"primary signer\"\" would, in ordinary parlance, mean the person borrowing the money and the co-signer (not consigner) would mean the one who is guaranteeing the repayment of the loan: if the borrower does not pay, the co-signer is liable for making the payments. Whose name is on the title of the car? Who borrowed the money to buy the car? Is the loan in your name and your son co-signed the loan to induce the bank to loan you money to purchase the car, or is it the other way around, that your son borrowed the money and you co-signed the loan in order to induce the bank to loan your son the money? If the car title and the loan are in your name, are you defaulting on the loan and so your son is making the loan payments that should have come from you? Or is it that your son borrowed the money to buy the car, his name is on the title, he is making the payments, and you are no longer interested in backing him up in case he defaults and the bank comes after you for the money?\"",
"title": ""
},
{
"docid": "453263",
"text": "Is your name on the title at all? You may have (slightly) more leverage in that case, but co-signing any loans is not a good idea, even for a friend or relative. As this article notes: Generally, co-signing refers to financing, not ownership. If the primary accountholder fails to make payments on the loan or the retail installment sales contract (a type of auto financing dealers sell), the co-signer is responsible for those payments, or their credit will suffer. Even if the co-signer makes the payments, they’re still not the owner if their name isn’t on the title. The Consumer Finance Protection Bureau (CFPB) notes: If you co-sign a loan, you are legally obligated to repay the loan in full. Co-signing a loan does not mean serving as a character reference for someone else. When you co-sign, you promise to pay the loan yourself. It means that you risk having to repay any missed payments immediately. If the borrower defaults on the loan, the creditor can use the same collection methods against you that can be used against the borrower such as demanding that you repay the entire loan yourself, suing you, and garnishing your wages or bank accounts after a judgment. Your credit score(s) may be impacted by any late payments or defaults. Co-signing an auto loan does not mean you have any right to the vehicle, it just means that you have agreed to become obligated to repay the amount of the loan. So make sure you can afford to pay this debt if the borrower cannot. Per this article and this loan.com article, options to remove your name from co-signing include: If you're name isn't on the title, you'll have to convince your ex-boyfriend and the bank to have you removed as the co-signer, but from your brief description above, it doesn't seem that your ex is going to be cooperative. Unfortunately, as the co-signer and guarantor of the loan, you're legally responsible for making the payments if he doesn't. Not making the payments could ruin your credit as well. One final option to consider is bankruptcy. Bankruptcy is a drastic option, and you'll have to weigh whether the disruption to your credit and financial life will be worth it versus repaying the balance of that auto loan. Per this post: Another not so pretty option is bankruptcy. This is an extreme route, and in some instances may not even guarantee a name-removal from the loan. Your best bet is to contact a lawyer or other source of legal help to review your options on how to proceed with this issue.",
"title": ""
},
{
"docid": "369075",
"text": "It doesn't matter to the credit agencies if there is a co-signer or not. However, your family member will need to take into consideration if they are willing to be responsible for the loan in the event you are unable to make payments. Being a co-signer means they are agreeing to pay the loan amount. It will also impact their credit score/report, either improve it if all goes well, or destroy it if neither one of you are able to pay the loan. So to you, assuming you can pay all the payments and not default, it makes no difference. But to the co-signer, it could create a huge impact. https://www.thebalance.com/does-co-signing-affect-credit-315368",
"title": ""
},
{
"docid": "157496",
"text": "From your viewpoint you paying the dealer directly is better. You know that the check went to the dealer, and was used to purchase a car. If you give the check to your friend they may say I can't find the car I want this week, so I will purchase it next week but first let me by groceries and a new suit. I will replace the funds after my next paycheck. Next thing you know they are still short of funds. This might not happen, but it could. From your friends viewpoint getting a check from you allows them to potentially keep your part of the transaction out of view of the dealer/lender. In a mortgage situation the lender will take a look at your bank account to make sure there isn't a hidden loan, but I am not sure they do when they are approving a car loan. What you want to avoid is being a co-signer for the loan. As a co-signer you will be responsible for all payments; and missed payments will hurt your credit score.",
"title": ""
},
{
"docid": "270952",
"text": "My grandmother passed away earlier this year. When I got my car 3 years ago, I did not have good enough credit to do it on my own or have her as a co-signer. We had arranged so that my grandmother was buying the car and I was co-signing. A similar situation was happening and I went to my bank and took out a re-finance loan prior to her passing. I explained to them that my grandmother was sick and on her death bed. They never once requested a power of attorney or required her signature. I am now the sole owner of the vehicle.",
"title": ""
},
{
"docid": "138419",
"text": "\"My personal rule is to not loan money (or co-sign) for any amount that I am not willing to give away. It can go wrong in so many ways, and having a family or friend involved means making a \"\"business\"\" decision is difficult. If a bank won't loan the person the money, why should I? Being a co-signer is the same as borrowing the money in my name and giving it right over to the borrower. There might be great reasons to do it. I would probably sign a loan to keep my family alive or healthy, but no other reason. There are many ways to help without signing a loan. Give a room and a place to live, loan a car. The other thing is if you really truly believe in the borrower, it won't do long term damage to your credit or your financial goals, and you are the only resort; go ahead. I am thinking about helping a teenager afford their first car or student loans.\"",
"title": ""
},
{
"docid": "467195",
"text": "\"You say Also I have been the only one with an income in our household for last 15 years, so for most of our marriage any debts have been in my name. She has a credit card (opened in 1999) that she has not used for years and she is also a secondary card holder on an American Express card and a MasterCard that are both in my name (she has not used the cards as we try to keep them only for emergencies). This would seem to indicate that the dealer is correct. Your wife has no credit history. You say that you paid off her student loans some years back. If \"\"some years\"\" was more than seven, then they have dropped off her credit report. If that's the most recent credit activity, then she effectively has none. Even if you get past that, note that she also doesn't have any income, which makes her a lousy co-signer. There's no real circumstance where you couldn't pay for the car but she could based on the historical data. She would have to get a job first. Since they had no information on her whatsoever, they probably didn't even get to that.\"",
"title": ""
},
{
"docid": "205196",
"text": "My son who is now 21 has never needed me to cosign on a loan for him and I did not need to establish any sort of credit rating for him to establish his own credit. One thing I would suggest is ditch the bank and use a credit union. I have used one for many years and opened an account there for my son as soon as he got his first job. He was able to get a debit card to start which doesn't build credit score but establishes his account work the credit union. He was able to get his first credit card through the same credit union without falling work the bureaucratic BS that comes with dealing with a large bank. His interest rate may be a bit higher due to his lack of credit score initially but because we taught him about finance it isn't really relevant because he doesn't carry a balance. He has also been able to get a student loan without needing a cosigner so he can attend college. The idea that one needs to have a credit score established before being an adult is a fallacy. Like my son, I started my credit on my own and have never needed a cosigner whether it was my first credit card at 17 (the credit union probably shouldn't have done that since i wasn't old enough to be legally bound), my first car at 18 or my first home at 22. For both my son and I, knowing how to use credit responsibly was far more valuable than having a credit score early. Before your children are 18 opening credit accounts with them as the primary account holder can be problematic because they aren't old enough to be legally liable for the debt. Using them as a cosigner is even more problematic for the same reason. Each financial institution will have their own rules and I certainly don't know them all. For what you are proposing I would suggest a small line of credit with a credit union. Being small and locally controlled you will probably find that you have the best luck there.",
"title": ""
},
{
"docid": "252859",
"text": "Considering I'm putting 30% down and having my father cosign is there any chance I would be turned down for a loan on a $100k car? According to BankRate, the average credit score needed to buy a new car is 714, but they also show average interest rates at 6.39% for new-car loans to people with credit scores in the 601-660 range. High income certainly helps offset credit score to some extent. Not every bank/dealership does things the same way. Being self-employed you'd most likely be required to show 2 years of tax returns, and they'd use those as a basis for your income rather than whatever you have made recently. If using a co-signer, their income matters. Another key factor is debt to income ratio, if too much of someone's income is already spoken for by other debts a lender will shy away. So, yes, there's a chance, given all the information we don't know and the variability with lender policies, that you could be turned down for a car loan. How should I go about this? If you're set on pursuing the car loan, just go talk to some lenders. You'll want to shop around for a good rate anyway, so no need to speculate just go find out. Include the dealership as a potential financing option, they can have great rates. Personally, I'd get a much cheaper car. Your insurance premium on a 100k car will be quite high due to your age. You might be rightly confident in your earning potential, but nothing is guaranteed, situations can change wildly in short order. A new car is not a good investment or a value-retaining asset, so why bother going into debt for one if you don't have to? If you buy something in cash now, you could upgrade in a few years without financing if your earning prediction holds and would save quite a bit in car insurance and interest over the years between.",
"title": ""
},
{
"docid": "322427",
"text": "The only thing that is important here is the documentation you and your daughter signed. If that documentation states that you were a co-signer and that your daughter was the primary on the loan, and then if the loan is not being reported in your daughter's name, you have a cause for action. If, however, the documentation says the loan is entirely in your name, the mistake is yours. Even in that case, though, your daughter may be able to take over the loan, or she may be able to take out a loan from a separate institution and use that to pay off the current loan. Obviously, this may be difficult if she does not have a credit history, which is what got you here in the first place. :(",
"title": ""
},
{
"docid": "320529",
"text": "As a former banker, the title of the car will be assigned to the loan account holder(s) because legally, he/she/they are responsible for payments. I've never heard of any case where the car title differs from the loan account holder(s). Throughout my career in the bank, I've come across quite a number of parents who did the same for their children and the car title was always assigned to the loan account holder's name. You do have a choice of applying for a joint loan with one of your parents unless if you are concerned about what your credit score might be. Once the loan has been paid off, the title could be changed to your name from your parents of course. As for insurance, there are numerous options where the insurance would cover all drivers of the car however at a slightly higher price like you've mentioned.",
"title": ""
},
{
"docid": "18257",
"text": "Never co-sign a loan for someone, especially family Taking out a loan for yourself is bad enough, but co-signing a loan is just plain stupid. Think about it, if the bank is asking for a co-signer its because they are not very confident that the applicant is going to be paying back the loan. So why would you then step up and say I'll pay back the loan if they don't, make me a co-signer please. Here is a list of things that people never think about when they cosign a loan for somebody. Now if you absolutely must co-sign a loan here is how I would do it. I, the co-signer would be the one who makes the payments to ensure that the loan was paid on time and I would be the one collecting the payment from the person who is getting the loan. Its a very simple way of preventing some of the worst situations that can arise and you should be willing to make the payments anyway after all thats what it means to cosign a loan. Your just turning things around and paying the loan upfront instead of paying after the applicant defaults and ruins every ones credit. (Source: user's own blog post Never co-sign a loan for someone, especially family)",
"title": ""
},
{
"docid": "402705",
"text": "There were several areas where the mortgage and car loan have affected your credit. The mortgage had the following impacts, The car loan (purchased shortly after the house) had the following impacts, You did not mention your payment history, but since you had an 800 prior to the house purchase, we can assume that your payment history is current (nothing late). You did not mention your credit utilization, but you want to keep your utilization low (various experts suggest 10%, 20% and 30% as thresholds). The down payment on the house likely drained your available funds, and replacing the car may have also put stress on your funds. And when you buy a house, often there are additional expenses that further strain budgets. My guess is that your utilization percentage has increased. My suggestion would be to reduce your utilization ratio on your revolving accounts. And since you have plenty of credit lines, you might want to payoff the car. Your Chase card has a good age, which helps with age of credit, and though you will find experts that say you should only have 2-4 revolving accounts (credit cards), other experience shows that having accounts with age on them is a good thing. And having a larger number of accounts does not cause problems (unless you have higher utilization or you miss payments). You did not mention whether the Chase card has any fees or expenses, as that would be a reason to either negotiate with Chase to reduce or eliminate the fees, or to cancel the card. Have you checked your credit report for errors? You can get a free report from each of the three bureaus once per year.",
"title": ""
},
{
"docid": "437574",
"text": "I believe that your son will need to get a new loan for the car in his name only and use the proceeds of that loan to pay off the one you co-signed on. The only way that will happen is if he can find a lender willing to loan him the money based on his credit only. From the current lender's perspective, if your son isn't a good credit risk, then why would they let someone out of the loan who might be able to pay if your son defaults? If he is a good credit risk, then they, or someone else, should be willing to lend to him without you as co-signer. Also, as Dilip Sarwate mentioned, you might have to do something with the title, depending on whose name it is in.",
"title": ""
},
{
"docid": "192641",
"text": "It may or may not be a good idea to borrow money from your family; there are many factors to consider here, not the least of which is what you would do if you got in serious financial trouble and couldn't make your scheduled payments on the loan. Would you arrange with them to sell the property ASAP? Or could they easily manage for a few months without your scheduled payments if it were necessary? A good rule of thumb that some people follow when lending to family is this: don't do it unless you're 100% OK with the possibility that they might not pay you back at all. That said, your question was about credit scores specifically. Having a mortgage and making on-time payments would factor into your score, but not significantly more heavily than having revolving credit (eg a credit card) and making on time payments, or having a car loan or installment loan and making on time payments. I bought my house in 2011, and after years of paying the mortgage on time my credit score hasn't changed at all. MyFico has a breakdown of factors affecting your credit score here: http://www.myfico.com/crediteducation/whatsinyourscore.aspx. The most significant are a history of on-time payments, low revolving credit utilization (carrying a $4900 balance on a card with a $5000 limit is bad, carrying a $10 balance on the same card is good), and overall length of your credit history. As to credit mix, they have this to say: Types of credit in use Credit mix determines 10% of my FICO Score The FICO® Score will consider your mix of credit cards, retail accounts, installment loans, finance company accounts and mortgage loans. It's not necessary to have one of each, and it's not a good idea to open credit accounts you don’t intend to use. The credit mix usually won’t be a key factor in determining your FICO Score—but it will be more important if your credit report does not have a lot of other information on which to base a score. Have credit cards – but manage them responsibly Having credit cards and installment loans with a good payment history will raise your FICO Score. People with no credit cards tend to be viewed as a higher risk than people who have managed credit cards responsibly.",
"title": ""
},
{
"docid": "285064",
"text": "Fundamentally interest rates reflect the time preference people place on money and the things money can buy. If I have a high time preference then I prefer money in my hand versus money promised to me at some date in the future. Thus, I will only loan my money to someone if they offer me an incentive which would be an amount of money to be received in the future that is larger than the amount of money I’m giving the debtor in the present (i.e. the interest rate). Many factors go into my time preference determination. My demand for cash (i.e. my cash balance), the credit rating of the borrower, the length of the loan, and my expectation of the change in currency value are just a few of the factors that affect what interest rate I will loan money. The first loan I make will have a lower interest rate than the last loan, ceteris paribus. This is because my supply of cash diminishes with each loan which makes my remaining cash more valuable and a higher interest rate will be needed to entice me to make additional loans. This is the theory behind why interest rates will rise when QE3 or QEinfinity ever stops. QE is where the Federal Reserve cartel prints new money to purchase bonds from cartel banks. If QE slows or ends the supply of money will stop increasing which will make cash more valuable and higher interest rates will be needed to entice creditors to loan money. Note that increasing the stock of money does not necessarily result in lower interest rates. As stated earlier, the change in value of the currency also affects the interest rate lenders are willing to accept. If the Federal Reserve cartel deposited $1 million everyday into every US citizen’s bank account it wouldn’t take long before lenders demanded very high interest rates as compensation for the decrease in the value of the currency. Does the Federal Reserve cartel affect interest rates? Yes, in two ways. First, as mentioned before, it prints new money that is loaned to the government. It either purchases the bonds directly or purchases the bonds from cartel banks which give them cash to purchase more government bonds. This keeps demand high for government bonds which lowers the yield on government bonds (yields move inverse to the price of the bond). The Federal Reserve cartel also can provide an unlimited amount of funds at the Federal Funds rate to the cartel member banks. Banks can borrow at this rate and then proceed to make loans at a higher rate and pocket the difference. Remember, however, that the Federal Reserve cartel is not the only market participant. Other bond holders, such as foreign governments and pension funds, buy and sell US bonds. At some point they could demand higher rates. The Federal Reserve cartel, which currently holds close to 17% of US public debt, could attempt to keep rates low by printing new money to buy all existing US bonds to prevent the yield on bonds from going up. At that point, however, holding US dollars becomes very dangerous as it is apparent the Federal Reserve cartel is just a money printing machine for the US government. That’s when most people begin to dump dollars en masse.",
"title": ""
},
{
"docid": "495482",
"text": "If you've been paying on the car for three years, it's possible that your credit is in a place where you don't need a co-signer any more. See if your bank will re-fi with you as the sole debtor. If they won't do it, find another institution who will. The re-fi will take your grandpa off the loan, and whichever institution that does the re-fi will still have a lien on the title until you pay it off. Then, if you can do this soon enough, figure out if grandpa can sign you off the title.",
"title": ""
},
{
"docid": "70885",
"text": "You may not have a good choice until you start that job. $2,000 is awfully low for a car, so it could be very risky. But you may not be able to get a loan until you start the new job. I would talk to a bank or credit union to get an idea of how much, if anything, you could borrow at this time. If you have a letter offering you the job that might help to get a loan. There are dealers who will finance a very cheap used car for anybody, but that kind of deal is likely to be at a very high interest rate and should be avoided. You could wind up with a debt and no car. One other possibility is to have a co-signer, such as a parent or other relative. That could make getting a car loan easy.",
"title": ""
},
{
"docid": "393553",
"text": "There is a difference between an owner and a signer. An owner is the legal owner of the funds. A signer has access to withdraw the funds. In most cases, when a new personal account is opened the name is added as an owner&signer. However, that is not always the case. A person could be an owner, but not a signer, in a custodial arrangement. For example, a minor child may be an owner only on their account with a custodial parent listed as a signer. The minor could not withdraw from the account. A person could be a signer, but not an owner, in a business or estate/trust account. The business or estate would be the owner with individuals listed as signers only. The business employees do not own the funds, they are only allowed to withdraw and disburse the funds on behalf of the company. The creditor can only garnish/withhold funds that are owned by the indebted. If the second person on the account is only a signer, those funds cannot be withheld as part of a judgment against the second person (they don't own those funds). However, simply titling the second person as a signer only is not sufficient. If you share access with the second person and allow them to spend the money for their own benefit, they are no longer just a signer. They have become an owner because you are sharing your funds with them. Think of the business relationship as an example. The employee is a signer so they can withdraw funds and pay business expenses, like the electric bill. If the employee withdrew funds and bought herself a new dress, she is stealing because she does not own those funds. If the second person on the account buys things for themselves, or transfers some of the money into their own account, they are demonstrating that more than a signer-only relationship exists. A true signer-only relationship is where the individual can only withdraw funds on the owner's behalf. For example, the owner is out of town and needs a bill paid, the signer can write a check and pay the bill for the owner. A limited power of attorney may be worth looking into. With a limited POA, the owner can define the scope and expiration of the power of attorney. With this arrangement, the second person becomes an executor of the owner under certain circumstances. For example, you could write a power of attorney that states something like: John Smith is hereby granted the limited power to withdraw funds from account 1234, on deposit at Anytown Bank, for the purpose of paying debts and obligations and otherwise maintain my estate in the event of my incapacitation or inability to attend to my own affairs. This Power of Attorney shall expire on it's fifth anniversary unless renewed. If the person you have granted the power of attorney abuses their access, you could sue them and you would only have to demonstrate that they overstepped the scope of their power.",
"title": ""
},
{
"docid": "82472",
"text": "\"It's rarely advisable to pay interest for something you can afford with cash. Just because you have no credit or loan history doesn't mean you aren't credit worthy. When applying for loans or credit, the lending institutions look at your credit report, not just your credit score. There are lots of things that show up on the reports they receive including (but not limited to): Right now, so many people are focused on their credit score, they're taking on unnecessary debt and potentially losing money in the long run. Yes, having a higher credit score will ultimately be beneficial, but your score will start growing naturally as you live your life. Unless of course you can and do pay for everything with cash. The concept of monitoring your score and striving to get it as high as possible is being shoved down our throats by advertisers at the moment. Don't fall for it. Rather than taking out a loan, which will cost you money in interest and actually show up as a closed account once it's paid off, you might be better served by applying for a credit card and using it sparingly just to start getting that credit history together. (Add usual \"\"don't spend more than you can pay back\"\" mantra here). Get a card with no annual fee and maybe some cash back options, and use it as the auto-payment for a utility if possible. You build credit history, increase your score, and it doesn't cost you any more than you'd be paying anyways. With regards to the investment question: With little to no credit history, you're not going to be approved for a loan with a low enough interest rate anyways. Think double digits. With a co-signer, you'll get a better rate, but then you need a co-signer. I don't know the exact math, but in today's market I'd say you'd need a loan interest rate of 2% or lower for investing to be worth thinking about. I believe this answer helps clarify the loan to invest math: https://money.stackexchange.com/a/26193/30798\"",
"title": ""
},
{
"docid": "403969",
"text": "\"You promised to pay the loan if he didn't. That was a commitment, and I recommend \"\"owning\"\" your choice and following it through to its conclusion, even if you never do that again. TLDR: You made a mistake: own it, keep your word, and embrace the lesson. Why? Because you keep your promises. (Nevermind that this is a rare time where your answer will be directly recorded, in your credit report.) This isn't moralism. I see this as a \"\"defining moment\"\" in a long game: 10 years down the road I'd like you to be wise, confident and unafraid in financial matters, with a healthy (if distant) relationship with our somewhat corrupt financial system. I know austerity stinks, but having a strong financial life will bring you a lot more money in the long run. Many are leaping to the conclusions that this is an \"\"EX-friend\"\" who did this deliberately. Don't assume this. For instance, it's quite possible your friend sold the (car?) at a dealer, who failed to pay off this note, or did and the lender botched the paperwork. And when the collector called, he told them that, thinking the collector would fix it, which they don't do. The point is, you don't know: your friend may be an innocent party here. Creditors generally don't report late payments to the credit bureaus until they're 30 days late. But as a co-signer, you're in a bad spot: you're liable for the payments, but they don't send you a bill. So when you hear about it, it's already nearly 30 days late. You don't get any extra grace period as a co-signer. So you need to make a payment right away to keep that from going 30 late, or if it's already 30 late, to keep it from going any later. If it is later determined that it was not necessary for you to make those payments, the lender should give them back to you. A less reputable lender may resist, and you may have to threaten small claims court, which is a great expense to them. Cheaper to pay you. They say France is the nation of love. They say America is the nation of commerce. So it's not surprising that here, people are quick to burn a lasting friendship over a temporary financial issue. Just saying, that isn't necessarily the right answer. I don't know about you, but my friends all have warts. Nobody's perfect. Financial issues are just another kind of wart. And financial life in America is hard, because we let commerce run amok. And because our obsession with it makes it a \"\"loaded\"\" issue and thus hard to talk about. Perhaps your friend is in trouble but the actual villain is a predatory lender. Point is, the friendship may be more important than this temporary adversity. The right answer may be to come together and figure out how to make it work. Yes, it's also possible he's a human leech who hops from person to person, charming them into cosigning for him. But to assume that right out of the gate is a bit silly. The first question I'd ask is \"\"where's the car?\"\" (If it's a car). Many lenders, especially those who loan to poor credit risks, put trackers in the car. They can tell you where it is, or at least, where it was last seen when the tracker stopped working. If that is a car dealer's lot, for instance, that would be very informative. Simply reaching out to the lender may get things moving, if there's just a paperwork issue behind this. Many people deal with life troubles by fleeing: they dread picking up the phone, they fearfully throw summons in the trash. This is a terrifying and miserable way to deal with such a situation. They learn nothing, and it's pure suffering. I prefer and recommend the opposite: turn into it, deal with it head-on, get ahead of it. Ask questions, google things, read, become an expert on the thing. Be the one calling the lender, not the other way round. This way it becomes a technical learning experience that's interesting and fun for you, and the lender is dreading your calls instead of the other way 'round. I've been sued. It sucked. But I took it on boldly, and and actually led the fight and strategy (albeit with counsel). And turned it around so he wound up paying my legal bills. HA! With that precious experience, I know exactly what to do... I don't fear being sued, or if absolutely necessary, suing. You might as well get the best financial education. You're paying the tuition!\"",
"title": ""
},
{
"docid": "138511",
"text": "Are you doing the right thing? Yes, paying back some of the expense of college is a great way to show your gratitude. Could your sister also pitch in a little to help pay the debt down? Will you get approved for a $30,000 unsecured loan? You don't mention your credit rating but that will have an effect obviously. You might consider visiting a credit union with your father and co-signing a loan since it is his debt that you are assuming. You might still want to write a loan for your dad to sign even if he isn't co-signed on a loan. This could protect you in case of his death if there are other assets to divide. If you are not approved for a loan, you could also simply join your dad in paying down the highest-rate cards first and have a loan agreement for him to pay back that money if/when it is possible. You've mentioned that you have no collateral. There aren't many options for loans with no collateral. Your dad's bank or a credit union might consider a debt consolidation loan with you as a co-signer. That's why I mentioned going to a credit union. Talking to a loan officer at a local financial institution will make it easier to get approved. If they see that you are taking responsible steps to pay off the debt, that reduces your credit risk. If you do get a debt consolidation loan, they will probably ask your dad to close some credit card accounts.",
"title": ""
},
{
"docid": "530987",
"text": "The SCHUFA in Germany works a bit different from the FICO score in the US. My background: I am a German currently living in the US. The information others want to see from the SCHUFA are a bit different. If you want to example rent a house or an apartment, the landlord often wants to see a SCHUFA statement which only shows that there are no negative entries. This statement you can get easily from online and they don't mention your credit score there. If you apply for a real credit or want to lease a car, they want to look deeper in your SCHUFA profile. However, very important is: They need signed permission to do this. Every participating company can submit entries to your profile where the score is calculated from. For example mobile phone plans, leasing a car, applying for a loan. Some lenders decide on the score itself, some on the overall profile and some also take your income into account. Since there is no hire & fire in Germany you are often asked to show your last 3 paychecks. This, in combination with your SCHUFA score is used for determination if you are eligible for a loan or not. However, they check through every entry which is made there and as long as it is reasonable and fits to your income (car for 800 EUR/month with a 1000 EUR salary does not!) you should not have a problem establishing a good score. The, in my eyes, unfair part about Schufa is that they take your zip code and your neighborhood into account when calculating their score. Also moving often affects the score negatively. To finally answer your question: Credit history is also built by mobile phone plans etc. in Germany. As long as you pay everything on time you should be fine. A bad score can definitely hurt you, but it is not as important to have a score as it is in the US because the banks also determine your creditworthiness based on your monthly income and your spending behavior.",
"title": ""
},
{
"docid": "556558",
"text": "\"I think the part of your question about not wanting to \"\"mess up more\"\" is the most important element. You say you know someone with good credit who is willing to co-sign for you, but let's be honest -- your credit isn't bad for no reason. Your credit's bad because you have a history of not paying on your obligations. Putting someone else's credit at risk, even though they may be willing to try and help, could be doing exactly what you said you're trying to avoid -- messing up more. This person's heart is in the right place, but you really have to ask yourself if you should put them in jeopardy by agreeing to guarantee your debts. So the vehicle you bought is older and has a lot of miles -- you knew that when you bought it. So you're paying a high interest rate because of your bad credit history -- you knew that when you bought it. Why you think the vehicle's only going to last another year is what confuses me. There are many vehicles out there with much higher mileage that are still on the road, and with proper preventative maintenance there's no reason your truck can't do the same. The fact is, you just don't like what you're paying or what you're driving (even though you were good with both when someone was willing to extend you credit), so now you see this other person's willingness to co-sign for you as your ticket out of a situation you no longer want to be in. My suggestion is that you stay with the loan you have, take care of the vehicle to make it last, and prove that you can pay your obligations. Hopping from loan to loan isn't going to do your credit any favors. One of the big factors for your credit score is the average age of accounts. Going and signing a new loan now will only drag that number down and hurt your score, not help it. And there's no guarantee the next car you buy with your friend's help is going to last the length of that loan either. I would be careful about this \"\"grass is greener on the other side\"\" attitude and just bear through your situation, if only to prove to yourself that you can do it. There's nothing saying your friend won't still be willing to co-sign for you later on down the line of something does happen to the truck, but you can show them that you're trying to be responsible in the meantime by following through on what you already agreed to.\"",
"title": ""
},
{
"docid": "64246",
"text": "Is it difficult to ask the credit card issuer for two cards, even if the account belongs to one person? You can most definitely get two cards for one account. People do it all the time. You just have to add her on as an authorized user. Would it be better for me to apply for the card on my own, or would there be an advantage to having her co-sign? It depends. If she co-signed, then that means she is also responsible for the credit card payments - which can help her credit score. If its is just you applying, then you are the only one responsible. If you don't want her lower credit score to impact what you could be approved for, then only you should apply. However, if you are the sole account holder, then you are responsible for the payments, which means, if in the event you guys break up and she maxes out the card before you cancel it, then you are on the hook for what she spend. As for improving her credit score, I do know that some banks report to the credit bureaus for the authorized user as well, so that could help her out too.",
"title": ""
},
{
"docid": "335808",
"text": "My family members, particularly my aunt (his daughter), are telling me that when my grandpa dies they are taking my car. Bring this up with Grandpa. If this is what he wants to have happen, then help him make it happen before you finish paying $12,000 on a car worth only $6,000. Let the Aunt and other relatives deal with the remaining $12,000. If that isn't what he wants to have happen, then work out how you and he can legally make sure that what he wants to have happen actually happens. If the Aunt or others bring it up, make sure they understand that you still owe $12,000 on the car, and if they get the car they also get the loan. If they refuse to pay the loan then make sure they know you will cooperate with the bank when they attempt to repossess the car - up to and including providing them with keys and location. This will hurt your credit, and you will be on the hook for the remaining portion of the loan, but you at least won't have to deal with all of it - they'll sell it at auction and your loan amount will fall a little. But the best course of action is to work with Grandpa, and make sure that he understands the family's threats, how that will affect you since you're on the loan, and what options you'd like to pursue.",
"title": ""
},
{
"docid": "272866",
"text": "I recently paid off a line of credit on an investment property that I own. I had some surplus cash and decided to pay off the line of credit rather than to make a principal payment on the primary mortgage with a higher interest rate. The interest rate on the line of credit was tiny and the balance was also pretty low. My reasoning was that by paying off the line of credit I would be done with that account and would have one less bill to pay each month, one less risk of something going wrong and a late payment hurting my credit, one less statement to reconcile each month, and one less bookkeeping core to manage. I could have grown my net worth by few couple of dollars each month had I kept the line of credit and made a principal payment on the primary loan. I judged that it wasn't worth the hassle and risks.",
"title": ""
},
{
"docid": "317461",
"text": "I have the mortgage from Lender A. Can I get a HELOC from Lender B? Yes. Do banks pull my credit to approve a HELOC account? Yes. How is it reported to the credit bureaus and how does it affect my credit (Let's say my limit is $30k and I use all of $30k)? It is reported as HELOC and the current balance. Similar to credit cards (in fact, some banks report it exactly as credit cards). Anything unique about it's tax deduction? Same as mortgage, except that the limit is $100K unless used for home improvement. Anything else to watch out for? LTV - Loan to Value. This is the ratio of your overall home value to the indebtedness secured by the home. Currently, your LTV is 93% (you have 7% equity). For HELOC, most banks require the LTV, including the HELOC, not to exceed 75%. So the chances you'll get a HELOC are pretty slim.",
"title": ""
}
] |
62212
|
Kevin Durant has contributed to a new media platform.
|
[
{
"docid": "Kevin_Durant",
"text": "Kevin Wayne Durant ( born September 29 , 1988 ) is an American professional basketball player for the Golden State Warriors of the National Basketball Association ( NBA ) . Durant has won an NBA Most Valuable Player Award , four NBA scoring titles , the NBA Rookie of the Year Award , and two Olympic gold medals . He has also been selected to seven All-NBA teams and eight All-Star teams . Durant was a heavily recruited high school prospect . He played one season of college basketball for the University of Texas , where he won numerous year-end awards and became the first freshman to be named Naismith College Player of the Year . In the 2007 NBA draft , he was selected with the second overall pick by the Seattle SuperSonics . After his rookie season , the team relocated to Oklahoma City and became the Thunder . Durant helped lead Oklahoma City to the 2012 NBA Finals , losing to the Miami Heat in five games . He played nine seasons for the Thunder organization before joining the Warriors in 2016 . Off the court , Durant often ranks as one of the highest-earning basketball players in the world , due in part to endorsement deals with companies such as Foot Locker and Nike . He has developed a reputation for his philanthropy and regularly leads the league in All-Star votes and jersey sales . In recent years , he has contributed to The Players ' Tribune as both a photographer and writer . In 2012 , he tried his hand at acting , appearing in the film Thunderstruck .",
"title": ""
},
{
"docid": "The_Players'_Tribune",
"text": "The Players ' Tribune is a new media platform that provides content written by professional athletes . Founded by former professional Major League Baseball player Derek Jeter , The Players ' Tribune provides daily sports conversation and publishes first-person stories directly from athletes . Content ranges from videos to podcasts to player polls and written pieces .",
"title": ""
}
] |
[
{
"docid": "BostInno",
"text": "BostInno is a local online news site and community publishing platform covering `` the view from inside '' innovation in Boston . It was founded in 2008 as a community startup blog by Chase Garbarino , CEO and co-founder of Streetwise Media , and Kevin McCarthy , CTO and co-founder . On December 7 , 2009 , BostInno was relaunched as a news platform profiling local innovation across verticals including tech , venture capital , city news , food , higher education , and sports . BostInno is operated by Streetwise Media , the online media company founded by Chase Garbarino , Kevin McCarthy , and Greg Gomer which seeks to reinvent the model of local news online . BostInno headquarters are in Faneuil Hall in Boston .",
"title": ""
},
{
"docid": "Nick_Huff_Barili",
"text": "Nick Huff Barili is an Argentinean-American journalist , television director & producer , and the founder of the premier multi-platform video production and entertainment company , Hard Knock TV . He is fluent in both Spanish and English . Over the course of his career , Nick has interviewed and profiled artists including Pharrell , Chris Martin , Kevin Hart , Kevin Durant , Andre 3000 , Eminem , Nas , Common , Eric Koston , Manny Pacquiao , Wu-Tang , 50 Cent , Ice Cube , Chuck D as well emerging talent like Kendrick Lamar , J. Cole , Macklemore , and Iggy Azalea .",
"title": ""
},
{
"docid": "Ron_Berkowitz",
"text": "Ron Berkowitz is an American entrepreneur , publicist and former sports journalist . He received national media attention and recognition for his role in the makeover of New York Yankee , Alex Rodriguez following a suspension for use of performance-enhancing drugs . Berkowitz is the CEO , president , and founder of the New York City-based Berk Communications . Berkowitz also represents some of Jay Z 's business ventures , several New York City nightclubs and does public relations work for Yoenis Cespedes , Robinson Cano , Kevin Durant and Dez Bryant .",
"title": ""
},
{
"docid": "List_of_career_achievements_by_Kevin_Durant",
"text": "This page details the records , statistics and career achievements of American basketball player Kevin Durant . Durant is an American basketball small forward who plays for the Golden State Warriors of the National Basketball Association .",
"title": ""
},
{
"docid": "2016–17_Golden_State_Warriors_season",
"text": "The 2016 -- 17 Golden State Warriors season is the 71st season of the franchise in the National Basketball Association ( NBA ) , and its 55th in the San Francisco Bay Area . Golden State entered the season as runners-up in the 2016 NBA Finals , after a record breaking regular-season in 2015 -- 16 . With the acquisition of free agent Kevin Durant in the offseason , the Warriors were hailed as a `` Superteam '' by the media and fans , forming a new All-Star `` Big Four '' of Durant , Stephen Curry , Klay Thompson and Draymond Green . The Warriors equaled their 2014 -- 15 regular-season record of 67 -- 15 , their second most wins in franchise history . In the postseason , Golden State clinched the top seed in the playoffs for the third successive year . The Warriors swept the Portland Trail Blazers 4 -- 0 in the first round , the Utah Jazz 4 -- 0 in the Western Conference semi-finals and the San Antonio Spurs 4 -- 0 in the Western Conference Finals . Golden State are the first team in NBA playoff history to start 12 -- 0 . Their current twelve game win-streak is tied third for most consecutive wins in the postseason . The Warriors will face the Cleveland Cavaliers in the NBA Finals , the first time in NBA history two teams have met for a third consecutive year . Golden State won the Pacific Division title and Western Conference Championship for the third consecutive season . The Warriors became only the second team in NBA history to win 30 road games in back-to-back seasons , joining the 1995 -- 96 and 1996 -- 97 Chicago Bulls . Stephen Curry set numerous three-point NBA records this season ; including most three-pointers made in a single game with 13 and most consecutive games ( regular-season and postseason combined ) with a made three-pointer with 196 . Curry also surpassed 300 three-pointers in the regular-season for the second time in NBA history , he finished with 324 . Kevin Durant , Stephen Curry , Klay Thompson and Draymond Green were all named to the All-Star Game , the first time Golden State have had four All-Stars and just the eighth time in NBA history a single team has had four players in the game . The Warriors were the only team with multiple players named to the All-NBA Team this season , with Curry , Durant and Green all selected . The Warriors were the fastest team in NBA history to clinch a playoff berth this season , achieving the feat on February 25 , 2017 .",
"title": ""
},
{
"docid": "Annapurna_Post",
"text": "Annapurna Post ( Nepali : अन्नपुर्ण पोस्ट ) is a Nepali language daily newspaper , published from Kathmandu , Itahari , Butwal , and Kohalpur of Nepal simultaneously . It was founded by Rameshwor Thapa . Yubaraj Ghimire has been the editor-in-chief of the newspaper since 2015 . The newspaper is owned by Nepal News Network International P. Ltd. ( 3NI ) , also known as Annapurna Media Network . History : Nepal News Network International Pvt. Ltd. ( 3NI ) is a growing multi-platform media house destined to enable social leadership and economic development through responsible media practices . Established in 2013 , it is an organization that believes in truth , ethics and ability . 3NI 's history precedes its establishment date . A clear void in responsible journalism in the nation gave birth to a concept of creating a media platform that could practice ethical journalism while contributing to the social leadership and economic growth of Nepal . After a few years of planning and strengthening the base for this vision the core team went on an all Nepal tour to research and learn about what the country required out of Nepal 's media . This proved to be a key moment in the history of 3NI as this tour provided the foundation of the organization 's strategies . In 2013 , after much deliberation and analysis , 3NI acquired Annapurna Post , one of the leading Nepali Newspaper in the country . With a clear business model , a strong team inspired by its own vision , 3NI is set towards its goal ; to make Annapurna Post the most effective national daily . Vision : To enable social leadership and economic development through responsible media practices Core Values : Truth : An organization that is based on truth . We have the courage to speak the truth . Ethics : Our organization has the ethical integrity to stand by the right . Ability -- We have the ability to voice , achieve , innovate , continuously change , and contribute to community and environment . Mission : Every content a purpose : We only publish news if we believe it serves a purpose . Expanding content market : We want to reach out to people from every corner of Nepal with news that relates to every aspect of the country . 360 Approach : We research story from every perspective and every angle possible to gain a 360o perspective that is unbiased and honest . Time to market : 3NI believes that news is relevant if it is on time and accurate . New networks - We are constantly expanding to different platforms and deliver news through different mediums .",
"title": ""
},
{
"docid": "Kevin_Wall",
"text": "Kevin Wall ( born March 15 , 1952 ) , is an American producer , new media entrepreneur , investor and activist who creates and produces large-scale global music events , several of which have attracted audiences of more than 1 billion viewers . Wall 's projects frequently promote environmental and social activism , and include Live Earth , Live 8 , the 2010 FIFA World Cup Kick Off Celebration Concert , and Chime For Change . Considered a pioneer in digital media and platform-agnostic content distribution , Wall received the first Emmy Award for interactive content .",
"title": ""
},
{
"docid": "Kevin_Gamble_(netcaster)",
"text": "Kevin Gamble ( born 14 June 1973 ) is a filmmaker , animation producer , and co-creator/co-star of the internet podcast Tiki Bar TV , in which he plays the role of Johnny Johnny the bartender . On October 14 , 2005 , during the Macworld 2005 Keynote presentation ( which introduced the new iPod with Video ) Steve Jobs showcased Tiki Bar TV to the audience as an example of a `` Video Podcast '' ( which , at that point in time , was a relatively new media format ) as something that could be loaded onto the new video iPod using Apple 's proprietary iTunes software for no charge . The next day , Tiki Bar TV moved to the # 1 slot in the iTunes Podcast charts , and as such Tiki Bar TV was one of the first user generated programs to gain worldwide popularity via the iTunes distribution model . Additionally , the still from Tiki Bar TV ( specifically , Kevin 's image ) appeared on the front webpage of Apple.com , and was composited inside of a Video iPod ) . For approximately one month , Kevin 's image remained on the Apple homepage next to pictures of iPods featuring U2 's Bono , ABC 's Lost and a picture of an audio book of Harry Potter . Kevin 's press mentions & appearances include Wired Magazine , The National Post , Tilzy , Epic-Fu and Tubefilter . Television mentions & appearances include CBC , CTV , G4 Tech TV ( Canada ) and CBS News and NBC News ( United States ) . In addition to his work in the new media & podcasting space , Kevin actively works in the children 's television & animation arena . He has been the Producer of several Television Series and TV Specials including `` Max Steel '' , `` The Scary Godmother Halloween Spooktakular '' , `` George of the Jungle '' and `` Casper 's Scare School '' . His DVD animated feature credits as Producer include `` Kung Fu Magoo '' and several of the popular `` Veggietales '' series ( including the most recent DVD in the `` Minnesota Cuke '' line , which parody the Indiana Jones movie franchise ) . In November 2009 , he was named VP of Development for Disney Television Animation . On January 27 , 2008 , Kevin saved a woman who had fallen on the track of a New York City Subway station by lifting her back onto the platform and performing first aid . On January 30 , 2016 , Kevin was seen successfully performing the Heimlich maneuver on an unknown woman in downtown Vancouver restaurant , Gyu Kaku . The woman recovered fully and the pair continued their dinner . On August 23 , 2016 , Canada Post confirmed that Kevin 's 2016 Burning Man Festival ticket was likely lost . He currently resides in Vancouver , British Columbia .",
"title": ""
},
{
"docid": "Apache_Marmotta",
"text": "Apache Marmotta is a Linked Data platform that comprises several components . In its most basic configuration it is a Linked Data server . Marmotta is one of the reference projects early implementing the new Linked Data Platform recommendation that is being developed by W3C . It has been contributed by Salzburg Research from the Linked Media Framework , and continues its versioning , hence starting at version 3.0.0 . Since April 2013 , it is listed among the Semantic Web tools by the W3C . In December 2013 , it has been nominated as `` one of the ASF 's most active projects '' .",
"title": ""
},
{
"docid": "Asia_Sentinel",
"text": "Asia Sentinel is a web-based Asian regional publication focused on news , business , arts and culture . The site was launched in August 2006 . `` Asia Sentinel was created to provide a platform for news , analysis and opinion on national and regional issues in Asia . It is independent of all governments and major media enterprises . It is open to contributions not only from journalists but from professionals in fields such as finance , diplomacy , science and the arts . It has no ideology other than a belief in the benefits of a free media . It will not publish editorials but give free rein to diverse opinions , '' says the founders ' statement on the site .",
"title": ""
},
{
"docid": "Durant_(surname)",
"text": "Durant is a surname of French and English origin . It ultimately derives from the Latin omen name Durandus , meaning `` enduring '' . Notable people with the surname include : Adrian Durant ( born 1984 ) , sprint athlete from the U.S. Virgin Islands Albert Durant ( 1892 -- ? ) , Belgian water polo player Ariel Durant ( 1898 -- 1981 ) , co-author of The Story of Civilization with husband Will Durant Cliff Durant ( 1890 -- 1937 ) , American racecar driver Darian Durant ( born 1982 ) , CFL football player Don Durant ( 1932 -- 2005 ) , American actor and singer George Durant ( 1632 -- 1692 ) , Attorney General from North Carolina Henry Durant ( 1802 -- 1875 ) , first president of the University of California Henry Bickersteth Durant ( 1871 -- 1932 ) , Bishop of Lahore ( 1913 -- 32 ) Henry Fowle Durant ( 1822 -- 1881 ) , American lawyer and philanthropist Hugh Durant ( 1877 -- 1916 ) , British sport shooter Isabelle Durant ( born 1954 ) , Belgian politician Joanne Durant ( born 1975 ) , Barbadian track and field sprinter Joe Durant ( born 1964 ) , American professional golfer John Charles Durant ( 1846 -- 1929 ) , English printer and Liberal politician Justin Durant ( born 1985 ) , NFL football player Kenneth W. Durant ( 1919 -- 1942 ) , U.S. Navy sailor Kevin Durant ( born 1988 ) , American basketball player Louis Durant ( 1910 -- 1972 ) , American racecar driver Michael Durant ( born 1961 ) , U.S. Army helicopter pilot held prisoner in Somalia in 1993 Mike Durant ( baseball ) ( born 1969 ) , former American Major League baseball player Paul Durant ( born 1959 ) , former American racecar driver Sam Durant ( born 1961 ) , American artist Thomas C. Durant ( 1820 -- 1885 ) , American financier Tony Durant ( born 1928 ) , British politician Will Durant ( 1885 -- 1981 ) , American philosopher , historian and author , husband of Ariel Durant William C. Durant ( 1861 -- 1947 ) , pioneer of U.S. automobile industry William West Durant ( 1850 -- 1934 ) , American architect and designer",
"title": ""
},
{
"docid": "Kevin_Popović",
"text": "Kevin Popović ( born July 4 , 1964 ) is an American communications author , and educator . He is the founder and CEO of the creative communications agency Ideahaus , as well as the Director of Idea Lab , part of the Zahn Innovation Platform at San Diego State University . Popović has written books focusing on communications and engagement , including Satellite Marketing : Using Social Media to Create Engagement ( 2016 ) and 20 Years Communications : 20 Leaders 20 Questions , 100s of Lessons ( 2013 )",
"title": ""
},
{
"docid": "New_Internationalist",
"text": "New Internationalist ( NI ) is an independent , non-profit , publishing co-operative , based in Oxford , United Kingdom . Predominantly known for its monthly independent magazine , it describes itself as existing to ` cover stories the mainstream media sidestep and provide alternative perspectives on today 's global critical issues . ' It covers social and environmental issues through its magazine , books and digital platforms . New Internationalist magazine has existed for over 40 years and currently is the largest magazine of its type in circulation in the United Kingdom . It has won the Utne Independent Press Award for `` Best International Coverage '' eight times , most recently in 2013 and an Amnesty International UK Media Awards 2012 award in the consumer magazine category as well as being recognized by the United Nations for its ` outstanding contribution to world peace and development ' . In March 2017 , New Internationalist published its 500th issue . New Internationalist is a worker run co-op with a non-hierarchical structure and strict editorial and environmental policies .",
"title": ""
},
{
"docid": "Stefano_Gallini-Durante",
"text": "Stefano Gallini-Durante ( aka Stefano Gallini ) is an Italian ( Milano ) born film producer based in Los Angeles , California . Son of Mario Gallini , an Italian industrialist , entrepreneur and 1960s sailing champion and Fernanda Durante ( 1930 -- 1978 ) , an author and journalist . He is the stepson of Cristina Formenton Mondadori , daughter of Italian publishing magnate Arnoldo Mondadori , founder of Arnoldo Mondadori Editore SpA , one of the largest European publishing and media conglomerates . Arnoldo Mondadori Editore SpA is a publishing and media company based in Milano ( Italy ) and is part of Fininvest SpA , the largest private Italian TV and media group , owned by former Italian Prime Minister Silvio Berlusconi .",
"title": ""
},
{
"docid": "Bjarne_Andre_Myklebust",
"text": "Bjarne Andre Myklebust ( born September 27 , 1972 ) is a Norwegian media professional and Head of IP Distribution at Norwegian Broadcasting Corporation NRK . He has developed and implemented Internet strategies for the Norwegian Broadcasting Corp. through roles as Development Manager , CTO , Managing Editor and Chief Editor and Head of new media for nrk.no and yr.no . In 2008 he received award as `` Best innovative editor '' of Oslo Editors ' Association . The jury pointed in particular on the success of the weather service yr.no contributed to NRK growth . yr.no is a joint service by the Norwegian Meteorological Institute and has over 3,000,000 unique visitors a week . In March 2014 Myklebust was recognized and named as the most influential person in the `` new television industry '' Nordic region by VODProfessional.com for his longstanding commitment on using the internet as a platform for modern distribution of television content . Myklebust topped the list again in 2015 .",
"title": ""
},
{
"docid": "Andrew_Durante",
"text": "Andrew James Durante ( born 3 May 1982 in Sydney , New South Wales ) is a New Zealand international footballer who plays for Wellington Phoenix in the A-League . Born in Sydney , Australia , Durante played youth football with Sydney Olympic before making his senior debut at the club . He also played for Parramatta Power before moving to Singapore to play for Balestier Khalsa . After returning to Australia to play for Sydney United , Durante joined in the newly formed A-League . Durante joined in 2008 , and is currently the player with the most appearances for the club . He has also spent time on loan at Sydney FC for the Asian Champions League in 2011 . Durante became eligible to play for New Zealand in 2013 , having lived in the country for five years , and made nine appearances for the national team before stepping aside from international football in 2015 . In September 2016 , he made himself available again for national team selection and was subsequently named in the team to tour the United States to play USA and Mexico in October 2016 .",
"title": ""
},
{
"docid": "Margery_Durant",
"text": "Margery Durant ( May 24 , 1887 -- February 3 , 1969 ) was the daughter of businessman and General Motors founder , Billy Durant . She was notable for authoring a book about her father , her contributions to increasing travel abroad via aviation , photographing her aviation adventures , and for being a socialite .",
"title": ""
},
{
"docid": "Adam_Ostrow",
"text": "Adam Ostrow is an American businessman , writer and speaker who serves as the Chief Strategy Officer at Mashable . He was hired by Pete Cashmore as online news site Mashable.com 's first Editor in Chief in 2007 and has contributed more than 2,500 articles to the site on topics including social media , technology and marketing trends . During his time at Mashable , Ostrow also spoke at numerous industry events and conferences , including the Cannes Lions , SXSW , Consumer Electronics Show and Digitas NewFront . His work at the site also included introducing Mashable 's video program and the Mashable Publisher Platform . Ostrow 's TED talk `` After the Final Status Update '' on the subject of how social media profiles live on after individual users die has been viewed more than 700,000 times as of September 2012 .",
"title": ""
},
{
"docid": "On_the_Ground_News_Reports",
"text": "On the Ground News Reports , `` OGNR '' or `` OG.NR '' , is a Citizen journalism news platform that collects , validates and distributes user-generated news in short form ( 250 words or less ) from Jamaica and around the world . Citizen Reporters , along with professional editors provide regular reports from the ground . OG.NR allows anyone who registers to contribute images , videos and other observations on local and global news . OG.NR Editors filter for spam , fact check for authenticity and assign an authentication status to each news report ( Confirmed , Corroborated , Unconfirmed ) . Once a report is published , other members can add context , and interact with the news by verifying , updating , commenting , or adding media such as pictures and video . OG.NR facilitates users being able to send and receive news reports through its Desktop Website , Mobile Site , Apps , Email and Browser extensions . OG.NR is also highly integrated with social media platforms Facebook and Twitter . Users can also subscribe to receive reports from their cell phones via Text Message . This is helpful for persons without a data plan , or where Internet penetration is low but mobile penetration is high .",
"title": ""
},
{
"docid": "Sam_Durant",
"text": "Sam Durant ( born 1961 , in Seattle ) is a multimedia artist whose works engage a variety of social , political , and cultural issues . Often referencing American history , his work explores the varying relationships between culture and politics , engaging subjects as diverse as the civil rights movement , southern rock music , and modernism . His work of the 90s was inspired largely by the work of Robert Smithson , an artist well known for his interest in history and entropy . Durant 's work has been widely exhibited internationally and in the United States . He has had solo museum exhibitions at the Museum of Contemporary Art , Los Angeles , Kunstverein für die Rheinlande und Westfalen , Düsseldorf , S.M.A.K. , Ghent , Belgium , and the Govett-Brewster Art Gallery in New Zealand . His work has been included in the Panamá , Sydney , Venice , and Whitney Biennials . Durant shows with several galleries including Blum & Poe in Los Angeles , Paula Cooper Gallery in New York , Praz-Delavallade in Paris and Sadie Coles HQ in London . His work has been extensively written about including seven monographic catalogs and books . In 2005 , his exhibition `` Proposal for White and Indian Dead Monument Transpositions , Washington D.C. '' was shown at the Paula Cooper Gallery in New York . This work derived out of a residency he was conducting at the Walker Art Center in 2002 . He reproduced 30 Indian massacre monuments that are based on similarities to the massive obelisk Washington monument . In 2006 , he compiled and edited a comprehensive monograph of Black Panther artist Emory Douglas ' work . His recent curatorial credits include Eat the Market at the Los Angeles County Museum and Black Panther : the Revolutionary Art of Emory Douglas at The Museum of Contemporary Art in Los Angeles and the New Museum in New York . He has co-organized numerous group shows and artists benefits and is a co-founder of Transforma , a cultural rebuilding collective project in New Orleans . In addition , he was a finalist for the 2008 Hugo Boss Prize and has received a United States Artists Broad Fellowship and a City of Los Angeles Individual Artist Grant . His work can be found in many public collections including The Art Gallery of Western Australia in Perth , Tate Modern in London , Project Row Houses in Houston , the Walker Art Center in Minneapolis , and the Museum of Modern Art in New York . Durant teaches art at the California Institute of the Arts in Valencia , California . Durant received a BFA in sculpture in 1986 from the Massachusetts College of Art and an MFA from California Institute of the Arts .",
"title": ""
},
{
"docid": "Red_Planet_Media",
"text": "Red Planet Media , Inc. is an American mobile entertainment services company . The company was a spun out of ClearSky Mobile Media , Inc. in 2007 to concentrate on the development of new mobile media platforms for the U.S. and Latin American markets . Since that time , the company has launched a multi-lingual mobile social networking platform called JumpInMobile.com and a mobile video-on-demand service called JumpInMobile.TV . Red Planet Media is headquartered in Orlando Florida .",
"title": ""
},
{
"docid": "Kevin_Brown_(author)",
"text": "Kevin Brown ( born September 3 , 1960 ) is a biographer , essayist and translator who has authored or contributed to three books . Kevin Brown has published brief lives of Romare Bearden and Malcolm X . He was a contributing editor to The New York Public Library African American Desk Reference Since 1978 , many of Brown 's essays , articles and reviews on the visual arts , cinema , dance , literature , music and politics have appeared in Afterimage , the American Book Review , American Visions , the Chicago Review , the Kansas City Star , Kirkus Reviews , the Times Literary Supplement , The Nation , New York Newsday , the Oakland Tribune , the Threepenny Review and the Washington Post Bookworld , among others . Brown 's 2005 translation into Spanish of Virginia Woolf 's little known essay `` Reviewing '' appeared in the Iowa University journal of literary translation eXchanges . His profile of translator Gregory Rabassa was published in 2006 by the University of Delaware 's Review of Latin American Studies .",
"title": ""
},
{
"docid": "Kevin_Wassong",
"text": "Kevin Wassong is a media executive . He was awarded the Emmy for his work and development of the first animated financial new programs `` Hoofy & Boo 's News & Views '' and `` Minyanville 's World in Review . '' Kevin is President of Minyanville Publishing and Multimedia . He joined the company in 2005 . From 1994 to 1997 Kevin worked on advertising campaigns for Little Caesars , Sun Microsystems , Merrill Lynch and Mercedes Benz . In 1998 , Kevin launched the digital marketing arm for J. Walter Thompson in the flagship New York City office , digital@jwt which became a top ten digital marketing organization . He was named by Mediapost as `` One of the most influential people in media '' in 2004 . Prior to his career in marketing and media he worked as an agent trainee and as an associate to the Chairman of Creative Artists Agency in California and worked on shows such as `` The Golden Girls , '' `` Empty Nest '' and `` Blossom . '' His writing credits include an episode of `` The Wubbulous World of Dr. Seuss '' on Nickelodeon . Kevin grew up in Rye NY and graduated in 1990 from Syracuse University 's S.I. Newhouse School .",
"title": ""
},
{
"docid": "Emily_Lakdawalla",
"text": "Emily Stewart Lakdawalla ( born February 8 , 1975 ) is Senior Editor of The Planetary Society , contributing as both a science writer and a blogger . She has also worked as a teacher and as an environmental consultant . She has performed research work in geology , Mars topography , and science communication and education . Lakdawalla is a science popularizer on various social media platforms , interacting with space professionals and enthusiasts on Facebook , Google + , and Twitter . She has appeared on NPR , BBC , and other media outlets discussing planetary science and space exploration .",
"title": ""
},
{
"docid": "Sheridan_(automobile)",
"text": "The Sheridan was a brand of American automobile manufactured from 1920 to 1921 . Manufacture of the car was based in Muncie , Indiana . The Sheridan nameplate has the distinction of being the first automotive brand started from scratch by General Motors . Prior to the Sheridan , General Motors , under William ( Billy ) Crapo Durant , grew its automotive marques - Chevrolet , Oakland , Oldsmobile , Buick and Cadillac - by acquiring independent manufacturers and then folding their operations into the GM structure . Throughout his years at GM , Billy Durant was interested acquiring outside companies and new products to grow the GM Empire , many times without great success . When Buick 's D.A. Burke approached Durant about the idea of designing a car from the ground up , and then marketing the car as a bridge vehicle between GM 's established divisions of Chevrolet and Oakland ( a four-cylinder ) , and between Buick and Cadillac ( an eight-cylinder ) , respectively . Durant approved the project and facility was secured in Muncie , Indiana . To market the vehicles , Sheridan hired World War I flying ace Eddie Rickenbacker , himself an accomplished automobile racer in his own right . Through prosaic marketing , and Rickenbacker 's endorsements , Sheridan officials felt the production target of 300 cars a day was not only achievable , but profitable as well . Just as production began to ramp up , Durant was fired for the second and final time from General Motors . Since the Sheridan was a Durant pet project , GM , now under Alfred Sloan , was left with Sheridan , one of Durant 's more costly but viable caprices . Durant on the other hand knew that the vehicle was soundly engineered and knew what GM paid for the Muncie facility . In May 1921 , Durant purchased the rights to the Sheridan and to the Muncie plant , with the intent on using the facility to continue building the Sheridan and Durant 's new project , the Durant and Princeton automobiles built by Durant Motors . After the takeover , the enterprise began to degrade for Sheridan , despite a back log of orders that went unfulfilled . By the summer of 1921 , Rickenbacker abandoned his role as the spokesman for the company , and the Sheridan ceased to exist by September , 1921 .",
"title": ""
},
{
"docid": "China_Current",
"text": "China Current is an independent news agency which publishes articles in both Chinese and English to cater to its different target audiences . While its core focus is on China , it covers news from all across the world . Its bases are on the Chinese mainland , Hong Kong , and Macau , North America and the United Kingdom . China Current is in the process building a leading public platform for independent news coverage . In addition to concentrating on current affairs , the economic environment and advances in science and technology , it also pays attention to the dark side of modern society and raise the profile of the plight of those who have suffered due to the market economy . China Current is a trailblazer in digging up `` the stories behind the news '' , and works to observe social trends in an objective and specialized manner . China Current has more than 60 volunteers , and almost 20 paid employees . Some hold positions in international media organisations or international companies . Some are graduate students from a wide range of fields . Most of these students have held internships at market media organisations or have contributed to research projects . Others are undergraduate students who have been carefully selected for high levels of academic achievement . These volunteers come from Oxford University , Harvard University , The University of British Columbia , The University of Hong Kong , Tsinghua University , and other well-known universities from across the world . China Current operates under two separate banners : China Current Connect and China Current Society . The former hopes to run salon-style events and forums to raise the level of social awareness with help from platforms provided by elite universities . China Current Connect also aspires to launch partnerships with well-regarded market media organisations from across Greater China , independent media , and campus media . The Chinese edition of China Current was established on January 1 , 2013 and International Edition was opened on September 1 , 2013 . It is a parent company of China Central Television , formerly `` Beijing Today . ''",
"title": ""
},
{
"docid": "Kathleen_Fitzpatrick_(American_academic)",
"text": "Kathleen Fitzpatrick ( born August 23 , 1967 ) is an American scholar of digital humanities and media studies . She is Director of Scholarly Communication of the Modern Language Association , Visiting Research Professor of English at New York University , co-editor of MediaCommons , and managing editor of PMLA . She was Professor of Media Studies at Pomona College from 1998 to 2013 . Fitzpatrick received her B.A. and M.F.A from Louisiana State University and her Ph.D. from New York University . Fitzpatrick is the author of Planned Obsolescence : Publishing , Technology and the Future of the Academy ( New York University Press , 2011 ) , which was released for open peer review by MediaCommons Press in 2009 . She is also the author of The Anxiety of Obsolescence ( Vanderbilt University Press , 2006 ) . Her other publications include articles on the online peer-review platform MediaCommons : `` MediaCommons : Scholarly Publishing in the Age of the Internet '' and `` CommentPress : New ( Social ) Structures for New ( Networked ) Texts . '' Fitzpatrick has written extensively on critical issues concerning the rise of digital humanities . She contributed two articles to the 2012 print edition of Debates In The Digital Humanities ( University of Minnesota Press , 2012 ) , a compilation of writings on the theory , methodologies and pedagogy of the digital humanities . Seeking to address ongoing concerns within this growing field , the book is now open-access and interactive , allowing the discussion to continue . Kathleen Fitzpatrick 's contributions to the collection are `` The Humanities , Done Digitally '' , and `` Beyond Metrics : Community Authorization and Open Peer Review '' .",
"title": ""
},
{
"docid": "Durant_(automobile)",
"text": "The Durant was a make of automobile assembled by Durant Motors Corporation of New York City , New York from 1921 to 1926 and again from 1928 to 1932 . Durant Motors was founded by William `` Billy '' Durant after he was terminated , for the second and final time , as the head of General Motors . Billy Durant 's intent was to build an automotive empire that could one day challenge General Motors . The Durant automobile is considered to be an example of an `` assembled '' automobile because so many of its components were obtained from outside suppliers . From 1921 to 1926 the vehicle was powered by a four cylinder or 6 cyl overhead valve Continental engine . The vehicle was directed at the Oakland automobile price point . Production of the vehicle was suspended for 1927 . When the Durant was reintroduced April 1928 , the car was redesigned and powered by a six cylinder Continental engine ; some of the early vehicles were marketed as the `` Durant-Star '' . Bodies for the vehicle were supplied by Budd Company . In 1930 , some Durants were built with all steel bodies , also supplied by Budd . Durant Motors was found insolvent and automobile production ended early in 1932 .",
"title": ""
},
{
"docid": "Hypebeast",
"text": "Hypebeast Limited ( stylized HYPEBEAST Limited ) is a digital media and e-commerce company based in Hong Kong.Founded as a sneaker culture blog by Kevin Ma in 2005 and later on taken over by young entrepreneur Stanley Yelnats in 2012 , Hypebeast has built a core offering of sneaker and fashion-focused digital media oriented towards youth and young adults . Its media properties include men 's fashion and lifestyle website Hypebeast which has regional offshoots in Traditional Chinese , Simplified Chinese , Japanese and Korean , female streetwear website Hypebae , Chinese-language women 's high fashion website Popbee , and quarterly print publication HYPEBEAST Magazine . Other operating arms include the HBX e-commerce platform and global creative studio Hypemaker . On April 11 2016 , Hypebeast Limited filed for an IPO on the Hong Kong Stock Exchange 's Growth Enterprise Market ( GEM ) , which is specifically designed for emerging companies . The company is currently valued at US$ 270 million .",
"title": ""
},
{
"docid": "Sali_Hughes",
"text": "Sali Hughes ( born 1975 ) is a Welsh journalist , writer and broadcaster . Her early career was spent in print media , but as well as continuing to write for magazines and newspapers she is now also a regular contributor to TV and radio programmes . Hughes has written features , opinion columns and celebrity interviews for Grazia , ELLE , Red , The Guardian , The Observer , Glamour , Stylist , Shortlist , Top Santé , Look , NOW and Cosmopolitan . Since January 2011 , she has also been The Guardians resident beauty columnist , featuring weekly in their Saturday magazine and online video tutorials . Hughes is a regular contributor on Sky News ' Press Preview and from June 2012 has been a regular press reviewer on ITV 's Daybreak . She has also regularly appeared on BBC Radio 5Live reviewing television , music and entertainment and has contributed to BBC Radio Four 's Woman 's Hour , The Chris Evans Show on BBC Radio 2 and on news and entertainment programmes on ITV , BBC , and Channel 4 . In September 2014 , Hughes ' first book , Pretty Honest , was published by the 4th Estate division of HarperCollins . In April 2015 , Hughes began writing a weekly opinion column for women 's digital platform , The Pool . She announced her imminent second marriage on the platform ( after a divorce a decade earlier ) in February 2017 .",
"title": ""
}
] |
1079
|
How do “held” amounts appear on statements and affect balances of traditional credit cards?
|
[
{
"docid": "384892",
"text": "\"The \"\"hold\"\" is just placeholder that prevents you from overspending until the transaction is settled. The merchant isn't \"\"holding\"\" your money, your bank or card provider is protecting itself from you overdrawing. In general, it takes 1-3 days for a credit transaction to settle. With a credit card, this usually isn't an issue, unless you have a very low credit line or other unusual things going on. With pre-paid and debit cards, it is an issue, since your spending power is contingent upon you having an available balance. I'm a contrarian on this topic, but I don't see any compelling reason to use debit or stored value cards, other than preventing yourself from overspending. I've answered a few other questions in detail in this area, if you're interested.\"",
"title": ""
}
] |
[
{
"docid": "474573",
"text": "\"@Joe's original answer and the example with proportionate application of the payment to the two balances is not quite what will happen with US credit cards. By US law (CARD Act of 2009), if you make only the minimum required payment (or less), the credit-card company can choose which part of the balance that sum is applied to. I am not aware of any company that chooses to apply such payments to anything other than that part of the balance which carries the least interest rate (including the 0% rate that \"\"results\"\" from acceptance of balance transfer offers). If you make more than the minimum required payment, then the excess must, by law, be applied to paying off the highest rate balance. If the highest rate balance gets paid off completely, any remaining amount must be applied to second-highest rate balance, and so on. Thus, it is not the case that that $600 payment (in Joe's example) is applied proportionately to the $5000 and $1000 balances owed. It depends on what the required minimum payment is. So, what would be the minimum required payment? The minimum payment is the total of (i) all finance charges incurred during that month, (ii) all service fees and penalties (e.g. fee for exceeding credit limit, fee for taking a cash advance, late payment penalty) and other charges (e.g. annual card fee) and (iii) a fraction of the outstanding balance that (by law) must be large enough to allow the customer to pay off the entire balance in a reasonable length of time. The law is silent on what is reasonable, but most companies use 1% (which would pay off the balance over 8.33 years). Consider the numbers in Joe's example together with the following assumptions: $5000 and $1000 are the balances owed at the beginning of the month, no new charges or service fees during that month, and the previous month's minimum monthly payment was made on the day that the statement paid so that the finance charge for the current month is on the balances stated). The finance charge on the $5000 balance is $56.25, while the finance charge on the $1000 balance is $18.33, giving a minimum required payment of $56.25+18.33+60 = $134.58. Of the $600 payment, $134.58 would be applied to the lower-rate balance ($5000 + $56.25 = $5056.25) and reduce it to $4921.67. The excess $465.42 would be applied to the high-rate balance of $1000+18.33 = $1018.33 and reduce it to $552.91. In general, it is a bad idea to take a cash advance from a credit card. Don't do it unless you absolutely must have cash then and there to buy something from a merchant who does not accept credit cards, only cash, and don't be tempted to use the \"\"convenience checks\"\" that credit-card companies send you from time to time. All such cash advances not only carry larger rates of interest (there may also be upfront fees for taking an advance) but any purchases made during the rest of the month also become subject to finance charge. In other words, there is no \"\"grace period\"\" for new charges, and this state of affairs will last for one month beyond the first credit-card statement whose statement is paid off in full in timely fashion. Finally, turning to the question asked, viz. \"\" I am trying to determine how much I need to pay monthly to zero the balance, ....\"\", as per the above calculations, if the OP makes the minimum required payment of $134.58 plus $1018.33, that $134.58 will be applied to the low-rate balance and the rest $1018.33 will pay off the high-rate balance in full if the payment is made on the day the statement is issued. If payment is made later, but before the due date, that $1018.33 will be accruing finance charges until the date the payment is made, and these will appear as 22% rate balance on next month's statement. Similarly for the low-rate balance. What if several monthly payments will be required? The best calculator known to me is at https://powerpay.org (free but it is necessary to set up a username and password). Enter in all the credit card balances and the different interest rates, and the total amount of money that can be used to pay off the balances, and the site will lay out a payment plan. (Basically, pay off the highest-interest rate balance as much as possible while making minimum required payments on the rest). Most people are surprised at how much can be saved (and how much shorter the time to be debt-free is) if one is willing to pay just a little bit more each month.\"",
"title": ""
},
{
"docid": "479095",
"text": "\"Curious, why are you interested in building/improving your credit score? Is it better to use your card and pay off the bill completely every month? Yes. How is credit utiltization calculated? Is it average utilization over the month, or total amount owed/credit_limit per month? It depends on how often your bank reports your balances to the reporting agencies. It can be daily, when your statement cycle closes, or some other interval. How does credit utilization affect your score? Closest to zero without actually being zero is best. This translates to making some charges, even $1 so your statement shows a balance each statement that you pay off. This shows as active use. If you pay off your balance before the statement closes, then it can sometimes be reported as inactive/unused. Is too much a bad thing? Yes. Is too little a bad thing? Depends. Being debt free has its advantages... but if your goal is to raise your credit score, then having a low utilization rate is a good metric. Less than 7% utilization seems to be the optimal level. \"\"Last year we started using a number, not as a recommendation, but as a fact that most of the people with really high FICO scores have credit utilization rates that are 7 percent or lower,\"\" Watts said. Read more: http://www.bankrate.com/finance/credit-cards/how-to-bump-up-your-credit-score.aspx Remember that on-time payment is the most important factor. Second is how much you owe. Third is length of credit history. Maintain these factors in good standing and you will improve your score: http://www.myfico.com/CreditEducation/WhatsInYourScore.aspx\"",
"title": ""
},
{
"docid": "125497",
"text": "\"I too am a full-monthly-statement-balance payer and I received a balance transfer offer from my credit-card company. This one was quite different from many others that I have read about on this forum. I could do a balance transfer for any amount up to $X from another credit card, or use the enclosed \"\"checks\"\" to pay some other (non-credit-card) bills, and I would not have to pay any interest for 12 months on the amount thus borrowed. But, There would be a 2% service charge on the amount I was borrowing. This amount would be billed on the next monthly statement, and it would have to be paid in full by the due date of that month's payment, that is, within the 25-day grace period allowed for payment of monthly statements. Else, interest would start being charged on the unpaid part of the service charge at the usual humongous rate of H% per month. If I had not paid the previous month's balance in full, I would be charged interest at H% per month on the service charge starting from Day One; no free ride till the due date of the next month's statement. Of course, the balance carried over from last month would also be charged interest at H%. If I had paid last month's bill in full, but there were any other charges (purchases) during the current month, then unless the entire amount due, this month's purchases plus service charge and that \"\"interest-free-for-twelve-months loan\"\" balance was paid off within the 25-day grace period, my purchases would be deemed unpaid and would start being charged interest. In short, the only way to avoid paying interest on the amount borrowed was to start with a card showing a $0 balance due on the previous month's statement, not make any charges on that card for a whole year, and pay off that 2% service charge within the grace period. It might also have required that one-twelfth of that interest-free loan be repaid each month, but I had stopped reading the offer at this point and filed it in the round circular file. In short, while @JoeTaxpayer's tale of how \"\"As a pay-in-full user, I've used the zero rate to throw $20K at the 5.25% mortgage\"\" is undoubtedly how things worked once, it is not at all clear that they still work that way. At least, they don't work that way for me. Heck, once upon a time, for a period of about 3 months, you could earn 1.5% interest per month from the credit card company by overpaying your credit card bill considerably. Their computers then just \"\"added on\"\" 1.5% interest by multiplying your credit balance -$X by 1.015 and so you got 1.5% per month interest from the credit card company. The credit card agreements (and the software!) got changed in a hurry, and nowdays all credit-card agreements state in the fine print that if you overpay your bill, you don't earn any interest on the overpayment.\"",
"title": ""
},
{
"docid": "143844",
"text": "\"There's a difference between missing a payment and \"\"carrying a balance\"\" (making an on-time payments that are less than the full balance due). I have heard mortgage brokers claim that, if you have no other credit history, carrying a small balance here and there on a credit card may improve your score. (\"\"Small\"\" is in relation to your available credit and your ability to pay it off.) But actually missing a payment will probably hurt your score. Example: You have a card with a credit limit of $1000. In July you charge $300 worth of stuff. You get the next statement and it shows the balance due of $300 and a minimum payment of $100. If you pay the entire $300 balance in that cycle, most cards won't charge you any interest. You are not carrying a balance, so the credit scores may not reflect that you actually took a $300 loan and paid it off. If you instead pay $200, you'll be in good standing (because $200 is greater than the minimum payment). But you'll be carrying a $100 balance into the next statement cycle. Plus interest will accrue on that $100. If you do this regularly, your credit score will probably take into account that you've taken a small loan and made the payments. For those with no other credit history, this may be an appropriate way to increase your credit score. (But you're paying interest, so it's not free.) And if the average balance you carry is considered high relative to your ability to pay or to the total credit available to you, then this could adversely affect your score (or, at least, the amount of credit another provider is willing to extend to you). If you instead actually miss a payment, or make a payment that's less than the minimum payment, that will almost certainly hurt your credit score. It will also incur penalties as well as interest. You want to avoid that whenever possible. My guess is that, in the game of telephone from the banker to you, the \"\"carrying a balance\"\" was misinterpreted as \"\"missing a payment.\"\"\"",
"title": ""
},
{
"docid": "277477",
"text": "The details of credit score calculation tend to change periodically, but the fundamentals are mostly consistent. Pay your bills, keep your average account age high, overpay your credit card minimums, and keep your overall debt low. And do soft pulls on your credit report to see what's happening. First, the simplest route: pay all your bills early or on time. Automatic deduction may be useful in this regard, especially for bills with predictable amounts. A corollary to this tip is to never leave an unpaid bill. What often happens to young people is in the course of moving around they leave the final bill unpaid and it gets reported to collections. Make sure you follow up online with all bills, even after canceling the service. Second, average account age and oldest account age matter. Open an account like a credit card and never close it, so you'll have an older account (hopefully a zero-fee card). Try to keep other accounts open rather than closing them (no need to cancel a zero-fee credit card) so your average account age stays higher. A card that works on internal systems (like a gift card) is not going to show up on a credit report; a card that works like any VISA/MC is likely going to show up. The rule of thumb is if they need your SSN to run a credit check for the application, then the card will appear on a credit report. You can pull your credit report to find out if the card is listed (you may have to allow time for lag before the card appears, but I'm not sure how long that might be). Third, a tip for extra credit score is to pay more than the minimum required on credit card bills. You can achieve this by either using your credit card at least once a month or by leaving a small hanging balance each month so there's always something to overpay next month. Credit card reporting will be either: unpaid, underpaid, minimum paid, or overpaid. Minimum payment helps your score and overpayment helps more. If you can use your credit card every month, that will give you something to overpay every month. Otherwise, you can leave a small debt left on the card but still pay over the monthly minimum. However, your total debt load, especially debt carried on your cards, counts against your score; aim for less than 10% of your limit. Finally, of course, is to pull your credit report periodically. You need to know what others are seeing. Since debt load utilization matters, make sure the reported card maximum is correct on your credit report. Talk to your bank or account issuer if the limit is wrong. If a collection appears, then you need to handle it. Often you can negotiate with the collector, but be careful to negotiate how they will report the resolution. You want them to agree to remove any negative information (either in exchange for payment or because of a mistake). Failing that, you want them to mark it paid in full or satisfied in full; letting them notate your score that you only partially paid is what you want to avoid, since it most signals someone with cash flow problems and credit issues. They control their reporting to credit bureaus, so if the person on the phone demurs, ask to speak to their supervisor or someone with negotiating authority. Try to get any agreements in writing. Remember that your total debt load is a factor in your credit score. Home loans and student loans do affect credit score. If you take on a smaller home loan, then it will affect your credit less harshly (and leave you with smaller monthly payments).",
"title": ""
},
{
"docid": "434289",
"text": "\"There are some loan types where your minimum payment may be less than the interest due in the current period; this is not true of credit cards in the US. Separately, if you have a minimum payment amount due of less than the interest due in the period, the net interest amount would just become principal anyway so differentiating it isn't meaningful. With credit cards in the US, the general minimum calculation is 1% of the principal outstanding plus all interest accrued in the period plus any fees. Any overpayment is applied to the principal outstanding, because this is a revolving line of credit and unpaid interest or fees appear as a charge just like your coffee and also begin to accrue interest. The issue arises if you have multiple interest rates. Maybe you did a balance transfer at a discounted interest rate; does that balance get credited before the balance carried at the standard rate? You'll have to call your lender. While there is a regulation in place requiring payment to credit the highest rate balance first the banks still have latitude on how the payment is literally applied; explained below. When there IS an amortization schedule, the issue is not \"\"principal or interest\"\" the issue is principle, or the next payment on the amortization schedule. If the monthly payment on your car loan is $200, but you send $250, the bank will use the additional $50 to credit the next payment due. When you get your statement next month (it's usually monthly) it will indicate an amount due of $150. When you've prepaid more than an entire payment, the next payment is just farther in to the future. You need to talk to your lender about \"\"unscheduled\"\" principal payments because the process will vary by lender and by specific loan. Call your lender. You are a customer, you have a contract, they will explain this stuff to you. There is no harm that can possibly come from learning the nuances of your agreement with them. Regarding the nuance to the payment regulation: A federal credit card reform law enacted in May 2009 requires that credit card companies must apply your entire payment, minus the required minimum payment amount, to the highest interest rate balance on your card. Some credit card issuers are aggressive here and apply the non-interest portion of the minimum payment to the lowest interest rate first. You'll need to call your bank and ask them.\"",
"title": ""
},
{
"docid": "358445",
"text": "\"Many people who do transfer a balance from one credit card to another have no clue as to what is going on and how credit cards work. If you transfer a balance from one credit card to another, you are charged a fee of anywhere from 3% upwards (subject to a minimum of $10 or so) up front. If Credit Card A has balance $1000 and you transfer it to Credit Card B which is offering no interest for a year on the transferred balance, you owe Credit Card B $1050 (say). In most cases, that $50 has to be paid off as part of the following month's bill. If you are carrying a revolving balance on Credit Card B, that $50 will typically be charged interest from the day of the transfer. Your monthly bill will not (necessarily) include that $1000 you owe for one year or six months or whatever the transfer agreement you accepted says. If you tend to pay anything less (even a penny) than full payment of each month's bill on Credit Card B, your partial payment will be applied to that $1000 first, and anything left over will be applied to the monthly balance. In short, if you don't pay in full each month, that $1000 will not be \"\"yours\"\" for a year; you may end up paying $50 interest for borrowing $1000 for just one or two months, and the rest of your balance is the gift that keeps on giving as the credit card company likes to say. UPDATE: This has changed slightly in the United States. Any amount paid over the minimum amount due is charged to the higher-interest balances. So in this case, if you had $1000 at a 0% promotional rate and a regular balance of $500, and the minimum payment was $100, and you paid $150, $100 would pay down the promotional balance, and the extra $50 would pay down the regular balance. About the only way to make the deal work in your favor is to Transfer money only if you have paid the full amount due on the last two statements before the date of the transfer and are not carrying a revolving balance. Check your monthly statements to make sure they show Finance Charge of 0.00. Many people have never seen such a sight and are unaware that this can be observed in nature. Make sure that you pay each month's bill in full (not the minimum monthly payment due) each month for a whole year after that. Make sure that the bill containing that $1000 (coming out a year after the transfer date) is also paid in full. Very many credit-card users do not have the financial discipline to go through with this program. That is why credit card companies love to push transfer balances on consumers: the whole thing is a cash cow for them where they in effect get to charge usurious rates of interest without running afoul of the law. $50 interest for a one-year loan of $1000 is pretty high at current rates; $50 interest for a two or three month loan where the customer does not even notice the screwing he is getting is called laughing all the way to the bank. See also the answers to this question\"",
"title": ""
},
{
"docid": "213242",
"text": "\"In the US, if your monthly statement was issued by the credit card company on January 1 and it showed a balance of $1000, then a payment must be made towards that balance by January 25 or so, not February 1 as you say, to keep the card in good standing. The minimum payment required to keep the card in good standing is specified in your monthly statement, and failure to meet this requirement can trigger various consequences such as an increase in the interest rate charged by the credit card company. With regard to interest charges, whether your purchase of $2000 on January 3 is charged interest or not depends entirely on what happened the previous two months. If you had paid both your monthly statements dated November 1 and December 1 of the previous year in full by the their respective due dates of November 25 and December 25, and the $1000 balance on the January 1 statement is entirely due to purchases (no cash advances) made in December, then you will not be charged interest on your January purchase of $2000 as long as you pay it off in full by February 25 (the charge will appear on your February 1 statement). But, if you had not paid your December 1 statement in full by December 25, then that $1000 billed to you on January 1 will include purchases made during December finance charges on the unpaid balance from the previous month plus finance charges on the purchases made during December. The finance charges will continue to accumulate during January until such time as you pay off the bill in full (these charges will appear on your February 1 statement), hopefully by the due date of January 25. But even if you pay off that $1000 in full on January 25, your charge of $2000 on January 3 will start to accumulate finance charges as of the day it hits the account and these finance charges will appear on your February 1 statement. If you paid off that $1000 on January 10, say, then maybe there will be no further finance charges on the $2000 purchase on January 3 after January 10 but now we are getting into the real fine print of what your credit card agreement says. Ditto for the case when you pay off that $1000 on January 2 and made the $2000 charge on January 3. You most likely will not be charged interest on that $2000 charge but again it depends on the fine print. For example, it might say that you will be charged interest on the average of the daily balances for January, but will not be charged interest on purchases during the February cycle (unless you miss the February 25 payment and the whole cycle starts all over again). As a general rule, it takes two monthly cycles of payment in full by the due date before one gets into the state of no finance charges for new purchases and effectively an \"\"interest-free\"\" loan of $2000 from January 3 (date of purchase) till February 25 (due date of payment). Matters become more complicated when cash advances are taken from a credit card which are charged interest from the day they are taken but don't trigger finance charges on new purchases or the so-called \"\"zero percent balance transfer offers\"\" are accepted.\"",
"title": ""
},
{
"docid": "550166",
"text": "No, it won't affect your score until your statement is posted. Paying your bill before your statement is posted is actually a good way to keep your credit utilization low. If you're worried about high credit utilization negatively affecting your credit score, consider paying your bill several times a month to ensure that when your final monthly statement is posted, your utilization is still low. When my credit limit was very low while I was in college, I did this almost every month, and I've seen other sites recommend this practice as well. From creditkarma.com: The easiest way [to lower credit utilization] is to make credit card payments more than once a month so that your balance never gets too high. and creditcards.com: Consider making payments to creditors more than once each month. Otherwise, if you put a major expense -- like a new appliance -- on a credit card, even if you plan to pay it off, your FICO score may take a hit. The reason is that credit scores are calculated as a snapshot in time, so if that happens to be right after you charged a new $700 washing machine, your utilization ratio will look worryingly high. Remember, though, that it's best to have some balance on your card when your statement is posted (assuming you pay it off in full each month), because as the chart shows, 0% utilization is about as bad as utilization > 31-40%: Also, remember that credit utilization affects your credit score in real time, so if you have high utilization one month but a lower utilization the next month, the hit to your score will disappear once a statement with low utilization is posted.",
"title": ""
},
{
"docid": "218709",
"text": "Paying up in full before the statement is posted does not seem a good idea. I feel you should keep some small amount to be posted as a statement balance and pay that in full each month. If you keep your statements as always 0 will give creditors an impression that you have cards and you don't utilize them, so they cant really gauge how you preform being debt, whether you are able to manage your debt well etc. I always keep <100 dollar in every credit card I have to be posted a statement balance. I have >100k credit line over 3 cards. So if I take air ticket to SE Asia runs into 3000$ for my family, I pay 2900.00 a day before statement generates and keep 100 for statement to be posted. pay 100 the next day or as auto debit. This way you have some utilization + lower credit card outstanding at any point make your utilization right in single digits.",
"title": ""
},
{
"docid": "188903",
"text": "\"I am interested in seeing what happens to your report after you test this, but I don't think it's possible in practice, would not affect your credit score, and also wouldn't be worth it for you to carry a negative balance like that. Having a -1% credit utilization essentially means that you are lending the credit card company money, which isn't really something that the credit card companies \"\"do\"\". They would likely not accept an agreement where you are providing the credit to them. Having credit is a more formal agreement than just 'I paid you too much this month'. Even if your payment does post before the transaction and it says you have a negative balance and gets reported to the credit bureau like that, this would probably get flagged for human review, and a negative credit utilization doesn't really reflect what is happening. Credit utilization is 'how much do you owe / amount of credit available to you', and it's not really correct to say that you owe negative dollars. Carrying a negative balance like that is money that could be invested elsewhere. My guess is that the credit card company is not paying you the APR of your card on the amount they owe you (if they are please provide the name of your card!). They probably don't pay you anything for that negative balance and it's money that's better used elsewhere. Even if it does benefit your credit score you're losing out on any interest (each month!) you could have earned with that money to get maybe 1-2% better rate on your next home or car loan (when will that be?). TLDR: I think credit utilization approaches a limit at 0% because it's based on the amount you owe and you don't really owe negative dollars. I am very interested in seeing the results of this experiment, please update us when you find out!\"",
"title": ""
},
{
"docid": "141579",
"text": "\"Circa 2002-2005, I was able to successfully \"\"transfer\"\" a balance from a debit card linked to a bank account to a Bank of America Visa credit card. As an example, I could say do a balance transfer from the card XXXX-XXXX-XXXX-XXXX (which was a valid debit card number) to the credit card, and the funds would appear in the checking account within a few days, and also the balance on the credit card would go up the amount plus any balance transfer fee. I think they've sealed off that loophole years ago.\"",
"title": ""
},
{
"docid": "478807",
"text": "\"What you are describing sounds a lot like the way we handle our household budget. This is possible, but quite difficult to do with an Excel spreadsheet. It is much easier to do with dedicated budgeting software designed for this purpose. When choosing personal budgeting software, I've found that the available packages fall in two broad categories: Some packages take what I would call a proactive approach: You enter in your bank account balances, and assign your money into spending categories. When you deposit your paycheck, you do the same thing: you add this money to your spending categories. Then when you spend money, you assign it to a spending category, and the software keeps track of your category balances. At any time, you can see both your bank balances and your spending category balances. If you need to spend money in a category that doesn't have any more money, you'll need to move money from a different category into that one. This approach is sometimes called the envelope system, because it resembles a digital version of putting your cash into different envelopes with different purposes. A few examples of software in this category are You Need a Budget (YNAB), Mvelopes, and EveryDollar. Other packages take more of a reactive approach: You don't bother assigning a job to the money already in your bank account. Instead, you just enter your monthly income and put together a spending plan. As you spend money, you assign the transactions to a spending category, and at the end of the month, you can see what you actually spent vs. what your plan was, and try to adjust your next budget accordingly. Software that takes this approach includes Quicken and Mint.com. I use and recommend the proactive approach, and it sounds from your question like this is the approach that you are looking for. I've used several different budgeting software packages, and my personal recommendation is for YNAB, the software that we currently use. I don't want this post to sound too much like a commercial, but I believe it will do everything you are looking for. One of the great things about the proactive approach, in my opinion, is how credit card accounts are handled. Since your spending category balances only include real money actually sitting in an account (not projected income for the month), when you spend money out of a category with your credit card, the software deducts the money from the spending category immediately, as it is already spent. The credit card balance goes negative. When the credit card bill comes and you pay it, this is handled in the software as an account transfer from your checking account to your credit card account. The money in the checking account is already set aside for the purpose of paying your credit card bill. Dedicated budgeting software generally has a reconcile feature that makes verifying your bank statements very easy. You just enter the date of your bank statement and the balance, and then the software shows you a list of the transactions that fall in those dates. You can check each one against the transactions on the statement, editing the ones that aren't right and adding any that are missing from the software. After everything checks out, the software marks the transactions as verified, so you can easily see what has cleared and what hasn't. Let me give you an example to clarify, in response to your comment. This example is specific to YNAB, but other software using the same approach would work in a similar way. Let's say that you have a checking account and a credit card account. Your checking account, named CHECKING, has $2,000 in it currently. Your credit card currently has nothing charged on it, because you've just paid your bill and haven't used it yet this billing period. YNAB reports the balance of your credit card account (we'll call this account CREDITCARD), as $0. Every dollar in CHECKING is assigned to a category. For example, you've got $200 in \"\"groceries\"\", $100 in \"\"fast food\"\", $300 in \"\"rent\"\", $50 in \"\"phone\"\", $500 in \"\"emergency fund\"\", etc. If you add up the balance of all of your categories, you'll get $2,000. Let's say that you've written a check to the grocery store for $100. When you enter this in YNAB, you tell it the name of the store, the account that you paid with (CHECKING), and the category that the expense belongs to (groceries). The \"\"groceries\"\" category balance will go down from $200 to $100, and the CHECKING account balance will go down from $2,000 to $1,900. Now, let's say that you've spent $10 on fast food with your credit card. When you enter this in YNAB, you tell it the name of the restaurant, the account that you paid with (CREDITCARD), and the category that the expense belongs to (fast food). YNAB will lower the \"\"fast food\"\" category balance from $100 to $90, and your CREDITCARD account balance will go from $0 to $-10. At this point, if you add up all the category balances, you'll get $1,890. And if you add up your account balances, you'll also get $1,890, because CHECKING has $1,900 and CREDITCARD has $-10. If you get your checking account bank statement at this time, the account balance of $1,900 should match the statement and you'll see the payment to the grocery store, assuming the check has cleared. And if the credit card bill comes now, you'll see the fast food purchase and the balance of $-10. When you write a check to pay this credit card bill, you enter this in YNAB as an account transfer of $10 from CHECKING to CREDITCARD. This transfer does not affect any of your category balances; they remain the same. But now your CHECKING account balance is down to $1,890, and CREDITCARD is back to $0. This works just as well whether you have one checking account and one credit card, or 2 checking accounts, 2 savings accounts, and 3 credit cards. When you want to spend some money, you look at your category balance. If there is money in there, then the money is available to spend somewhere in one of your accounts. Then you pick an account you want to pay with, and, looking at the account balance, if there isn't enough money in that account to pay it, you just need to move some money from another account into that one, or pick a different account. When you pay for an expense with a credit card, the money gets deducted from the category balances immediately, and is no longer available to spend on something else.\"",
"title": ""
},
{
"docid": "520205",
"text": "Patience is the key here, I hate to say! There are five factors to FICO credit scores: Payment history is adversely affected by late payments - so always pay on time, otherwise your report will be haunted for seven years! 👻 Credit utilization has to do with how much of your available credit is currently in use - lower is better, but 0% isn't good either because they want to see that you're using credit. 10% or less is a good goal, and try to keep any single card balance to 30% or less when its statement close date rolls around. Credit history is based on the average age of all of your accounts, cards or otherwise, the older the better. Don't close either of your other cards (because that would cause your average account age to fall), and make sure to use the store card at least occasionally, because lenders sometimes decide to close unused lines of credit. Credit mix has to do with the different types of credit you hold and is why your bank's website suggested taking out a loan. It also has to do with the number of accounts overall; I've never found a satisfactory answer for what the sweet spot is, but I suspect it's in the 6-12 range? You wouldn't want to get several new ones at the same time because... New credit is affected by the credit inquiries (hard pulls) that occur when you apply for new cards or loans. Inquiries stay on your report for two years before falling off. This is almost certainly where your score dropped. You also mentioned not knowing if some hospital bills are still affecting your score. You'll want to review your credit reports and find out, plus checking your credit reports regularly is a really great habit to get into because errors (and fraud) can and do happen. There are three credit reporting agencies: Experian, Equifax, and TransUnion, and you'll want to review all three. You can get one free report from each of them every year: https://www.usa.gov/credit-reports It can take a couple of months for a new credit account to show up on your credit report, so your score should recover and go even higher once that happens. Sit tight, as annoying as that is!",
"title": ""
},
{
"docid": "585890",
"text": "You are in luck, I have an ANZ credit card as well. I have just checked my paper statement with online, and was able to find a matching online statement in less than a minute. You simply click on your credit card account from the list of accounts. Under Date Range it will have the Current incomplete statement period. You simply click on the down arrow and select the last complete date range ending sometime in late April (depending on your credit card cycle). You then press on View next to the drop down box. This should provide you with a list of purchases and payment/credits for that period, followed by a line with your Credit Limit, Available Funds and Closing Balance. The line below that then shows your Due Date, and Overdue/Overlimit, the Minimum Payment and Amount Due Now If you are after paying only the minimum amount then you pay this amount by the due date (you will be charged interest if you only pay this amount). If, on the otherhand, you wish to avoid paying any interest then you need to pay the full Closing Balance before the due date. You should also be able to get electronic statements sent to your email address.",
"title": ""
},
{
"docid": "474795",
"text": "Think about how loans work for you personally. When you charge a $50 dinner for two to your Visa card, you did not earn $50 in income. You did not pay income tax on that $50. The money you use to pay back that $50 at the end of the month is not tax deductible. Interest on a loan is a business expense. Repayment of principal is not a business expense, just as receiving the loan in the first place is not business income. Effectively this means the LLC repays the loan with after-tax dollars. Just like you do with your Visa card. When I do corporate accounting, payment of loan interest shows up on the expense side of the Profit/Loss statement, and it makes the Balance Sheet net assets go down. However payment of loan principal is effectively null. It doesn't appear on the Profit/Loss at all -- and it's a wash on the Balance Sheet, as both Assets and Liabilities fall by the same amount.",
"title": ""
},
{
"docid": "208169",
"text": "It's not so much a credit card, but a financial institution's online platform that either provides this functionality or not. The following Canadian financial institutions show an itemized list of pre-authorized transactions (not an exhaustive list): The following institutions show a total value of pre-authorized transactions: Most other institutions show the available credit (e.g. Chase Financial used by Amazon Rewards), which give an indication of how much you have to spend. By subtracting the current balance and the available balance from the total credit limit, you can get an indication of the total amount of pre-authorized transactions. Example: $1000 - $500 - $400 = $100 is the amount of pre-authorized transactions. From TD's EasyWeb demo (http://tdeasywebdemo.com/v2/#/en/PFS/accounts/activity/chq), it appears that they don't include pre-authorized transactions in the Available Credit. You can verify for yourself by logging in to online banking after you make a purchase and comparing the Available Credit to [Credit Limit - Current Balance]. If it is equal, then they don't include, if it is different (most likely for the value of the transaction), then they do.",
"title": ""
},
{
"docid": "271472",
"text": "\"I have some experience with this. I have had fraudulent charges appear on my credit card statement and had to change my card number several times, despite (I believe) no carelessness on my part. Every time that this has happened, I have never lost a penny due to fraud on my credit card. The bank has ultimately removed the fraudulent charges in every instance. Given this, you'd think the consumer doesn't need to worry about this at all. But it seems like credit card companies beg to differ. Yes, because although I have never lost a penny to fraud, the bank (or the merchant) loses money every time it happens. The $0 liability protects you; the card security measures protect the bank. But... why should a consumer ever bother worrying about these in the first place, when he knows he legally can't be held responsible for fraudulent charges? What exactly is this new \"\"peace of mind\"\" that he supposedly gets by (say) using features like virtual account numbers that he doesn't already have? Although you shouldn't end up out any money when this happens, it is an inconvenience. The bank will cancel your card and issue you a new number. It may take a few days for you to receive your new card. If you have another card to use, this isn't a big deal. If you are out of state the day before you need to check out of a hotel and return a rental car with no backup credit card (as I have been), it is a big deal. (In my case, I had to have the credit card company talk to the hotel to give them the new card number, and they were able to overnight me a new credit card so I could get home. I now make sure I carry a backup credit card.) Should a consumer put any effort into worrying about this at all? (Why?) In my opinion, it makes sense to be careful what you do with your credit card number, if only to avoid the inconvenience. Don't type your credit card number into an e-mail message, for example, and only use it on websites that you trust. That having been said, it is not worth it to be paranoid about it, either. No matter how careful you are, eventually you will probably use it at a store that gets hacked, or your card will get skimmed somewhere, and you'll need to get a new credit card number. The best way to protect yourself is to make sure that you go over your credit card statement each month and look for any fraudulent charges that the bank didn't catch.\"",
"title": ""
},
{
"docid": "170481",
"text": "Good credit is calculated (by many lenders) by taking your FICO score which is calculated based upon what is in your credit report. Building credit generally means building up your FICO score. Your FICO score is impacted my many factors, one small one of which is your utilization ratio of your installment loans like student loans. This is the ratio of the current balance to your original balance. To improve your score (slightly) you would want a lower ratio. I would recommend paying your student loan down to 75% ratio as fast as you can and then you can go back to $50/month. A much better way to improve your FICO score is to have revolving credit. Your student loans are not revolving, they are installment loans. Therefore, you should open at least one credit card (assuming you currently have none) right away. The longer you have had a credit card open, the better your FICO score gets. Your revolving credit utilization ratio is way more important than your installment loan ratio. Therefore, to maximize your FICO, try to never have more than 10% utilization on your revolving credit report to the credit bureaus each month. Only the current month's ratio affects your score at any given moment. You can ensure you don't go above 10% by paying your balance before the statement cuts each month to get it below 10% way before any payment would be due. (You should always pay your remaining credit card statement balance in full each month by the due date after the statement cuts to avoid any interest charges.) Note that there is a slight FICO advantage to having at least one major bank credit card instead of just only credit union credit cards. Also, never let all your revolving credit report a zero balance in a month, you must always have at least $1 reporting to the credit bureaus on at least one of your open credit cards or your FICO score will take a big negative hit. If you cannot get a normal credit card, go to a credit union and find one that offers secured credit cards, or a bank that does. A secured credit card is where you place a deposit with the bank that they hold and give you a credit limit to match your security. Ideally it would be a card that graduates to unsecured after your demonstrate good history with them. For example, the Navy Federal Credit Union secured card unsecures for many people. I also believe the Wells Fargo Bank credit card (you can join if there is a family member who served or a roomate who did) also will unsecure. The reason you want it to unsecure and not be forced to open a new account to get an unsecured account is that you want your average age and oldest age of open revolving credit accounts to be as high as possible as this is another impact on your FICO score. Credit unions that anyone can join include, Digital Federal Credit Union, the Pentagon Federal Credit Union (which offers a secured card that does not graduate), and The State Department Federal Credit Union (also offers secured card that I think does not graduate). One other method to boost your FICO score is to get added as an authorized user on one of your parent's credit cards that has been open a long time. Not all lenders will report such an authorized user, however, ones that are known to do so are: Bank of America, Citi Bank, and Capital One. It is a good sign that it will report if they ask for the social security number of the authorized user. However, note that the Authorized User addition can have no impact if the lender is using one of the newer versions of the FICO scoring model, only the older versions reward you for the age of accounts for which you are an authorized user. A very long term boost is to open your first American Express card underwritten directly by Amex such as their Zync card which is pretty easy to get. The advantage of American express is that they remember the date your first credit card was opened with them and if you open new accounts in the future they will back date the date of their opening to match the date your first card was opened. If you let your membership lapse, be sure to record the account number and date opened in your personal files so that you can help them locate it again if you reopen as they can have trouble if it has been on the order of ten years or more. Finally, note that the number of accounts opened in the last twelve months is a small negative mark on your score (along with number of inquiries), so if you open a lot of accounts all at once, in addition to bringing down your average age of accounts, you will also get dinged for how many were opened in the last year.",
"title": ""
},
{
"docid": "195726",
"text": "Hi, This is treated as a electronic balance transfer. There may be a fee for performing this. Cash advance interest will apply on the EBT. You may get a teaser rate for a limited amount of time. After it expires, the normal cash advance interest rate for the credit card will kick in. Check your credit card statement. Somewhere, you'll see a section listing the interest rates. One for retail purchases, one for cash transactions. Do not do this. If you need to borrow money to pay off a large debt, do one of the following: 1) Switch to the lowest interest rate card your bank offers 2) Apply for a credit card with another bank that is offering a great teaser rate, transfer the balance, cut your living expenses and send every penny to paying off the balance before the teaser rate expires 3) If you cannot get access new credit or switch credit cards, seek advice from a professional credit counsellor on your options and the best one to choose Sorry to ramble. I've seen far too many people fall into the debt trap. You don't want to go there. Source: I work for a bank which offers credit card products.",
"title": ""
},
{
"docid": "539859",
"text": "In general, minors cannot enter into legally binding contracts -- which is what credit accounts are -- so an individually held card is probably not an option for you right now. You will not be approved for a credit card because you are minor. The only option credit card wise for you is for your parents to add you on as an authorized user onto their accounts. The upside is that you and your parents can work out a monthly payment for the amount you spend on your equipment, the downside is that if your parents don't pay their credit card bill, your credit score/report can be negatively affected. (This also depends on the bank, however, all the banks I bank with report monthly payment activities on authorized users' credit reports as well. There might be a bank that doesn't.) In terms of credit cards, there is nothing you can do. What you could do as the comments have suggested is either save up money for the equipment you want, or buy something cheaper.",
"title": ""
},
{
"docid": "81416",
"text": "When you give your credit card number and authorize a merchant to charge your credit card, the merchant then gives the information to their merchant processor which in turns bills the bank that issued the card (it's a little more complex and it all happens instantly unless the merchant is using the very old fasion imprinting gizmos). It is possible for a merchant to attempt to charge you more than you authorized but if they do they risk a fine ($25-$50 for a chargeback) from their processor, the legitimate portion of the charge as well as increasing the processing fees charged by their processor or even the possibility of loosing their merchant account entirely and being permanently blacklisted by Visa/Mastercard. In short no legitimate business is going to intentionally over charge your credit card. There really isn't significant risk in using a reputable online retailer's order forms. There is the possibility that their database could be compromised but that risk is lower than the risk of having an employee steal your credit number when you give it to them in person. Besides in the US at least the most you can legally be held liable for is $50 assuming you notice the discrepancy within 60 days of statement the charge appears on and most banks limit liability to $0. Over the years I have had a number of different credit card numbers stolen and used fraudulently and I have never had to pay any fraudulent charges.",
"title": ""
},
{
"docid": "42044",
"text": "Credit cards are meant to be used so generally it doesn't hurt your credit score to use them. To top it off you even get an interest grace period so you don't have to rush home and pay balances as soon as they're charged. In general you accrue charges during your statement period, we'll call it September 1 through September 30. The statement due date is something like 20 days after the close of the statement period, so we'll call it October 20. As long as you habitually pay your entire statement balance by the due date you will never pay interest. You charge your laptop on September 3, it shows up on your statement as $1,300, you pay $1,300 on October 18, you pay no interest. However, if you pay $1,000 on October 18 leaving a $300 balance to be carried in to the next statement period (a carried balance) you will pay interest. Generally interest is calculated based on your average daily balance during the statement period, which is now be the October 1 to October 31 period. You'll notice that you didn't pay anything until the October 18, that means the entire $1,300 will be included in your average daily balance up to the 18th of the month. Add to that, anything else you charge on the card now will be included in your average daily balance for interest charge calculation purposes. The moral of the story is, use your card, and pay your entire statement balance before the due date. Now how much will this impact your credit score? It's tough to say. Utilization is not a bad thing until it's a big number. I've read that 70% utilization and over is really the point at which lenders will raise an eyebrow and under 30% is considered excellent. If you have one card and $1,300 is a significant portion of your available limit, then yes you should probably pay it down quickly. Spend six or so months using the card and paying it, then call your bank and ask for a credit line increase.",
"title": ""
},
{
"docid": "24138",
"text": "You're going to have a huge problem getting approved for anything as long as you have an unpaid bill on your report. Pay it and make sure its reported as paid in full - ASAP. Once that settled, your credit will start to improve slowly. Can't do anything about that, it will take time. You can make the situation improve a bit faster by lending money to yourself and having it reported regularly on your report. How? Easy. Get a secured credit card. What does it mean? You put X amount of money in a CD and the bank will issue you a credit card secured by that CD. Your credit line will be based on the amount in that CD, and you'll probably pay some fees to the bank for the service (~$20-50/year, shop around). You might get lucky and find a secured card without fees, if you look hard enough. Secured cards are reported as revolving credit (just as any other credit card) and are easy to get because the bank doesn't take the risk - you do. If you default on your payments - your CD goes to cover the debt, and the card gets cancelled. But make absolutely sure that you do not default. Charge between 10% and 30% of the credit limit each month, not more. Pay the balance shown on your credit card statement in full every month and by the due date shown on your monthly statement. It will take a while, but you would typically start noticing the improvement within ~6-12 months. Stop applying for stuff. Not store cards, not car loans, you're not going to get anything, and will just keep dragging your scores down. Each time you have a pull on your report, the score goes down. A lot of pulls, frequent pulls - the score goes down a lot. Lenders can see when one is desperate, and no-one wants to lend money to desperate people. Optimally lenders want to lend money to people who doesn't need loans, but in order to keep the business running they'll settle for slightly less - people who don't usually need loans, and pay the loans they do have on time. You fail on both, as you're desperate for a loan and you have unpaid bills on your report.",
"title": ""
},
{
"docid": "198349",
"text": "\"Check whether you're being charged a \"\"Cash advance\"\" fee with your withdrawals, because it's being withdrawn from your credit card account. If that's happening to you, then having a positive balance on your credit card account will dramatically reduce the fees. Quoting from my answer to a similar question on Travel Stack Exchange: It turns out that even though \"\"Cash advance fee - ATM\"\" has \"\"ATM\"\" in it, it doesn't mean that it's being charged by the ATM you're withdrawing from. It's still being charged by the bank of your home country. And depending on your bank, that fee can be minimized by having a positive balance in your credit card account. This isn't just for cards specially marketed at globehoppers and globeshoppers (mentioned in an answer to a similar question), but even for ordinary credit cards: Help minimise and avoid fees An administrative charge of 2% of the value of the transaction will apply to each cash advance made on your card account, where your account has a negative (debit) balance after the transaction has been posted to it. A minimum charge of $2.50 and a maximum charge of $150 will apply in these circumstances. Where your account has a positive (credit) balance after the transaction has been posted to it, a charge of $2.50 will apply to the transaction. Any such charge will appear on your credit card statement directly below the relevant cash advance. A $2.50 charge if your account is positive, versus $20 if the account is negative? That's a bit of a difference!\"",
"title": ""
},
{
"docid": "504384",
"text": "\"There are always little tricks you can play with your credit card. For example, the due date of your statement balance is not really set in stone as your bank would like you to believe. Banks have a TOS where they can make you liable to pay interest from the statement generation date (which is a good 25 days before your due date) on your balance, if you don't pay off your balance by your due date. However, you can choose to not pay your balance by your due date upto 30 days and they will not report your late payment to credit agencies. If they ask you to pay interest, you can negotiate yourself out of it as well (although not sure if it will work every-time if you make it a habit!) Be careful though: not all banks report your credit utilization based on your statement balance! DCU for example, reports your credit utilization based on your end-of-the-month balance. This can affect your short term credit score (history?) and mess around with your chances of pulling off these tricks with the bank CSRs. These \"\"little tricks\"\" can effectively net you more than 60 days of interest free loans, but I am not sure if anyone will condone this as a habit, especially on this website :-)\"",
"title": ""
},
{
"docid": "336792",
"text": "\"Its called a \"\"Grace Period\"\" and you are not paying interest on the 0% BT, you are paying interest on the amount you spent in purchases If you do not pay your balance in full by the due date your grace period ends. This means that you have to pay interest on the purchased amount from the day it is made. This is why when you do a balance transfer the card should be put in the Sock Drawer until the BT is paid off. In order to restore the grace period you must pay the balance in full and the grace period will start during the Next Payment Cycle. Lets Assume: Statement cuts on the 1st and Due date is the 20th. you make the minimum payment of $10 Balance now is $100 Since you have a balance of $100 from the previous statement and a new purchase of $50.00, when the next statement cuts you will have to pay interest according to the terms on the $50.00 portion. In order to get the grace period back you will have to pay in full and wait for the next cycle In case I did not explain it well here is a quote from creditcards dot com website: The cost of carrying a balance This is because carrying a balance of any size into the next billing cycle means there is no grace period on your purchases during that cycle. The card company will begin charging interest on your purchases the day you make them. So leaving even $1 in unpaid balance on your card will cost you considerably more than the measly finance charges on that dollar. To see how this works let's consider an imaginary card user named Sally. She's so happy she got a new credit card that she charges $1,500 in purchases on the first day of her monthly billing cycle. After the cycle ends, Sally pays off the entire $1,500 by the due date, wiping her balance to zero. As a result, her purchases during the second month are also free of interest. She has used her grace period wisely to avoid finance charges. What happens if Sally leaves just $1 of her balance from the first month unpaid? That $1 begins to accrue interest starting the first day of the billing cycle. It's just $1, so the interest is not a big deal -- but because she used up her grace period without paying off her entire debt, her new purchases during the second month also start to get hit with interest charges immediately, starting the day of the transaction. Assuming she makes another $1,500 in purchases at the average annual interest rate of about 13 percent, that means $16 in finance charges for the month. If Sally repeats this pattern, the interest costs add up to $190 over the course of a year.\"",
"title": ""
},
{
"docid": "247199",
"text": "\"As Dheer has already told you in his answer, your plan is perfectly legal, and there are no US tax issues other than making sure that you report all the interest that you earn in all your NRE accounts (not just this one) as well as all your NRO accounts, stock and mutual fund dividends and capital gains, rental income, etc to the IRS and pay appropriate taxes. (You do get a credit from the IRS for taxes paid to India on NRO account income etc) You also may also need to report the existence of accounts if the balance exceeds $10K at any time etc. But, in addition to the foreign exchange conversion risk that Dheer has pointed out to you, have you given any thought to what is going to happen with that credit card? That 0% interest balance of $5K does not mean an interest-free loan 0f $5K for a year (with $150 service charge on that transaction). Instead, consider the following. If you use the card for any purchases, then after the first month, your purchases will be charged interest from the day that you make them till the day they are paid off: there is no 25-day grace period. The only way to avoid this is to pay off the full balance ($5K 0% interest loan PLUS $150 service charge as well as any other service charges, annual fees etc PLUS all purchases PLUS any interest) shown on the first monthly statement that you receive after taking that loan. If you choose this option, then, in effect, have taken a $5K loan for only about 55 days and have paid 3% interest (sorry, I meant to write) service fee for the privilege. If you don't use the card for any purchases at all, then the first monthly statement will show a statement balance of $5130 and (most likely) a minimum required payment of $200. By law, the minimum required payment is all interest charged for that month($0) PLUS all service fees charged during that month ($150) PLUS 1% of the rest ($50). Well, actually the law says something like \"\"a sufficient fraction of the balance to ensure that a person making the required minimum payment each month can pay off the debt in a reasonable time\"\" and most credit card companies choose 1% as the sufficient fraction and 108 months as a reasonable time. OK, so you pay the $200 and feel that you have paid off the service fee and $50 of that 0% interest loan. Not so! If you make the required minimum payment, the law allows that amount to be be applied to any part of the balance owing. It is only the excess over the minimum payment that the law says must be applied to the balance being charged the highest rate. So, you have paid off $200 of that $5K loan and still owe the service fee. The following month's statement will include interest on that unpaid $150. In short, to leave only the 0% balance owing, you have to pay $350 that first month so that next month's statement balance will be $4800 at 0%. The next month's required minimum payment will be $48, and so on. In short, you really need to keep on top of things and understand how credit-card payments really work in order to pull off your scheme successfully. Note also that the remaining part of that 0% interest balance must be paid off by the end of the period or else a humongous rate of interest will be applied retroactively from Day One, more than enough to blow away all that FD interest. So make sure that you have the cash handy to pay it off in timely fashion when it comes due.\"",
"title": ""
},
{
"docid": "490529",
"text": "\"To expand on @JoeTaxpayer's answer, the devil is actually in the fine print. All the \"\"credit-card checks\"\" that I have ever received in the mail explicitly says that the checks cannot be used to pay off (or pay down) the balance on any other credit card issued by the same bank, whether the card is branded with the bank logo or is branded with a department-store or airline logo etc. The checks can be used to pay utilities, or even taxes, without paying the \"\"service fee\"\" that is charged for using a credit card for such payments. The payee is paid the face amount of the check, in contrast to charges on a credit card from a merchant who gets to collect only about 95%-98% of the amount on the \"\"charge slip\"\". Generally speaking, balance transfer offers are a bad deal regardless of whether you pay only the minimum amount due each month or whether you pay each month's statement balance in full by the due date or anything in between. The rest of this answer is an explanation in support of the above assertion. Feel free to TL;DR it if you like. If you make only the minimum payment due each month and some parts of the balance that you are carrying has different interest rates applicable than other parts, then your payment can be applied to any part of the balance at the bank's discretion. It need hardly be said that the bank invariably chooses to apply it to pay off the lowest-rate portion. By law (CARD Act of 2009), anything above the minimum payment due must be applied to pay off the highest-rate part (and then the next highest rate part, etc), but minimum payment or less is at the bank's discretion. As an illustration, suppose that you are not using your credit cards any more and are conscientiously paying down the balances due by making the minimum payment due each month. Suppose also that you have a balance of $1000 carrying 12% APR on Card A, and pay off the entire balance of $500 on Card B, transferring the amount at 0% APR to Card A for which you are billed a 2% fee. Your next minimum payment will be likely be $35; computed as $10 (interest on $1000) + $10 transfer fee + $15 (1% of balance of $1500). If you make only the minimum payment due, that payment will go towards paying off the $500, and so for next month, your balance will be $1500 of which $1035 will be charged 1% interest, and $465 will be charged 0% interest. In the months that follow, the balance on which you owe 1% interest per month will grow and the 0% balance will shrink. You have to pay more than the minimum amount due to reduce the amount that you owe. In this example, in the absence of the balance transfer, the minimum payment would have been $20 = $10 (interest on $1000 at 1% per month) + $10 (1% of balance) and would have left you with $990 due for next month. To be at the same point with the balance transfer offer, you would need to pay $30 more than the minimum payment of $35 due. This extra $30 will pay off the interest and transfer fee ($20) and the rest will be applied to the $1000 balance to reduce it to $990. There would be no balance transfer fee in future months and so the extra that you need to pay will be a little bit smaller etc. If you avoid paying interest charges on credit cards by never taking any cash advances and by paying off the monthly balance (consisting only of purchases made within the past month) in full by the due date, then the only way to avoid paying interest on the purchases made during the month of the balance transfer offer is to pay off that month's statement in full (including the balance just transferred over and the balance transfer fee) by the due date. So, depending on when in the billing cycle the transfer occurs, you are getting a loan of the balance transfer amount for 25 to 55 days and being charged 2% or 3% for the privilege. If you are getting offers of 2% balance transfer fees instead of 3%, you are probably among those who pay their balances in full each month, and the bank is trying to tempt you into doing a balance transfer by offering a lower fee. (It is unlikely that they will make a no-transfer-fee offer.) They would prefer laughing all the way to themselves by collecting a 2% transfer fee from you (and possibly interest too if you fail to read the fine print) than having you decline such offers at 3% as being too expensive. Can you make a balance transfer offer work in your favor? Sure. Don't make any purchases on the card in the month of the balance transfer or during the entire time that the 0% APR is being offered. In the month of the transfer, pay the minimum balance due plus the balance transfer fee. In succeeding months, pay the minimum balance due (typically 1% of the balance owed) each month. All of it will go to reducing the 0% APR balance because that is the only amount owing. Just before the 0% APR expires (anywhere from 6 to 24 months), pay off the remaining balance in full. But remember that you are losing the use of this card for this whole period of time. Put it away in a locked trunk in the attic because using the card to make a purchase will mean paying interest on charges from the day they post, something that might be totally alien to you.\"",
"title": ""
},
{
"docid": "65982",
"text": "There are a couple of things to consider. First, in order to avoid interest charges you generally just need to pay the statement balance before the statement due date. This is your grace period. You don't need to monitor your activity every day and send immediate payments. If you're being really tight with money, you can actually make a little profit by letting your cash sit in an interest bearing account before you pay your credit card before the due date. Second, credit card interest rates are pretty terrible, and prescribed minimum payments are comically low. If you buy furniture using your credit card you will pay some interest, be sure to pay way more than the minimum payment. You should avoid carrying a balance on a credit card. At 20% interest the approximate monthly interest charge on $1,000 is $16.67. Third, if you carry a balance on your credit card you lose the interest grace period (the first point above) on new charges. If you buy your couch, and carry the balance, when you buy a soda at 7-11, the soda begins to accrue interest immediately. If you decide to carry a balance on a credit card, stop using that card for new charges. It generally takes two consecutive billing period full balance payments to restore the grace period. Fourth, to answer your question, using a credit card to carry a balance has no impact on your score. Make your payments on time, don't exceed your limits, keep your utilization reasonable. The credit agencies have no idea if you're carrying a balance or how much interest you're paying. To Appease the people who think point four needs more words: Your credit report contains your limit, your reported balance (generally your statement balance), and approximate minimum payment. There is no indication related to whether or not the balance contains a carried balance and/or accrued interest. The mere fact of carrying a balance will not impact your credit score because the credit reporting bureaus don't know you're carrying a balance. Paying interest doesn't help or hurt your score. Obviously if your carried balance and interest charges push your utilization up that will impact your score because of the increased utilization. Make your payments on time, don't exceed your limits, keep your utilization reasonable and your score will be fine.",
"title": ""
}
] |
92102
|
Dennis Hopper made films.
|
[
{
"docid": "Dennis_Hopper",
"text": "Dennis Lee Hopper ( May 17 , 1936 -- May 29 , 2010 ) was an American actor , filmmaker , photographer and artist . He attended the Actors Studio , made his first television appearance in 1954 , and soon after appeared alongside James Dean in Rebel Without a Cause ( 1955 ) and Giant ( 1956 ) . In the next ten years he made a name in television , and by the end of the 1960s had appeared in several films . Hopper also began a prolific and acclaimed photography career in the 1960s . Hopper made his directorial film debut with Easy Rider ( 1969 ) , which he and co-star Peter Fonda wrote with Terry Southern . The film earned Hopper a Cannes Film Festival Award for `` Best First Work '' and a nomination for the Academy Award for Best Original Screenplay ( shared with Fonda and Southern ) . Journalist Ann Hornaday wrote : `` With its portrait of counterculture heroes raising their middle fingers to the uptight middle-class hypocrisies , Easy Rider became the cinematic symbol of the 1960s , a celluloid anthem to freedom , macho bravado and anti-establishment rebellion '' . Film critic Matthew Hays notes that , `` no other persona better signifies the lost idealism of the 1960s than that of Dennis Hopper '' . He worked on various small projects until he found new fame for his role as the American photojournalist in Apocalypse Now ( 1979 ) . He went on to helm his third directorial work Out of the Blue ( 1980 ) , for which he was again honored at Cannes , and appeared in Rumble Fish ( 1983 ) and The Osterman Weekend ( 1983 ) . He saw a career resurgence in 1986 when he was widely acclaimed for his performances in Blue Velvet and Hoosiers , the latter of which saw him nominated for the Academy Award for Best Supporting Actor . His fourth directorial outing came about through Colors ( 1988 ) , followed by an Emmy-nominated lead performance in Paris Trout ( 1991 ) . Hopper found even greater fame for portraying the villains of the films Super Mario Bros. ( 1993 ) , Speed ( 1994 ) and Waterworld ( 1995 ) . Hopper 's later work included a leading role in the short-lived television series Crash ( 2008 -- 2009 ) , inspired by the Academy Award-winning film of the same name . Production on his final film , The Last Film Festival ( 2016 ) , completed just before his death ; originally slated for 2011 distribution , the project was picked up for theatrical release in late 2016 by Monterey Home Video . Hopper has an additional posthumous credit in the completed , but unreleased Orson Welles drama The Other Side of the Wind , acquired for distribution by Netflix .",
"title": ""
}
] |
[
{
"docid": "Dennis_Hopper_filmography",
"text": "Dennis Hopper ( May 17 , 1936May 29 , 2010 ) was an American actor , filmmaker , photographer and artist . He made his first television appearance in 1955 , and appeared in two films featuring James Dean , Rebel Without a Cause ( 1955 ) and Giant ( 1956 ) . Over the next ten years , Hopper appeared frequently on television in guest roles , and by the end of the 1960s had played supporting roles in several films . He directed and starred in Easy Rider ( 1969 ) , winning an award at the Cannes Film Festival and was nominated for an Academy Award for Best Writing ( Original Screenplay ) as co-writer . He had a featured role in Apocalypse Now ( 1979 ) . He subsequently appeared in Rumble Fish ( 1983 ) and The Osterman Weekend ( 1983 ) , and received critical recognition for his work in Blue Velvet and Hoosiers , with the latter film garnering him an Academy Award nomination for best Supporting Actor . He directed Colors ( 1988 ) . Hopper starred in the 1990 Motion Picture Flashback which was inspired by the 1960s Love Movement . He also played the villain in Speed ( 1994 ) . A total of six films starring Dennis Hopper have been selected for preservation in the National Film Registry . Hopper died of prostate cancer on May 29 , 2010 , 12 days after his 74th birthday and two months after he received a star on the Hollywood Walk of Fame .",
"title": ""
},
{
"docid": "Catchfire",
"text": "Catchfire is a 1990 American action thriller film directed by Dennis Hopper and starring Jodie Foster , Dennis Hopper , Fred Ward and Vincent Price . Several other notable actors have cameos . The film was disowned by Hopper before release and he is therefore credited under the fictional pseudonym Alan Smithee . The original screenplay was written by Rachel Kronstadt Mann , then re-written by Ann Louise Bardach , who was hired by Dennis Hopper and producer Steven Reuther . During the 1988 Writers Guild of America strike , Hopper hired Alex Cox to do another polish while the film was shooting . Hopper released a director 's cut of the film in the United States on cable television titled Backtrack , which runs 18 minutes longer than the theatrical version .",
"title": ""
},
{
"docid": "Out_of_the_Blue_(1980_film)",
"text": "Out of the Blue ( released in Canada as No Looking Back ) is a 1980 Canadian drama film directed by and starring Dennis Hopper . The film was written and produced by Gary Jules Jouvenat . It competed for the Palme d'Or at the 1980 Cannes Film Festival . This was the first film Hopper directed since 1971 's The Last Movie , stepping in at the last minute to replace the original director ( screenwriter Leonard Yakir ) . Film Critic Jonathan Rosenbaum considers it one of the 15 best films of the 1980s . It centers on Cebe , a rebellious and troubled young girl , played by Linda Manz -- interested only in Elvis Presley and punk rock music -- as well as her ex-convict father Don Barnes ( Dennis Hopper ) , and her high-strung mother Kathy ( Sharon Farrell ) . The title is taken from the Neil Young song `` My My , Hey Hey ( Out of the Blue ) '' . The film was made in Vancouver , British Columbia , Canada and various icons of Vancouver in that era are featured in the film , including the Pointed Sticks , one of the leading bands of Vancouver 's punk era . The film was aired in full on UK TV Channel 4 as part of the Red Triangle series on January 10 , 1987 . The song `` Kill All Hippies '' , from Scottish rock band Primal Scream 's 2000 album XTRMNTR , features a sample of Manz ' dialogue from the movie .",
"title": ""
},
{
"docid": "Nails_(1992_film)",
"text": "Nails is a 1992 film directed by John Flynn , written by Larry Ferguson , and starring Dennis Hopper . It was made for Showtime but released theatrically in Europe .",
"title": ""
},
{
"docid": "Alpha_and_Omega_(film)",
"text": "Alpha and Omega is a 2010 American 3D computer-animated adventure comedy-drama film directed by Anthony Bell and Ben Gluck . Starring Justin Long , Hayden Panettiere , Dennis Hopper , Danny Glover and Christina Ricci , the film was written by Christopher Denk and Steve Moore , based on a story by Moore and Gluck . The film premiered at the Toronto International Film Festival on September 8 , 2010 , and was released nationwide in 2-D and 3-D on September 17 , 2010 by Lionsgate Films . The film was dedicated to the memory of Dennis Hopper , as he died from prostate cancer a few months before it was released , and this was his final performance prior to his death . A direct-to-DVD sequel , entitled A Howl-iday Adventure , was released on October 8 , 2013 . Another sequel , The Great Wolf Games , was released on March 25 , 2014 . The Legend of the Saw Tooth Cave was released on September 23 , 2014 . Family Vacation was released to DVD on August 4 , 2015 . Dino Digs was released on DVD and Digital HD on May 10 , 2016 . Two more sequels were made , these include The Big Freeze and Journey To The Bear Kingdom .",
"title": ""
},
{
"docid": "Americano_(2005_film)",
"text": "Americano is a 2005 American film . The film stars Joshua Jackson , Leonor Varela , Timm Sharp , Ruthanna Hopper , and Dennis Hopper . It was written and directed by Kevin Noland .",
"title": ""
},
{
"docid": "Paris_Trout",
"text": "Paris Trout is a 1991 made-for-television drama film directed by Stephen Gyllenhaal , starring Dennis Hopper , Barbara Hershey , and Ed Harris . It is based on the novel Paris Trout by author Pete Dexter .",
"title": ""
},
{
"docid": "The_Last_Film_Festival",
"text": "The Last Film Festival is an American comedy film starring Dennis Hopper , Leelee Sobieski , Katrina Bowden , Chris Kattan and Jacqueline Bisset . It is written and directed by Linda Yellen . It was filmed in 2010 , shortly before Hopper died . After extensive delays , the film was finally released theatrically in Los Angeles on 30 September 2016 , followed by a VOD release . Monterey Media acquired the distribution rights in June 2016 .",
"title": ""
},
{
"docid": "Skinner's_Dress_Suit",
"text": "Skinner 's Dress Suit is a 1926 American silent comedy film produced and distributed by Universal Pictures and starring Reginald Denny . William Seiter was the director of the film which was based on the 1916 novel of the name by Henry Irving Dodge . Laura La Plante and Hedda Hopper co-star in this comedy which has seen video and DVD releases . A previous silent film based on this story had been made in 1917 directed by Harry Beaumont for the Essanay Company .",
"title": ""
},
{
"docid": "Crash_(2008_TV_series)",
"text": "Crash is an American television drama series set in Los Angeles , California that starred Dennis Hopper and Eric Roberts . It is the first original series produced by the Starz network . The network ordered a 13 episode season which premiered on October 17 , 2008 . The series is based on the 2004 film of the same name . It was developed for television by Glen Mazzara . In Canada , Crash can be seen on Super Channel . Starz ordered a second season that premiered in September 2009 before concluding in December 2009 . Lead actor Dennis Hopper died in May 2010 and the series did not continue .",
"title": ""
},
{
"docid": "The_Keeper_(2004_film)",
"text": "The Keeper is a 2004 film starring Dennis Hopper and Asia Argento .",
"title": ""
},
{
"docid": "The_Sky_Is_Falling_(1979_film)",
"text": "The Sky Is Falling , also known as Las Flores Del Vicio ( English : The Flowers of Vice ) , released in the United States as Bloodbath , is a 1979 Spanish surrealist thriller film directed by Silvio Narizzano and written by Gonzalo Suarez . It stars Dennis Hopper , Carroll Baker , and Win Wells as hopeless American expatriates living in a Spanish village where citizens are dying mysterious deaths after the arrival of a religious cult . The film has been characterized as an example of the frenetic roles played by Hopper in the 1970s .",
"title": ""
},
{
"docid": "Easy_Rider",
"text": "Easy Rider is a 1969 American road movie written by Peter Fonda , Dennis Hopper , and Terry Southern , produced by Fonda and directed by Hopper . It tells the story of two bikers ( played by Fonda and Hopper ) who travel through the American Southwest and South after selling a large score of cocaine . The success of Easy Rider helped spark the New Hollywood era of filmmaking during the early 1970s . The film was added to the Library of Congress National Film Registry in 1998 . A landmark counterculture film , and a `` touchstone for a generation '' that `` captured the national imagination '' , Easy Rider explores the societal landscape , issues , and tensions in the United States during the 1960s , such as the rise and fall of the hippie movement , drug use , and communal lifestyle . In Easy Rider , real drugs were used in scenes showing the use of marijuana and other substances .",
"title": ""
},
{
"docid": "Key_Witness_(1960_film)",
"text": "Key Witness is a black and white 1960 crime film directed by Phil Karlson and starring Jeffrey Hunter , Pat Crowley and Dennis Hopper .",
"title": ""
},
{
"docid": "Night_Tide",
"text": "Night Tide is a 1961 thriller film , written and directed by Curtis Harrington and starring Dennis Hopper . It was filmed in 1960 , premiered in 1961 , but was held up from general release until 1963 . The film was restored by the Academy Film Archive in 2007 .",
"title": ""
},
{
"docid": "Blue_Velvet_(film)",
"text": "Blue Velvet is a 1986 American neo-noir mystery film , written and directed by David Lynch . Blending psychological horror with film noir , the film stars Kyle MacLachlan , Isabella Rossellini , Dennis Hopper and Laura Dern . The title is taken from Bobby Vinton 's 1963 song of the same name . The screenplay of Blue Velvet had been passed around multiple times in the late 1970s and early 1980s , with many major studios declining it because of its strong sexual and violent content . After the commercial and critical failure of Lynch 's Dune ( 1984 ) , the director made attempts at developing a more `` personal story '' , somewhat characteristic of the surrealist style displayed in his debut Eraserhead ( 1977 ) . The independent studio De Laurentiis Entertainment Group , owned at the time by Italian film producer Dino De Laurentiis , agreed to finance and produce the film . Blue Velvet initially received a divided critical response , with many stating that its objectionable content served little artistic purpose . It nevertheless earned Lynch his second Academy Award nomination for Best Director and came to achieve cult status . As an example of a director casting against the norm , it was credited for re-launching Hopper 's career and for providing Rossellini with a dramatic outlet beyond her previous work as a fashion model and a cosmetics spokeswoman . In the years since , the film has generated significant academic attention with regard to its thematic symbolism , and is now widely regarded as one of Lynch 's major works and one of the greatest films of the 1980s . Publications including Sight & Sound , Time , Entertainment Weekly and BBC Magazine have ranked it among the greatest American films of all time . In 2008 , Blue Velvet was chosen by the American Film Institute as one of the greatest American mystery films ever made .",
"title": ""
},
{
"docid": "List_of_accolades_received_by_Blue_Velvet",
"text": "Blue Velvet is a 1986 American mystery film written and directed by David Lynch . The movie exhibits elements of both film noir and surrealism . The film features Kyle MacLachlan , Isabella Rossellini , Dennis Hopper , and Laura Dern . The title is taken from the 1963 Bobby Vinton song of the same name , which is featured in the film . Although initially detested by some mainstream critics , the film has now become widely acclaimed . Blue Velvet was a critical success for Rossellini and Hopper , earning both several awards for their roles -- Hopper 's portrayal of the film 's antagonist Frank Booth earned him six nominations with four wins , and Rossellini was successful in her Independent Spirit Awards nomination for Best Female Lead -- while the film also earned Lynch his second Academy Award nomination for Best Director . As an example of a director casting against the norm , Blue Velvet is also noted for re-launching Hopper 's career and for providing Rossellini with a dramatic outlet beyond the work as a fashion model and a cosmetics spokeswoman for which she had until then been known . The film centers on college student Jeffrey Beaumont ( MacLachlan ) , who , returning from a hospital visit to his ill father , discovers a human ear in a field in his hometown of Lumberton . He proceeds to investigate the ear with help from a high school student , Sandy Williams ( Dern ) , who provides him with information and leads from her father , a local police detective . Jeffrey 's investigation draws him deeper into his hometown 's seedy underworld , and sees him forming a sexual relationship with the alluring torch singer , Dorothy Vallens ( Rossellini ) , and uncovering psychotic criminal Frank Booth ( Hopper ) , who engages in drug abuse , kidnapping , and sexual violence .",
"title": ""
},
{
"docid": "The_American_Way_(film)",
"text": "The American Way , also known as Riders of the Storm , is a 1986 American science fiction comedy film directed by Maurice Phillips and starring Dennis Hopper and Michael J. Pollard .",
"title": ""
},
{
"docid": "The_Inside_Man_(film)",
"text": "The Inside Man ( also titled Slagskämpen ) is a 1984 Swedish-British thriller film directed by Tom Clegg and starring Dennis Hopper . It is based on the book Slagskämpen by Harry Kullman .",
"title": ""
},
{
"docid": "Ticker_(2001_film)",
"text": "Ticker is a 2001 American action film directed by Albert Pyun , starring Tom Sizemore , Jaime Pressly , Dennis Hopper , Steven Seagal , Ice-T , Kevin Gage , and Nas .",
"title": ""
},
{
"docid": "Colors_(film)",
"text": "Colors is a 1988 American police procedural action crime film starring Sean Penn and Robert Duvall , and directed by Dennis Hopper . The film takes place in the gang ridden neighborhoods of 1980s ' South Central Los Angeles , East Los Angeles and the LAPD Rampart Division , and centers on Bob Hodges ( Duvall ) , an experienced Los Angeles Police Department CRASH officer , and his rookie partner , Danny McGavin ( Penn ) , who try to stop the gang violence between the Bloods , the Crips , and Hispanic street gangs . Colors relaunched Hopper as a director 19 years after Easy Rider , and inspired discussion over its depiction of gang life and gang violence .",
"title": ""
},
{
"docid": "Flashback_(1990_film)",
"text": "Flashback is a 1990 American adventure comedy film starring Dennis Hopper , Kiefer Sutherland and Carol Kane , written by David Loughery and directed by Franco Amurri . The film received an R rating by the Motion Picture Association of America ( MPAA ) .",
"title": ""
},
{
"docid": "The_Wild_Angels",
"text": "The Wild Angels is a 1966 Roger Corman film , made on location in Southern California . The Wild Angels was made three years before Easy Rider and was the first film to associate actor Peter Fonda with Harley-Davidson motorcycles and 1960s counterculture . It was also the film that inspired the outlaw biker film genre that continued into the early 1970s . The Wild Angels , released by American International Pictures ( AIP ) , stars Fonda as the fictitious Hell 's Angels San Pedro , California chapter president `` Heavenly Blues '' ( or `` Blues '' ) , Nancy Sinatra as his girlfriend `` Mike '' , Bruce Dern as doomed fellow outlaw `` the Loser '' , and Dern 's real-life wife Diane Ladd as the Loser 's on-screen wife , `` Gaysh '' . Small supporting roles are played by Michael J. Pollard and Gayle Hunnicutt and , according to literature promoting the film , members of the Hell 's Angels from Venice , California . Members of the Coffin Cheaters motorcycle club also appeared . In 1967 AIP followed this film with Devil 's Angels , The Glory Stompers with Dennis Hopper , and The Born Losers .",
"title": ""
},
{
"docid": "Bert_Schneider",
"text": "Berton `` Bert '' Jerome Schneider ( May 5 , 1933December 12 , 2011 ) was an American film and television producer . He was responsible for several topical films of the late 1960s and early 1970s , including the road film Easy Rider ( 1969 ) , directed by Dennis Hopper .",
"title": ""
},
{
"docid": "King_of_the_Mountain_(film)",
"text": "King of the Mountain is a 1981 American drama film starring Harry Hamlin , Joseph Bottoms , Deborah Van Valkenburgh , Richard Cox , Seymour Cassel and Dennis Hopper about a group that race their cars up and down Mulholland Drive for both money and prestige . The film 's primary focus is Steve ( Harry Hamlin ) , who has found himself generally content with his uncomplicated life of working and racing . This creates some amount of tension between him and his friends , who have been losing their interest in racing and have been attempting to make serious inroads in the music industry . Steve 's blossoming relationship with singer Tina ( Deborah Van Valkenburgh ) causes him to re-think his mantra , as he realizes that a truly fulfilling life involves more than just work and play . The film was poorly regarded critically and did not perform well in the box office , although it was significant in being among the first films about street racing and communities of street racers , as well as because it was inspired by the activities of real people who raced in the Los Angeles area . It also marked somewhat of a return for Dennis Hopper , who had spent several months secluded away from Los Angeles prior to making his appearance .",
"title": ""
},
{
"docid": "Tracks_(1977_film)",
"text": "Tracks is a 1977 American drama film written and directed by Henry Jaglom . The film stars Dennis Hopper , Taryn Power and Dean Stockwell . The story involves a returned Vietnam veteran escorting a fellow soldier 's coffin across the United States for burial .",
"title": ""
},
{
"docid": "Tom_Folsom",
"text": "Tom Folsom is a writer living in New York City . He is best known as the author of a bestselling biography of Crazy Joe Gallo , The Mad Ones : Crazy Joe Gallo and the Revolution at the Edge of the Underworld . On March 5 , 2013 , the It Books imprint of HarperCollins published Folsom 's definitive biography on Dennis Hopper , Hopper : A Journey into the American Dream , charting the actor 's wide-ranging career and place in American popular culture in art , music , photography and film .",
"title": ""
},
{
"docid": "Held_for_Ransom_(2000_film)",
"text": "Held for Ransom is a 2000 direct-to-video film , starring Dennis Hopper , Zachery Ty Bryan , Morgan Fairchild and Debi Mazar . It was directed and written by Lee Stanley based on the novel by Lois Duncan .",
"title": ""
},
{
"docid": "Witch_Hunt_(1994_film)",
"text": "Witch Hunt ( 1994 ) is a horror , detective HBO film starring Dennis Hopper and Eric Bogosian , directed by Paul Schrader and written by Joseph Dougherty . The original music score was composed by Angelo Badalamenti .",
"title": ""
},
{
"docid": "Elegy_(film)",
"text": "Elegy is a 2008 drama film directed by Spanish director Isabel Coixet and adapted by Nicholas Meyer from the Philip Roth novel , The Dying Animal . The film stars Penélope Cruz , Ben Kingsley , and Dennis Hopper , and co-stars Patricia Clarkson and Peter Sarsgaard in supporting roles . The film was set in New York City but filmed in Vancouver .",
"title": ""
}
] |
PLAIN-985
|
CT scan
|
[
{
"docid": "MED-3626",
"text": "Objectives The Radiation Protection of Patients Unit of the International Atomic Energy Agency (IAEA) is concerned about the effectiveness of justification of diagnostic medical exposures. Recent published work and the report of an initial IAEA consultation in the area gave grounds for such concerns. There is a significant level of inappropriate usage, and, in some cases, a poor level of awareness of dose and risk among some key groups involved. This article aims to address this. Methods The IAEA convened a second group of experts in November 2008 to review practical and achievable actions that might lead to more effective justification. Results This report summarises the matters that this group considered and the outcome of their deliberations. There is a need for improved communication, both within professions and between professionals on one hand, and between professionals and the patients/public on the other. Coupled with this, the issue of consent to imaging procedures was revisited. The need for good evidence-based referral guidelines or criteria of acceptability was emphasised, as was the need for their global adaptation and dissemination. Conclusion Clinical audit was regarded as a key tool in ensuring that justification becomes an effective, transparent and accountable part of normal radiological practice. In summary, justification would be facilitated by the “3 As”: awareness, appropriateness and audit.",
"title": "Justification of diagnostic medical exposures: some practical issues. Report of an International Atomic Energy Agency Consultation"
},
{
"docid": "MED-3623",
"text": "This article presents an analysis of issues related to low-dose radiation, with a focus on pediatric computed tomography (CT). It references several early studies that are seldom quoted in radiation research papers, then quantifies the excess lifetime fatal cancer yield attributable to an estimated 6.5 million pediatric abdominal CT scans. The authors highlight an important policy document issued jointly by the National Cancer Institute and the Society for Pediatric Radiology--specifically, its conclusion that a small dose from CT represents \"a public health concern.\" Finally, the article identifies several contentious issues and proposes policy initiatives that, if implemented, could result in significant reductions of future radiogenic cancers and chronic injuries. The authors call for discussions between professional radiology societies and public interest health organizations, thereby involving all stakeholders.",
"title": "Pediatric CT research elevates public health concerns: low-dose radiation issues are highly politicized."
},
{
"docid": "MED-3624",
"text": "OBJECTIVE: In light of the rapidly increasing frequency of pediatric CT examinations, the purpose of our study was to assess the lifetime cancer mortality risks attributable to radiation from pediatric CT. MATERIALS AND METHODS: Organ doses as a function of age-at-diagnosis were estimated for common CT examinations, and estimated attributable lifetime cancer mortality risks (per unit dose) for different organ sites were applied. Standard models that assume a linear extrapolation of risks from intermediate to low doses were applied. On the basis of current standard practice, the same exposures (milliampere-seconds) were assumed, independent of age. RESULTS: The larger doses and increased lifetime radiation risks in children produce a sharp increase, relative to adults, in estimated risk from CT. Estimated lifetime cancer mortality risks attributable to the radiation exposure from a CT in a 1-year-old are 0.18% (abdominal) and 0.07% (head)-an order of magnitude higher than for adults-although those figures still represent a small increase in cancer mortality over the natrual background rate. In the United States, of approximately 600,000 abdominal and head CT examinations annually performed in children under the age of 15 years, a rough estimate is that 500 of these individuals might ultimately die from cancer attributable to the CT radiation. CONCLUSION: The best available risk estimates suggest that pediatric CT will result in significantly increased lifetime radiation risk over adult CT, both because of the increased dose per milliampere-second, and the increased lifetime risk per unit dose. Lower milliampere-second settings can be used for children without significant loss of information. Although the risk-benefit balance is still strongly tilted toward benefit, because the frequency of pediatric CT examinations is rapidly increasing, estimates that quantitative lifetime radiation risks for children undergoing CT are not negligible may stimulate more active reduction of CT exposure settings in pediatric patients.",
"title": "Estimated risks of radiation-induced fatal cancer from pediatric CT."
},
{
"docid": "MED-3627",
"text": "BACKGROUND: The use of computed tomographic (CT) scans in the United States (US) has increased more than 3-fold since 1993 to approximately 70 million scans annually. Despite the great medical benefits, there is concern about the potential radiation-related cancer risk. We conducted detailed estimates of the future cancer risks from current CT scan use in the US according to age, sex, and scan type. METHODS: Risk models based on the National Research Council's \"Biological Effects of Ionizing Radiation\" report and organ-specific radiation doses derived from a national survey were used to estimate age-specific cancer risks for each scan type. These models were combined with age- and sex-specific scan frequencies for the US in 2007 obtained from survey and insurance claims data. We estimated the mean number of radiation-related incident cancers with 95% uncertainty limits (UL) using Monte Carlo simulations. RESULTS: Overall, we estimated that approximately 29 000 (95% UL, 15 000-45 000) future cancers could be related to CT scans performed in the US in 2007. The largest contributions were from scans of the abdomen and pelvis (n = 14 000) (95% UL, 6900-25 000), chest (n = 4100) (95% UL, 1900-8100), and head (n = 4000) (95% UL, 1100-8700), as well as from chest CT angiography (n = 2700) (95% UL, 1300-5000). One-third of the projected cancers were due to scans performed at the ages of 35 to 54 years compared with 15% due to scans performed at ages younger than 18 years, and 66% were in females. CONCLUSIONS: These detailed estimates highlight several areas of CT scan use that make large contributions to the total cancer risk, including several scan types and age groups with a high frequency of use or scans involving relatively high doses, in which risk-reduction efforts may be warranted.",
"title": "Projected cancer risks from computed tomographic scans performed in the United States in 2007."
},
{
"docid": "MED-3625",
"text": "Short abstract Radiological and nuclear medicine examinations confer a definite (albeit low) long term risk of cancer, but patients undergoing such examinations often receive no or inaccurate information about these risks. Picano argues that this disregard of patient autonomy is no longer acceptable and suggests a practicable way of communicating risk",
"title": "Informed consent and communication of risk from radiological and nuclear medicine examinations: how to escape from a communication inferno"
}
] |
[
{
"docid": "MED-2940",
"text": "In the past 3 decades, the total number of CT scans performed has grown exponentially. In 2007, > 70 million CT scans were performed in the United States. CT scan studies of the chest comprise a large portion of the CT scans performed today because the technology has transformed the management of common chest diseases, including pulmonary embolism and coronary artery disease. As the number of studies performed yearly increases, a growing fraction of the population is exposed to low-dose ionizing radiation from CT scan. Data extrapolated from atomic bomb survivors and other populations exposed to low-dose ionizing radiation suggest that CT scan-associated radiation may increase an individual's lifetime risk of developing cancer. This finding, however, is not incontrovertible. Because this topic has recently attracted the attention of both the scientific community and the general public, it has become increasingly important for physicians to understand the cancer risk associated with CT scan and be capable of engaging in productive dialogue with patients. This article reviews the current literature on the public health debate surrounding CT scan and cancer risk, quantifies radiation doses associated with specific studies, and describes efforts to reduce population-wide CT scan-associated radiation exposure. CT scan examinations of the chest, including CT scan pulmonary and coronary angiography, high-resolution CT scan, low-dose lung cancer screening, and triple rule-out CT scan, are specifically considered.",
"title": "Radiation and chest CT scan examinations: what do we know?"
},
{
"docid": "MED-3193",
"text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.",
"title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma"
},
{
"docid": "MED-3787",
"text": "Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.",
"title": "11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma"
},
{
"docid": "MED-5317",
"text": "BACKGROUND Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. METHODS We analyzed 3640 consecutive 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET–CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of 18F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. RESULTS Substantial depots of brown adipose tissue were identified by PET–CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher 18F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P= 0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P = 0.007). CONCLUSIONS Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of 18F-FDG PET–CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.",
"title": "Identification and Importance of Brown Adipose Tissue in Adult Humans"
},
{
"docid": "MED-5320",
"text": "Increased (18)F-FDG activity in fatty tissue has previously been reported with PET/CT. We previously named this activity uptake in supraclavicular area fat (\"USA-Fat\"). We and others have speculated that this uptake exists in metabolically active brown adipose tissue (BAT). Such tissue might be expected to have varying metabolic activity depending on the ambient temperature. The purpose of this study was to evaluate the frequency of USA-Fat and its relationship to the outdoor temperature. METHODS: Between July 2001 and June 2002, 1,017 consecutive whole-body scans were obtained with a PET/CT scanner and (18)F-FDG for clinical patients. PET images were reviewed for the presence of USA-Fat. RESULTS: USA-Fat was observed in 68 scans obtained from 62 patients (51 female and 11 male). The incidence of USA-Fat was highest, at 13.7%, in January through March, while outside temperatures were low, and was significantly lower, at 4.1%, during the rest of the year. CONCLUSION: The incidence of USA-Fat is clearly increased during the cooler period of the year. This finding suggests that stimulation by cold temperatures increases the frequency with which USA-Fat occurs, supporting underlying BAT as the etiology for this activity.",
"title": "\"USA-Fat\": prevalence is related to ambient outdoor temperature-evaluation with 18F-FDG PET/CT."
},
{
"docid": "MED-3562",
"text": "Invasive cervical cancer is the third most common gynecologic malignancy. The prognosis is based on the stage, size, and histologic grade of the primary tumor and the status of the lymph nodes. Assessment of the stage of disease is important in determining whether the patient may benefit from surgery or will receive radiation therapy. The official clinical staging system of the International Federation of Gynecology and Obstetrics has led to errors of 65%-90% in stage III and IV disease; the result has been unofficial extended staging with cross-sectional imaging modalities such as computed tomography (CT). CT is useful in staging advanced disease and in monitoring patients for recurrence. The primary tumor is heterogeneous and hypoattenuating relative to normal stroma on contrast material-enhanced scans. Obliteration of the periureteral fat plane and a soft-tissue mass are the most reliable signs of parametrial extension. Less than 3 mm separation of the tumor from the pelvic muscles and vascular encasement are signs of pelvic side wall invasion. Lymphatic spread is along the external and internal iliac nodal chains and the presacral route to the paraaortic nodes. Distant metastases are seen with primary or recurrent disease and can involve the liver, lung, and bone.",
"title": "CT evaluation of cervical cancer: spectrum of disease."
},
{
"docid": "MED-1733",
"text": "INTRODUCTION: Glyphosate-surfactant herbicide (GlySH) is widely used as a non-selective herbicide. Most intoxicated cases are from ingestion, inhalation, and skin exposure. Intramuscular injection of GlySH has never been reported. We present a case of GlySH intoxication via intramuscular injection. CASE REPORT: A 42-year-old woman came to the emergency department complaining of painful swelling of left upper limb for 12 h. She had performed an intramuscular injection of 6 mL of GlySH over the lateral aspect of the left elbow 15 h previously. Physical examination disclosed painful swelling over left distal arm, elbow, and forearm with three needle punctures. CT scan revealed ill-defined areas of heterogeneous high density with marked swelling at subcutaneous tissue over posterior aspect of the elbow. DISCUSSION: The mechanism of toxicity of GlySH is complicated and surfactant was thought to play an important role in GlySH intoxication. Intramuscular GlySH poisoning is different from oral GlySH intoxication. Care should be taken when monitoring acute rhabdomyolysis and compartment syndrome, which may develop rapidly and contribute to the surfactant component of glyphosate formulation.",
"title": "Rhabdomyolysis from an intramuscular injection of glyphosate-surfactant herbicide."
},
{
"docid": "MED-5155",
"text": "Objective: To determine if a supplement of soy protein improves body composition, body fat distribution, and glucose and insulin metabolism in non-diabetic postmenopausal women compared to an isocaloric casein placebo. Design: Randomized, double-blind, placebo-controlled 3-month trial Setting: Clinical Research Center Patients: 15 postmenopausal women Interventions: CT scans at L4/L5, dual energy x-ray absorptiometry (DXA), hyperglycemic clamps Main outcome measures: Total fat, total abdominal fat, visceral fat, subcutaneous abdominal fat, and insulin secretion. Results: Weight by DXA did not change between groups (+1.38 ± 2.02 kg for placebo vs. +0.756 ± 1.32 kg for soy, p=0.48, means ± S.D.). Total and subcutaneous abdominal fat increased more in the placebo compared to the soy group (for differences between groups in total abdominal fat: +38.62 ± 22.84 cm2 for placebo vs. −11.86 ± 31.48 cm2 for soy, p=0.005; subcutaneous abdominal fat: +22.91 ± 28.58 cm2 for placebo vs. −14.73 ± 22.26 cm2 for soy, p=0.013). Insulin secretion, visceral fat, total body fat, and lean mass did not differ between groups. Isoflavone levels increased more in the soy group. Conclusion: A daily supplement of soy protein prevents the increase in subcutaneous and total abdominal fat observed with an isocaloric casein placebo in postmenopausal women.",
"title": "Effect of a Daily Supplement of Soy Protein on Body Composition and Insulin Secretion in Postmenopausal Women"
},
{
"docid": "MED-5313",
"text": "The supraclavicular region is a common site for lymph node metastases. A commonly reported type of nonmalignant (18)F-FDG uptake on PET imaging in the supraclavicular region is \"muscle uptake\" purportedly due to muscle contraction in tense patients during the (18)F-FDG uptake phase. PET/CT offers the unique opportunity to correlate PET findings with CT anatomy in the supraclavicular region. METHODS: Images from the first 359 consecutive clinical whole-body studies (in 347 patients) using (18)F-FDG and a PET/CT scanner (with CT attenuation correction and ordered-subsets expectation maximization [OSEM] reconstruction) were retrospectively reviewed. The supraclavicular region was evaluated for the presence of abnormal uptake on PET images, and the corresponding CT findings were assessed. Three distinct patterns of abnormal (18)F-FDG uptake were noted: pattern A (uptake localizing to supraclavicular area fat [USA-fat], i.e., without corresponding lymph node or muscle uptake on CT), pattern B (uptake localizing to muscle on CT), and pattern C (uptake localizing to lymph nodes or soft-tissue masses on CT). RESULTS: Forty-nine patients (14.1%) (32 female, 17 male; mean age, 51.4 +/- 15.6 y; age range, 12-77 y) showed abnormal (18)F-FDG uptake in the supraclavicular region. Twenty patients (5.8%) had muscle uptake (group B); 15 (4.3%) had definite abnormal lymph nodes (group C). However, 14 patients (4.0%) had USA-fat (group A) and foci of very low Hounsfield units on CT. These foci were also present on (68)Ge attenuation-corrected images (when obtained) and non-attenuation-corrected images. Uptake in USA-fat was typically bilateral and symmetric, intense, more often multifocal than linear, and located in fat on PET/CT. Age was not significantly different for group C versus the 2 other groups. Intensity; mean standardized uptake value, lean (SUV(L MEAN)); or maximum standardized uptake value, lean (SUV(L MAX)), did not allow differentiation between patterns A and C (P > 0.05). Standardized uptake values (SUV(L MAX), 3.1; SUV(L MEAN), 2.1) were significantly lower in group B than in the 2 other groups (P < 0.005). CONCLUSION: So-called muscle uptake in the supraclavicular region may be caused in a significant proportion of cases by an unrelated process we call the USA-fat finding, with (18)F-FDG uptake in tissues of low-Hounsfield (fat) density. This finding most likely reflects an underlying nonpathologic process that we hypothesize to be in foci of brown fat. This intense supraclavicular uptake should be recognized and should not be misinterpreted as a malignant metastatic process or as muscle uptake.",
"title": "Uptake in supraclavicular area fat (\"USA-Fat\"): description on 18F-FDG PET/CT."
},
{
"docid": "MED-2947",
"text": "PURPOSE: To measure prospectively and directly both organ dose and effective dose (ED) for adult cardiac and pulmonary computed tomographic (CT) angiography by using current clinical protocols for 64-detector CT in an anthropomorphic female phantom and to estimate lifetime attributable risk of breast and lung cancer incidence on the basis of measured ED and organ dose. MATERIALS AND METHODS: Cardiac and pulmonary 64-detector CT angiography was performed by using current clinical protocols to evaluate the pulmonary veins (electrocardiographically [ECG] gated, 64 sections at 0.625-mm collimation, 120 kVp, 300 mA, 0.35-second tube rotation), native coronary arteries (ECG gated; 64 sections at 0.625 mm; 120 kVp; maximum current, 500-750 mA; minimum, 100-350 mA; 0.35-second tube rotation) and pulmonary embolus (64 sections at 1.25 mm, 140 kVp, 645 mA, 0.5-second tube rotation). Absorbed organ doses were measured by using an anthropomorphic female phantom and metal oxide semiconductor field effect transistor detectors. ED was calculated from measured organ doses and the dose-length product. RESULTS: ED for current adult cardiac and pulmonary 64-detector CT angiography protocols were 12.4-31.8 mSv. Overall, skin, breast, and esophagus and heart had the highest recorded absorbed organ doses. Relative risk for breast cancer incidence for girls and women was 1.004-1.042 for a single examination. Relative risk for lung cancer incidence for men and women was 1.005-1.076 from a single examination. CONCLUSION: EDs and organ doses from 64-detector CT are higher than those previously reported for adult cardiac and pulmonary CT angiography protocols. Risk for breast and lung cancer induction from these studies is greatest for the younger patient population. (c) RSNA, 2007.",
"title": "Radiation dose from contemporary cardiothoracic multidetector CT protocols with an anthropomorphic female phantom: implications for cancer induction."
},
{
"docid": "MED-5213",
"text": "Dry eye disease (DED) treatment is an area of increasing complexity, with the emergence of several new treatment agents in recent years. Evaluation of the efficacy of these agents is limited by heterogeneity in outcomes definition and the small number of comparative studies. We provide a systematic review of clinical trials (CTs) related to DED treatment and a critical appraisal of CT public databases. CT reports obtained from eight databases were reviewed, as well as public free-access electronic databases for CT registration. Data evaluation was based on endpoints such as symptoms, Schirmer test, ocular surface staining scores, recruitment of patients, type and efficacy of the drug, and the design and site of performance of the study. Forty-nine CTs were evaluated involving 5,189 patients receiving DED treatment. Heterogeneity in study design prevented meta-analysis from yielding meaningful results, and a descriptive analysis of these studies was conducted. The most frequent categories of drugs for DED in these studies were artificial tears, followed by anti-inflammatory drugs and secretagogues. Although 116 studies have been completed, according to the registration database for clinical trials, only 17 of them (15.5%) were published. Out of 185 registered CTs related to DED, 72% were performed in the USA. The pharmaceutical industry sponsored 78% of them. The identification of effective DED treatment strategies is hindered by the lack of an accepted set of definitive criteria for evaluating disease severity. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Dry eye disease treatment: a systematic review of published trials and a critical appraisal of therapeutic strategies."
},
{
"docid": "MED-2672",
"text": "To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.",
"title": "Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks."
},
{
"docid": "MED-4309",
"text": "Biogenic monoamines such as serotonin, tryptamine, and tyramine function as neurotransmitters and mitogenic factors in animals and are involved in flowering, morphogenesis, and protection from and adaptation to environmental changes in plants. In plants, serotonin and tyramine are conjugated to form phenolic compounds via thioester linkages during the synthesis of hydroxycinnamic acid amides, including p-coumaroylserotonin (CS), feruloylserotonin (FS), p-coumaroyltyramine (CT), and feruloyltyramine (FT). In this study, we determined the amounts of the biogenic monoamines CS, FS, CT, and FT in commonly consumed vegetables using high-performance liquid chromatography. Serotonin, tryptamine, and tyramine were detected in all vegetables tested. The serotonin levels ranged from 1.8 to 294 microg/g of dry weight, the tryptamine levels ranged from 0.8 to 372 microg/g of dry weight, and the tyramine levels ranged from 1.4 to 286 microg/g of dry weight. The highest serotonin and tryptamine contents were found in tomato and cherry tomato (140.3-222 microg/g of dry weight), while paprika and green pepper had higher tyramine contents than the other vegetables (286 and 141.5 microg/g of dry weight, respectively). Overall, the levels of CS, FS, CT, and FT ranged from 0.03 to 13.8 microg/g of dry weight, with green onion possessing the highest levels of CS (0.69 microg/g of dry weight), FT (1.99 microg/g of dry weight), and CT (13.85 microg/g of dry weight).",
"title": "HPLC analysis of serotonin, tryptamine, tyramine, and the hydroxycinnamic acid amides of serotonin and tyramine in food vegetables."
},
{
"docid": "MED-5315",
"text": "The existence of brown adipose tissue (BAT) in humans has previously been assessed in vivo via sequential 18F-FDG PET/CT imaging. We developed a MRI protocol to detect BAT mass based on BAT’s property of having higher water-to-fat ratio than white adipose tissue (WAT). We showed that the signal contrast obtained between water-saturation and without water-saturation was higher in BAT than in WAT in fast spin echo images and in T2-weighted images. The water-to-fat ratio was also higher in BAT via contrasting the water and fat images of the Dixon method. The MRI measured volume and location of BAT was similar to PET/CT results in the same subjects. In addition, we also demonstrated that cold challenges (14 °C) led to significant fMRI BOLD signal increases in BAT.",
"title": "Measurement of Human Brown Adipose Tissue Volume and Activity Using Anatomical MRI and Functional MRI"
},
{
"docid": "MED-1020",
"text": "PURPOSE OF REVIEW: Diabetic retinopathy is the leading cause of visual impairment in working-age adults worldwide. Pan retinal photocoagulation (PRP) has provided an effective treatment to decrease the risk of severe vision loss in patients with proliferative diabetic retinopathy for the past four decades. Pattern scan laser (PASCAL) was developed to minimize the side effects of PRP. The purpose of this review is to discuss the differences between the traditional argon laser and the PASCAL. RECENT FINDINGS: PASCAL can achieve comparable results with the conventional argon PRP in the treatment of patients with diabetic retinopathy. The PASCAL delivery system creates well aligned arrays of retinal lesions in a shorter period. PASCAL provides amore comfortable profile when compared to the argon laser. SUMMARY: The PASCAL is now being substituted for the conventional argon laser for PRP in many clinics. Ophthalmologists should keep in mind that adjusting the PASCAL settings (including the duration, number, and size of laser burns) might become necessary to maintain regression and eliminate recurrence of neovascularization in patients with proliferative diabetic retinopathy. Further studies are needed to determine the parameters for optimal safety and efficacy on the PASCAL.",
"title": "Pan retinal photocoagulation for proliferative diabetic retinopathy: pattern scan laser versus argon laser."
},
{
"docid": "MED-1281",
"text": "The calcium ion (Ca2+) is a ubiquitous second messenger that is crucial for the regulation of a wide variety of cellular processes. The diverse transient signals transduced by Ca2+ are mediated by intracellular Ca2+-binding proteins, also known as Ca2+ sensors. A key obstacle to studying many Ca2+-sensing proteins is the difficulty in identifying the numerous downstream target interactions that respond to Ca2+-induced conformational changes. Among a number of Ca2+ sensors in the eukaryotic cell, calmodulin (CaM) is the most widespread and the best studied. Employing the mRNA display technique, we have scanned the human proteome for CaM-binding proteins and have identified and characterized a large number of both known and previously uncharacterized proteins that interact with CaM in a Ca2+-dependent manner. The interactions of several identified proteins with Ca2+/CaM were confirmed by using pull-down assays and coimmunoprecipitation. Many of the CaM-binding proteins identified belong to protein families such as the DEAD/H box proteins, ribosomal proteins, proteasome 26S subunits, and deubiquitinating enzymes, suggesting the possible involvement of Ca2+/CaM in different signaling pathways. The selection method described herein could be used to identify the binding partners of other calcium sensors on the proteome-wide scale.",
"title": "Scanning the human proteome for calmodulin-binding proteins"
},
{
"docid": "MED-3525",
"text": "Although the hormone melatonin is a key factor for the proper functioning of the circadian timing system (CTS) and exogenous melatonin has been shown to be beneficial in cases of CTS disturbances, a deficit of melatonin has yet to be defined as a disorder. The aim of our study was to collect a normative data set on 24-h melatonin excretion in healthy human adults living in a natural environment. Urine samples were collected from 75 healthy subjects (45 women/30 men; mean age 47.2, SD 19.5, range 20-84) after five consecutive periods: 2300-0700, 0700-1100, 1100-1800, 1800-2300 and 2300-0700 h. 6-Sulfatoxymelatonin (aMT6s) concentrations were analyzed in duplicate by IBL (Hamburg) using a highly sensitive, competitive ELISA kit. Twenty-four hour-aMT6s total amount (rho=-0.68, p<0.001), aMT6s nighttime excretion (rho=-0.69, p<0.001), aMT6s morning excretion (rho=-0.66, p<0.001) and evening excretion (r=-0.26, p=0.023) were negatively associated with age, whereas daytime excretion (r=-0.17, p=0.15) was not. The intra-subject night-day ratio varied up to 10.5 (mean 6.0) in young subjects (aged 20-35) and up to 5.4 (mean 2.8) in older individuals (age>65). The total amount of 24 h-aMT6s (range 7.5-58 microg) as well as the amount of aMT6s excreted during the nighttime period (range 327-6.074 ng/h) varied as much as 20-fold between individuals. Our data show an age-related decline in melatonin excretion in healthy subjects living in a natural environment. The high inter-individual variability of excretion rates may explain why a normative data set is of no use in replacement strategies.",
"title": "Normative data on the daily profile of urinary 6-sulfatoxymelatonin in healthy subjects between the ages of 20 and 84."
},
{
"docid": "MED-4403",
"text": "Samples of Mimolette (France) and Milbenkase (Germany) cheeses traditionally ripened by mites were analyzed to determine the mite species present on each sample. Scientific literature was reviewed to understand which mite species most commonly infest cheese. Morphological features possessed by mites were then studied to understand what unique characteristics are required to ensure accurate identification. After identification and compilation of a detailed key of stored food mites (subclass Acari, order Astigmata) and their delineating features, the mites were viewed through a cryogenic scanning electron microscope. It was determined that Mimolette cheese is inoculated with Acarus siro L. The features studied to identify this mite species included idiosomal length and shape, setae length and arrangement, leg size, placement of anus and genitals, and solenidia shape. The Milbenkase cheese is inoculated with Tyrolichus casei Oudemans, which was evident after viewing the same features used to identify A. siro and the supracoxal seta shape. With this knowledge, further research can be conducted on the 2 cheese varieties to understand what chemical, physical, and microbial changes occur within the cheeses because of mites. It is important to identify the mite species present on each cheese variety to improve our understanding of their role in creating the distinctive characteristics that set these cheeses apart from others. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.",
"title": "Identification of cheese mite species inoculated on Mimolette and Milbenkase cheese through cryogenic scanning electron microscopy."
},
{
"docid": "MED-4925",
"text": "Context Millions of postmenopausal women use multivitamins, often believing that supplements prevent chronic diseases such as cancer and cardiovascular disease. Objective To examine associations between multivitamin use and risk of cancer, cardiovascular disease and mortality in postmenopausal women. Design, Setting and Participants 161,808 participants from the Women’s Health Initiative Clinical Trials (n=68,132 in three overlapping trials of hormone therapy, dietary modification and calcium-vitamin D) or Observational Study (n=93,676). Detailed data were collected on multivitamin use at baseline and follow-up time points. Study enrollment occurred between 1993–1998; women were followed for a median of 8.0 years in the clinical trials and 7.9 years in the observational study. Disease endpoints were collected through 2005. Outcome Measures Cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary and lung; cardiovascular disease (myocardial infarction, stroke, venous thrombosis); and total mortality. Results 41.5% of participants used multivitamins. After a median of 8.0 years of follow-up in the CT and 7.9 years in the OS, 9,619 cases of breast, colorectal, endometrium, kidney, bladder, stomach lung or ovary cancer; 8,751 CVD events and 9,865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamins with risk of cancer (breast HR=0.98, 95%CI 0.91–1.05; colorectal HR = 0.99, 95% CI 0.88–1.11; endometrial HR = 1.05, 95%CI= 0.90–1.21; lung HR = 1.0, 95% CI=0.88–1.13; ovary HR = 1.07, 95%CI =0.88–1.29); CVD (MI HR= 0.96, 95%CI= 0.89–1.03; stroke HR = 0.99, 95%CI =0.91–1.07; VT HR = 1.05, 95%CI =0.85–1.29); or mortality (HR = 1.02, 95% CI=0.97–1.07). Conclusion After a median follow-up of 8.0 and 7.9 years in the CT and OS, respectively, the WHI cohorts provide convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease or total mortality in postmenopausal women. Clinical Trial Registration clinicaltrials.gov identifier: NCT00000611",
"title": "MULTIVITAMIN USE AND RISK OF CANCER AND CARDIOVASCULAR DISEASE IN THE WOMEN’S HEALTH INITIATIVE COHORTS"
},
{
"docid": "MED-1575",
"text": "Background Epithelial barrier function is impaired in Crohn's disease. Aim To define the underlying cellular mechanisms with special attention to tight junctions. Methods Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling and 4′,6‐diamidino‐2‐phenylindole staining. Results Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore‐forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor α. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. Conclusion Upregulation of pore‐forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.",
"title": "Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease"
},
{
"docid": "MED-980",
"text": "Background An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease. Trial Registration Controlled-Trials.com ISRCTN94410159",
"title": "Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial"
},
{
"docid": "MED-2157",
"text": "Patients with cirrhosis are at greatest risk for development of hepatocellular carcinoma (HCC) and should undergo semiannual surveillance using ultrasound, with or without alpha fetoprotein. Patients with positive surveillance testing should undergo contrast-enhanced MRI or 4-phase CT for diagnostic evaluation. There are therapeutic options for most patients with any tumor stage; however, treatment decisions must be individualized after accounting for degree of liver dysfunction and patient performance status. A multidisciplinary approach to care is recommended for optimal communication and treatment delivery. The aim of this review is to provide an up-to-date summary of the diagnosis and management of HCC. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "Hepatocellular carcinoma and other liver lesions."
},
{
"docid": "MED-3178",
"text": "Neurocysticercosis (NCC) is the most frequent parasitic disease of the human brain. Modern imaging studies, CT and MRI, have defined the diagnosis and characterization of the disease. Through these studies the therapeutic approach for each case may be individualized with the aid of antihelmintics, steroids, symptomatic medicines, or surgery. The use of one or various therapeutic measures largely depends on the peculiar combination of number, location, and biological stage of lesions as well as the degree of inflammatory response to the parasites. Although there is not a typical clinical picture of NCC, epilepsy is the most frequent manifestation of parenchymal NCC, whereas hydrocephalus is the most frequent manifestation of meningeal NCC. Eradication of cysticercosis is an attainable goal by public education and sanitary improvement in endemic areas.",
"title": "Clinical manifestations, diagnosis, and treatment of neurocysticercosis."
},
{
"docid": "MED-3544",
"text": "Whole-body PET-scan studies in brains of tobacco smokers have shown a decrease in monoamine oxidase (MAO) activity, which reverts to control level when they quit smoking. The observed decrease in MAO activity in smokers is presumably due to their exposure to tobacco constituents that possess MAO-inhibiting properties. The inhibition of MAO activity seems, however, not to be a unique feature of tobacco smoking as subjects with Type II alcoholism have been reported to show a similar decrease in MAO activity that reverses when they cease to use alcohol. The present review summarizes the data on MAO-inhibiting tobacco constituents and explains that the decrease in MAO activity observed in alcoholics is probably due to concomitant tobacco use. It is concluded that the inhibition of MAO by constituents contained in tobacco and tobacco smoke, enhances the addiction induced by tobacco smoking.",
"title": "Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction."
},
{
"docid": "MED-3962",
"text": "Pathological colonic tissues were investigated with an Environmental Scanning Electron Microscope technique to verify the presence of inorganic, non-biodegradable pollutants, i.e. micro- and nano-debris of exogenous origin, after debris in liver and kidney had been discovered. In all, 18 samples of colon tissues affected by cancer and Crohn's disease were evaluated and found in all the cases to contain micro- and nano-particles. Their chemistry, detected with an X-ray microprobe, indicated a heterogeneous nature, whereas the size of the particles was homogeneous. Three control samples of healthy, young, cadavers were analysed and showed the absence of debris within the normal, healthy colon mucosa. The study reveals the presence of particulate debris, generally considered as biocompatible, in pathological specimens of human colon. The findings suggest a possible link between the presence of such particles and the underlying pathology in the cases analysed.",
"title": "Biocompatibility of micro- and nano-particles in the colon. Part II."
},
{
"docid": "MED-4839",
"text": "We encountered a 62-year-old woman with a progressively worsening sore throat and a sharp lump located in her left upper neck, which appeared several hours before admission. After questioning, she underwent rigid esophagoscopy at a local hospital for suspected fish bone impaction but this gave a negative result. Unusual signs caused us to arrange a computed tomography scan, which showed that a foreign body had penetrated the left sternocleidomastoid muscle to the subcutaneous layer, with extensive emphysema in the neck. We extracted the foreign body with a 1-cm horizontal incision of the neck under general anesthesia. The patient returned to a normal diet and was discharged on day 5 of hospitalization without further morbidity. This is another rare case of a migrating foreign body presenting as a neck lump. On reviewing the literature, most cases involving subcutaneously migrating fish bones show development of a neck lump several weeks to months after ingestion, with relatively stable conditions. However, our case showed a neck lump 1 day after ingestion with acute toxic symptoms.",
"title": "Migrating fish bone presenting as acute onset of neck lump."
},
{
"docid": "MED-3181",
"text": "OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.",
"title": "Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil."
},
{
"docid": "MED-4357",
"text": "The peptide mixture from housefly pupae has broad spectrum antimicrobial activity but has not previously been reported as a food preservative. In this study, the preservation effects of a housefly pupae peptide mixture, nisin, and sodium dehydroacetate (DHA-S) on the number of mesophilic aerobic bacteria (MAB), total volatile basic nitrogen (TVB-N), and pH value of chilled pork were compared. All results showed that a good preservation effect was observed among 3 treatments with the peptide mixture of housefly pupae, nisin, and DHA-S and that there was no significant difference among them. These results indicate that housefly peptide mixture has a great potential as a food preservative. The results of scanning electron microscope and transmission electron microscopy suggest that the primary mechanism of housefly pupae peptide mixture may be bacterial cytoplasmic membrane lysis and pores induced in the membranes. Practical Applications: Peptide mixture extracted from housefly pupae using low-cost and simple method has broad spectrum antimicrobial activity. According to the effect on chilled pork preservation, extracted housefly peptide mixture has a great potential as a food preservative.",
"title": "Effect of extracted housefly pupae peptide mixture on chilled pork preservation."
},
{
"docid": "MED-1276",
"text": "Previous evidence for spatial clustering of amyotrophic lateral sclerosis is inconclusive. Studies that have identified apparent clusters have often been based on a small number of cases, which means the results may have occurred by chance processes. Also, most studies have used the geographic location at the time of death as the basis for cluster detection, rather than exploring clusters at other points in the life cycle. In this study, the authors examine 1,000 cases of amyotrophic lateral sclerosis distributed throughout Finland who died between June 1985 and December 1995. Using a spatial-scan statistic, the authors examine whether there are significant clusters of the disease at both time of birth and time of death. Two significant, neighboring clusters were identified in southeast and south-central Finland at the time of death. A single significant cluster was identified in southeast Finland at the time of birth, closely matching one of the clusters identified at the time of death. These results are based on a large sample of cases, and they provide convincing evidence of spatial clustering of this condition. The results demonstrate also that, if the cluster analysis is conducted at different stages of the cases' life cycle, different conclusions about where potential risk factors may exist might result.",
"title": "Spatial clustering of amyotrophic lateral sclerosis in Finland at place of birth and place of death."
},
{
"docid": "MED-854",
"text": "INTRODUCTION: Ingestion of a small amount of concentrated hydrogen peroxide can cause cerebral air gas embolism (CAGE). Hyperbaric oxygen therapy (HBOT) is the standard of care in the treatment of CAGE. We report a case of CAGE after accidental ingestion of 33%hydrogen peroxide treated with HBOT resulting in reversal of both the clinical and radiologic abnormalities. CASE REPORT: A 48 year-old male took two sips of 33% hydrogen peroxide. A short time later, he developed hematemesis, left sided hemiplegia, confusion, and left homonymous hemianopsia. Initial laboratory studies, chest x-ray, and brain CT were normal. MRI demonstrated areas of restricted diffusion and T2 hyper intensities in multiple vascular territories consistent with ischemia due to CAGE. Eighteen hours after arrival, the patient underwent HBOT at 3 atmospheres absolute (ATA) for 30 minutes and 2.5 ATA for 60 minutes with clinical improvement. Follow-up MRI at six months demonstrated resolution of the hyper intensities. DISCUSSION: A search of MEDLINE from 1950 to present revealed only two cases of CAGE from ingestion of concentrated hydrogen peroxide treated with HBOT. Both cases, similar to ours, had complete resolution of symptoms. Of the seven reported cases of CAGE from hydrogen peroxide that did not undergo HBOT, only in one patient was there a report of symptom resolution. CONCLUSION: Ingestion of even a small amount of concentrated hydrogen peroxide can result in cerebral air gas embolism. Hyperbaric oxygen therapy may be of benefit in reversing the symptoms and preventing permanent neurological impairment.",
"title": "Cerebral air gas embolism from concentrated hydrogen peroxide ingestion."
}
] |
9272
|
Why does a company's stock price affect its ability to raise debt?
|
[
{
"docid": "509659",
"text": "As JB hints, it is likely due to superior or improving, fundamentals. If the fundamentals of a company improve then its ability to repay loans improves. If its ability to repay improves then more sources of cash become willing to lend to the company. Also if fundamentals are improving then more sources are willing to buy and/or hold the stock.",
"title": ""
}
] |
[
{
"docid": "537862",
"text": "ChelseaFC rocked number 2, so before I try to answer number 1, I'll just mention that academics generally ignored negative *real* interest rates, and have always admitted that negative *nominal* rates were perfectly possible. There's nothing in his explanation that I think is controversial at this point though. As for number 1, a drop in a company's share price affects the company's ability to raise cash in the present and future. In a closely related issue, that drop can affect the company's ability to compensate its employees through options and restricted stock grants. In the long run (and I suspect you already know this), and drop in the share price affects the shareholders' wealth, and can lead them to demand that changes be made to be firm's operations (usually, changes made to who's running the firm). If a firm doesn't need more financing, and it doesn't pay any employees with stock or derivatives on its stock, then changes to its stock price won't affect the firm's operations in the slightest. Naturally, this assuming that the change in stock prices isn't indicative of changes to the economy, but that's a causal relationship in the other direction (the stock price reflects changes in operations, not the other way around).",
"title": ""
},
{
"docid": "133919",
"text": "In case you didn't see over the past few years, especially in banks, falling stock prices often lead to ratings downgrades. The logic is that a bank who's stock price is low, or falling, is suffering from a decrease in their ability to tap the equity markets in times of need. With less ability to tap the equity markets in times of need, this means it is less likely the bank can raise funds to pay off debt, and thus, makes their debt more risky. It's unfair for me to imply a 100% causal relationship here, because that's not the case, but each of the markets interact with each other in some way. You will at least notice that, whether leading or trailing, companies that have a decreasing stock price also often have a decreasing credit rating. You'll also notice that stocks which slip under $5 often times get put on credit watch. The logic could go any which way around the circle, but a company that cuts its dividend may lose some investors who were in it for the dividend. This can cause stock price to fall. Credit agencies, depending on the situation, may approve of companies that cut their dividend (more cash to pay off debt), or, may indicate the dividend cut is not enough to make up for the company's falling profits. In the absence of full information, a cut in the dividend is often seen as a sign of weakness or a sign of tough times for the company in the future. Companies which have changes in dividend are looked at as less stable, more unpredictable, blah blah blah. Again, I'm not implying a 100% causal relationship here, but, each of these markets work with each other somehow, and a bank which cuts its dividend may be expecting lower profitability, slower growth, need the funds to cover lawsuit payouts or settlements with insert-regulatory-agency, or any number of other situations.",
"title": ""
},
{
"docid": "402967",
"text": "Many of the major indices retreated today because of this news. Why? How do the rising budget deficits and debt relate to the stock markets? The major reason for the market retreating is the uncertainty regarding the US Dollar. If the US credit rating drops that will have an inflationary effect on the currency (as it will push up the cost of US Treasuries and reduce confidence in the USD). If this continues the loss of USD confidence could bring an end to the USD as the world's reserve currency which could also create inflation (as world banks could reduce their USD reserves). This can make US assets appear overvalued. Why is there such a large emphasis on the S&P rating? S&P is a large trusted rating agency so the market will respond to their analysis much like how a bank would respond to any change in your rating by Transunion (Consumer Credit Bureau) Does this have any major implications for the US stock markets today, in the short term and in July? If you are a day-trader I'm sure it does. There will be minor fluctuations in the market as soon as news comes out (either of its extension or any expected delays in passing that extension). What happens when the debt ceiling is reached? Since the US is in a deficit spending situation it needs to borrow more to satisfy its existing obligations (in short it pays its debt with more debt). As a result, if the debt ceiling isn't raised then eventually the US will be unable to pay its existing obligations. We would be in a default situation which could have devastating affects on the value of the USD. How hard the hit will depend on how long the default situation lasts (the longer we go without an increased ceiling after the exhaustion point the more we default on). In reality, Congress will approve a raise, but they will drag it out to the last possible minute. They want to appear as if they are against it, but they understand the catastrophic effects of not doing so.",
"title": ""
},
{
"docid": "371720",
"text": "Most of stock trading occurs on what is called a secondary market. For example, Microsoft is traded on NASDAQ, which is a stock exchange. An analogy that can be made is that of selling a used car. When you sell a used car to a third person, the maker of your car is unaffected by this transaction and the same goes for stock trading. Still within the same analogy, when the car is first sold, money goes directly to the maker (actually more complicated than that but good enough for our purposes). In the case of stock trading, this is called an Initial Public Offering (IPO) / Seasoned Public Offering (SPO), for most purposes. What this means is that a drop of value on a secondary market does not directly affect earning potential. Let me add some nuance to this. Say this drop from 20$ to 10$ is permanent and this company needs to finance itself through equity (stock) in the future. It is likely that it would not be able to obtain as much financing in this matter and would either 1) have to rely more on debt and raise its cost of capital or 2) obtain less financing overall. This could potentially affect earnings through less cash available from financing. One last note: in any case, financing does not affect earnings except through cost of capital (i.e. interest paid) because it is neither revenue nor expense. Financing obtained from debt increases assets (cash) and liabilities (debt) and financing obtained from stock issuance increases assets (cash) and shareholder equity.",
"title": ""
},
{
"docid": "11311",
"text": "\"Why only long term investments? What do they care if I buy and sell shares in a company in the same year? Simple, your actually investing when you hold it for a long term. If you hold a stock for a week or a month there is very little that can happen to change the price, in a perfect market the value of a company should stay the same from yesterday to today so long as there is no news(a perfect market cannot exist). When you hold a stock for a long term you really are investing in the company and saying \"\"this company will grow\"\". Short term investing is mostly speculation and speculation causes securities to be incorrectly valued. So when a retail investor puts money into something like Facebook for example they can easily be burned by speculation whether its to the upside or downside. If the goal is to get me to invest my money, then why not give apply capital gains tax to my savings account at my local bank? Or a CD account? I believe your gains on these accounts are taxed... Not sure at what rate. If the goal is to help the overall health of business, how does it do that? During an IPO, the business certainly raises money, but after that I'm just buying and selling shares with other private shareholders. Why does the government give me an incentive to do this (and then hold onto it for at least a year)? There are many reasons why a company cares about its market price: A companies market cap is calculated by price * shares outstanding. A market cap is basically what the market is saying your company is worth. A company can offer more shares or sell shares they currently hold in order to raise even more capital. A company can offer shares instead of cash when buying out another company. It can pay for many things with shares. Many executives and top level employees are payed with stock options, so they defiantly want to see there price higher. these are some basic reasons but there are more and they can be more complex.\"",
"title": ""
},
{
"docid": "534870",
"text": "Why do companies exist? Well, the corporate charter describes why the company exists. Usually the purpose is to enrich the shareholders. The owners of a company want to make money, in other words. There are a number of ways that a shareholder can make money off a stock: As such, maintaining the stock price and dividend payouts are generally the number one concern for any company in the long term. Most of the company's business is going to be directed towards making the company more valuable for a future buyout, or more valuable in terms of what it can pay its shareholders directly. Note that the company doesn't always need to be worried about the specifics of the day-to-day moves of the stock. If it keeps the finances in line - solid profits, margins, earnings growth and the like - and can credibly tell people that it's generally a valuable business, it can usually shrug off any medium-term blips as market craziness. Some companies are more explicitly long-term about things than others (e.g. Berkshire Hathaway basically tells people that it doesn't care all that much about what happens in the short term). Of course, companies are abstractions, and they're run by people. To make the people running the company worry about the stock price, you give them stock. Or stock options, or something like that. A major executive at a big company is likely to have a significant amount of stock. If the company does well, he does well; if it does poorly, he does poorly. Despite a few limitations, this is really a powerful incentive. If a company is losing a lot of money, or if its profits are falling so it's just losing a lot of its value as a business, the owners (stockholders) tend to get upset, and may vote in new management, or launch some sort of shareholder lawsuit. And, as previously noted, to raise funds, a company can also issue new shares to the market as a secondary offering as well (and they can issue fewer shares if the price is high - meaning that whatever the company is worth afterward, the existing owners own proportionally more of it).",
"title": ""
},
{
"docid": "50253",
"text": "There have been many interesting and correct answers but to give a direct answer to your first question, dividend yield is simply dividend over current share price. So, if the share price drops, your dividend yield increases proportionately. Dividend yield is not something one should use as the only source of information of whether a stock is a good/bad buy. It does not show many important factors: the riskiness of the company business, its financial position, profitability, ability to generate cash. Furthermore, dividend yield is just a snapshot of an income gain at a given point in time. It does not mean that this very dividend policy is going to continue in the future (especially not so if the company finances this dividend payments using not its own cash reserves but outside capital by issuing debt securities, which is unsustainable).",
"title": ""
},
{
"docid": "280091",
"text": "\"You're missing the point here. The goal of ratings firms is **not** to accurately price debt. That's the market's job. The goal of ratings companies is to evaluate the ability of the company to service their debt instrument, much like how the goal of a public accounting firm is to assure that a company's financial statements follow GAAP. The article implicitly makes the assertion that Aaa rated securities have pretty low default rates; it's mainly only the area of CDO backed securities that there's a large disconnect between the rating and default risk. While this does raise questions about the worthiness of these ratings and the way they went about modeling and rationalizing them, it hardly suggests that they are \"\"wrong over 50% of the time.\"\" As a side note, why not make it against the law for mutual funds to have rules that allow them to only hold Aaa rated securities? These funds that demand high credit ratings are only contributing to the conflict of interest by essentially \"\"asking for it.\"\"\"",
"title": ""
},
{
"docid": "566205",
"text": "\"I'm not a financial expert, but saying that paying a $1 dividend will reduce the value of the stock by $1 sounds like awfully simple-minded reasoning to me. It appears to be based on the assumption that the price of a stock is equal to the value of the assets of a company divided by the total number of shares. But that simply isn't true. You don't even need to do any in-depth analysis to prove it. Just look at share prices over a few days. You should easily be able to find stocks whose price varied wildly. If, say, a company becomes the target of a federal investigation, the share price will plummet the day the announcement is made. Did the company's assets really disappear that day? No. What's happened is that the company's long term prospects are now in doubt. Or a company announces a promising new product. The share price shoots up. They may not have sold a single unit of the new product yet, they haven't made a dollar. But their future prospects now look improved. Many factors go into determining a stock price. Sure, total assets is a factor. But more important is anticipated future earning. I think a very simple case could be made that if a stock never paid any dividends, and if everyone knew it would never pay any dividends, that stock is worthless. The stock will never produce any profit to the owner. So why should you be willing to pay anything for it? One could say, The value could go up and you could sell at a profit. But on what basis would the value go up? Why would investors be willing to pay larger and larger amounts of money for an asset that produces zero income? Update I think I understand the source of the confusion now, so let me add to my answer. Suppose that a company's stock is selling for, say, $10. And to simplify the discussion let's suppose that there is absolutely nothing affecting the value of that stock except an expected dividend. The company plans to pay a dividend on a specific date of $1 per share. This dividend is announced well in advance. Everyone knows that it will be paid, and everyone is extremely confidant that in fact the company really will pay it -- they won't run out of money or any such. Then in a pure market, we would expect that as the date of that dividend approaches, the price of the stock would rise until the day before the dividend is paid, it is $11. Then the day after the dividend is paid the price would fall back to $10. Why? Because the person who owns the stock on the \"\"dividend day\"\" will get that $1. So if you bought the stock the day before the dividend, the next day you would immediately receive $1. If without the dividend the stock is worth $10, then the day before the dividend the stock is worth $11 because you know that the next day you will get a $1 \"\"refund\"\". If you buy the stock the day after the dividend is paid, you will not get the $1 -- it will go to the person who had the stock yesterday -- so the value of the stock falls back to the \"\"normal\"\" $10. So if you look at the value of a stock immediately after a dividend is paid, yes, it will be less than it was the day before by an amount equal to the dividend. (Plus or minus all the other things that affect the value of a stock, which in many cases would totally mask this effect.) But this does not mean that the dividend is worthless. Just the opposite. The reason the stock price fell was precisely because the dividend has value. BUT IT ONLY HAS VALUE TO THE PERSON WHO GETS IT. It does me no good that YOU get a $1 dividend. I want ME to get the money. So if I buy the stock after the dividend was paid, I missed my chance. So sure, in the very short term, a stock loses value after paying a dividend. But this does not mean that dividends in general reduce the value of a stock. Just the opposite. The price fell because it had gone up in anticipation of the dividend and is now returning to the \"\"normal\"\" level. Without the dividend, the price would never have gone up in the first place. Imagine you had a company with negligible assets. For example, an accounting firm that rents office space so it doesn't own a building, its only tangible assets are some office supplies and the like. So if the company liquidates, it would be worth pretty much zero. Everybody knows that if liquidated, the company would be worth zero. Further suppose that everyone somehow knows that this company will never, ever again pay a dividend. (Maybe federal regulators are shutting the company down because it's products were declared unacceptably hazardous, or the company was built around one genius who just died, etc.) What is the stock worth? Zero. It is an investment that you KNOW has a zero return. Why would anyone be willing to pay anything for it? It's no answer to say that you might buy the stock in the hope that the price of the stock will go up and you can sell at a profit even with no dividends. Why would anyone else pay anything for this stock? Well, unless their stock certificates are pretty and people like to collect them or something like that. Otherwise you're supposing that people would knowingly buy into a pyramid scheme. (Of course in real life there are usually uncertainties. If a company is dying, some people may believe, rightly or wrongly, that there is still hope of reviving it. Etc.) Don't confuse the value of the assets of a company with the value of its stock. They are related, of course -- all else being equal, a company with a billion dollars in assets will have a higher market capitalization than a company with ten dollars in assets. But you can't calculate the price of a company's stock by adding up the value of all its assets, subtracting liabilities, and dividing by the number of shares. That's just not how it works. Long term, the value of any stock is not the value of the assets but the net present value of the total future expected dividends. Subject to all sorts of complexities in real life.\"",
"title": ""
},
{
"docid": "576564",
"text": "It would be very unusual (and very erroneous) to have a company's stock be included in the Long Term Investments on the balance sheet. It would cause divergent feedback loops which would create unrepresentative financial documents and stock prices. That's how your question would be interpreted if true. This is not the case. Stock prices are never mentioned on the financial documents. The stock price you hear being reported is information provided by parties who are not reporting as part of the company. The financial documents are provided by the company. They will be audited internally and externally to make sure that they can be presented to the market. Stock prices are quoted and arbitrated by brokers at the stock exchange or equivalent service. They are negotiated and the latest sale tells you what it has sold for. What price this has been reported never works its way onto the financial document. So what use are stock prices are for those within the company? The stock price is very useful for guessing how much money they can raise by issuing stock or buying back stock. Raising money is important for expansion of the company or to procure money for when avenues of debt are not optimal; buying back stock is important if major shareholders want more control of the company.",
"title": ""
},
{
"docid": "241175",
"text": "Can a company not bargain with a dying company for example and buy a falling stock at lower than market value? Of course. If the shareholders agree to it. But why would they, if the market value is higher, agree to sell to someone who offers less? If there's a compelling reason - it can happen. It might happen during a hostile takeover, for example. In the case of buying the company for more than market value, are the stocks bought for significantly more, or slightly more than the current market value? Again, depends on how valuable the shareholders think the company is. If the shareholders think that the company has a potential which has not yet affected the stock price, they'll want a higher premium (and they'd think that, otherwise why would they hold the stock?). How much higher? Depends on the bargaining abilities of the sides.",
"title": ""
},
{
"docid": "442324",
"text": "What drives the stock of bankrupt companies? The company's potential residual assets. When a company goes bankrupt it is required to sell its assets to pay off its debts. The funds raised from selling assets go to the following entities: The usual order of debt repayment, in terms of the lender, will be the government, financial institutions, other creditors (i.e. suppliers and utility companies), bondholders, preferred shareholders and, finally, common shareholders. Depending on the amount of debt and the value of a company's assets, the common shareholders may receive some left over from liquidated assets. This would drive the stock price of a bankrupt company.",
"title": ""
},
{
"docid": "42625",
"text": "\"This question drives at what value a shareholder actually provides to a corporation, and by extent, to the economy. If you subscribe for new shares (like in an Initial Public Offering), it is very straightforward to say \"\"I have provided capital to the corporation, which it is using to advance its business.\"\" If you buy shares that already exist (like in a typical share purchase on a public exchange), your money doesn't go to the company. Instead, it goes to someone who paid someone who paid someone who paid someone (etc.) who originally contributed money to the corporation. In theory, the value of a share price does not directly impact the operation of the company itself, apart from what @DanielCarson aptly noted (employee stock options are affected by share price, impacting morale, etc.). This is because in theory, the true value of a company (and thus, the value of a share) is the present value of all future cashflows (dividends + final liquidation). This means that in a technical sense, a company's share price should result from the company's value. The company's true value does not result from the share price. But what you are doing as a shareholder is impacting the liquidity available to other potential investors (also as mentioned by @DanielCarson, in reference to the desirability for future financing). The more people who invest their money in the stock market, the more liquid those stocks become. This is the true value you add to the economy by investing in stocks - you add liquidity to the market, decreasing the risk of capital investment generally. The fewer people there are who are willing to invest in a particular company, the harder it is for an investor to buy or sell shares at will. If it is difficult to sell shares in a company, the risk of holding shares in that company is higher, because you can't \"\"cash out\"\" as easily. This increased risk then does change the value of the shares - because even though the corporation's internal value is the same, the projected cashflows of the shares themselves now has a question mark around the ability to sell when desired. Whether this actually has an impact on anything depends on how many people join you in your declaration of ethical investing. Like many other forms of social activism, success relies on joint effort. This goes beyond the direct and indirect impacts mentioned above; if 'ethical investing' becomes more pronounced, it may begin to stigmatize the target companies (fewer people wanting to work for 'blacklist' corporations, fewer people buying their products, etc.).\"",
"title": ""
},
{
"docid": "584901",
"text": "News about a company is not the only thing that affects its stock's price. There is also supply and demand. That, of course, is influenced by news, but it is not the only actor. An insider, with a large position in their company's stock, may want to diversify his overall portfolio and thus need to sell a large amount of stock. That may be significant enough to increase supply and likely reduce the stock's price somewhat. That brings me to another influence on stock price: perception. Executives, and other insiders with large positions in their company's stock, have to be careful about how and when they sell some of that stock as to not worry the markets. Many investors watch insider selling to gauge the health of the company. Which brings me to another important point. There are many things that may be considered news which is material to a certain company and its stock. It is not just quarterly filings, earnings reports and such. There is also news related to competitors, news about the economy or a certain sector, news about some weather event that affects a major supplier, news about a major earthquake that will impact the economy of a nation which can then have knock-on effects to other economies, etc... There are also a lot of investors with varying needs which will influence supply and demand. An institutional investor, needing to diversify, may reduce their position in a stock and thus increase supply enough that it impacts the stock's price. Meanwhile, individual investors will make their transactions at varying times during the day. In the aggregate, that may have significant impacts on supply and demand. The overall point being that there are a lot of inputs and a lot of actors in a complicated system. Even if you focus just on news, there are many things that fall into that category. News does not come out at regular intervals and it does not necessarily spread evenly. That alone could make for a highly variable environment.",
"title": ""
},
{
"docid": "306149",
"text": "Fully Paid up Partly Paid up: A company may issue stock to you which is only partly paid up, for example, a company may issue a stock of face value 10 to you and ask you to pay 5 now and other 5 will be adjusted later by some other mechanism. This stock shall be partly paid up. Usually, these stocks are issued in different circumstances, for example as part payment for debentures, preference shares or other capital structuring. On the other hand for a fully paid up share no more money needs to be paid by you or no other adjustments need to be made. So, above, the company is issuing you with stocks for which you will need to pay no further money, they are fully paid for. Authorized Capital: Authorized capital of a company is the amount of money a company can raise by selling stock (not debt, equity). This number is registered when the company is incorporated, subsequently, this number can be revised upward by applying to the registrar of companies. Now, this means that at max. the company is authorized to raise this much capital and no more. However, a company may raise less than this, which is called Issued Capital. In your case, the company is raising its authorized capital by applying to the registrar of companies, though in this case they are looking at their full authorized capital to be issued capital, it was not necessary to do so. Increase of Authorized capital: The main benefit is that the company can get more money in form of equity and utilize the same, perhaps, for expansion of business etc., that is the primary benefit. Bonus Share: Usually, companies keep some surplus as reserve, this money comes out of the profit the company makes and is essentially money of the shareholders. This reserve surplus is maintained for situations, when the money may be required for exigencies. However, this surplus grows over a few years and the company usually the company plans for an expansion of business. However, this money cannot be just taken, as it belongs to the shareholder, so shareholders are issued extra equity in proportion to their current holding and this surplus is capitalized i.e. used as part of the company's equity capital. Bonus declaration does not add t o the value of the company and the share prices fall in proportion (but not quite) to the bonus.",
"title": ""
},
{
"docid": "329527",
"text": "The problem with predicting with accuracy what a stock price will do in any given situation is that there are two main factors that affect a stocks price. The first factor is based somewhat in math as it takes into account numbers such as supply and demand, earnings per share, expected earnings, book value, debt ratio and a wide variety of other numbers. You can compile all those numbers into a variety of formulas and come up with a rational estimate of what the stock should sell for. This is all well and good and if the market were entirely rational it would rarely make news because it would be predictable and boring. This is where our second factor throws a wrench in the works. The second factor affecting stock price is emotional. There are many examples of people's emotions affecting stock price but if you would like a good example look up the price fluctuations of Apple (AAPL) after their last couple earnings reports. Numerically their company looks good, their earnings were healthy, their EPS is below average yet their price fell following the report. Why is that? There really isn't a rational reason for it, it is driven by the emotions behind unmet expectations. In a more general sense sometimes price goes down and people get scared and sell causing further decline, sometimes people get excited and see it as opportunity to buy in and the price stabilizes. It is much more difficult to anticipate the reaction the market will have to people's emotional whims which is why predicting stock price with accuracy is near impossible. As a thought along the same line ask yourself this question; if the stock market were entirely rational and price could be predicted with accuracy why is there such a wide range of available strike prices available in the options market? It seems that if stock price could be predicted with anything remotely reassembling accuracy the options market need a much smaller selection of available strike prices.",
"title": ""
},
{
"docid": "100546",
"text": "\"A company doesn't offer up 100% of its shares to the market. There's a float amount of varying significance, maybe 30% of the shares are put up for public offer. Generally some amount of current shareholders will pledge some or all of their shares for offer to the public. This may be how the venture capital, private equity or other current investors cash out their initial investment. The company may issue new shares in order to raise money for some initiative. It may be a combination of existing shares and new. Additionally, a company may hold some \"\"treasury shares\"\" on its balance sheet. In this instance fluctuations in the share price directly affect the health of the balance sheet. As far as incentive goes, stock options to management and C-Suite employees keep everyone interested in an increasing stock price.\"",
"title": ""
},
{
"docid": "306782",
"text": "\"As I understand it, a company raises money by sharing parts of it (\"\"ownership\"\") to people who buy stocks from it. It's not \"\"ownership\"\" in quotes, it's ownership in a non-ironic way. You own part of the company. If the company has 100 million shares outstanding you own 1/100,000,000th of it per share, it's small but you're an owner. In most cases you also get to vote on company issues as a shareholder. (though non-voting shares are becoming a thing). After the initial share offer, you're not buying your shares from the company, you're buying your shares from an owner of the company. The company doesn't control the price of the shares or the shares themselves. I get that some stocks pay dividends, and that as these change the price of the stock may change accordingly. The company pays a dividend, not the stock. The company is distributing earnings to it's owners your proportion of the earnings are equal to your proportion of ownership. If you own a single share in the company referenced above you would get $1 in the case of a $100,000,000 dividend (1/100,000,000th of the dividend for your 1/100,000,000th ownership stake). I don't get why the price otherwise goes up or down (why demand changes) with earnings, and speculation on earnings. Companies are generally valued based on what they will be worth in the future. What do the prospects look like for this industry? A company that only makes typewriters probably became less valuable as computers became more prolific. Was a new law just passed that would hurt our ability to operate? Did a new competitor enter the industry to force us to change prices in order to stay competitive? If we have to charge less for our product, it stands to reason our earnings in the future will be similarly reduced. So what if the company's making more money now than it did when I bought the share? Presumably the company would then be more valuable. None of that is filtered my way as a \"\"part owner\"\". Yes it is, as a dividend; or in the case of a company not paying a dividend you're rewarded by an appreciating value. Why should the value of the shares change? A multitude of reasons generally revolving around the company's ability to profit in the future.\"",
"title": ""
},
{
"docid": "499344",
"text": "\"The correlation I heard most about in economics/finance was that stock prices and bond yields were negatively correlated; as the stock market does better, bond yields fall (company's doing well as evidenced by stocks, so it's a good credit risk, so YTM of its bonds on the market goes down). The correlation, if any, between the stock and futures market should be visible in the actual price histories. Index prices may be useful, but what's more likely is that various future prices have correlation with various companies' stocks. Where the future reflects the price of a raw material that is a significant cost of goods sold for a company, you'll see these two move inversely to each other in the short term. I think that if there is a causative relationship here, its that futures prices influence stock prices, not the other way around. The futures market generally represents the cost side of a consumer goods producer's bottom line. The stock market represents its profits. As futures go up, profit expectations go down, putting pressure on stock prices. Industries that deal in services, or in other types of goods, can still be affected because a rise in the cost of something consumers need will cause them to spend less on other things which affects margins in those other areas. So, in the short and medium term, when the futures market goes up the stock market sees a dip, and vice versa. However, companies adapt; they can put upward pressure on prices for their goods to restore their desired margins, usually by slowly increasing them to prevent sticker shock (though elasticity of demand plays a part; the more we need something no matter what it costs, the faster prices can increase). To maintain costs, they can make things cheaper using less expensive materials (more plastic, less steel). They can restructure production processes (translated: move factories offshore, or at least to \"\"right-to-work\"\" states with less union strength) to save costs elsewhere. All of these reduce costs and thus increase profits, but take time to implement. Many of these things reduce direct costs, reducing demand for the commodity and causing the futures prices to go back down. So, over the long term, these differences even out, and it's down to the things that affect the entire market (inflation, consumer/investor confidence, monetary policy).\"",
"title": ""
},
{
"docid": "35919",
"text": "Just playing devil's advocate: A falling stock price impairs the firm's ability to raise equity capital efficiently. In these times, additional regulatory capital requirements continue to be levied on the banks, and they are faced with raising capital inefficiently, which may impair their ability to pay their debt, which may lead to a ratings downgrade.",
"title": ""
},
{
"docid": "575554",
"text": "Selling stock means selling a portion of ownership in your company. Any time you issue stock, you give up some control, unless you're issuing non-voting stock, and even non-voting stock owns a portion of the company. Thus, issuing (voting) shares means either the current shareholders reduce their proportion of owernship, or the company reissues stock it held back from a previous offering (in which case it no longer has that stock available to issue and thus has less ability to raise funds in the future). From Investopedia, for exmaple: Secondary offerings in which new shares are underwritten and sold dilute the ownership position of stockholders who own shares that were issued in the IPO. Of course, sometimes a secondary offering is more akin to Mark Zuckerberg selling some shares of Facebook to allow him to diversify his holdings - the original owner(s) sell a portion of their holdings off. That does not dilute the ownership stake of others, but does reduce their share of course. You also give up some rights to dividends etc., even if you issue non-voting stock; of course that is factored into the price presumably (either the actual dividend or the prospect of eventually getting a dividend). And hopefully more growth leads to more dividends, though that's only true if the company can actually make good use of the incoming funds. That last part is somewhat important. A company that has a good use for new funds should raise more funds, because it will turn those $100 to $150 or $200 for everyone, including the current owners. But a company that doesn't have a particular use for more money would be wasting those funds, and probably not earning back that full value for everyone. The impact on stock price of course is also a major factor and not one to discount; even a company issuing non-voting stock has a fiduciary responsibility to act in the interest of those non-voting shareholders, and so should not excessively dilute their value.",
"title": ""
},
{
"docid": "236146",
"text": "\"Inflation as defined in the general, has many impacts at a personal level. For example, you say that the reduction in the price of oil has no impact on you. That's absolutely not true, unless you're a hermit living off of the land. Every box or can or jar of food you buy off the shelf of the grocery store has the price of oil baked into it, because it had to get there somehow. High fuel costs for trucks mean increased costs to put food on shelves, which mean increased prices for that food. Even tobacco prices can affect you, because they affect what other people are spending. Demand is always a significant factor in prices, particularly retail prices, and if people are spending more money on tobacco, they're probably spending less on other things - either buying less snacks, for example, or buying cheaper brands of those snacks. So the price of Doritos may drop a bit (or not rise), for example. General inflation also tends to drive raises, particularly in industries with relatively small performance ties to raises. If inflation is 3%, wages need to raise 3% or so in order to keep up, on average; even if your personal cost-of-living went up 0%, or 5%, or 10%, the default wage inflation will be closer to that of the national average. Any raise less than national average is effectively a pay cut (which is one reason why inflation is needed in a healthy economy). So your company probably has a cost-of-living raise everyone gets that's a bit less than inflation, and then good performers get a bump up to a bit more than inflation. You can read more on this topic for a more in-depth explanation. Finally, inflation rates tend to be major factors in stock market movement. Inflation that is too high, or too low, can lead to higher volatility; inflation that is \"\"right\"\" can lead to higher stability. An economy that has consistently \"\"right\"\" inflation (around 2-3% typically) will tend to have more stable stock market in general, and thus more reliable returns from that market. There are many other factors that lead to stock markets rising and falling, but inflation is one very relevant one, particularly if it's not in the \"\"right\"\" zone.\"",
"title": ""
},
{
"docid": "552343",
"text": "This is a tough question SFun28. Let's try and debug the metric. First, let's expand upon the notion share price is determined in an efficient market where prospective buyers and sellers have access to info on an enterprises' cash balance and they may weigh that into their decision making. Therefore, a desirable/undesirable cash balance may raise or lower the share price, to what extent, we do not know. We must ask How significant is cash/debt balance in determining the market price of a stock? As you noted, we have limited info, which may decrease the weight of these account balances in our decision process. Using a materiality level of 5% of net income of operations, cash/debt may be immaterial or not considered by an investor. investors oftentimes interpret the same information differently (e.g. Microsoft's large cash balance may show they no longer have innovative ideas worth investing in, or they are well positioned to acquire innovative companies, or weather a contraction in the sector) My guess is a math mind would ignore the affect of account balances on the equity portion of the enterprise value calculation because it may not be a factor, or because the affect is subjective.",
"title": ""
},
{
"docid": "262925",
"text": "\"It is important to first understand that true causation of share price may not relate to historical correlation. Just like with scientific experiments, correlation does not imply causation. But we use stock price correlation to attempt to infer causation, where it is reasonable to do so. And to do that you need to understand that prices change for many reasons; some company specific, some industry specific, some market specific. Companies in the same industry may correlate when that industry goes up or down; companies with the same market may correlate when that market goes up or down. In general, in most industries, it is reasonable to assume that competitor companies have stocks which strongly correlate (positively) with each-other to the extent that they do the same thing. For a simple example, consider three resource companies: \"\"Oil Ltd.\"\" [100% of its assets relate to Oil]; \"\"Oil and Iron Inc.\"\" [50% of its value relates to Oil, 50% to Iron]; and \"\"Iron and Copper Ltd.\"\" [50% of its value relates to Iron, 50% to Copper]. For each of these companies, there are many things which affect value, but one could naively simplify things by saying \"\"value of a resource company is defined by the expected future volume of goods mined/drilled * the expected resource price, less all fixed and variable costs\"\". So, one major thing that impacts resource companies is simply the current & projected price of those resources. This means that if the price of Oil goes up or down, it will partially affect the value of the two Oil companies above - but how much it affects each company will depend on the volume of Oil it drills, and the timeline that it expects to get that Oil. For example, maybe Oil and Iron Ltd. has no currently producing Oil rigs, but it has just made massive investments which expect to drill Oil in 2 years - and the market expects Oil prices to return to a high value in 2 years. In that case, a drop in Oil would impact Oil Inc. severely, but perhaps it wouldn't impact Oil and Iron Ltd. as much. In this case, for the particular share price movement related to the price of Oil, the two companies would not be correlated. Iron and Copper Ltd. would be unaffected by the price of Oil [this is a simplification; Oil prices impact many areas of the economy], and therefore there would be no correlation at all between this company's shares. It is also likely that competitors face similar markets. If consumer spending goes down, then perhaps the stock of most consumer product companies would go down as well. There would be outliers, because specific companies may still succeed in a falling market, but in generally, there would be a lot of correlation between two companies with the same market. In the case that you list, Sony vs Samsung, there would be some factors that correlate positively, and some that correlate negatively. A clean example would be Blackberry stock vs Apple stock - because Apple's success had specifically negative ramifications for Blackberry. And yet, other tech company competitors also succeeded in the same time period, meaning they did not correlate negatively with Apple.\"",
"title": ""
},
{
"docid": "8643",
"text": "Large-scale price range of a stock isn't directly meaningful; that reflects how many shares exist, not just how desirable they are. A stock split, for example, doubles the number of shares everyone holds while cutting the value of each share in half; that's meaningless except that it makes the shares a bit easier to trade in. Change in price is more interesting. In the case of energy companies, that often reflects major changes in energy supply, distribution, use, or how well positioned people feel the company is for the next change in these. Fracking's surge and the questions raised against it, whether a major pipeline will or won't be built, international energy price trends, breakthroughs in renewables... if it might affect energy price, it might affect the company's strength, both absolute and relative to others. In other words, the same kinds of things that affect any stock.",
"title": ""
},
{
"docid": "168382",
"text": "\"In one personal finance book I read that if a company is located in a country with credit rating X it can't have credit rating better (lower - i.e. further from AAA level) than X. This is simply wrong. Real world evidence proves it wrong. Automatic Data Processing (ADP), Exxon Mobile (XOM), Johnson & Johnson (JNJ), and Microsoft (MSFT) all have a triple-A rating today, even though the United States doesn't. Toyota (TM) remained triple-A for many years even after Japanese debt was downgraded. The explanation was the following: country has rating X because risk of doing business with it is X and so risk of doing business with any company located in that country automatically can't be better than X. When reading financial literature, you should always be critical. Let's evaluate this statement. First off, a credit rating is not the \"\"risk of doing business.\"\" That is way too generic. Specifically, a credit rating attempts to define an individual or company's ability to repay it's obligations. Buying treasuries constitutes as doing business with the gov't, but you can argue that buying stamps at USPS is also doing business with the gov't, and a credit rating won't affect the latter too much. So a credit rating reflects the ability of an entity to repay it's obligations. What does the ability of a government to repay have to do with the ability of companies in that country to repay? Not much. Certainly, if a company keeps it's surplus cash all in treasuries, then downgrading the government will affect the company, but in general, the credit rating of a company determines the company's ability to pay.\"",
"title": ""
},
{
"docid": "332323",
"text": "Stock trading (as opposed to IPO) doesn't directly benefit the company. But it affects their ability to raise additional funds; if they're valued higher, they don't need to sell as many shares to raise a given amount of money. And the stockholders are part owners of the company; their votes in annual corporate meetings and the like can add up to a substantial influence on the company's policies, so the company has an interest in keeping them (reasonably) happy. Dividends (distributing part of the company's profits to the stockholders) are one way of doing so. You're still investing in the company. The fact that you're buying someone else's share just means you're doing so indirectly, and they're dis-investing at the same time.",
"title": ""
},
{
"docid": "91363",
"text": "As said previously, most of the time volume does not affect stock prices, except with penny stocks. These stocks typically have a small volume in the 3 or 4 figure range and because of this they typically experience very sharp rises and drops in stock prices, contrasting normal stocks that go up and down constantly every minute. Volume is not one thing you should be looking at when analyzing a stock in most cases, since it is simply the number of people of trades made in a day. That has no effect on the value of the company, whereas looking at P/E ratios, dividend growth, etc all can be analyzed to see if a company is growing and is doing well in its field. If I buy an iPhone, it doesn't matter if 100 other people or 100,000 other people have bought it as well, since they won't really affect my experience with the product. Whereas the type of iPhone I buy will.",
"title": ""
},
{
"docid": "421371",
"text": "\"It's been said before, but to repeat succinctly, a company's current share price is no more or less than what \"\"the market\"\" thinks that share is worth, as measured by the price at which the shares are being bought and sold. As such, a lot of things can affect that price, some of them material, others ethereal. A common reason to own stock is to share the profits of the company; by owning 1 share out of 1 million shares outstanding, you are entitled to 1/1000000 of that company's quarterly profits (if any). These are paid out as dividends. Two key measurements are based on these dividend payments; the first is \"\"earnings per share\"\", which is the company's stated quarterly profits, divided by outstanding shares, with the second being the \"\"price-earnings ratio\"\" which is the current price of the stock divided by its EPS. Your expected \"\"yield\"\" on this stock is more or less the inverse of this number; if a company has a P/E ratio of 20, then all things being equal, if you invest $100 in this stock you can expect a return of $5, or 5% (1/20). As such, changes in the expected earnings per share can cause the share price to rise or fall to maintain a P/E ratio that the pool of buyers are willing to tolerate. News that a company might miss its profit expectations, due to a decrease in consumer demand, an increase in raw materials costs, labor, financing, or any of a multitude of things that industry analysts watch, can cause the stock price to drop sharply as people look for better investments with higher yields. However, a large P/E ratio is not necessarily a bad thing, especially for a large stable company. That stability means the company is better able to weather economic problems, and thus it is a lower risk. Now, not all companies issue dividends. Apple is probably the most well-known example. The company simply retains all its earnings to reinvest in itself. This is typically the strategy of a smaller start-up; whether they're making good money or not, they typically want to keep what they make so they can keep growing, and the shareholders are usually fine with that. Why? Well, because there's more than one way to value a company, and more than one way to look at a stock. Owning one share of a stock can be seen quite literally as owning a share of that company. The share can then be valued as a fraction of the company's total assets. Sounds simple, but it isn't, because not every asset the company owns has a line in the financial statements. A company's brand name, for instance, has no tangible value, and yet it is probably the most valuable single thing Apple owns. Similarly, intellectual property doesn't have a \"\"book value\"\" on a company's balance sheet, but again, these are huge contributors to the success and profitability of a company like Apple; the company is viewed as a center of innovation, and if it were not doing any innovating, it would very quickly be seen as a middleman for some other company's ideas and products. A company can't sustain that position for long even if it's raking in the money in the meantime. Overall, the value of a company is generally a combination of these two things; by owning a portion of stock, you own a piece of the company's assets, and also claim a piece of their profits. A large company with a lot of material assets and very little debt can be highly valued based solely on the sum of its parts, even if profits are lagging. Conversely, a company more or less operating out of a storage unit can have a patent on the cure for cancer, and be shoveling money into their coffers with bulldozers.\"",
"title": ""
},
{
"docid": "298794",
"text": "It's more complicated than that. Governments raise money in a number of ways. First, they tax economic activity within their borders and for connected companies and individuals. Then, some governments have actual revenues from state-owned enterprises (licences, patents, courts, business revenues, and so on). Whatever shortage arises between state expenditure and this income is the deficit which is usually financed through debt. Government usually issues a bond (Wikipedia for a list of government bonds) of various types, some with extremely lengthy maturation dates. These bonds can be purchased both locally and by foreign investment funds. The nature of who buys is important. From the Wikipedia link you'll see that most government debt is very highly rated based on the ability of the state to simply raise taxes in order to fund redemption. Pension funds are legally bound to only invest in highly-rated investment classes and the bulk of bonds may be purchased to support local pensioners. A state that defaults on debt will first hit its own most vulnerable citizens. In addition, the fall-out will result in a savage cut in ratings. Countries like Argentina and Zimbabwe, which have both refused to repay their debts even to the IMF, are currently unable to raise investment at all. This has a tremendous impact on local economic development. So, default is out of the question without severe penalties. The second part of your question is about paying down the debt. As debts increase, more and more of the revenue that a country does earn is spent on servicing debt repayments. Sometimes bonds are issued merely to refinance old debt. A country that spends too much on refinancing debt is no different from an individual. Less and less money is available to do other things. In conclusion: governments can neither default nor binge-borrow unless they wish to severely limit economic opportunities for their citizens.",
"title": ""
}
] |
81656
|
LeBron James appeared on Saturday Night Live.
|
[
{
"docid": "LeBron_James",
"text": "LeBron Raymone James ( -LSB- ləˈbrɒn -RSB- born December 30 , 1984 ) is an American professional basketball player for the Cleveland Cavaliers of the National Basketball Association ( NBA ) . James has won three NBA championships , four NBA Most Valuable Player Awards , three NBA Finals MVP Awards , two Olympic gold medals , an NBA scoring title , and the NBA Rookie of the Year Award . He has also been selected to 13 NBA All-Star teams , 13 All-NBA teams , and six All-Defensive teams , and is the Cavaliers ' all-time leading scorer . James played high school basketball at St. Vincent -- St. Mary High School in his hometown of Akron , Ohio , where he was highly promoted in the national media as a future NBA superstar . After graduating , he was selected by his home team , the Cleveland Cavaliers , as the first overall pick of the 2003 NBA draft . James led Cleveland to the franchise 's first Finals appearance in 2007 , ultimately losing to the San Antonio Spurs . In 2010 , he left the Cavaliers for the Miami Heat in a highly publicized ESPN special titled The Decision . James spent four seasons with the Heat , reaching the Finals all four years and winning back-to-back championships in 2012 and 2013 . In 2013 , he led Miami on a 27-game winning streak , the third longest in league history . Following his final season with the Heat , James opted out of his contract and returned to the Cavaliers . Behind his leadership , Cleveland immediately advanced to two consecutive Finals against the Golden State Warriors , winning the championship in 2016 to end Cleveland 's fifty-two year professional sports title drought . Off the court , James has accumulated considerable wealth and fame from numerous endorsement contracts . His public life has been the subject of much scrutiny , and he has been ranked as one of America 's most influential and popular athletes . He has been featured in books , documentaries , and television commercials . He also hosted the ESPY Awards , Saturday Night Live , and appeared in the 2015 film Trainwreck .",
"title": ""
}
] |
[
{
"docid": "List_of_recurring_Saturday_Night_Live_characters_and_sketches",
"text": "__ NOTOC __ The following is a list of recurring Saturday Night Live sketches , organized by the season and date in which the sketch first appeared . For an alphabetical list , see Recurring Saturday Night Live characters and sketches ( listed alphabetically ) .",
"title": ""
},
{
"docid": "Recurring_Saturday_Night_Live_characters_and_sketches_(listed_alphabetically)",
"text": "__ NOTOC __ The following is a list of recurring Saturday Night Live sketches , organized alphabetically by title . The referenced date is the date when the sketch first appeared . For a chronological list , see Recurring Saturday Night Live characters and sketches .",
"title": ""
},
{
"docid": "Live_from_New_York",
"text": "Live from New York may refer to `` Live from New York , it 's Saturday Night ! '' , a line ending the cold opening of each episode of the American television show Saturday Night Live ( SNL ) . Other SNL-related references include : Gilda Radner : Live From New York , a 1979 one-woman show by Gilda Radner , later released as the film Gilda Live Live from New York : An Uncensored History of Saturday Night Live , a 2002 book by Tom Shales and James Andrew Miller Live from New York ! , a 2015 documentary film on the history of SNL",
"title": ""
},
{
"docid": "James_Signorelli",
"text": "James Signorelli is an American film director and cinematographer , best known for his work on the TV show Saturday Night Live . He has been the film segment producer for more than 400 episodes of Saturday Night Live since 1976 . He has produced many of the commercial parodies for which the show is noted .",
"title": ""
},
{
"docid": "Saturday_Night_(2010_film)",
"text": "Saturday Night is a 2010 documentary directed by James Franco . The film examines the production process of the NBC late-night live television sketch comedy series Saturday Night Live . Shot over a period of six days from December 1 -- 6 , 2008 , the film was originally a school assignment for Franco at New York University . The film premiered at the 2010 South by Southwest Film Festival on March 14 , 2010 , but was shelved for several years due to legal matters regarding its distributor and NBC . It was released on September 26 , 2014 on Hulu .",
"title": ""
},
{
"docid": "Saturday_Live_(UK_TV_series)",
"text": "Saturday Live was a British television comedy and music show broadcast by Channel 4 from 1985 to 1987 , and in 1988 as Friday Night Live . Influenced by the American show Saturday Night Live ( in particular its use of guest hosts ) , it was produced by Paul Jackson . The series made stars of Ben Elton , Harry Enfield , Stephen Fry and Hugh Laurie , and featured appearances ( in some cases first television appearances ) by Patrick Marber , Morwenna Banks , Chris Barrie , Emo Philips , Tracey Ullman , Craig Ferguson , Craig Charles and many others . The show featured comic duo Adrian Edmondson and Rik Mayall in their act The Dangerous Brothers . All episodes were transmitted live , although some material was pre-recorded . Recordings of shows were edited into compilation repeats , retitled Saturday Almost Live . The show was succeeded by Friday Night Live , a shorter and slightly more tightly-formatted show with Elton as the permanent host , which ran for a single series in 1988 . The show 's titles consisted of reforming clay animations , highly comparable to early MTV idents .",
"title": ""
},
{
"docid": "List_of_Saturday_Night_Live_commercial_parodies",
"text": "The following is a partial list of Saturday Night Live commercial parodies . On Saturday Night Live ( SNL ) , a parody advertisement is commonly shown after the host 's opening monologue . Many of the parodies were produced by James Signorelli . Fast food , beer , feminine hygiene products , toys , medications , financial institutions , and automobiles have been frequent targets . The commercial parodies have even targeted the SNL producers . A self-parody commercial featured `` The Best of the First 20 Minutes '' , a parody of Broadway Video 's series of SNL compilation videos . It offered a compilation of bits from the Cameron Diaz/Smashing Pumpkins September 1998 episode before that episode had even finished . In 1991 , Kevin Nealon and Victoria Jackson hosted a clip show featuring many commercials entitled Saturday Night Live Goes Commercial . In early 1999 , Will Ferrell hosted a follow-up special . In late 2005 and in March 2009 , the special was updated , featuring commercials created since the airing of the original special .",
"title": ""
},
{
"docid": "Night_Fever",
"text": "`` Night Fever '' is a song written and performed by the Bee Gees . It first appeared on the soundtrack to Saturday Night Fever . Producer Robert Stigwood wanted to call the film Saturday Night , but singer Robin Gibb expressed hesitation at the title . Stigwood liked the title Night Fever but was wary of marketing a movie with that name . The B-side was a live version of `` Down the Road '' in 1977 , previously released on Here at Last ... Bee Gees ... Live .",
"title": ""
},
{
"docid": "Margarita_Pracatan",
"text": "Margarita Pracatan is a Cuban novelty singer , who found success in the 1990s when Clive James had her perform live on his TV show on numerous occasions . Radio DJ Martin Kelner also played her frequently on his BBC Night Network and BBC Radio 2 programmes . Pracatan 's father was a union leader in Cuba . She began singing at home when she was three years old . She worked in a store selling men 's underwear while singing at night . She is divorced with one daughter . James showed clips of her highly individual , heavily Hispanic-inflected performances of pop hits ( notably Lionel Richie 's Hello and New York , New York ) to great popular success on his BBC series Saturday Night Clive . According to her website , Clive James discovered her Manhattan public-access television cable TV program in 1994 and invited her to the UK to appear on his show . He sweet-talked her into believing he was serious , and she signed up . Not once on the show did he make it overt that he knew what he was doing , but his introductions to her end-of-show performances contained a tiny amount of teasing irony . James said of Pracatan , `` She never lets the words or melody get in her way . She is us , without the fear of failure . '' Pracatan can be seen on the Manhattan Neighborhood Network public-access television channel 56 on Saturday nights at 9:30 pm . She has also toured in the United Kingdom . She has also toured Australia , appearing as part of the Sydney Gay and Lesbian Mardi Gras festival , during the mid 1990s .",
"title": ""
},
{
"docid": "Saturday_Night_at_the_Garden",
"text": "Saturday Night at the Garden was an American sports series broadcast by the DuMont Television Network from October 7 , 1950 , to March 31 , 1951 . The program aired sports , primarily boxing , live from Madison Square Garden in New York City . The program aired Saturday nights at 9pm ET and was 120 to 150 minutes long . All or part of this series may have been hosted by Dennis James .",
"title": ""
},
{
"docid": "Wayne's_World",
"text": "`` Wayne 's World '' was originally a recurring sketch from the NBC television series Saturday Night Live . It evolved from a segment titled `` Wayne 's Power Minute '' ( 1987 ) on the CBC Television series It 's Only Rock & Roll , as the main character first appeared in that show . The Saturday Night Live sketch spawned two films , and several catchphrases which have since entered the pop-culture lexicon . The sketch centered on a local public-access television program in Aurora , Illinois , hosted by Wayne Campbell ( Mike Myers , the same actor from `` Wayne 's Power Minute '' ) , an enthusiastic and sardonic long-haired metalhead , and his timid and sometimes high-strung , yet equally metal-loving sidekick and best friend , Garth Algar ( Dana Carvey ) . Wayne lives with his parents and broadcasts his show `` live '' from the basement of their house every Friday evening at 10:30 . The first `` Wayne 's World '' sketch appeared in the 13th Saturday Night Live episode of 1988/1989 .",
"title": ""
},
{
"docid": "The_LeBrons",
"text": "The LeBrons are a mock family of LeBron James featured in commercials for Nike 's line of LeBron James shoes . The four members of the family each represent an aspect of LeBron 's personality competing for control over him . The commercials consist of two `` seasons '' , each being like a miniature episode of a TV show . `` The LeBrons '' is an animated series from NBA player LeBron James . Based on the series of Nike commercials of the same name , `` The LeBrons '' launched on YouTube in April 2011 . The original animated series , produced by Believe Entertainment Group and Spring Hill Productions , with various logo cameos of HP , Intel , Sprite , and Beats by Dr. Dre features a first season of 10 original episodes that are released once a week over the course of 10 weeks . The LeBrons is currently in the process of being pitched to Cartoon Network , in order to become a full-length series .",
"title": ""
},
{
"docid": "Saturday_Night_Live_with_Howard_Cosell",
"text": "Saturday Night Live with Howard Cosell was an American television comedy-variety program that ran on ABC from September 1975 to January 1976 , hosted by Howard Cosell and executive-produced by Roone Arledge . The series ran for 18 episodes before being cancelled . The show was later remembered by its director Don Mischer as `` one of the greatest disasters in the history of television '' , largely because Cosell and Arledge -- both veterans of sports broadcasting -- were entirely unfamiliar with comedy and variety programming . Despite having highly notable celebrities both as cast members and guests , Saturday Night Live with Howard Cosell has never been made available on home video . Saturday Night Live with Howard Cosell is consistently confused with the sketch comedy program Saturday Night Live . In October 1975 , rival network NBC began airing the late night comedy show NBC 's Saturday Night , the creation of producer Lorne Michaels . The shows did not compete for the same time slot . Cosell 's Saturday Night Live aired at 8 p.m. ET/PT , whereas NBC 's Saturday Night aired at 11:30 p.m. . After Cosell 's show was cancelled , the NBC show was renamed Saturday Night Live .",
"title": ""
},
{
"docid": "Ann_Risley",
"text": "Anna `` Ann '' Risley ( born September 30 , 1949 ) is an American actress and comedian . She was a cast member of the TV series Saturday Night Live for the 12 episodes of the 1980 -- 1981 season . These 12 broadcasts were the first episodes after producer Lorne Michaels left the show . She is a member of SAG , AFTRA , Equity , and an independent actor 's equity . Risley was born in Madison , Wisconsin . Woody Allen spotted her in a theatre production of his material and encouraged her to pursue an acting career in New York . Risley was cast in small parts in Allen 's films Annie Hall , Manhattan and Stardust Memories . Before joining the cast of Saturday Night Live , she had a cameo on the show in 1976 as a psychiatrist 's patient . She was cast for Saturday Night Live by Jean Doumanian , who had previously been the show 's guest-booker , then associate producer . After 12 episodes , Doumanian was let go and replaced by Dick Ebersol , who fired Gilbert Gottfried , Charles Rocket , and Risley from the cast before his first episode . In a 1999 article in People , Risley was quoted as saying her SNL experience was `` horrible '' . Prior to ( and after ) Saturday Night Live , Risley had roles in nine feature films , including Honky Tonk Freeway and Come Back to the Five and Dime , Jimmy Dean , Jimmy Dean . She appeared in starring roles in two television pilots ( Off Campus and Night After Night ) , was a five-week guest star on the daytime soap The Doctors , and appeared in five made-for-TV movies , including The Young Riders and Telling Secrets . No longer a screen actor , Ann ( who now goes by the name of Anna ) continues to run her own acting/improv studio in Tucson , Arizona .",
"title": ""
},
{
"docid": "The_Boston_Teens",
"text": "The Boston Teens are fictional characters featured on the American television show Saturday Night Live . `` The Boston Teens '' debuted in 1999 and have appeared in 13 sketches to date . TV Guide named The Boston Teens among Saturday Night Lives 40 greatest characters in a list compiled in honor of the show 's 40th anniversary in 2015 .",
"title": ""
},
{
"docid": "One_More_Saturday_Night_(song)",
"text": "`` One More Saturday Night '' is a song written by Bob Weir and performed by the Grateful Dead , of which he was a member . The song had been performed in concert by the Grateful Dead starting in 1971 , but it first appeared on record on Weir 's debut solo album Ace in 1972 . It subsequently appeared on several Grateful Dead live albums .",
"title": ""
},
{
"docid": "Live_at_the_Famous_Spiegeltent",
"text": "Live at the Famous Spiegeltent is the debut album from Melbourne singer and songwriter , Harry James Angus , and was released at concerts around Australia throughout 2008 and 2009 . It was recorded on 24 and 25 October , at The Famous Spiegeltent in Melbourne . It was recorded and mixed by Sam Lowe and Andy Hunt of Salt Studios . Track 8 , `` Yakini ( The Last Gorilla ) '' , also appears on The Conglomerate 's second album , Hold Your Breath - Harry is also a member of this band . On both the 24th and 25th , recordings of the entire show were released 15 minutes after the show had finished . This album is a combination of both recordings ( mainly the 25th/Saturday night recording as the Friday night show was plagued with technical difficulties ) .",
"title": ""
},
{
"docid": "The_Land_of_Gorch",
"text": "The Land of Gorch was a recurring skit that appeared in season one of the American comedy television program Saturday Night Live , featuring Jim Henson 's Muppets . Prior to his work for children on Sesame Street , Henson had created puppetry work , including his show Sam and Friends , for adult audiences . His characters appeared regularly on the late-night comedy television programs , and The Ed Sullivan Show . After Sesame Street , Henson feared he would become typecast into working on children 's television series . His talent agent Bernie Brillstein , who represented Gilda Radner , Dan Aykroyd , and John Belushi , helped him transition to Saturday Night Live . The premise of The Land of Gorch featured Muppet characters , who were members of a royal family , in a faraway locale . They behaved boorishly and made frequent references to drug abuse , sexual innuendo , and consumption of alcohol . Characters included King Ploobis , Queen Peutra , their son , and servants Scred and Vazh . These characters often consulted their oracle Mighty Favog for advice . The writers of Saturday Night Live clashed with Henson 's vision for the program . Michael O'Donoghue , Alan Zweibel , and Al Franken often tried to avoid writing the weekly sketches . Henson felt they were trying to write for situational comedy rather than staying within his intended story . Frank Oz eventually agreed the partnership between Henson 's team and the show 's writers was imperfect , and was thankful they moved on to The Muppet Show . The Land of Gorch had a significant impact on later Muppet works , including both the 1982 feature film The Dark Crystal and the 1991 television show Dinosaurs . Commentators agreed the reception for The Land of Gorch was universally negative ; The A.V. Club said it was an in-joke that nobody wanted to keep the sketches on Saturday Night Live . San Francisco Chronicle called the characters the opposite of Kermit the Frog and compared them to trolls . DVD Talk called the feature the worst mistake in the first season of Saturday Night Live . Academic Michael J. Bernsten wrote in his essay `` The Muppetry of Nightmares '' that the idea failed because the characters were irredeemable and unfunny .",
"title": ""
},
{
"docid": "Land_Shark_(Saturday_Night_Live)",
"text": "The Land Shark ( also land shark , landshark , LandShark ) was a recurring character from the sketch comedy television series Saturday Night Live . The character first appeared in the fall of 1975 as a response to the release of the film Jaws , and the subsequent hysteria over purported shark sightings . It was one of the most popular and imitated sketches of SNL 's first season .",
"title": ""
},
{
"docid": "Pat_(Saturday_Night_Live)",
"text": "Pat is an androgynous fictional character created and performed by Julia Sweeney for the American sketch comedy show Saturday Night Live , and later featured in the film It 's Pat . The central humorous aspect of sketches featuring Pat is the inability of others to determine the character 's gender . Pat was revealed to be a woman by Norm MacDonald during an appearance on CONAN on 17 November 2016 .",
"title": ""
},
{
"docid": "List_of_Saturday_Night_Live_guests_(E–H)",
"text": "The following is a list of people who have been guests on Saturday Night Live . This section consists of people who fall between the letter E through H. The list below shows the people who have appeared on the show . Split into three sections : Host , if they hosted the show at any given time , Musical Guest , if a person was the musical guest on the show at any given time and a Cameo , which is for a person who has appeared on the show but did not act as host or musical guest at any given time . With help provided by",
"title": ""
},
{
"docid": "List_of_Saturday_Night_Live_guests_(I–L)",
"text": "The following is a list of people who have been guests on Saturday Night Live . This section consists of people who fall between the letters I and L. The list below shows the people who have appeared on the show . It is split into three sections : Host , if they hosted the show at any given time , Musical Guest , if a person was the musical guest on the show at any given time , and a Cameo , which is for a person who has appeared on the show but did not act as host or musical guest at any given time . Help is provided by .",
"title": ""
},
{
"docid": "List_of_Saturday_Night_Live_guests_(M–P)",
"text": "The following is a list of people who have been guests on Saturday Night Live . This section consists of people who fall between the letters M and P. The list below shows the people who have appeared on the show . It is split into three sections : Host , if they hosted the show at any given time , Musical Guest , if a person was the musical guest on the show at any given time , and a Cameo , which is for a person who has appeared on the show but did not act as host or musical guest at any given time . Help is provided by .",
"title": ""
},
{
"docid": "List_of_Saturday_Night_Live_guests_(Q–T)",
"text": "The following is a list of people who have been guests on Saturday Night Live . This section consists of people who fall between the letters Q and T. The list below shows the people who have appeared on the show . It is split into three sections : Host , if they hosted the show at any given time , Musical Guest , if a person was the musical guest on the show at any given time , and a Cameo , which is for a person who has appeared on the show but did not act as host or musical guest at any given time . Help is provided by .",
"title": ""
},
{
"docid": "List_of_Saturday_Night_Live_guests_(U–Z)",
"text": "The following is a list of people who have been guests on Saturday Night Live . This section consists of people who fall between the letters U and Z. The list below shows the people who have appeared on the show . It is split into three sections : Host , if they hosted the show at any given time , Musical Guest , if a person was the musical guest on the show at any given time , and a Cameo , which is for a person who has appeared on the show but did not act as host or musical guest at any given time . Help is provided by .",
"title": ""
},
{
"docid": "Celebrity_Jeopardy!_(Saturday_Night_Live)",
"text": "Celebrity Jeopardy! is a series of sketches that aired regularly on the television comedy/variety show Saturday Night Live between 1996 and 2002 , the years when Will Ferrell was a cast member . It parodies the same-named special event on the television quiz show Jeopardy! that features competition between notable individuals with all winnings going towards charitable organizations , and significant reductions to the game 's level of difficulty . Fifteen sketches aired between December 1996 and February 2015 : two sketches per season from 1996 to 2002 , when Ferrell was a regular on the show ; and one each in 2005 and 2009 , when Ferrell returned to the show as host . The sketch was revived for the Saturday Night Live 40th Anniversary Special on February 15 , 2015 . Ferrell portrays Jeopardy! host Alex Trebek . Darrell Hammond also appeared in each sketch , usually portraying Sean Connery , in an impersonation that `` often questions Trebek 's sexuality and sometimes implies that he has known Trebek 's mother in a carnal sense . '' Norm Macdonald appeared as Burt Reynolds in six sketches . Jimmy Fallon also appeared six times , each time portraying a different character . On several occasions , Celebrity Jeopardy! sketches have been referenced during actual episodes of Jeopardy! .",
"title": ""
},
{
"docid": "Maya_Rudolph",
"text": "Maya Khabira Rudolph ( born July 27 , 1972 ) is an American actress , comedian , and singer . After becoming a member of The Groundlings improv troupe in the late 1990s , Rudolph joined the NBC television series Saturday Night Live , on which she was a cast member from 2000 to 2007 . She then ventured into film , appearing in 50 First Dates ( 2004 ) and A Prairie Home Companion ( 2006 ) . Since leaving Saturday Night Live , Rudolph has appeared in Grown Ups ( 2010 ) , Bridesmaids ( 2011 ) , Grown Ups 2 ( 2013 ) and Sisters ( 2015 ) . She has also lent her voice to the animated films Shrek the Third ( 2007 ) and Big Hero 6 ( 2014 ) . In addition to her film appearances , Rudolph also starred as Ava Alexander on the NBC sitcom Up All Night from 2011 to 2012 , and co-hosted her own variety show Maya & Marty .",
"title": ""
},
{
"docid": "James_Flaherty",
"text": "James Flaherty is an American actor and stand-up comedian . Flaherty attended Rensselaer Polytechnic Institute in New York State and later worked as a high school teacher in Longmeadow , Massachusetts . He worked for a short time as a full-time actor , and now acts while maintaining a full-time teaching career in Western Massachusetts . He is known for his impressions of former president Bill Clinton , as well as Regis Philbin , Donald Trump and Ted Turner . He has appeared in episodes of Saturday Night Live , The Sopranos , Law & Order and Chappelle 's Show .",
"title": ""
},
{
"docid": "List_of_Saturday_Night_Live_guests_(A–D)",
"text": "The following is a list of people who have been guests on Saturday Night Live . This section consists of people whose surnames start with the letters A to D. The list is split into three sections : Host , if they hosted the show at any given time , Musical Guest , if a person was the musical guest on the show at any given time and a Cameo , which refers to someone who has appeared on the show but not in the capacity as host or musical guest .",
"title": ""
},
{
"docid": "Saturday_Night_Live_Korea",
"text": "Saturday Night Live Korea ( ; abbreviated as SNL Korea or SNLK is a South Korean late-night live television sketch comedy and variety television program broadcast on general service cable channel tvN . It is adapted from the long-running American TV show Saturday Night Live on NBC . The weekly program premiered on December 3 , 2011 , and aired on Saturdays at 23:00 .",
"title": ""
}
] |
900
|
Oxidative phosphorylation is one of the primary glycometabolic pathways in cells.
|
[
{
"docid": "18678095",
"text": "Fast axonal transport (FAT) requires consistent energy over long distances to fuel the molecular motors that transport vesicles. We demonstrate that glycolysis provides ATP for the FAT of vesicles. Although inhibiting ATP production from mitochondria did not affect vesicles motility, pharmacological or genetic inhibition of the glycolytic enzyme GAPDH reduced transport in cultured neurons and in Drosophila larvae. GAPDH localizes on vesicles via a huntingtin-dependent mechanism and is transported on fast-moving vesicles within axons. Purified motile vesicles showed GAPDH enzymatic activity and produced ATP. Finally, we show that vesicular GAPDH is necessary and sufficient to provide on-board energy for fast vesicular transport. Although detaching GAPDH from vesicles reduced transport, targeting GAPDH to vesicles was sufficient to promote FAT in GAPDH deficient neurons. This specifically localized glycolytic machinery may supply constant energy, independent of mitochondria, for the processive movement of vesicles over long distances in axons.",
"title": "Vesicular Glycolysis Provides On-Board Energy for Fast Axonal Transport"
}
] |
[
{
"docid": "14496749",
"text": "Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. Here, we demonstrate that the protein kinase MST1 mediates oxidative-stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors. MST1 phosphorylates FOXO proteins at a conserved site within the forkhead domain that disrupts their interaction with 14-3-3 proteins, promotes FOXO nuclear translocation, and thereby induces cell death in neurons. We also extend the MST-FOXO signaling link to nematodes. Knockdown of the C. elegans MST1 ortholog CST-1 shortens life span and accelerates tissue aging, while overexpression of cst-1 promotes life span and delays aging. The cst-1-induced life-span extension occurs in a daf-16-dependent manner. The identification of the FOXO transcription factors as major and evolutionarily conserved targets of MST1 suggests that MST kinases play important roles in diverse biological processes including cellular responses to oxidative stress and longevity.",
"title": "A Conserved MST-FOXO Signaling Pathway Mediates Oxidative-Stress Responses and Extends Life Span"
},
{
"docid": "19957813",
"text": "Oxidative phosphorylation (OXPHOS) is the major pathway for ATP production in humans. Deficiencies in OXPHOS can arise from mutations in either mitochondrial or nuclear genomes and comprise the largest collection of inborn errors of metabolism. At present we lack a complete catalog of human genes and pathways essential for OXPHOS. Here we introduce a genome-wide CRISPR \"death screen\" that actively selects dying cells to reveal human genes required for OXPHOS, inspired by the classic observation that human cells deficient in OXPHOS survive in glucose but die in galactose. We report 191 high-confidence hits essential for OXPHOS, including 72 underlying known OXPHOS diseases. Our screen reveals a functional module consisting of NGRN, WBSCR16, RPUSD3, RPUSD4, TRUB2, and FASTKD2 that regulates the mitochondrial 16S rRNA and intra-mitochondrial translation. Our work yields a rich catalog of genes required for OXPHOS and, more generally, demonstrates the power of death screening for functional genomic analysis.",
"title": "A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation."
},
{
"docid": "7005276",
"text": "The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid) and BML-275 (an AMPKα inhibitor). Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.",
"title": "Acetic Acid Activates the AMP-Activated Protein Kinase Signaling Pathway to Regulate Lipid Metabolism in Bovine Hepatocytes"
},
{
"docid": "15381976",
"text": "Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA-) sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs) were challenged by tumor necrosis factor alpha (TNF-α). The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL-) 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2',7'-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were abolished by morin, implying that ROS/MAPK signaling contributes to the relief of airway inflammation. Our findings indicate for the first time that morin alleviates airway inflammation in chronic asthma, which probably occurs via the oxidative stress-responsive MAPK pathway, highlighting a novel profile of morin as a potent agent for asthma management.",
"title": "Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling."
},
{
"docid": "26658659",
"text": "Hydrogen sulfide (H(2)S) was recently discovered to be synthesized in mammalian tissues by several different enzymes. Numerous studies have shown that H(2)S has vasodilator and antihypertensive effects in the cardiovascular system. However, intracellular mechanisms of the H(2)S-induced vasodilation and its interactions with other endothelium-derived relaxing factors, such as nitric oxide (NO), remain unclear. We investigated whether H(2)S directly regulates endothelial NO synthase (eNOS) activity and NO production in endothelial cells. NaHS, a H(2)S donor, dose-dependently increased NO production in cultured endothelial cells. This effect was abolished by a calcium chelator (BAPTA-AM), but not by the absence of extracellular calcium. The NaHS-induced NO production was partially blocked by inhibitors of ryanodine receptor (dantrolene) or inositol 1,4,5-triphosphate receptor (xestospongin C). NaHS significantly increased intracellular calcium concentrations, and this effect was attenuated by dantrolene or xestospongin C. NaHS induced phosphorylation of eNOS at the activating phosphoserine residue 1179. The NaHS-induced eNOS phosphorylation and NO production were not affected by a PI3K/Akt inhibitor (wortmannin). The data of this study suggest that H(2)S directly acts on endothelial cells to induce eNOS activation and NO production by releasing calcium from the intracellular store in endoplasmic reticulum, which may explain one of mechanisms of its vasodilator function.",
"title": "Hydrogen sulfide increases nitric oxide production with calcium-dependent activation of endothelial nitric oxide synthase in endothelial cells."
},
{
"docid": "4306711",
"text": "Human mitochondrial ribosomes are specialized in the synthesis of 13 proteins, which are fundamental components of the oxidative phosphorylation system. The pathway of mitoribosome biogenesis, the compartmentalization of the process, and factors involved remain largely unknown. Here, we have identified the DEAD-box protein DDX28 as an RNA granule component essential for the biogenesis of the mitoribosome large subunit (mt-LSU). DDX28 interacts with the 16S rRNA and the mt-LSU. RNAi-mediated DDX28 silencing in HEK293T cells does not affect mitochondrial mRNA stability or 16S rRNA processing or modification. However, it leads to reduced levels of 16S rRNA and mt-LSU proteins, impaired mt-LSU assembly, deeply attenuated mitochondrial protein synthesis, and consequent failure to assemble oxidative phosphorylation complexes. Our findings identify DDX28 as essential during the early stages of mitoribosome mt-LSU biogenesis, a process that takes place mainly near the mitochondrial nucleoids, in the compartment defined by the RNA granules.",
"title": "The Human Mitochondrial DEAD-Box Protein DDX28 Resides in RNA Granules and Functions in Mitoribosome Assembly."
},
{
"docid": "3973445",
"text": "Adenosine 5′-monophosphate–activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser515 and Ser518) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser515 and Ser518 and was abolished in cells lacking AMPK catalytic subunits. Mutation of Ser515 and Ser518 abolished AMPK-mediated inhibition of JAK-STAT signaling stimulated by either the sIL-6Rα/IL-6 complex or the expression of a constitutively active V658F-mutant JAK1 in human fibrosarcoma cells. Clinically used AMPK activators metformin and salicylate enhanced the inhibitory phosphorylation of endogenous JAK1 and inhibited STAT3 phosphorylation in primary vascular endothelial cells. Therefore, our findings reveal a mechanism by which JAK1 function and inflammatory signaling may be suppressed in response to metabolic stress and provide a mechanistic rationale for the investigation of AMPK activators in a range of diseases associated with enhanced activation of the JAK-STAT pathway.",
"title": "Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling"
},
{
"docid": "27093166",
"text": "BACKGROUND Ketamine, as an anesthetic agent, has an anti-inflammatory effect. In the present study, we investigated whether ketamine inhibits release of high mobility group box 1 (HMGB1), a late-phase cytokine of sepsis, in lipopolysaccharide (LPS)-stimulated macrophages through heme oxygenase-1 (HO-1) induction. METHODS Macrophages were preincubated with various concentrations of ketamine and then treated with LPS (1 μg/mL). The cell culture supernatants were collected to measure inflammatory mediators (HMGB1, nitric oxide, tumor necrosis factor-α, and interleukin 1β) by enzyme-linked immunosorbent assay. Moreover, HO-1 protein expression, the phosphorylation and degradation of IκB-α, and the nuclear translocation of nuclear factor E2-related factor 2 and nuclear factor κB (NF-κB) p65 were tested by Western blot analysis. In addition, to further identify the role of HO-1 in this process, tin protoporphyrin (SnPP), an HO-1 inhibitor, was used. RESULTS Ketamine treatment dose-dependently attenuated the increased levels of proinflammatory mediators (HMGB1, nitric oxide, tumor necrosis factor α, and interleukin 1β) and increased the HO-1 protein expression in LPS-activated macrophages. Furthermore, ketamine suppressed the phosphorylation and degradation of IκB-α as well as the LPS-stimulated nuclear translocation of NF-κB p65 in macrophages. In addition, the present study also demonstrated that ketamine induced HO-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 in macrophages. The effects of ketamine on LPS-induced proinflammatory cytokines production were partially reversed by the HO inhibitor tin protoporphyrin (SnPP). CONCLUSION Ketamine inhibits the release of HMGB1 in LPS-stimulated macrophages, and this effect is at least partly mediated by the activation of the Nrf2/HO-1 pathway and NF-κB suppression.",
"title": "Ketamine reduces LPS-induced HMGB1 via activation of the Nrf2/HO-1 pathway and NF-κB suppression."
},
{
"docid": "6923795",
"text": "Cytochrome P450 (P450)-dependent metabolites of arachidonic acid, the epoxyeicosatrienoic acids (EETs), are proposed to be endothelium-derived hyperpolarizing factors (EDHF) that affect vascular tone; however, the effects of EDHF on endothelial-derived nitric oxide biosynthesis remain unknown. We examined the regulation of endothelial nitric-oxide synthase (eNOS) by EDHF and investigated the relevant signaling pathways involved. The P450 epoxygenases CYP102 F87V mutant, CYP2C11-CYPOR, and CYP2J2 were transfected into cultured bovine aortic endothelial cells, and the effects of endogenously formed or exogenously applied EETs on eNOS expression and activity were assessed. Transfection with the P450 epoxygenases led to increased eNOS protein expression, an effect that was attenuated by cotreatment with the P450 inhibitor 17-ODYA. Northern analysis demonstrated that P450 transfection led to increased eNOS mRNA levels consistent with an effect at the pretranslational level. P450 epoxygenase transfection resulted in increased eNOS activity as measured by the conversion of L-arginine to L-citrulline. Addition of synthetic EETs (50-200 nM) to the culture media also increased eNOS expression and activity. Treatment with mitogen-activated protein kinase (MAPK), MAPK kinase, and protein kinase C inhibitors apigenin, 2'-amino-3'-methoxyflavone (PD98059), and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), respectively, significantly inhibited the effects of P450 transfection on eNOS expression. Overexpression of P450 epoxygenases or addition of synthetic EETs increased Thr495 phosphorylation of eNOS, an effect that was inhibited by both apigenin and PD98059. Overexpression of P450 epoxygenases in rats resulted in increased aortic eNOS expression, providing direct evidence that EDHF can influence vascular eNOS levels in vivo. Based on this data, we conclude that EDHF up-regulates eNOS via activation of MAPK and protein kinase C signaling pathways.",
"title": "Up-regulation of endothelial nitric-oxide synthase by endothelium-derived hyperpolarizing factor involves mitogen-activated protein kinase and protein kinase C signaling pathways."
},
{
"docid": "19922508",
"text": "Reactive oxygen species (ROS) are potentially harmful to cells because of their ability to oxidize cell constituents such as DNA, proteins, and lipids. However, at low levels, and under tight control, this feature makes them excellent modifiers in a variety of signal transduction pathways, including autophagy. Autophagy was traditionally associated with oxidative stress, acting in the degradation of oxidized proteins and organelles. Recently, a signaling role was suggested for ROS in the regulation of autophagy, leading, under different circumstances, either to survival or to death. To study the effects of ROS on this pathway, one must determine the localization, intensity, kinetics, and essentiality of the oxidative signal in autophagy. Moreover, once characterized, detection and manipulation of ROS formation could be used to monitor and control autophagic activity. In this chapter we discuss methods to examine ROS in the context of autophagy.",
"title": "Monitoring starvation-induced reactive oxygen species formation."
},
{
"docid": "83308790",
"text": "In mammals, the canonical nuclear factor κB (NF-κB) signaling pathway activated in response to infections is based on degradation of IκB inhibitors. This pathway depends on the IκB kinase (IKK), which contains two catalytic subunits, IKKα and IKKβ. IKKβ is essential for inducible IκB phosphorylation and degradation, whereas IKKα is not. Here we show that IKKα is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-κB target genes, and processing of the NF-κB2 (p100) precursor. IKKα preferentially phosphorylates NF-κB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-κB–inducing kinase (NIK). IKKα is therefore a pivotal component of a second NF-κB activation pathway based on regulated NF-κB2 processing rather than IκB degradation.",
"title": "Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway"
},
{
"docid": "33912020",
"text": "Semaphorin3A (Sema3A) is a repulsive guidance molecule for axons, which acts by inducing growth cone collapse through phosphorylation of CRMP2 (collapsin response mediator protein 2). Here, we show a role for CRMP2 oxidation and thioredoxin (TRX) in the regulation of CRMP2 phosphorylation and growth cone collapse. Sema3A stimulation generated hydrogen peroxide (H2O2) through MICAL (molecule interacting with CasL) and oxidized CRMP2, enabling it to form a disulfide-linked homodimer through cysteine-504. Oxidized CRMP2 then formed a transient disulfide-linked complex with TRX, which stimulated CRMP2 phosphorylation by glycogen synthase kinase-3, leading to growth cone collapse. We also reconstituted oxidation-dependent phosphorylation of CRMP2 in vitro, using a limited set of purified proteins. Our results not only clarify the importance of H2O2 and CRMP2 oxidation in Sema3A-induced growth cone collapse but also indicate an unappreciated role for TRX in linking CRMP2 oxidation to phosphorylation.",
"title": "Thioredoxin mediates oxidation-dependent phosphorylation of CRMP2 and growth cone collapse."
},
{
"docid": "38143689",
"text": "Serotonin 5-HT2C receptors (5-HT(2C)Rs) are almost exclusively expressed in the CNS, and implicated in disorders such as obesity, depression, and schizophrenia. The present study investigated the mechanisms governing the coupling of the 5-HT(2C)R to the extracellular signal-regulated kinases (ERKs) 1/2, using a Chinese hamster ovary (CHO) cell line stably expressing the receptor at levels comparable to those found in the brain. Using the non-RNA-edited isoform of the 5-HT(2C)R, constitutive ERK1/2 phosphorylation was observed and found to be modulated by full, partial and inverse agonists. Interestingly, agonist-directed trafficking of receptor stimulus was also observed when comparing effects on phosphoinositide accumulation and intracellular Ca2+ elevation to ERK1/2 phosphorylation, whereby the agonists, [+/-]-2,5-dimethoxy-4-iodoamphetamine (DOI) and quipazine, showed reversal of efficacy between the phosphoinositide/Ca2+ pathways, on the one hand, and the ERK1/2 pathway on the other. Subsequent molecular characterization found that 5-HT-stimulated ERK1/2 phosphorylation in this cellular background requires phospholipase D, protein kinase C, and activation of the Raf/MEK/ERK module, but is independent of both receptor- and non-receptor tyrosine kinases, phospholipase C, phosphoinositide 3-kinase, and endocytosis. Our findings underscore the potential for exploiting pathway-selective receptor states in the differential modulation of signaling pathways that play prominent roles in normal and abnormal neuronal signaling.",
"title": "Characterization of serotonin 5-HT2C receptor signaling to extracellular signal-regulated kinases 1 and 2."
},
{
"docid": "26019505",
"text": "The Hippo pathway regulates organ size and tissue homeostasis in response to multiple stimuli, including cell density and mechanotransduction. Pharmacological inhibition of phosphatases can also stimulate Hippo signaling in cell culture. We defined the Hippo protein-protein interaction network with and without inhibition of serine and threonine phosphatases by okadaic acid. We identified 749 protein interactions, including 599 previously unrecognized interactions, and demonstrated that several interactions with serine and threonine phosphatases were phosphorylation-dependent. Mutation of the T-loop of MST2 (mammalian STE20-like protein kinase 2), which prevented autophosphorylation, disrupted its association with STRIPAK (striatin-interacting phosphatase and kinase complex). Deletion of the amino-terminal forkhead-associated domain of SLMAP (sarcolemmal membrane-associated protein), a component of the STRIPAK complex, prevented its association with MST1 and MST2. Phosphatase inhibition produced temporally distinct changes in proteins that interacted with MOB1A and MOB1B (Mps one binder kinase activator-like 1A and 1B) and promoted interactions with upstream Hippo pathway proteins, such as MST1 and MST2, and with the trimeric protein phosphatase 6 complex (PP6). Mutation of three basic amino acids that are part of a phospho-serine- and phospho-threonine-binding domain in human MOB1B prevented its interaction with MST1 and PP6 in cells treated with okadaic acid. Collectively, our results indicated that changes in phosphorylation orchestrate interactions between kinases and phosphatases in Hippo signaling, providing a putative mechanism for pathway regulation.",
"title": "Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions."
},
{
"docid": "24721866",
"text": "Macrophage-derived foam cells play important roles in the progression of atherosclerosis. We reported previously that ERK1/2-dependent granulocyte/macrophage colony-stimulating factor (GM-CSF) expression, leading to p38 MAPK/ Akt signaling, is important for oxidized low density lipoprotein (Ox-LDL)-induced macrophage proliferation. Here, we investigated whether activation of AMP-activated protein kinase (AMPK) could suppress macrophage proliferation. Ox-LDL-induced proliferation of mouse peritoneal macrophages was assessed by [(3)H]thymidine incorporation and cell counting assays. The proliferation was significantly inhibited by the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and restored by dominant-negative AMPKalpha1, suggesting that AMPK activation suppressed macrophage proliferation. AICAR partially suppressed Ox-LDL-induced ERK1/2 phosphorylation and GM-CSF expression, suggesting that another mechanism is also involved in the AICAR-mediated suppression of macrophage proliferation. AICAR suppressed GM-CSF-induced macrophage proliferation without suppressing p38 MAPK/Akt signaling. GM-CSF suppressed p53 phosphorylation and expression and induced Rb phosphorylation. Overexpression of p53 or p27(kip) suppressed GM-CSF-induced macrophage proliferation. AICAR induced cell cycle arrest, increased p53 phosphorylation and expression, and suppressed GM-CSF-induced Rb phosphorylation via AMPK activation. Moreover, AICAR induced p21(cip) and p27(kip) expression via AMPK activation, and small interfering RNA (siRNA) of p21(cip) and p27(kip) restored AICAR-mediated suppression of macrophage proliferation. In conclusion, AMPK activation suppressed Ox-LDL-induced macrophage proliferation by suppressing GM-CSF expression and inducing cell cycle arrest. These effects of AMPK activation may represent therapeutic targets for atherosclerosis.",
"title": "Activation of AMP-activated protein kinase suppresses oxidized low-density lipoprotein-induced macrophage proliferation."
},
{
"docid": "6363093",
"text": "BACKGROUND Glioblastoma multiforme (GBM) is an umbrella designation that includes a heterogeneous group of primary brain tumors. Several classification strategies of GBM have been reported, some by clinical course and others by resemblance to cell types either in the adult or during development. From a practical and therapeutic standpoint, classifying GBMs by signal transduction pathway activation and by mutation in pathway member genes may be particularly valuable for the development of targeted therapies. METHODOLOGY/PRINCIPAL FINDINGS We performed targeted proteomic analysis of 27 surgical glioma samples to identify patterns of coordinate activation among glioma-relevant signal transduction pathways, then compared these results with integrated analysis of genomic and expression data of 243 GBM samples from The Cancer Genome Atlas (TCGA). In the pattern of signaling, three subclasses of GBM emerge which appear to be associated with predominance of EGFR activation, PDGFR activation, or loss of the RAS regulator NF1. The EGFR signaling class has prominent Notch pathway activation measured by elevated expression of Notch ligands, cleaved Notch receptor, and downstream target Hes1. The PDGF class showed high levels of PDGFB ligand and phosphorylation of PDGFRbeta and NFKB. NF1-loss was associated with lower overall MAPK and PI3K activation and relative overexpression of the mesenchymal marker YKL40. These three signaling classes appear to correspond with distinct transcriptomal subclasses of primary GBM samples from TCGA for which copy number aberration and mutation of EGFR, PDGFRA, and NF1 are signature events. CONCLUSIONS/SIGNIFICANCE Proteomic analysis of GBM samples revealed three patterns of expression and activation of proteins in glioma-relevant signaling pathways. These three classes are comprised of roughly equal numbers showing either EGFR activation associated with amplification and mutation of the receptor, PDGF-pathway activation that is primarily ligand-driven, or loss of NF1 expression. The associated signaling activities correlating with these sentinel alterations provide insight into glioma biology and therapeutic strategies.",
"title": "Glioblastoma Subclasses Can Be Defined by Activity among Signal Transduction Pathways and Associated Genomic Alterations"
},
{
"docid": "3882374",
"text": "The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs). In murine cells, LIN28A and LIN28B facilitate conversion from naive to primed pluripotency. Proteomic and metabolomic analysis highlighted roles for LIN28 in maintaining the low mitochondrial function associated with primed pluripotency and in regulating one-carbon metabolism, nucleotide metabolism, and histone methylation. LIN28 binds to mRNAs of proteins important for oxidative phosphorylation and modulates protein abundance. Thus, LIN28A and LIN28B play cooperative roles in regulating reprogramming, naive/primed pluripotency, and stem cell metabolism.",
"title": "LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency."
},
{
"docid": "9588931",
"text": "Vascular calcification is a strong independent predictor of increased cardiovascular morbidity and mortality and has a high prevalence among patients with chronic kidney disease. The present study investigated the effects of quercetin on vascular calcification caused by oxidative stress and abnormal mitochondrial dynamics both in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial potential and ATP production. Disruption of mitochondrial structural integrity was also observed in a rat model of adenine-induced aortic calcification. Increased production of reactive oxygen species, enhanced expression and phosphorylation of Drp1, and excessive mitochondrial fragmentation were also observed in Pi-treated VSMCs. These effects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol and subsequent activation of caspase-3. Quercetin was shown to block Pi-induced apoptosis and calcification of VSMCs by inhibiting oxidative stress and decreasing mitochondrial fission by inhibiting the expression and phosphorylation of Drp1. Quercetin also significantly ameliorated adenine-induced aortic calcification in rats. In summary, our findings suggest that quercetin attenuates calcification by reducing apoptosis of VSMCs by blocking oxidative stress and inhibiting mitochondrial fission.",
"title": "Quercetin attenuates vascular calcification by inhibiting oxidative stress and mitochondrial fission."
},
{
"docid": "1605196",
"text": "Successful generation of induced pluripotent stem cells entails a major metabolic switch from mitochondrial oxidative phosphorylation to glycolysis during the reprogramming process. The mechanism of this metabolic reprogramming, however, remains elusive. Here, our results suggest that an Atg5-independent autophagic process mediates mitochondrial clearance, a characteristic event involved in the metabolic switch. We found that blocking such autophagy, but not canonical autophagy, inhibits mitochondrial clearance, in turn, preventing iPSC induction. Furthermore, AMPK seems to be upstream of this autophagic pathway and can be targeted by small molecules to modulate mitochondrial clearance during metabolic reprogramming. Our work not only reveals that the Atg5-independent autophagy is crucial for establishing pluripotency, but it also suggests that iPSC generation and tumorigenesis share a similar metabolic switch.",
"title": "Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming"
},
{
"docid": "6121555",
"text": "The aim of this study was to investigate the mechanism through which Sphingosine kinase-1 (SPHK1) exerts its anti-apoptosis activity in glioma cancer cells. We here report that dysregulation of SPHK1 alters the sensitivity of glioma to apoptosis both in vitro and in vivo. Further mechanistic study examined the expression of Bcl-2 family members, including Bcl-2, Mcl-1, Bax and Bim, in SPHK1-overexpressing glioma cells and revealed that only pro-apoptotic Bim was downregulated by SPHK1. Moreover, the transcriptional level of Bim was also altered by SPHK1 in glioma cells. We next confirmed the correlation between SPHK1 and Bim expression in primary glioma specimens. Importantly, increasing SPHK1 expression in glioma cells markedly elevated Akt activity and phosphorylated inactivation of FOXO3a, which led to downregulation of Bim. A pharmacological approach showed that these effects of SPHK1 were dependent on phosphatidylinositol 3-kinase (PI3K). Furthermore, effects of SPHK1 on Akt/FOXO3a/Bim pathway could be reversed by SPHK1 specific RNA interference or SPHK1 inhibitor. Collectively, our results indicate that regulation of the Akt/FOXO3a/Bim pathway may be a novel mechanism by which SPHK1 protects glioma cells from apoptosis, thereby involved in glioma tumorigenesis.",
"title": "Sphingosine Kinase 1 Regulates the Akt/FOXO3a/Bim Pathway and Contributes to Apoptosis Resistance in Glioma Cells"
},
{
"docid": "24185667",
"text": "The stress-activated kinase JNK mediates key cellular responses to oxidative stress. Here we show that DAP kinase (DAPk), a cell death promoting Ser/Thr protein kinase, plays a main role in oxidative stress-induced JNK signaling. We identify protein kinase D (PKD) as a novel substrate of DAPk and demonstrate that DAPk physically interacts with PKD in response to oxidative stress. We further show that DAPk activates PKD in cells and that induction of JNK phosphorylation by ectopically expressed DAPk can be attenuated by knocking down PKD expression or by inhibiting its catalytic activity. Moreover, knockdown of DAPk expression caused a marked reduction in JNK activation under oxidative stress, indicating that DAPk is indispensable for the activation of JNK signaling under these conditions. Finally, DAPk is shown to be required for cell death under oxidative stress in a process that displays the characteristics of caspase-independent necrotic cell death. Taken together, these findings establish a major role for DAPk and its specific interaction with PKD in regulating the JNK signaling network under oxidative stress.",
"title": "DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress"
},
{
"docid": "39291138",
"text": "Cells develop by reading mixed signals. Nowhere is this clearer than in the highly dynamic processes that propel embryogenesis, when critical cell-fate decisions are made swiftly in response to well-orchestrated growthfactor combinations. Learning how diverse signaling pathways are integrated is therefore essential for understanding physiology. This requires the identification, in tangible molecular terms, of key nodes for pathway integration that operate in vivo. A report in this issue, on the integration of Smad and Ras/MAPK pathways during neural induction (Pera et al. 2003), provides timely insights into the relevance of one such node. Pera et al. (2003) report that FGF8 and IGF2—two growth factors that activate the Ras/MAPK pathway— favor neural differentiation and mesoderm dorsalization in Xenopus by inhibiting BMP (Bone Morphogenetic Protein) signaling. Mesoderm is formed from ectoderm in response to Nodal-related signals from the endoderm at the blastula stage and beyond (Fig. 1; for review, see De Robertis et al. 2000). BMP induces differentiation of ectoderm into epidermal cell fates at the expense of neural fates, and it ventralizes the mesoderm at the expense of dorsal fates (for review, see Weinstein and HemmatiBrivanlou 1999; De Robertis et al. 2000). Accordingly, neural differentiation and dorsal mesoderm formation are favored when BMP signaling is attenuated. Noggin, Chordin, Cerberus, and Follistatin, secreted by the Spemann organizer on the dorsal side at the gastrula stage, facilitate the formation of neural tissue by sequestering BMP (Weinstein and Hemmati-Brivanlou 1999; De Robertis et al. 2000). Experimentally blocking BMP signaling with a dominant-negative BMP receptor has a similar effect of promoting ectoderm neuralization (Weinstein and Hemmati-Brivanlou 1999). As it turns out, neural induction can also be achieved with FGF (fibroblast growth factor; Kengaku and Okamoto 1993; Lamb and Harland 1995; Hongo et al. 1999; Hardcastle et al. 2000; Streit et al. 2000; Wilson et al. 2000) and IGF (insulin-like growth factor; Pera et al. 2001; Richard-Parpaillon et al. 2002). Injection of transcripts encoding FGF8 or IFG2 into one animal-pole blastomere of a fourto eight-cell embryo results in an expanded neural plate at the injected side (Pera et al. 2003). Surprisingly, expression of a dominant-negative FGF receptor prevents neuralization of ectoderm explants by the BMP blocker Noggin (Launay et al. 1996). Likewise, the potent neuralizing effect of Chordin can be blocked by a dominant-negative FGF receptor or a morpholino oligonucleotide targeting the IGF receptor (Pera et al. 2003). Thus, the neuralizing effect of BMP inhibitors is somehow tied to FGF and IFG signaling. The question is, how? Because FGF8 and IFG2 activate MAPK, Pera et al. (2003) took heed from previous work showing that MAPK inhibits the BMP signal-transduction factor Smad1 (Kretzschmar et al. 1997a). Smad1 is directly phosphorylated by the BMP receptor, resulting in Smad1 activation (Kretzschmar et al. 1997b), and by MAPK in response to EGF, resulting in Smad1 inhibition (Kretzschmar et al. 1997a; Fig. 2). Smad transcription factors mediate gene responses to the entire TGF (Transforming Growth Factor) family, to which the BMPs belong (for review, see Massague 2000; Derynck and Zhang 2003). Smads 1, 5, and 8 act primarily downstream of BMP receptors and Smads 2 and 3 downstream of TGF , Activin and Nodal receptors. Smad proteins have two conserved globular domains—the MH1 and MH2 domains (Fig. 2). The MH1 domain is involved in DNA binding and the MH2 domain in binding to cytoplasmic retention factors, activated receptors, nucleoporins in the nuclear pore, and DNA-binding cofactors, coactivators, and corepressors in the nucleus (for review, see Shi and Massague 2003). Receptor-mediated phosphorylation occurs at the carboxy-terminal sequence SXS. This enables the nuclear accumulation of Smads and their association with the shared partner Smad4 to form transcriptional complexes that are interpreted by the cell as a function of the context (Massague 2000). Between the MH1 and MH2 domains lies a linker region of variable sequence and length. Attention was drawn to this region when it was found that EGF (epidermal growth factor), a classical activator of the Ras/ MAPK pathway, causes phosphorylation of the Smad1 linker at four MAPK sites (PXSP sequences; Kretzschmar et al. 1997a). This prevents the nuclear localization of Smad1 and inhibits BMP signaling. Mutation of these E-MAIL [email protected]; FAX (212) 717-3298. Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/ gad.1167003.",
"title": "Integration of Smad and MAPK pathways: a link and a linker revisited."
},
{
"docid": "28937856",
"text": "The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.",
"title": "Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase."
},
{
"docid": "24498673",
"text": "Holliday junctions (HJs) are four-way DNA intermediates that form during homologous recombination, and their efficient resolution is essential for chromosome segregation. Here, we show that three structure-selective endonucleases, namely SLX1-SLX4, MUS81-EME1, and GEN1, define two pathways of HJ resolution in human cells. One pathway is mediated by GEN1, whereas SLX1-SLX4 and MUS81-EME1 provide a second and genetically distinct pathway (SLX-MUS). Cells depleted for SLX-MUS or GEN1 pathway proteins exhibit severe defects in chromosome segregation and reduced survival. In response to CDK-mediated phosphorylation, SLX1-SLX4 and MUS81-EME1 associate at the G2/M transition to form a stable SLX-MUS holoenzyme, which can be reconstituted in vitro. Biochemical studies show that SLX-MUS is a HJ resolvase that coordinates the active sites of two distinct endonucleases during HJ resolution. This cleavage reaction is more efficient and orchestrated than that mediated by SLX1-SLX4 alone, which exhibits a potent nickase activity that acts promiscuously upon DNA secondary structures.",
"title": "Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells."
},
{
"docid": "7506409",
"text": "Human mesenchymal stem cells (hMSCs) have been widely studied as a source of primary adult stem cells for cell therapy because of their multidifferentiation potential; however, the growth arrest (also known as \"premature senescence\") often found in hMSCs cultured in vitro has been a major obstacle to the in-depth characterization of these cells. In addition, the inability to maintain constant cell growth hampers the development of additional genetic modifications aimed at achieving desired levels of differentiation to specific tissues; however, the molecular mechanisms that govern this phenomenon remain unclear, with the exception of a few studies demonstrating that induction of p16INK4a is responsible for this senescence-like event. Here, we observed that the premature growth arrest in hMSCs occurs in parallel with the induction of p16INK4a, following abrogation of inhibitory phosphorylation of retinoblastoma protein. These stress responses were concurrent with increased formation of reactive oxygen species (ROSs) from mitochondria and increased p38 mitogen-activated protein kinase (MAPK) activity. The introduction of Wip1 (wild-type p53 inducible phosphatase-1), a well-studied stress modulator, significantly lowered p16INK4a expression and led to p38 MAPK inactivation, although it failed to affect the levels of ROSs. Moreover, the suppression of stress responses by Wip1 apparently extended the life span of hMSCs, compared with control conditions, while maintaining their multilineage differentiation potential. Based on these results, we suggest that senescent growth arrest in hMSCs may result from activation of stress signaling pathways and consequent onset of stress responses, due in part to ROS production during prolonged in vitro culture.",
"title": "Senescent growth arrest in mesenchymal stem cells is bypassed by Wip1-mediated downregulation of intrinsic stress signaling pathways."
},
{
"docid": "7155555",
"text": "Listeria monocytogenes is widely used as a model to study immune responses against intracellular bacteria. It has been shown that neutrophils and macrophages play an important role to restrict bacterial replication in the early phase of primary infection in mice, and that the cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) are essential for protection. However, the involved signaling pathways and effector mechanisms are still poorly understood. This study investigated mouse strains deficient for the IFN-dependent transcription factors interferon consensus sequence binding protein (ICSBP), interferon regulatory factor (IRF)1 or 2 for their capacity to eliminate Listeria in vivo and in vitro and for production of inducible reactive nitrogen intermediates (RNI) or reactive oxygen intermediates (ROI) in macrophages. ICSBP−/− and to a lesser degree also IRF2−/− mice were highly susceptible to Listeria infection. This correlated with impaired elimination of Listeria from infected peritoneal macrophage (PEM) cultures stimulated with IFN-γ in vitro; in addition these cultures showed reduced and delayed oxidative burst upon IFN-γ stimulation, whereas nitric oxide production was normal. In contrast, mice deficient for IRF1 were not able to produce nitric oxide, but they efficiently controlled Listeria in vivo and in vitro. These results indicate that (a) the ICSBP/IRF2 complex is essential for IFN-γ–mediated protection against Listeria and that (b) ROI together with additional still unknown effector mechanisms may be responsible for the anti-Listeria activity of macrophages, whereas IRF1-induced RNI are not limiting.",
"title": "Crucial Role of Interferon Consensus Sequence Binding Protein, but neither of Interferon Regulatory Factor 1 nor of Nitric Oxide Synthesis for Protection Against Murine Listeriosis"
},
{
"docid": "14972169",
"text": "Exposure during the organogenesis stage of the mouse embryo to the model teratogen, hydroxyurea (HU), induces curly tail and limb malformations. Oxidative stress contributes to the developmental toxicity of HU. Reactive oxygen species (ROS) interact with polyunsaturated bilipid membranes to form α,β-unsaturated reactive aldehydes; 4-hydroxy-2-nonenal (4-HNE), one of the most cytotoxic of these aldehydes, covalently adducts with proteins, lipids, and nucleic acids. The goal of the current study is to determine if HU exposure of CD1 mice on gestation day 9 generates region-specific 4-HNE-protein adducts in the embryo and to identify the proteins targeted. The formation of 4-HNE-protein adducts was elevated in the caudal region of control embryos; HU exposure further increased 4-HNE-protein adduct formation in this area. Interestingly, three of the 4-HNE-modified proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutamate oxaloacetate transaminase 2, and aldolase 1, A isoform, are involved in energy metabolism. The formation of 4-HNE-GAPDH protein adducts reduced GAPDH enzymatic activity by 20% and attenuated lactate production by 40%. Furthermore, HU exposure induced the nuclear translocation of GAPDH in the caudal region of exposed embryos; this nuclear translocation may be associated with the reactivation of oxidized proteins involved in DNA repair, such as apurinic/apyrimidinic endonuclease-1, and the stimulation of E1A-associated P300 protein/creb-binding protein (p300/CBP) activity, initiating cell death in a p53-dependent pathway. We propose that GAPDH is a redox-sensitive target in the embryo and may play a role in a stress response during development.",
"title": "Teratogen-Induced Oxidative Stress Targets Glyceraldehyde-3-Phosphate Dehydrogenase in the Organogenesis Stage Mouse Embryo"
},
{
"docid": "33370",
"text": "Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioblastoma stem cells (GSCs). GSCs are regulated by molecular pathways distinct from the bulk tumor that may be useful therapeutic targets. We determined that A20 (TNFAIP3), a regulator of cell survival and the NF-kappaB pathway, is overexpressed in GSCs relative to non-stem glioblastoma cells at both the mRNA and protein levels. To determine the functional significance of A20 in GSCs, we targeted A20 expression with lentiviral-mediated delivery of short hairpin RNA (shRNA). Inhibiting A20 expression decreased GSC growth and survival through mechanisms associated with decreased cell-cycle progression and decreased phosphorylation of p65/RelA. Elevated levels of A20 in GSCs contributed to apoptotic resistance: GSCs were less susceptible to TNFalpha-induced cell death than matched non-stem glioma cells, but A20 knockdown sensitized GSCs to TNFalpha-mediated apoptosis. The decreased survival of GSCs upon A20 knockdown contributed to the reduced ability of these cells to self-renew in primary and secondary neurosphere formation assays. The tumorigenic potential of GSCs was decreased with A20 targeting, resulting in increased survival of mice bearing human glioma xenografts. In silico analysis of a glioma patient genomic database indicates that A20 overexpression and amplification is inversely correlated with survival. Together these data indicate that A20 contributes to glioma maintenance through effects on the glioma stem cell subpopulation. Although inactivating mutations in A20 in lymphoma suggest A20 can act as a tumor suppressor, similar point mutations have not been identified through glioma genomic sequencing: in fact, our data suggest A20 may function as a tumor enhancer in glioma through promotion of GSC survival. A20 anticancer therapies should therefore be viewed with caution as effects will likely differ depending on the tumor type.",
"title": "Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth"
},
{
"docid": "16242975",
"text": "In mammalian mitochondria, 22 species of tRNAs encoded in mitochondrial DNA play crucial roles in the translation of 13 essential subunits of the respiratory chain complexes involved in oxidative phosphorylation. Following transcription, mitochondrial tRNAs are modified by nuclear-encoded tRNA-modifying enzymes. These modifications are required for the proper functioning of mitochondrial tRNAs (mt tRNAs), and the absence of these modifications can cause pathological consequences. To date, however, the information available about these modifications has been incomplete. To address this issue, we isolated all 22 species of mt tRNAs from bovine liver and comprehensively determined the post-transcriptional modifications in each tRNA by mass spectrometry. Here, we describe the primary structures with post-transcriptional modifications of seven species of mt tRNAs which were previously uncharacterized, and provide revised information regarding base modifications in five other mt tRNAs. In the complete set of bovine mt tRNAs, we found 15 species of modified nucleosides at 118 positions (7.48% of total bases). This result provides insight into the molecular mechanisms underlying the decoding system in mammalian mitochondria and enables prediction of candidate tRNA-modifying enzymes responsible for each modification of mt tRNAs.",
"title": "A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs"
},
{
"docid": "4423401",
"text": "Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the ‘GABA (γ-aminobutyric acid) shunt’ pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.",
"title": "Succinate is an inflammatory signal that induces IL-1β through HIF-1α"
}
] |
218730
|
Oh Yeon-seo is a former member of a South Korean girl group.
|
[
{
"docid": "Oh_Yeon-seo",
"text": "Oh Yeon-seo ( born Oh Haet-nim , on June 22 , 1987 ) , is a South Korean actress and former member of South Korean girl group , LUV . She is best known for her roles in television dramas My Husband Got a Family ( 2012 ) , Jang Bo-ri is Here ! ( 2014 ) , Shine or Go Crazy ( 2015 ) and Please Come Back , Mister ( 2016 ) .",
"title": ""
}
] |
[
{
"docid": "Ji-yeon_(name)",
"text": "Ji-yeon , also spelled Ji-youn , Ji-yeoun , Ji-yean , Ji-yun , Chee-yun , or Chi-yun , is a Korean feminine given name . The meaning differs based on the hanja used to write each syllable of the name . There are 46 hanja with the reading `` ji '' and 39 hanja with the reading `` yeon '' on the South Korean government 's official list of hanja which may be used in given names . Ji-yeon was the seventh-most popular name for baby girls born in South Korea in 1980 . People with this name include : Entertainers Myung Ji-yun ( born 1975 ) , South Korean television actress Gummy ( singer ) ( born Park Ji-yeon , 1981 ) , South Korean singer Cha Ji-yeon ( born 1982 ) , South Korean singer and actress Lina ( South Korean singer ) ( born Lee Ji-yeon , 1984 ) , member of The Grace and disbanded duo Isak N Jiyeon Lim Ji-yeon ( born 1990 ) , South Korean actress Park Ji-yeon ( born 1992 ) , South Korean singer , member of girl group Glam Park Ji-yeon ( born 1993 ) , South Korean singer , member of girl group T-ara Kei ( singer ) ( born Kim Ji-yeon , 1995 ) , member of girl group Lovelyz Bona ( born Kim Jiyeon , 1995 ) , member of girl group Cosmic Girls Sportspeople Hong Ji-yeon ( born 1970 ) , South Korean volleyball player Nam Jie-youn ( born 1983 ) , South Korean volleyball player Kim Ji-yeon ( born 1988 ) , South Korean sabre fencer Seo Ji-yeon ( born 1993 ) , South Korean sabre fencer Park Ji-yeon ( gymnast ) ( born 1994 ) , South Korean gymnast Others Melissa Lee ( Korean name Lee Jiyun ; born 1960s ) , South Korean-born New Zealand politician Kim Chee-yun ( born 1970 ) , South Korean violinist Jeanne You ( Korean name You Ji-yeoun ; born 1978 ) , South Korean classical pianist Ji-Yeon Yuh , American sociologist of Korean descent Fictional characters with this name include : Kwon Ji-yeon , in American television series Lost , for whom the episode Ji-yeon is named",
"title": ""
},
{
"docid": "Seung-ah",
"text": "Seung-ah is a Korean female given name . People with this name include : Seo Seung-ah ( born 1983 ) , South Korean actress Yoon Seung-ah ( born 1983 ) , South Korean actress Son Seung-ah , South Korean singer , member of girl group Nine Muses Oh Seung-ah ( birth name Oh Se-mi ) , South Korean singer and actress , former member of girl group Rainbow Lee Seung-ah , South Korean singer , member of Sunny Hill Fictional characters with this name include : Oh Seung-ah , in 2009 South Korean television series On Air",
"title": ""
},
{
"docid": "Seo-yeon",
"text": "Seo-yeon is a Korean feminine given name . The meaning differs based on the hanja used to write each syllable of the name . There are 38 hanja with the reading `` seo '' and 39 hanja with the reading `` yeon '' on the South Korean government 's official list of hanja which may be registered for use in given names . Seo-yeon was the most popular name for baby girls in South Korea in 2008 and 2009 . In 2010 it was also the most popular new name for adult women changing their names from previous names such as those which they felt were too old-fashioned . People with this name include : Shim Seo-yeon ( born 1989 ) , South Korean football defender Kim Seo-yeon ( born 1992 ) , South Korean beauty pageant contestant , Miss Korea 2014 Fictional characters with this name include : Kim Seo-yeon , in 2009 South Korean television series Cain and Abel Lee Seo-yeon , in 2011 South Korean television series A Thousand Days ' Promise Yang Seo-yeon , in 2012 South Korean film Architecture 101",
"title": ""
},
{
"docid": "Seung-yeon",
"text": "Seung-yeon is a Korean unisex given name . The meaning differs based on the hanja used to write each syllable of the name . There are 15 hanja with the reading `` seung '' and 39 hanja with the reading `` yeon '' on the South Korean government 's official list of hanja which may be registered for use in given names . People with this name include : Kim Seung-yeon ( born 1952 ) , South Korean businessman Lee Seung-yeon ( born 1968 ) , South Korean actress Lee Seung-yeon ( born 1977 ) , South Korean actress Woo Seung-yeon ( 1983 -- 2009 ) , South Korean model and actress Han Seung-yeon ( born 1988 ) , South Korean singer and actress , former member of girl group Kara Hong Seung-yeon ( born 1992 ) , South Korean female tennis player Gong Seung-yeon ( born 1993 as Yoo Seung-yeon ) South Korean actress Son Seung-yeon ( born 1993 ) , South Korean female singer Jang Seung-yeon ( born 1996 ) , South Korean singer , leader and member of girl group CLC",
"title": ""
},
{
"docid": "My_Sassy_Girl_(TV_series)",
"text": "My Sassy Girl is a 2017 South Korean television drama starring Joo Won , Oh Yeon-seo , Lee Jung-shin and Kim Yoon-hye , based on the 2001 South Korean movie My Sassy Girl by Kwak Jae-yong , but during Joseon period . It aired on SBS every Monday and Tuesday at 22:00 ( KST ) , starting May 29 , 2017 .",
"title": ""
},
{
"docid": "Yeon_(Korean_given_name)",
"text": "Yeon is the Revised Romanisation spelling of an element in Korean given names . The meaning differs based on the hanja used to write it . There are 39 hanja with the reading `` yeon '' on the South Korean government 's official list of hanja which may be registered for use in given names . In 1980 , one name containing this element , Ji-yeon , was the 7th-most popular name for newborn girls in South Korea . In the 2000s and 2010s , another name containing this element , Seo-yeon , became the most popular name for newborn girls in South Korea , as well as a common name for adult women name changing their names once name changes began to be allowed in 2000 . Names containing this element include : First syllable Yeon-hee Yeon-seok Yeon-woo Second syllable Bo-yeon Do-yeon Ji-yeon Mi-yeon Se-yeon Seo-yeon Seung-yeon Si-yeon Soo-yeon Tae-yeon",
"title": ""
},
{
"docid": "Hyun-a_(name)",
"text": "Hyun-a is a Korean feminine given name . Its meaning differs based on the hanja used to write each syllable of the name . There are 35 hanja with the reading `` hyun '' and 20 hanja with the reading `` a '' on the South Korean government 's official list of hanja which may be used in given names . Notable people with the name include : Kim Hyun-ah ( born 1971 ) , stage name Kim Jung-nan , South Korean actress Kong Hyun-ah ( born 1972 ) , South Korean sport shooter Sung Hyun-ah ( born 1975 ) , South Korean actress Moon Hyuna ( born 1987 ) , stage name Hyuna , South Korean singer , former member of girl group Nine Muses Kim Hyuna ( born 1992 ) , stage name Hyuna , South Korean singer , former member of girl groups 4minute and Wonder Girls Jo Hyuna , South Korean singer , member of Urban Zakapa Fictional characters with this name include : Seo Hyun-ah , in 2005 South Korean television series Super Rookie Hyun-ah , in 2009 South Korean film Sisters on the Road Oh Hyun-ah , in 2011 South Korean television series A Thousand Days ' Promise",
"title": ""
},
{
"docid": "Here_Comes_Mr._Oh",
"text": "Here Comes Mr. Oh ( ; lit . `` Here Comes Oh Ja-ryong '' or `` Oh Ja-ryong is Coming '' ) is a 2012 South Korean television series starring Lee Jang-woo , Oh Yeon-seo , Jin Tae-hyun , and Seo Hyun-jin . The daily drama aired on MBC on Mondays to Fridays at 19:15 from November 19 , 2012 to May 17 , 2013 for 129 episodes .",
"title": ""
},
{
"docid": "Seo-hyeon",
"text": "Seo-hyeon , also spelled Seo-hyun , is a Korean feminine given name . It was the fourth-most popular name for baby girls born in South Korea in 2008 , rising to third place in 2009 . The meaning differs based on the hanja used to write each syllable of the name . There are 38 hanja with the reading `` seo '' and 68 hanja with the reading `` hyeon '' on the South Korean government 's official list of hanja which may be used in given names . People with this name include : Seohyun ( born 1991 as Seo Ju-hyun ) , South Korean singer and actress , member of girl group Girls ' Generation Katie Kim ( South Korean singer ) ( Korean name Kim Seo-hyeon , born 1993 ) Ahn Seo-hyun ( born 2004 ) , South Korean actress",
"title": ""
},
{
"docid": "Min-ji",
"text": "Min-ji , also spelled Min-jee , is a Korean feminine given name . Its meaning differs based on the hanja used to write each syllable of the name . There are 27 hanja with the reading `` min '' and 46 hanja with the reading `` ji '' on the South Korean government 's official list of hanja which may be used in given names . Min-ji was the fourth-most popular name for baby girls born in South Korea in 1990 . People with this name include : Entertainers Lee Min-ji ( actress , born 1984 ) , South Korean actress and singer Yeon Min-ji ( born 1984 ) , South Korean actress Lee Min-ji ( actress , born 1988 ) , South Korean actress Park Min-ji ( born 1989 ) , South Korean actress Im Minji ( born 1989 ) , stage name Linzy , South Korean idol singer and member of girl group Fiestar Lee Min-ji ( Miss Korea ) ( born 1991 ) , South Korean beauty pageant titleholder Won Min-ji ( born 1991 ) , stage name Anda , South Korean singer Ahn Minji ( born 1992 ) , stage name Cheska , South Korean rapper and former member of girl group Fiestar Kim Min-ji ( actress ) ( born 1992 ) , South Korean actress Seo Min-ji ( born 1992 ) , South Korean actress Kim Minji ( born 1993 ) , stage name Kimi , South Korean rapper and member of girl group Bulldok Gong Min-ji ( born 1994 ) , stage name Minzy , South Korean idol singer Sportspeople Shim Min-ji ( born 1983 ) , South Korean swimmer Kim Min-ji ( volleyball ) ( born 1985 ) , South Korean volleyball player Kim Min-jee ( born 1986 ) , South Korean short track skater Kang Min-jee ( born 1989 ) , South Korean group rhythmic gymnast Kim Min-ji ( sport shooter ) ( born 1989 ) , South Korean sport shooter Um Min-ji ( born 1991 ) , South Korean curler Yeo Min-ji ( born 1993 ) , South Korean football player Minjee Lee ( born 1996 ) , Korean Australian amateur golfer",
"title": ""
},
{
"docid": "Seo_Hyun-jin",
"text": "Seo Hyun-jin ( born February 27 , 1985 ) is a South Korean singer and actress who is the former lead vocalist of the girl group M.I.L.K. . After her group 's disbandment in 2003 , she has transitioned to acting and has since starred in television dramas Let 's Eat 2 ( 2015 ) , Another Oh Hae-young ( 2016 ) and Romantic Doctor , Teacher Kim ( 2016-2017 ) .",
"title": ""
},
{
"docid": "Do-yeon",
"text": "Do-yeon is a Korean unisex given name . Its meaning differs based on the hanja used to write each syllable of the name . There are 44 hanja with the reading `` do '' and 39 hanja with the reading `` yeon '' on the South Korean government 's list of hanja which may be registered for use in given names . People with this name include : Kim Do-yeon ( politician ) ( 1894 -- 1967 ) , Korean male independence activist , later a South Korean politician Jeon Do-yeon ( born 1973 ) , South Korean actress Kim Do-yeon ( footballer ) ( born 1988 ) , South Korean female footballer Hwang Do-Yeon ( born 1991 ) , South Korean male footballer Kim Do-yeon ( singer ) ( born 1999 ) , South Korean female singer , member of I.O.I Fictional characters with this name include : Seo Do-yeon , in 2013 South Korean television series I Can Hear Your Voice",
"title": ""
},
{
"docid": "Se-yeon",
"text": "Se-yeon is a Korean unisex given name . People with this name include : Choi Se-yeon , stage name Choi Kang-hee ( born 1977 ) , South Korean actress Jin Se-yeon ( born 1994 ) , South Korean actress Kim Se-yeon , member of South Korean girl group She ' z Fictional characters with this name include : Kang Se-yeon , in 2006 South Korean television series Lovers",
"title": ""
},
{
"docid": "Park_So-yeon_(singer)",
"text": "Park So-yeon ( born October 5 , 1987 ) , better known mononymously as Soyeon , is a South Korean singer and actress . She is best known as the former lead vocalist and member of South Korean girl group T-ara .",
"title": ""
},
{
"docid": "Cheese_in_the_Trap_(film)",
"text": "Cheese in the Trap is an upcoming South Korean film starring Park Hae-jin , Oh Yeon-seo and Park Ki-woong It is based on the Korean webtoon of the same name .",
"title": ""
},
{
"docid": "Ye-won",
"text": "Ye-won is a Korean feminine given name . Its meaning depends on the hanja used to write each syllable of the name . There are 34 hanja with the reading `` ye '' and 35 hanja with the reading `` won '' on the South Korean government 's official list of hanja which may be used in given names . People with this name include : Kang Ye-won ( born 1980 ) , South Korean actress Kim Ye-won ( actress , born 1987 ) ( born Kim Shin-ah , 1987 ) , South Korean actress and singer Kim Ye-won ( singer ) ( born 1989 ) , South Korean singer and actress , former member of girl group Jewelry Kim Ye-won ( actress , born 1997 ) , South Korean actress Kim Ye-won ( born 1998 ) , stage name Umji , South Korean singer , member of girl group GFriend Choi Ye-won ( born 1999 ) , stage name Arin , South Korean singer , member of girl group Oh My Girl Kim Ye-won ( born 1999 ) , stage name Yehana , South Korean singer , member of girl group Pristin",
"title": ""
},
{
"docid": "Shim_Seo-yeon",
"text": "Shim Seo-yeon ( , -LSB- ɕim.sʌ.jʌn -RSB- ; born 15 April 1989 ) is a South Korean women 's football defender , who plays for Goyang Daekyo WFC in South Korean WK-League and South Korea women 's national football team .",
"title": ""
},
{
"docid": "Soo-yeon",
"text": "Soo-yeon , also spelled Su-yeon or Soo-yun , is a Korean unisex given name , primarily feminine . Its meaning differs based on the hanja used to write each syllable of the name . There are 67 hanja with the reading `` soo '' and 39 hanja with the reading `` yeon '' on the South Korean government 's official list of hanja which may be registered for use in given names . People with this name include : Entertainers Kang Soo-yeon ( born 1966 ) , South Korean actress Oh Soo-yeon ( born 1968 ) , South Korean female television screenwriter Chunja ( singer ) ( born Hong Su-yeon , 1979 ) , South Korean female singer Cha Soo-yeon ( born 1981 ) , South Korean actress Han Soo-yeon ( born Lee Mae-ri , 1983 ) , South Korean actress Jessica Jung ( Korean name Jung Soo-yeon , born 1989 ) , American female singer in South Korea Sportspeople Kang Soo-yun ( born 1976 ) , South Korean female golfer Kim Soo-yeon ( born 1983 ) , South Korean male footballer Soo Yeon Lee ( born 1981 ) , South Korean female table tennis player and model Back Su-yeon ( born 1991 ) , South Korean female swimmer Jo Su-yeon ( born 1994 ) , South Korean female handball player Others Won Soo-yeon ( born 1961 ) , South Korean female manhwa artist Oh Soo-yeon ( novelist ) ( born 1964 ) , South Korean female novelist Fictional characters with this name include : Bae Su-yeon , in 2003 South Korean film A Tale of Two Sisters Ji Soo-yeon , in 2013 South Korean television series Iris II : New Generation Lee Soo-yeon , in 2012 South Korean television series Missing You",
"title": ""
},
{
"docid": "Kim_Hyo-yeon",
"text": "Kim Hyo-yeon ( born September 22 , 1989 ) , better known mononymously as Hyoyeon , is a South Korean singer and television personality . She debuted as a member of girl group Girls ' Generation in August 2007 , who went on to be one of the best-selling artists in South Korea and one of South Korea 's most popular girl groups worldwide .",
"title": ""
},
{
"docid": "Jang_Bo-ri_is_Here!",
"text": "Jang Bo-ri is Here ! is a 2014 South Korean weekend television drama series broadcast by MBC starring Oh Yeon-seo , Kim Ji-hoon , Lee Yoo-ri and Oh Chang-seok . It premiered on April 5 , 2014 , airing every Saturday and Sunday at 20:40 for 52 episodes . It won Drama of the Year at the 2014 MBC Drama Awards",
"title": ""
},
{
"docid": "Park_Ji-yeon",
"text": "Park Ji-yeon ( born June 7 , 1993 ) , better known by the mononym Jiyeon , is a South Korean singer and actress . She is best known as a member of the South Korean girl group T-ara and its sub-group , T-ara N4 .",
"title": ""
},
{
"docid": "Han_Seung-yeon",
"text": "Han Seung-yeon ( born July 24 , 1988 ) , better known mononymously as Seungyeon , is a South Korean singer and actress . She is best known as former main vocalist of the South Korean girl group Kara .",
"title": ""
},
{
"docid": "Seo_Yu-na",
"text": "Seo Yu-na ( born December 30 , 1992 ) , better known by the mononym Yuna , is a South Korean singer and actress . She is a member of the South Korean girl group AOA and its sub-groups , AOA Black and AOA Cream .",
"title": ""
},
{
"docid": "Jung_Chae-yeon",
"text": "Jung Chae-yeon ( born December 1 , 1997 ) , better known by the mononym Chaeyeon , is a South Korean singer and actress . She is best known for being a member of the South Korean girl group DIA , and for finishing 7th in the survival show Produce 101 , making her a member of I.O.I.",
"title": ""
},
{
"docid": "Seo_Hye-lin",
"text": "Seo Hye-lin ( born August 23 , 1993 ) , better known by the mononym Hyelin , is a South Korean singer . She is best known as a member of the South Korean girl group EXID .",
"title": ""
},
{
"docid": "Luv_(band)",
"text": "LUV ( ; -LSB- ləːbɯ -RSB- ) was a short-lived K-pop girls group founded by SidusHQ , consisting of Jo Eun-byul , Jeon Hye-bin , and Oh Yeon-seo . As stated by LUV in an interview , LUV stands for `` Love yoUr Voice '' , stating that everyone should love themselves and their strengths and flaws in their hearts .",
"title": ""
},
{
"docid": "Seo_Jeong-yeon",
"text": "Seo Jeong-yeon is a South Korean actress . She starred in television series such as Valid Love ( 2014 ) , and Descendants of the Sun ( 2016 ) .",
"title": ""
},
{
"docid": "Rain_(Taeyeon_song)",
"text": "`` Rain '' is a song by South Korean singer Kim Tae-yeon , a member of the South Korean girl group Girls ' Generation . It was released digitally by S.M. Entertainment on February 3 , 2016 .",
"title": ""
},
{
"docid": "Seo_Ji-yeon",
"text": "Seo Ji-yeon ( -LSB- sʌ.dʑi.jʌn -RSB- or -LSB- sʌ -RSB- -LSB- tɕi.jʌn -RSB- born March 3 , 1993 ) is a South Korean fencer .",
"title": ""
},
{
"docid": "Medical_Top_Team",
"text": "Medical Top Team is a South Korean television series written by Yoon Kyung-ah and directed by Kim Do-hoon . It starred Kwon Sang-woo , Jung Ryeo-won , Ju Ji-hoon , Oh Yeon-seo and Choi Minho . The series began filming in August 2013 , and aired on MBC from October 9 to December 12 , 2013 on Wednesdays and Thursdays at 21:55 for 20 episodes . The medical drama focuses on the lives of doctors and nurses who are members of an elite medical team from the fictional Gwang Hae University Hospital .",
"title": ""
}
] |
28
|
A T helper 2 cell (Th2) environment impedes disease development in patients with systemic lupus erythematosus (SLE).
|
[
{
"docid": "12670680",
"text": "In systemic lupus erythematosus (SLE), self-reactive antibodies can target the kidney (lupus nephritis), leading to functional failure and possible mortality. We report that activation of basophils by autoreactive IgE causes their homing to lymph nodes, promoting T helper type 2 (T(H)2) cell differentiation and enhancing the production of self-reactive antibodies that cause lupus-like nephritis in mice lacking the Src family protein tyrosine kinase Lyn (Lyn(-/-) mice). Individuals with SLE also have elevated serum IgE, self-reactive IgEs and activated basophils that express CD62 ligand (CD62L) and the major histocompatibility complex (MHC) class II molecule human leukocyte antigen-DR (HLA-DR), parameters that are associated with increased disease activity and active lupus nephritis. Basophils were also present in the lymph nodes and spleen of subjects with SLE. Thus, in Lyn(-/-) mice, basophils and IgE autoantibodies amplify autoantibody production that leads to lupus nephritis, and in individuals with SLE IgE autoantibodies and activated basophils are factors associated with disease activity and nephritis.",
"title": "BASOPHILS AND THE T HELPER 2 ENVIRONMENT CAN PROMOTE THE DEVELOPMENT OF LUPUS NEPHRITIS"
}
] |
[
{
"docid": "14938990",
"text": "Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.",
"title": "Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene"
},
{
"docid": "28149602",
"text": "PURPOSE OF REVIEW Recent discoveries implicate neutrophils as important regulators of innate and adaptive immunity and in the development of organ damage in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). RECENT FINDINGS Various putative SLE biomarkers are neutrophil-related, including neutrophil granular proteins and histones undergoing post-translational modifications during neutrophil extracellular trap (NET) formation. In the bone marrow, lupus neutrophils can drive B and T cell abnormalities, at least in part, by their enhanced production of type-I interferons, tumor necrosis factor-alpha (TNFα) and the B-cell stimulating factors B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Lupus neutrophils and, in particular, lupus low-density granulocytes (a distinct pathogenic subset) display epigenetic modifications and genomic alterations that may be relevant to their deleterious roles in SLE. Proteins and enzymes externalized by lupus NETs can affect vascular health by inducing endothelial apoptosis and oxidizing lipoproteins. Hampering NET formation through peptidylarginine deiminase inhibitors abrogates lupus phenotype and atherosclerosis in murine studies. SUMMARY Recent discoveries support the notion that neutrophils, low-density granulocytes and aberrant NET formation and clearance play important roles in lupus pathogenesis. Future studies should focus on how to selectively target these immunostimulatory pathways in this disease.",
"title": "The role of neutrophils in the pathogenesis of systemic lupus erythematosus."
},
{
"docid": "28015516",
"text": "Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a breakdown of tolerance to nuclear antigens and the development of immune complexes. Genomic approaches have shown that human SLE leukocytes homogeneously express type I interferon (IFN)-induced and neutrophil-related transcripts. Increased production and/or bioavailability of IFN-α and associated alterations in dendritic cell (DC) homeostasis have been linked to lupus pathogenesis. Although neutrophils have long been shown to be associated with lupus, their potential role in disease pathogenesis remains elusive. Here, we show that mature SLE neutrophils are primed in vivo by type I IFN and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). SLE NETs contain DNA as well as large amounts of LL37 and HMGB1, neutrophil proteins that facilitate the uptake and recognition of mammalian DNA by plasmacytoid DCs (pDCs). Indeed, SLE NETs activate pDCs to produce high levels of IFN-α in a DNA- and TLR9 (Toll-like receptor 9)-dependent manner. Our results reveal an unsuspected role for neutrophils in SLE pathogenesis and identify a novel link between nucleic acid-recognizing antibodies and type I IFN production in this disease.",
"title": "Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus."
},
{
"docid": "5448119",
"text": "Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 × 10−8): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P≤ 1 × 10−5. A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 × 10−3) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.",
"title": "A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus"
},
{
"docid": "1834762",
"text": "Research on the human microbiome has established that commensal and pathogenic bacteria can influence obesity, cancer, and autoimmunity through mechanisms mostly unknown. We found that a component of bacterial biofilms, the amyloid protein curli, irreversibly formed fibers with bacterial DNA during biofilm formation. This interaction accelerated amyloid polymerization and created potent immunogenic complexes that activated immune cells, including dendritic cells, to produce cytokines such as type I interferons, which are pathogenic in systemic lupus erythematosus (SLE). When given systemically, curli-DNA composites triggered immune activation and production of autoantibodies in lupus-prone and wild-type mice. We also found that the infection of lupus-prone mice with curli-producing bacteria triggered higher autoantibody titers compared to curli-deficient bacteria. These data provide a mechanism by which the microbiome and biofilm-producing enteric infections may contribute to the progression of SLE and point to a potential molecular target for treatment of autoimmunity.",
"title": "Amyloid-DNA Composites of Bacterial Biofilms Stimulate Autoimmunity."
},
{
"docid": "27466734",
"text": "Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.",
"title": "Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study"
},
{
"docid": "7115651",
"text": "IL-21 is a pleiotropic type 1 cytokine that shares the common cytokine receptor γ-chain, γ(c), with IL-2, IL-4, IL-7, IL-9, and IL-15. IL-21 is most homologous to IL-2. These cytokines are encoded by adjacent genes, but they are functionally distinct. Whereas IL-2 promotes development of regulatory T cells and confers protection from autoimmune disease, IL-21 promotes differentiation of Th17 cells and is implicated in several autoimmune diseases, including type 1 diabetes and systemic lupus erythematosus. However, the roles of IL-21 and IL-2 in CNS autoimmune diseases such as multiple sclerosis and uveitis have been controversial. Here, we generated Il21-mCherry/Il2-emGFP dual-reporter transgenic mice and showed that development of experimental autoimmune uveitis (EAU) correlated with the presence of T cells coexpressing IL-21 and IL-2 into the retina. Furthermore, Il21r(-/-) mice were more resistant to EAU development than wild-type mice, and adoptive transfer of Il21r(-/-) T cells induced much less severe EAU, underscoring the need for IL-21 in the development of this disease and suggesting that blocking IL-21/γ(c)-signaling pathways may provide a means for controlling CNS auto-inflammatory diseases.",
"title": "Key role for IL-21 in experimental autoimmune uveitis."
},
{
"docid": "14853989",
"text": "Autoantibodies to DNA and histones (chromatin) are the defining antigen specificity in systemic lupus erythematosus (SLE) and related musculoskeletal disorders but the mechanisms responsible for their induction remain mysterious. That situation rapidly changed once neutrophil extracellular chromatin traps (NETs) were discovered and observed to play a conserved role in innate immune responses to a broad variety of microbial pathogens. At the center of an infectious process, neutrophils exert various antimicrobial defenses, including the release of nuclear chromatin into the extracellular space. The externalized NETs, a complex meshwork of nuclear chromatin and antimicrobial proteins, serve to immobilize and degrade microbial pathogens. Here, we critically evaluate the evidence supporting NETs versus apoptotic bodies as a source for nuclear antigens in autoimmunity. We also discuss the possibility that NET chromatin forms an essential component of immune deposits in the pathogenesis of glomerulonephritis in SLE and other autoimmune immune complex diseases.",
"title": "Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity"
},
{
"docid": "8639034",
"text": "IL-10 gene transcription and IL-10 protein production was assessed in both type 1 (Th1) and type 2 (Th2) CD4+ human T cell clones by polymerase chain reaction and ELISA, respectively. Although Th2 clones apparently showed higher IL-10 mRNA levels, IL-10 mRNA expression was consistently found in Th1 clones, as well. Likewise, measurable IL-10 levels were found in the supernatants of both Th1 and Th2 clones. The effect of human IL-10 (h-IL-10) and viral IL-10 (v-IL-10) on the proliferative response and cytokine production by Th1 and Th2 human clones was also investigated. Addition in culture of h-IL-10 and v-IL-10 significantly reduced the proliferation of both Th1 and Th2 clones in response to the specific Ag and to PHA, but it had no inhibitory effect on the proliferative response of Th1 and Th2 clones to IL-2. h-IL-10 and v-IL-10 also inhibited the Ag-induced production of gamma-interferon (IFN-gamma) by Th1 clones and the production of IL-4 and IL-5 by Th2 clones, whereas they had no effect on the cytokine synthesis by the same clones stimulated with PMA plus anti-CD3 antibody. Preincubation of APC, but not of clonal T blasts, with h-IL-10 resulted in the inhibition of Ag-induced proliferation of both Th1 and Th2 clones, supporting the view that h-IL-10 primarily affects APC. These data demonstrate that, unlike the murine system where IL-10 is a product of Th2 (but not Th1) cells and seems to mainly down-regulate the Th1 response, in the human system, IL-10 is produced by, and down-regulates the function of, both Th1 and Th2 cells.",
"title": "Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production."
},
{
"docid": "14311986",
"text": "The molecular basis for the distinctive cytokine expression of CD4+ T helper 1 (Th1) and T helper 2 (Th2) subsets remains elusive. Here, we report that the proto-oncogene c-maf, a basic region/leucine zipper transcription factor, controls tissue-specific expression of IL-4. c-Maf is expressed in Th2 but not Th1 clones and is induced during normal precursor cell differentiation along a Th2 but not Th1 lineage. c-Maf binds to a c-Maf response element (MARE) in the proximal IL-4 promoter adjacent to a site footprinted by extracts from Th2 but not Th1 clones. Ectopic expression of c-Maf transactivates the IL-4 promoter in Th1 cells, B cells, and nonlymphoid cells, a function that maps to the MARE and Th2-specific footprint. Furthermore, c-Maf acts in synergy with the nuclear factor of activated T cells (NF-ATp) to initiate endogeneous IL-4 production by B cells. Manipulation of c-Maf may alter Th subset ratios in human disease.",
"title": "The Proto-Oncogene c-maf Is Responsible for Tissue-Specific Expression of Interleukin-4"
},
{
"docid": "21258863",
"text": "In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to tissue destruction and fibrosis, which causes much of the morbidity and mortality associated with this disease. Here we show the importance of IL-13 in the pathogenesis of schistosomiasis, and demonstrate, perhaps for the first time, the therapeutic efficacy of an IL-13 inhibitor, sIL-13Ralpha2-Fc, in the control of hepatic fibrosis. T-helper type 2 (Th2) cytokines dominate the immune response in mice infected with Schistosoma mansoni, yet the specific contributions of IL-13 and IL-4 to the development of fibrosis were not previously investigated. Our studies demonstrate that both cytokines play redundant roles in granuloma formation, which explains the ability of IL-4-deficient mice to form granulomas around eggs. More importantly, however, these studies demonstrate that IL-13 is the dominant Th2-type cytokine regulating fibrosis. IL-13 stimulated collagen production in fibroblasts, and procollagen I and procollagen III mRNA expression was decreased in sIL-13Ralpha2-Fc-treated mice. Moreover, the reduction in fibrosis observed in IL-4-deficient mice was much less pronounced than that in sIL-13Ralpha2-Fc-treated animals. Fibrosis is a major pathological manifestation of a number of allergic, autoimmune, and infectious diseases. Thus, our findings provide evidence that IL-13 inhibitors may be of general therapeutic benefit in preventing damaging tissue fibrosis resulting from Th2-dominated inflammatory responses.",
"title": "An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response."
},
{
"docid": "696006",
"text": "Patients with asthma, a major public health problem, are at high risk for serious disease from influenza virus infection, but the pathogenic mechanisms by which influenza A causes airway disease and asthma are not fully known. We show here in a mouse model that influenza infection acutely induced airway hyper-reactivity (AHR), a cardinal feature of asthma, independently of T helper type 2 (TH2) cells and adaptive immunity. Instead, influenza infection induced AHR through a previously unknown pathway that required the interleukin 13 (IL-13)–IL-33 axis and cells of the non-T cell, non-B cell innate lymphoid type called 'natural helper cells'. Infection with influenza A virus, which activates the NLRP3 inflammasome, resulted in much more production of IL-33 by alveolar macrophages, which in turn activated natural helper cells producing substantial IL-13.",
"title": "Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity"
},
{
"docid": "1049501",
"text": "Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.",
"title": "Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease"
},
{
"docid": "26068103",
"text": "RSV lower respiratory tract infections (LRTI) are among the most common diseases necessitating hospital admission in children. In addition to causing acute respiratory failure, RSV infections are associated with sequelae such as secondary bacterial infections and reactive airway disease. One characteristic host response observed in severe RSV-induced LRTI and/or subsequent development of asthma is increased expression of interleukin (IL)-10. However, contradictory results have been reported regarding whether IL-10 inhibits asthmatic responses or intensifies the disease. We aimed to reconcile these discordant observations by elucidating the role of IL-10 in regulating the host response to RSV LRTI. In this study, we used a lung-specific, inducible IL-10 over-expression (OE) transgenic mouse model to address this question. Our results showed that the presence of IL-10 at the time of RSV infection not only attenuated acute inflammatory process (i.e. 24 h post-infection), but also late inflammatory changes [characterized by T helper type 2 (Th2) cytokine and chemokine expression]. While this result appears contradictory to some clinical observations where elevated IL-10 levels are observed in asthmatic patients, we also found that delaying IL-10 OE until the late immune response to RSV infection, additive effects rather than inhibitory effects were observed. Importantly, in non-infected, IL-10 OE mice, IL-10 OE alone induced up-regulation of Th2 cytokine (IL-13 and IL-5) and Th2-related chemokine [monocyte chemoattractant protein 1 (MCP-1), chemokine (C-C motif) ligand 3 (CCL3) and regulated upon activation normal T cell expressed and secreted (RANTES)] expression. We identified a subset of CD11b(+)CD11c(+)CD49b(+)F4/80(-)Gr-1(-) myeloid cells as a prinicipal source of IL-10-induced IL-13 production. Therefore, the augmented pathological responses observed in our 'delayed' IL-10 over-expression model could be attributed to IL-10 OE alone. Taken together, our study indicated dual roles of IL-10 on RSV-induced lung inflammation which appear to depend upon the timing of when elevated IL-10 is expressed in the lung.",
"title": "Dual role of interleukin-10 in the regulation of respiratory syncitial virus (RSV)-induced lung inflammation."
},
{
"docid": "40365566",
"text": "Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b(+) monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b(+) cDCs but not CD103(+) cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l(-/-) mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b(+) cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung.",
"title": "Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen."
},
{
"docid": "2042250",
"text": "Interleukin-33 (IL-33), a newly described member of the IL-1 family, is expressed by many cell types following pro-inflammatory stimulation and is thought to be released on cell lysis. The IL-33 receptor, consisting of ST2 and IL-1 receptor accessory protein, is also widely expressed, particularly by T helper 2 (TH2) cells and mast cells. IL-33 is host-protective against helminth infection and reduces atherosclerosis by promoting TH2-type immune responses. However, IL-33 can also promote the pathogenesis of asthma by expanding TH2 cells and mediate joint inflammation, atopic dermatitis and anaphylaxis by mast cell activation. Thus IL-33 could be a new target for therapeutic intervention across a range of diseases.",
"title": "Disease-associated functions of IL-33: the new kid in the IL-1 family"
},
{
"docid": "22852120",
"text": "Type 2 immune responses are defined by the cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, which can either be host protective or have pathogenic activity. Type 2 immunity promotes antihelminth immunity, suppresses type 1-driven autoimmune disease, neutralizes toxins, maintains metabolic homeostasis, and regulates wound repair and tissue regeneration pathways following infection or injury. Nevertheless, when type 2 responses are dysregulated, they can become important drivers of disease. Type 2 immunity induces a complex inflammatory response characterized by eosinophils, mast cells, basophils, type 2 innate lymphoid cells, IL-4-and/or IL-13-conditioned macrophages and T helper 2 (TH2) cells, which are crucial to the pathogenesis of many allergic and fibrotic disorders. As chronic type 2 immune responses promote disease, the mechanisms that regulate their maintenance are thought to function as crucial disease modifiers. This Review discusses the many endogenous negative regulatory mechanisms that antagonize type 2 immunity and highlights how therapies that target some of these pathways are being developed to treat type 2-mediated disease.",
"title": "Type 2 cytokines: mechanisms and therapeutic strategies"
},
{
"docid": "20388894",
"text": "IL-4 promotes the differentiation of naive CD4+ T cells into IL-4-producing T helper 2 (Th2) cells. Previous work provided suggestive but not conclusive evidence that the transcription factor c-Maf directed the tissue-specific expression of IL-4. It was not known whether c-Maf controlled the transcription of other Th2 cytokine genes. To elucidate the role of c-Maf in vivo, we examined cytokine production in mice lacking c-Maf (c-maf(-/-)). CD4+ T cells and NK T cells from c-maf(-/-) mice were markedly deficient in IL-4 production. However, the mice produced normal levels of IL-13 and IgE, and, when differentiated in the presence of exogenous IL-4, c-maf(-/-) T cells produced approximately normal levels of other Th2 cytokines. We conclude that c-Maf has a critical and selective function in IL-4 gene transcription in vivo.",
"title": "The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines."
},
{
"docid": "17829012",
"text": "Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signalling is an important determinant of IL-4 expression in Tfh cells. Batf deficiency impairs the generation of IL-4-producing Tfh cells that results in protection against allergic asthma. Our results thus indicate a positive role of Batf in promoting the generation of pro-allergic IL-4-producing Tfh cells.",
"title": "Batf is important for IL-4 expression in T follicular helper cells"
},
{
"docid": "6723450",
"text": "Probiotics are promoted as being beneficial to health and positive effects on the immune system have been reported. Beneficial immune effects have been attributed to several mechanisms, including stimulating T helper 1 (Th1) immunity. To explore the effects of the probiotic Bifidobacterium animalis on Th1- and Th2-mediated immune responses, two different animal models representing either Th1- or Th2-mediated immune responses were used: a rat model for experimental autoimmune encephalomyelitis (EAE) (Th1) and a mouse model for respiratory allergy induced by ovalbumin (OVA) (Th2). B. animalis administration started when the mice or rats were 2 weeks old. Respiratory allergy or EAE were induced when the animals were 6-7 weeks old. In the allergy model, B. animalis modestly reduced the number of infiltrating eosinophils and lymphocytes in the lungs, but no effects on allergen-specific serum immunoglobulin E levels were found. Cytokine profiles assessed after culturing spleen cells with the mitogen concanvalin A (ConA) showed that B. animalis skewed the Th1/Th2 balance towards Th1 in females. However, allergen-induced cytokine production in females was not affected by B. animalis. In males, B. animalis significantly decreased ConA-induced interleukin-13 and a trend towards lower levels of OVA-induced Th2 cytokines. In the EAE model, B. animalis significantly reduced the duration of clinical symptoms by almost 2 days in males and improved the body weight gain during the experimental period compared with the control group. Our data show that B. animalis reduced several immune parameters in the allergy as well as in the autoimmunity model.",
"title": "Effects of Bifidobacterium animalis administered during lactation on allergic and autoimmune responses in rodents."
},
{
"docid": "13798951",
"text": "CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.",
"title": "Differentiation of effector CD4 T cell populations (*)."
},
{
"docid": "30774694",
"text": "Autophagy is a recently recognized immune effector mechanism against intracellular pathogens. The role of autophagy in innate immunity has been well established, but the extent of its regulation by the adaptive immune response is less well understood. The T helper 1 (Th1) cell cytokine IFN-gamma induces autophagy in macrophages to eliminate Mycobacterium tuberculosis. Here, we report that Th2 cytokines affect autophagy in macrophages and their ability to control intracellular M. tuberculosis. IL-4 and IL-13 abrogated autophagy and autophagy-mediated killing of intracellular mycobacteria in murine and human macrophages. Inhibition of starvation-induced autophagy by IL-4 and IL-13 was dependent on Akt signaling, whereas the inhibition of IFN-gamma-induced autophagy was Akt independent and signal transducer and activator of transcription 6 (STAT6) dependent. These findings establish a mechanism through which Th1-Th2 polarization differentially affects the immune control of intracellular pathogens.",
"title": "T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis."
},
{
"docid": "10831818",
"text": "OBJECTIVE Multiple sclerosis (MS) is a disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Based on infiltrating immune cells, deposition of humoral factors and loss of oligodendrocytes and/or myelin proteins, four lesion patterns have been described. Pattern II is characterized by antibody and complement deposition in addition to T-cell infiltration. MS is considered a T-cell-mediated disease, but until now the study of pathogenic T cells has encountered major challenges, most importantly the limited access of brain-infiltrating T cells. Our objective was to identify, isolate, and characterize brain-infiltrating clonally expanded T cells in pattern II MS lesions. METHODS We used next-generation sequencing to identify clonally expanded T cells in demyelinating pattern II brain autopsy lesions, subsequently isolated these as T-cell clones from autologous cerebrospinal fluid and functionally characterized them. RESULTS We identified clonally expanded CD8(+) but also CD4(+) T cells in demyelinating pattern II lesions and for the first time were able to isolate these as live T-cell clones. The functional characterization shows that T cells releasing Th2 cytokines and able to provide B cell help dominate the T-cell infiltrate in pattern II brain lesions. INTERPRETATION Our data provide the first functional evidence for a putative role of Th2/Tc2 cells in pattern II MS supporting the existence of this pathogenic phenotype and questioning the protective role that is generally ascribed to Th2 cells. Our observations are important to consider for future treatments of pattern II MS patients.",
"title": "Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions"
},
{
"docid": "25453683",
"text": "OBJECTIVE T cell immunoglobulin and mucin domain (Tim) proteins are expressed by numerous immune cells, recognize phosphatidylserine on apoptotic cells, and function as costimulators or coinhibitors. Tim-1 is expressed by activated T cells but is also found on dendritic cells and B cells. Tim-4, present on macrophages and dendritic cells, plays a critical role in apoptotic cell clearance, regulates the number of phosphatidylserine-expressing activated T cells, and is genetically associated with low low-density lipoprotein and triglyceride levels. Because these functions of Tim-1 and Tim-4 could affect atherosclerosis, their modulation has potential therapeutic value in cardiovascular disease. APPROACH AND RESULTS ldlr(-/-) mice were fed a high-fat diet for 4 weeks while being treated with control (rat immunoglobulin G1) or anti-Tim-1 (3D10) or -Tim-4 (21H12) monoclonal antibodies that block phosphatidylserine recognition and phagocytosis. Both anti-Tim-1 and anti-Tim-4 treatments enhanced atherosclerosis by 45% compared with controls by impairment of efferocytosis and increasing aortic CD4(+)T cells. Consistently, anti-Tim-4-treated mice showed increased percentages of activated T cells and late apoptotic cells in the circulation. Moreover, in vitro blockade of Tim-4 inhibited efferocytosis of oxidized low-density lipoprotein-induced apoptotic macrophages. Although anti-Tim-4 treatment increased T helper cell (Th)1 and Th2 responses, anti-Tim-1 induced Th2 responses but dramatically reduced the percentage of regulatory T cells. Finally, combined blockade of Tim-1 and Tim-4 increased atherosclerotic lesion size by 59%. CONCLUSIONS Blockade of Tim-4 aggravates atherosclerosis likely by prevention of phagocytosis of phosphatidylserine-expressing apoptotic cells and activated T cells by Tim-4-expressing cells, whereas Tim-1-associated effects on atherosclerosis are related to changes in Th1/Th2 balance and reduced circulating regulatory T cells.",
"title": "Blockade of Tim-1 and Tim-4 Enhances Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice."
},
{
"docid": "13106686",
"text": "Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3' repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.",
"title": "Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing."
},
{
"docid": "20311968",
"text": "Cellular therapy with chimeric antigen receptor (CAR)-redirected cytotoxic T cells has shown impressive efficacy in the treatment of hematologic malignancies. We explored a regulatory T cell (Treg)-based therapy in the treatment of allergic airway inflammation, a model for asthma, which is characterized by an airway hyper-reactivity (AHR) and a chronic, T helper-2 (Th2) cell-dominated immune response to allergen. To restore the immune balance in the lung, we redirected Tregs by a CAR toward lung epithelia in mice upon experimentally induced allergic asthma, closely mimicking the clinical situation. Adoptively transferred CAR Tregs accumulated in the lung and in tracheobronchial lymph nodes, reduced AHR and diminished eosinophilic airway inflammation, indicated by lower cell numbers in the bronchoalveolar lavage fluid and decreased cell infiltrates in the lung. CAR Treg cells furthermore prevented excessive pulmonary mucus production as well as increase in allergen-specific IgE and Th2 cytokine levels in exposed animals. CAR Tregs were more efficient in controlling asthma than non-modified Tregs, indicating the pivotal role of specific Treg cell activation in the affected organ. Data demonstrate that lung targeting CAR Treg cells ameliorate key features of experimental airway inflammation, paving the way for cell therapy of severe allergic asthma.",
"title": "Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma"
},
{
"docid": "1855679",
"text": "It was recently demonstrated that interleukin (IL)-23–driven IL-17–producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases. We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I–deficient (IL-1RI−/−) mice. Furthermore, the incidence of experimental autoimmune encephalomyelitis (EAE) was significantly lower in IL-1RI−/− compared with wild-type mice, and this correlated with a failure to induce autoantigen-specific ThIL-17 cells, whereas induction of Th1 and Th2 responses was not substantially different. However, EAE was induced in IL-1RI−/− mice by adoptive transfer of autoantigen-specific cells from wild-type mice with EAE. IL-23 alone did not induce IL-17 production by T cells from IL-1RI−/− mice, and IL-23–induced IL-17 production was substantially enhanced by IL-1α or IL-1β, even in the absence of T cell receptor stimulation. We demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor κB, and novel protein kinase C isoforms in IL-1– and IL-23–mediated IL-17 production. Tumor necrosis factor α also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent. Our findings demonstrate that IL-1 functions upstream of IL-17 to promote pathogenic ThIL-17 cells in EAE.",
"title": "A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis"
},
{
"docid": "8063697",
"text": "Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.",
"title": "Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model."
},
{
"docid": "5476778",
"text": "One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS). There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5,6,7). HAM/TSP patients develop antibodies to neurons. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.",
"title": "Autoimmunity due to molecular mimicry as a cause of neurological disease"
},
{
"docid": "20148808",
"text": "The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4 (IL4)-producing CD4+ T cells and decreased levels of circulating immunoglobulin E (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less motile in response to CCL19 in vitro, and exhibit a dampened ability to transport inhaled allergens to lung draining nodes. Our data thus demonstrate that gut dysbiosis can exacerbate allergic lung inflammation through both T cell- and DC-dependent mechanisms that are inhibited by SCFAs.",
"title": "Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids"
}
] |
105275
|
Franklin D. Roosevelt spearheaded federal legislation.
|
[
{
"docid": "Franklin_D._Roosevelt",
"text": "Franklin Delano Roosevelt ( -LSB- ˈroʊzəvəlt -RSB- , his own pronunciation , or -LSB- - en ˈroʊzəvɛlt -RSB- January 30 , 1882 -- April 12 , 1945 ) , commonly known as FDR , was an American statesman and political leader who served as the 32nd President of the United States from 1933 until his death in 1945 . A Democrat , he won a record four presidential elections and emerged as a central figure in world events during the mid-20th century . He directed the United States government during most of the Great Depression and World War II . As a dominant leader of his party , he built the New Deal Coalition , realigning American politics into the Fifth Party System and defining American liberalism throughout the middle third of the 20th century . He is often rated by scholars as one of the three greatest U.S. Presidents , along with George Washington and Abraham Lincoln . Roosevelt was born in 1882 to an old , prominent Dutch family from Dutchess County , New York and attended Groton School . He went on to graduate from Harvard College in 1903 and attended Columbia Law School . At age 23 in 1905 , he married Eleanor Roosevelt , and the couple went on to have six children . He entered politics in 1910 , serving in the New York State Senate , and then as Assistant Secretary of the Navy under President Woodrow Wilson . In 1920 , presidential candidate James M. Cox selected Roosevelt as his running mate , but the Cox/Roosevelt ticket lost to the Republican ticket of Warren Harding and Calvin Coolidge . In 1921 , Roosevelt was stricken with debilitating polio , which cost him the use of his legs . The disability put his future political career in jeopardy , but he attempted to recover from the illness and founded the treatment center in Warm Springs , Georgia for people with polio . Roosevelt returned to political life when he nominated Alfred E. Smith at the 1924 Democratic National Convention . At Smith 's behest , Roosevelt successfully ran for Governor of New York in 1928 . He was in office from 1929 to 1933 and served as a reform governor , promoting the enactment of programs to combat the depression besetting the United States at the time . In the 1932 presidential election , Roosevelt defeated incumbent Republican president Herbert Hoover in a landslide to win the presidency . Roosevelt took office while the United States was in the midst of the worst economic crisis in its history . Energized by his personal victory over polio , FDR relied on his persistent optimism and activism to renew the national spirit . During his first 100 days in office , Roosevelt spearheaded unprecedented federal legislation and issued a profusion of executive orders that instituted the New Deal -- a variety of programs designed to produce relief ( government jobs for the unemployed ) , recovery ( economic growth ) , and reform ( through regulation of Wall Street , banks and transportation ) . He created numerous programs to support the unemployed and farmers , and to encourage labor union growth while more closely regulating business and high finance . His support for the repeal of Prohibition in 1933 added to his popularity , helping him win re-election by a landslide in 1936 . The economy improved rapidly from 1933 -- 37 , but then relapsed into a deep recession in 1937 -- 38 . The bipartisan Conservative Coalition that formed in 1937 prevented his packing the Supreme Court , and blocked almost all proposals for major liberal legislation ( except the minimum wage , which did pass ) . When the war began and unemployment ended , conservatives in Congress repealed the two major relief programs , the Works Progress Administration ( WPA ) and Civilian Conservation Corps ( CCC ) . However , they kept most of the regulations on business . Along with several smaller programs , major surviving programs include the Securities and Exchange Commission , the Wagner Act , the Federal Deposit Insurance Corporation and Social Security . With World War II looming after 1938 with the Japanese invasion of China and the aggression of Nazi Germany , Roosevelt gave strong diplomatic and financial support to China and the United Kingdom , while remaining officially neutral . His goal was to make America the `` Arsenal of Democracy '' , which would supply munitions to the Allies . In March 1941 , Roosevelt , with Congressional approval , provided Lend-Lease aid to Britain and China . Following the Japanese surprise attack on Pearl Harbor on December 7 , 1941 , which he famously called `` a date which will live in infamy '' , Roosevelt sought and obtained the quick approval on the following day for Congress to declare war on Japan and , a few days later , on Germany . Assisted by his top aide Harry Hopkins , and with very strong national support , he worked closely with British Prime Minister Winston Churchill , Soviet leader Joseph Stalin and Chinese Generalissimo Chiang Kai-shek in leading the Allies against Nazi Germany , Fascist Italy and Imperial Japan in World War II . He supervised the mobilization of the U.S. economy to support the war effort , and also ordered the internment of 100,000 Japanese American civilians . As an active military leader , Roosevelt implemented a war strategy on two fronts that ended in the defeat of the Axis Powers , and he initiated the development of the world 's first atomic bomb . His work also influenced the later creation of the United Nations and Bretton Woods . Roosevelt 's physical health seriously declined during the war years , and he died weeks into his fourth term . He was then succeeded by his vice president Harry S. Truman , and a few months after Truman 's inauguration , the United States bombed the Japanese cities of Hiroshima and Nagasaki , leading to Japan 's surrender .",
"title": ""
}
] |
[
{
"docid": "Emergency_Price_Control_Act_of_1942",
"text": "The Emergency Price Control Act of 1942 is a United States statute imposing an economic intervention as restrictive measures to control inflationary spiraling and pricing elasticity of goods and services while providing economic efficiency to support the United States national defense and security . The Act of Congress established the Office of Price Administration ( OPA ) as a federal independent agency being officially created by Franklin D. Roosevelt on April 11 , 1941 . The H.R. 5990 legislation was passed by the 77th U.S. Congressional session and enacted into law by Franklin D. Roosevelt on January 30 , 1942 .",
"title": ""
},
{
"docid": "List_of_federal_judges_appointed_by_Franklin_D._Roosevelt",
"text": "Following is a list of all United States federal judges appointed by President Franklin D. Roosevelt during his presidency . In total Roosevelt appointed 193 federal judges , more than twice as many as the previous record of 79 appointed by Calvin Coolidge . These included eight Justices to the Supreme Court of the United States , elevated one to Chief Justice , appointed 51 judges to the United States Courts of Appeals , and 134 judges to the United States district courts .",
"title": ""
},
{
"docid": "Inauguration_of_Franklin_D._Roosevelt",
"text": "Inauguration of Franklin D. Roosevelt may refer to : First inauguration of Franklin D. Roosevelt , 1933 Second inauguration of Franklin D. Roosevelt , 1937 Third inauguration of Franklin D. Roosevelt , 1941 Fourth inauguration of Franklin D. Roosevelt , 1945",
"title": ""
},
{
"docid": "Franklin_Roosevelt_(disambiguation)",
"text": "Franklin Roosevelt ( 1882 -- 1945 ) was the 32nd President of the United States . Franklin Roosevelt may also refer to : Franklin Delano Roosevelt Memorial , Washington , D.C. , presidential memorial USS Franklin D. Roosevelt , American aircraft carrier Roosevelt Dime , American 10 cent coin Franklin D. Roosevelt ( Paris Métro ) , a station serving lines 1 and 9 of Paris , France 's Métro Franklin Roosevelt State Park , a state park in Georgia People Franklin Delano Roosevelt , Jr. ( 1914 -- 1988 ) , American politician , fifth child of Franklin D. Roosevelt Franklin Delano Roosevelt III ( born 1938 ) , American economist , grandson of Franklin D. Roosevelt Roosevelt , Franklin",
"title": ""
},
{
"docid": "List_of_diplomatic_missions_during_World_War_II",
"text": "Below is a list of diplomatic missions during World War II that were undertaken by the allied forces . Arcadia ( 1941 ) -- Washington Conference between President of the United States Franklin D. Roosevelt and Prime MInister of the United Kingdom Winston Churchill Argonaut ( 1945 ) -- linked sequence of conferences Cricket ( 1945 ) -- pre-Yalta Conference at Malta between Franklin D. Roosevelt and Winston Churchill Magneto ( 1945 ) -- Yalta Conference between Franklin D. Roosevelt , Premier of the Soviet Union Joseph Stalin and Winston Churchill Eureka ( 1943 ) -- conference between Franklin D. Roosevelt , Winston Churchill and Joseph Stalin at Tehran Octagon ( 1944 ) -- conference between Franklin D. Roosevelt and Winston Churchill at Quebec City to discuss Morgenthau Plan Quadrant ( 1943 ) -- conference between Franklin D. Roosevelt and Winston Churchill at Quebec City Riviera ( 1941 ) -- Franklin D. Roosevelt/Winston Churchill conference at Placentia Bay , Newfoundland Sextant 1 ( 1943 ) -- conference between Franklin D. Roosevelt , Winston Churchill and Premier of China Chiang Kai-shek at Cairo Sextant 2 ( 1943 ) -- conference between Franklin D. Roosevelt , Winston Churchill and President of Turkey İsmet İnönü at Cairo Symbol ( 1943 ) -- conference between Franklin D. Roosevelt , Winston Churchill and the leader of the Free French , Charles de Gaulle , at Casablanca Terminal ( 1945 ) -- conference between Franklin D. Roosevelt , Winston Churchill , Clement Attlee and Joseph Stalin at Potsdam Trident ( 1943 ) -- third Washington conference between Franklin D. Roosevelt and Churchill",
"title": ""
},
{
"docid": "Presidency_of_Franklin_D._Roosevelt",
"text": "The presidency of Franklin D. Roosevelt began on March 4 , 1933 , when he was inaugurated as the 32nd President of the United States , and ended upon his death on April 12 , 1945 , a span of ( 4422 days ) . Roosevelt assumed the presidency in the midst of the Great Depression . Starting with his landslide victory over Republican President Herbert Hoover in the 1932 election . He won a record four presidential terms , and became a central figure in world affairs during World War II . His program for relief , recovery and reform , known as the New Deal , involved a great expansion of the role of the federal government in the economy . Under his steady leadership , the Democratic Party built a `` New Deal Coalition '' of labor unions , big city machines , white ethnics , African Americans , and rural white Southerners , that would significantly realign American politics for the next several decades in the Fifth Party System and also define modern American liberalism . During his first hundred days in office , Roosevelt spearheaded unprecedented major legislation and issued a profusion of executive orders that instituted the New Deal -- a variety of programs designed to produce relief ( government jobs for the unemployed ) , recovery ( economic growth ) , and reform ( through regulation of Wall Street , banks and transportation ) . He created numerous programs to support the unemployed and farmers , and to encourage labor union growth while more closely regulating business and high finance . The repeal of Prohibition in 1933 added to his popularity , helping him win re-election by a landslide in 1936 . The economy improved rapidly from 1933 to 1937 , but then relapsed into a deep recession in 1937 -- 38 . The bipartisan Conservative Coalition that formed in 1937 prevented his attempted packing of the Supreme Court , and blocked most of his legislative proposals , aside from the Fair Labor Standards Act . When the war began and unemployment largely became a non-issue , conservatives in Congress repealed the two major relief programs , the WPA and CCC , but kept most of the regulations on business . Along with several smaller programs , major surviving programs from the New Deal include the Securities and Exchange Commission , the Wagner Act , the Federal Deposit Insurance Corporation , and Social Security . A potential worldwide war loomed after 1937 , with the Japanese invasion of China and the aggression of Nazi Germany , which invaded Poland in September 1939 . Roosevelt remained officially neutral but gave strong diplomatic and financial support to China , the United Kingdom , Free France , and the Soviet Union via initiatives such as the Lend-Lease programs . Following the Japanese attack on Pearl Harbor on December 7 , 1941 , Roosevelt sought and obtained a declaration of war upon Japan . A few days later , he sought and obtained a declaration of war upon the other major Axis powers , Germany and Italy . Assisted by his top aide Harry Hopkins , and with very strong national support , he worked closely with British Prime Minister Winston Churchill , Soviet leader Joseph Stalin , and Chinese Generalissimo Chiang Kai-shek in leading the Allies during World War II . He supervised the mobilization of the U.S. economy to support the war effort , and the war saw the end of the massive unemployment that characterized the Great Depression . Roosevelt sought to desegregate the federal workforce with the Fair Employment Practice Committee , but he also controversially ordered the internment of 100,000 Japanese American civilians . As an active military leader , Roosevelt implemented a war strategy on two fronts that ended in the defeat of the Axis Powers and the development of the world 's first nuclear bomb . Though he died months before the end of the war , his work on the post-war order shaped the new United Nations and the Bretton Woods international financial system . Roosevelt 's health seriously declined during the war years , and he died three months into his fourth term . He was succeeded by Vice President Harry S. Truman . It was on Roosevelt 's watch that the Democratic Party was returned to dominance , prosperity returned , and two great military enemies were destroyed . Scholars , historians and the public typically rank Roosevelt alongside Abraham Lincoln and George Washington as one of the three greatest U.S. Presidents .",
"title": ""
},
{
"docid": "Roosevelt_Memorial",
"text": "Roosevelt Memorial may refer to : Franklin Delano Roosevelt Memorial , a presidential memorial in Washington , DC List of things named after Franklin D. Roosevelt See Franklin D. Roosevelt #Legacy for other memorials Theodore Roosevelt Island , an island and presidential memorial in Washington , DC See Theodore Roosevelt #Memorials for other memorials",
"title": ""
},
{
"docid": "Electoral_history_of_Franklin_D._Roosevelt",
"text": "Electoral history of Franklin D. Roosevelt , 32nd President of the United States ( 1933 -- 1945 ) ; 44th Governor of New York ( 1929 -- 1932 ) . New York United States Senate election , 1914 ( Democratic primary ) : James Gerard -- 133,815 ( 62.08 % ) Franklin D. Roosevelt -- 63,879 ( 29.64 % ) James S. McDonough -- 17,862 ( 8.29 % ) 1920 Democratic National Convention ( Vice Presidential tally ) : Franklin D. Roosevelt -- 1,094 ( 100.00 % ) United States presidential election , 1920 Warren G. Harding/Calvin Coolidge ( R ) -- 16,144,093 ( 60.3 % ) and 404 electoral votes ( 37 states carried ) James M. Cox/Franklin D. Roosevelt ( D ) -- 9,139,661 ( 34.1 % ) and 127 electoral votes ( 11 states carried ) Eugene Debs/Seymour Stedman ( Socialist ) -- 913,693 ( 3.4 % ) Parley P. Christensen/Maximillian Sebastian Hayes ( Farmer-Labor ) -- 265,411 ( 1.0 % ) Aaron S. Watkins/D . Leigh Colvin ( Prohibition ) -- 188,787 ( 0.7 % ) James E. Ferguson/William Jervis Hough ( American ) -- 47,968 ( 0.2 % ) William Wesley Cox/August Gillhaus ( Socialist Labor ) -- 31,716 ( 0.1 % ) New York gubernatorial election , 1928 : Franklin D. Roosevelt/Herbert H. Lehman ( D ) -- 2,130,193 ( 48.96 % ) Albert Ottinger/Charles Clapp Lockwood ( R ) -- 2,104,129 ( 48.36 % ) Louis Waldman/Herman J. Hahn ( Socialist ) -- 101,859 ( 2.34 % ) William F. Dunne/Franklin P. Brill ( Workers ) -- 10,741 ( 0.25 % ) Charles Hunter Corregan/John E. DeLee ( Socialist Labor ) -- 4,213 ( 0.10 % ) New York gubernatorial election , 1930 : Franklin D. Roosevelt/Herbert H. Lehman ( D ) ( inc. ) -- 1,770,342 ( 56.49 % ) Charles H. Tuttle/Caleb H. Baumes ( R ) -- 1,045,341 ( 33.36 % ) Robert P. Carroll ( Law Preservation ) -- 190,666 ( 6.08 % ) Louis Waldman/Elizabeth C. Roth ( Socialist ) -- 100,444 ( 3.21 % ) William Z. Foster/J . Louis Engdahl ( Communist ) -- 18,034 ( 0.58 % ) Jeremiah D. Crowley/Charles M. Carlson ( Socialist Labor ) -- 9,096 ( 0.29 % )",
"title": ""
},
{
"docid": "Timeline_of_the_presidency_of_Franklin_D._Roosevelt",
"text": "The presidency of Franklin D. Roosevelt began on March 4 , 1933 when Franklin D. Roosevelt was inaugurated as President of the United States , and ended on April 12 , 1945 upon his death .",
"title": ""
},
{
"docid": "Franklin_D._Roosevelt_(Paris_Métro)",
"text": "Franklin D. Roosevelt is a station of the Paris Métro serving both Lines 1 and 9 . With 12.19 m passengers annually , Franklin D. Roosevelt is the fourteenth busiest station in the Paris Métro system .",
"title": ""
},
{
"docid": "Hyde_Park,_New_York",
"text": "Hyde Park is a town in Dutchess County , New York , bordering the Hudson River north of Poughkeepsie . Within the town are the hamlets of Hyde Park , Staatsburg , and Haviland . Hyde Park is known as the hometown of Franklin D. Roosevelt , the 32nd President of the United States . His house there , the Home of Franklin D. Roosevelt National Historic Site , is listed on the U.S. National Register of Historic Places , as are the homes of Eleanor Roosevelt , Isaac Roosevelt , and Frederick William Vanderbilt , along with Franklin D. Roosevelt High School . Hyde Park is home to the main campus of the Culinary Institute of America , a four-year college for culinary and baking and pastry arts , and the Franklin D. Roosevelt Presidential Library and Museum , the first presidential library in the United States . Hyde Park 's population was 21,571 at the 2010 census . US Route 9 passes through the town near the Hudson River .",
"title": ""
},
{
"docid": "Franklin_D._Roosevelt_Four_Freedoms_Park",
"text": "The Franklin D. Roosevelt Four Freedoms Park is a 4 acre memorial to Franklin D. Roosevelt that celebrates the Four Freedoms he articulated in his 1941 State of the Union address . It is located adjacent to the historic Smallpox Hospital in New York City at the southernmost point of Roosevelt Island , in the East River between Manhattan Island and Queens . It was designed by the architect Louis Kahn .",
"title": ""
},
{
"docid": "78th_United_States_Congress",
"text": "The Seventy-eighth United States Congress was a meeting of the legislative branch of the United States federal government , composed of the United States Senate and the United States House of Representatives . It met in Washington , DC from January 3 , 1943 to January 3 , 1945 , during the last two years of Franklin D. Roosevelt 's presidency . The apportionment of seats in the House of Representatives was based on the Sixteenth Census of the United States in 1940 . Both chambers had a Democratic majority .",
"title": ""
},
{
"docid": "First_100_days_of_Franklin_D._Roosevelt's_presidency",
"text": "During the first hundred days of Franklin D. Roosevelt 's presidency , President Franklin D. Roosevelt planned to end the Great Depression . When Roosevelt took office on March 4 , 1933 , he immediately addressed the effects of the depression . His main four priorities were to get Americans back to work , protect their savings and create prosperity , provide relief for the sick and elderly , and get industry and agriculture back on their feet . 15 major laws were enacted in Roosevelt 's first 100 days .",
"title": ""
},
{
"docid": "Smith–Connally_Act",
"text": "The Smith -- Connally Act or War Labor Disputes Act ( 50 U.S.C. App . 1501 et seq. ) was an American law passed on June 25 , 1943 , over President Franklin D. Roosevelt 's veto . The legislation was hurriedly created after 400,000 coal miners , their wages significantly lowered due to high wartime inflation , struck for a $ 2-a-day wage increase . The Act allowed the federal government to seize and operate industries threatened by or under strikes that would interfere with war production , and prohibited unions from making contributions in federal elections . The war powers bestowed by the Act were first used in August 1944 when the Fair Employment Practices Commission ordered the Philadelphia Transportation Company to hire African-Americans as motormen . The 10,000 members of the Philadelphia Rapid Transit Employees Union ( PRTEU ) , a labor union unaffiliated with either the American Federation of Labor or the Congress of Industrial Organizations , led a sick-out strike , now known as the Philadelphia transit strike of 1944 , for six days . President Roosevelt sent 8,000 United States Army troops to the city to seize and operate the transit system , and threatened to draft any PRTEU member who did not return to the job within 48 hours . Roosevelt 's actions broke the strike .",
"title": ""
},
{
"docid": "President_Roosevelt",
"text": "President Roosevelt may refer to : Theodore Roosevelt ( 1858 -- 1919 ) , 26th President of the United States Presidency of Theodore Roosevelt , his presidency Franklin D. Roosevelt ( 1882 -- 1945 ) , 32nd President of the United States and fifth cousin of the 26th President Presidency of Franklin D. Roosevelt , his presidency",
"title": ""
},
{
"docid": "Theodore_and_Franklin_D._Roosevelt_Prize_in_Naval_History",
"text": "The Theodore and Franklin D. Roosevelt Prize in Naval History is an annual prize established in 1986 and given by The New York Council of the Navy League of the United States , the Roosevelt Institute , and the Theodore Roosevelt Association . It is given for the best book on American naval history published in the previous calendar year . The prize commemorates Theodore Roosevelt and Franklin D. Roosevelt , who both served as Assistant Secretary of the Navy , and who both supported the United States Navy as Presidents of the United States . The judges for the prize include specialists in naval history such as faculty members at the U.S. Naval Academy , U.S. Naval War College , U.S. Merchant Marine Academy , U.S. Coast Guard Academy , U.S. Military Academy , The Citadel , and Princeton University .",
"title": ""
},
{
"docid": "76th_United_States_Congress",
"text": "The Seventy-sixth United States Congress was a meeting of the legislative branch of the United States federal government , composed of the United States Senate and the United States House of Representatives . It met in Washington , DC from January 3 , 1939 to January 3 , 1941 , during the seventh and eighth years of Franklin D. Roosevelt 's presidency . The apportionment of seats in the House of Representatives was based on the Fifteenth Census of the United States in 1930 . Both chambers had a Democratic majority . It is the most recent Congress to have held a third session .",
"title": ""
},
{
"docid": "79th_United_States_Congress",
"text": "The Seventy-ninth United States Congress was a meeting of the legislative branch of the United States federal government , composed of the United States Senate and the United States House of Representatives . It met in Washington , DC from January 3 , 1945 to January 3 , 1947 , during the last months of Franklin D. Roosevelt 's presidency , and the first two years of Harry S. Truman 's presidency . The apportionment of seats in this House of Representatives was based on the Sixteenth Census of the United States in 1940 . Both chambers had a Democratic majority .",
"title": ""
},
{
"docid": "Home_of_Franklin_D._Roosevelt_National_Historic_Site",
"text": "The Home of Franklin D. Roosevelt National Historic Site preserves the Springwood estate in Hyde Park , New York . Springwood was the birthplace , lifelong home , and burial place of the 32nd President of the United States , Franklin Delano Roosevelt . The National Historic Site was established in 1945 .",
"title": ""
},
{
"docid": "Franklin_D._Roosevelt_Lake",
"text": "Franklin D. Roosevelt Lake ( also called Lake Roosevelt ) is the reservoir created in 1941 by the impoundment of the Columbia River by the Grand Coulee Dam in Washington state . It is named for Franklin D. Roosevelt , who was President during the construction of the dam . Covering 125 mi2 , it stretches about 150 mi from the Canada -- US border to Grand Coulee Dam , with over 600 mi of shoreline ; by surface area it is the largest lake and reservoir in Washington . It is the home of the Lake Roosevelt National Recreation Area . The reservoir lies in parts of five counties in northeastern Washington ; roughly in descending order of lake acreage they are Ferry , Stevens , Lincoln , Okanogan , and Grant counties . A good indication of the extent of the lake can be seen from a map centered about the town of Inchelium .",
"title": ""
},
{
"docid": "Franklin_D._Roosevelt_Presidential_Library_and_Museum",
"text": "The Franklin D. Roosevelt Presidential Library and Museum holds the records of Franklin Delano Roosevelt , the 32nd President of the United States ( 1933 -- 1945 ) . Located on the grounds of Springwood , the Roosevelt family estate in Hyde Park , New York , the library was built under the President 's personal direction in 1939-1940 , and dedicated on June 30 , 1941 . It is the first presidential library in the United States and one of the thirteen presidential libraries under the auspices of the National Archives and Records Administration .",
"title": ""
},
{
"docid": "Second_inauguration_of_Franklin_D._Roosevelt",
"text": "The second inauguration of Franklin D. Roosevelt as President of the United States was held on January 20 , 1937 . The inauguration marked the commencement of the second four-year term of Franklin D. Roosevelt as President and John Nance Garner as Vice President . It was the first inauguration to take place on January 20 as per the 20th Amendment to the U.S.Constitution . This was also the first time the Vice President took his Oath on the Inaugural Platform during the ceremonies . It rained all morning and during the inauguration - the crowds hastily dispersed once it was over .",
"title": ""
},
{
"docid": "Ethel_du_Pont",
"text": "Ethel du Pont Roosevelt-Warren ( January 30 , 1916 -- May 25 , 1965 ) was an American heiress and socialite and a member of the prominent du Pont family . She is known for her widely publicized marriage to Franklin D. Roosevelt Jr. , son of the 32nd President Franklin D. Roosevelt and Eleanor Roosevelt and her eventual suicide in 1965 .",
"title": ""
},
{
"docid": "Black_Cabinet",
"text": "The Black Cabinet , or Federal Council of Negro Affairs or Black Brain Trust , was the informal term for a group of African-Americans who served as public policy advisors to President Franklin D. Roosevelt and his wife Eleanor Roosevelt in his 1933-45 terms in office . There was no official organization . The term was coined in 1936 by Mary McLeod Bethune and was occasionally used in the press . By mid-1935 , there were 45 African Americans working in federal executive departments and New Deal agencies .",
"title": ""
},
{
"docid": "75th_United_States_Congress",
"text": "The Seventy-fifth United States Congress was a meeting of the legislative branch of the United States federal government , composed of the United States Senate and the United States House of Representatives . It met in Washington , DC from January 3 , 1937 to January 3 , 1939 , during the first two years of the second administration of U.S. President Franklin D. Roosevelt . ( Because of the 20th amendment , starting in 1937 the new Presidential term began 17 days after that of the new Congress ) . The apportionment of seats in the House of Representatives was based on the Fifteenth United States Census , conducted in 1930 . Both chambers had a Democratic supermajority .",
"title": ""
},
{
"docid": "Franklin_Delano_Roosevelt_III",
"text": "Franklin Delano `` Frank '' Roosevelt III ( born July 19 , 1938 ) is an American economist and academic . Through his father , he is a grandson of President Franklin D. Roosevelt and Eleanor Roosevelt , and through his mother he is a member of the prominent du Pont family .",
"title": ""
},
{
"docid": "List_of_executive_actions_by_Franklin_D._Roosevelt",
"text": "Executive Orders numbered 6071 -- 9537 signed by President Franklin D. Roosevelt ( 1933 -- 1945 ) .",
"title": ""
},
{
"docid": "Humphrey's_Executor_v._United_States",
"text": "Humphrey 's Executor v. United States , , was a United States Supreme Court case decided during the Franklin Delano Roosevelt presidency , regarding the powers that a President of the United States has to remove certain executive officials of a `` quasi-legislative , '' `` quasi-judicial '' administrative body created by Congress , for purely political reasons and without the consent of Congress . Roosevelt was dissatisfied with William Humphrey , a member of the Federal Trade Commission , as Humphrey did not , in Roosevelt 's view , support his New Deal policies vigorously enough . Twice , Roosevelt requested Humphrey to resign from the FTC , requests to which Humphrey did not yield . The third time , Roosevelt fired Humphrey : `` Effective as of this date you are hereby removed from the office of Commissioner of the Federal Trade Commission . '' Nevertheless , Humphrey continued to come to work at the FTC even after he was formally fired . However , the Federal Trade Commission Act permitted the President to dismiss an FTC member only for `` inefficiency , neglect of duty , or malfeasance in office . '' Roosevelt 's decision to dismiss Humphrey was based solely on political differences rather than job performance or alleged acts of malfeasance . The case went to the Supreme Court , but Humphrey died before the case could be decided . The case was then pursued by the executors of his estate ; thus , the case obtained the title `` Humphrey 's Executor '' . The Court distinguished between executive officers and quasi-legislative or quasi-judicial officers . The latter may be removed only with procedures consistent with statutory conditions enacted by Congress ; the former serve at the pleasure of the President and may be removed at his discretion . The Court ruled that the Federal Trade Commission was a quasi-legislative body because of other powers it had and so the President could not fire an FTC member solely for political reasons ; thus , Humphrey 's firing was improper . U.S. Attorney General Robert H. Jackson , later to join the Supreme Court himself , said in his memoirs that Roosevelt was particularly annoyed by the Court 's decision , as the President felt that it had been rendered for spite .",
"title": ""
},
{
"docid": "Franklin_D._Roosevelt_in_Central_New_York",
"text": "Franklin D. Roosevelt ( FDR ) made several visits to Central New York as acting governor , campaigning for his presidency and visiting .",
"title": ""
}
] |
109661
|
Tupac is ranked as one of the greatest musicians of all time.
|
[
{
"docid": "Tupac_Shakur",
"text": "Tupac Amaru Shakur ( -LSB- ˈtuːpɑːk_ʃəˈkʊər -RSB- ; born Lesane Parish Crooks ; June 16 , 1971September 13 , 1996 ) , also known by his stage names 2Pac , Makaveli , and Pac , was an American rapper , record producer , actor , and poet . As of 2007 , Shakur has sold over 75 million records worldwide . His double disc albums All Eyez on Me and his Greatest Hits are among the best-selling albums in the United States . He has been listed and ranked as one of the greatest artists of all time by many publications , including Rolling Stone , which ranked him 86th on its list of The 100 Greatest Artists of All Time . He is consistently ranked as one of the greatest and most influential rappers of all time . On April 7 , 2017 , Shakur was inducted into the Rock and Roll Hall of Fame . Shakur began his career as a roadie , backup dancer , and MC for the alternative hip hop group Digital Underground , eventually branching off as a solo artist . Most of the themes in Shakur 's songs revolved around the violence and hardship in inner cities , racism , and other social problems . Both of his parents and several other people in his family were members of the Black Panther Party , whose ideals were reflected in his songs . During the latter part of his career , Shakur was a vocal participant during the East Coast -- West Coast hip hop rivalry , becoming involved in conflicts with other rappers , producers , and record-label staff members , most notably The Notorious B.I.G. and the label Bad Boy Records . On September 7 , 1996 , Shakur was fatally shot in a drive-by shooting at the intersection of Flamingo Road and Koval Lane in Las Vegas , Nevada . He was taken to the University Medical Center of Southern Nevada , where he died six days later .",
"title": ""
}
] |
[
{
"docid": "Jimmy_Page",
"text": "James Patrick Page , ( born 9 January 1944 ) is an English musician , songwriter , and record producer who achieved international success as the guitarist and founder of the rock band Led Zeppelin . Page began his career as a studio session musician in London and , by the mid-1960s , alongside Big Jim Sullivan , was one of the most sought-after session guitarists in Britain . He was a member of the Yardbirds from 1966 to 1968 . In late 1968 , he founded Led Zeppelin . Page is widely considered to be one of the greatest and most influential guitarists of all time . Rolling Stone magazine has described Page as `` the pontiff of power riffing '' and ranked him number 3 in their list of the `` 100 Greatest Guitarists of All Time . '' In 2010 , he was ranked number two in Gibson 's list of `` Top 50 Guitarists of All Time '' and , in 2007 , number four on Classic Rock '' 's `` 100 Wildest Guitar Heroes . '' He was inducted into the Rock and Roll Hall of Fame twice ; once as a member of the Yardbirds ( 1992 ) and once as a member of Led Zeppelin ( 1995 ) . Page has been described by Uncut as `` rock 's greatest and most mysterious guitar hero . '' Los Angeles Times '' magazine voted Jimmy Page the 2nd greatest guitarist of all time .",
"title": ""
},
{
"docid": "Robert_Plant",
"text": "Robert Anthony Plant , ( born 20 August 1948 ) is an English singer , songwriter , and musician , best known as the lead singer and lyricist of the rock band Led Zeppelin . A powerful and wide vocal range ( particularly evident in his high-pitched vocals ) has given him a successful singing career spanning over 50 years . Plant is regarded as one of the greatest singers in the history of rock and roll ; he has influenced fellow rock singer-songwriters such as Freddie Mercury , Axl Rose and Chris Cornell . In 2006 , Heavy Metal magazine Hit Parader named Plant the `` Greatest Metal Vocalist of All Time '' . In 2009 , Plant was voted `` the greatest voice in rock '' in a poll conducted by Planet Rock . In 2008 , Rolling Stone editors ranked him number 15 on their list of the 100 best singers of all time . In 2011 , Rolling Stone readers ranked Plant the greatest of all lead singers .",
"title": ""
},
{
"docid": "Nas",
"text": "Nasir Bin Olu Dara Jones ( -LSB- nɑːˈsɪər -RSB- born September 14 , 1973 ) , better known by his stage name Nas -LSB- ˈnɑːz -RSB- , is an American rapper , record producer , actor , and entrepreneur . The son of jazz musician Olu Dara , Nas has released eight consecutive platinum and multi-platinum albums and has sold over 25,000,000 records worldwide . He is also an entrepreneur through his own record label ; he serves as associate publisher of Mass Appeal magazine and is the owner of a Fila sneaker store . He is currently signed to Mass Appeal Records . His musical career began in 1991 , as a featured artist on Main Source 's `` Live at the Barbeque '' . His debut album Illmatic ( 1994 ) received universal acclaim from both critics and the hip-hop community and is frequently ranked as the greatest hip hop album of all time . Nas 's follow-up It Was Written debuted at # 1 on the Billboard 200 , stayed on top for four consecutive weeks , went double platinum in two months , and made Nas internationally known . From 2001-05 , Nas was involved in a highly publicised feud with fellow New York rapper Jay Z. Nas signed to Def Jam in 2006 . In 2010 , he released Distant Relatives , a collaboration album with reggae musician Damian Marley , donating all royalties to charities active in Africa . His eleventh studio album , Life Is Good ( 2012 ) was nominated for Best Rap Album at the 55th Annual Grammy Awards . Nas is often named as one of the greatest hip-hop artists . MTV ranked him at number 5 on their list of `` The Greatest MCs of All Time '' . In 2012 , The Source ranked him number two on their list of the `` Top 50 Lyricists of All Time '' . In 2013 , Nas was ranked fourth on MTV 's `` Hottest MCs in the Game '' list . About.com ranked him first on their list of the `` 50 Greatest MCs of All Time '' in 2014 , and a year later , Nas was featured on `` The 10 Best Rappers of All Time '' list by Billboard . In 2016 , Nas began narrating The Get Down and rapping as Adult Ezekiel of 1996 .",
"title": ""
},
{
"docid": "Jay_Z",
"text": "Shawn Corey Carter ( born December 4 , 1969 ) , known professionally as Jay Z ( and formerly Jay-Z ) , is an American rapper and businessman . He is one of the best-selling musicians of all time , having sold more than 100 million records , while receiving 21 Grammy Awards for his music . MTV ranked him the `` Greatest MC of all time '' in 2006 . Rolling Stone ranked three of his albums -- Reasonable Doubt ( 1996 ) , The Blueprint ( 2001 ) , and The Black Album ( 2003 ) -- among the 500 greatest albums of all time . In 2017 , Forbes estimated his net worth at $ 810 million , making him second richest hip hop artist in the U.S. Jay Z co-owns the New York 40/40 Club sports bar , and is the co-creator of the clothing line Rocawear . He is the former president of Def Jam Recordings , co-founder of Roc-A-Fella Records , and the founder of the entertainment company Roc Nation . He also founded the sports agency Roc Nation Sports and is a certified NBA and MLB sports agent . As an artist , he holds the record for most number one albums by a solo artist on the Billboard 200 with 13 . He has also had four number ones on the Billboard Hot 100 , one ( `` Empire State of Mind '' ) as lead artist . In 2009 , he was ranked the tenth-most successful artist of the 2000s by Billboard as well as the fifth top solo male artist and fourth top rapper behind Eminem , Nelly , and 50 Cent . He was also ranked the 88th-greatest artist of all time by Rolling Stone . Jay Z married singer-songwriter Beyoncé in 2008 . As a couple , they have a combined net worth of $ 1.16 billion .",
"title": ""
},
{
"docid": "Slash_(musician)",
"text": "Saul Hudson ( born July 23 , 1965 ) , better known by his stage name Slash , is a British-American musician and songwriter . He is best known as the lead guitarist of the American rock band Guns N ' Roses , with whom he achieved worldwide success in the late 1980s and early 1990s . During his later years with Guns N ' Roses , Slash formed the side project Slash 's Snakepit . After leaving Guns N ' Roses in 1996 , he co-founded the supergroup Velvet Revolver , which re-established him as a mainstream performer in the mid to late 2000s . Slash has since released three solo albums : Slash ( 2010 ) , featuring an array of famous guest musicians , and Apocalyptic Love ( 2012 ) and World on Fire ( 2014 ) , recorded with his band , Myles Kennedy and the Conspirators . He returned to Guns N ' Roses in 2016 , nearly 20 years after he had left . Slash has received critical acclaim and is considered as one of the greatest rock guitarists . Time Magazine named him runner-up on their list of `` The 10 Best Electric Guitar Players '' in 2009 , while Rolling Stone Magazine placed him at No. 65 on their list of `` The 100 Greatest Guitarists of All Time '' in 2011 . Guitar World ranked his guitar solo in `` November Rain '' No. 6 on their list of `` The 100 Greatest Guitar Solos '' in 2008 , and Total Guitar placed his riff in `` Sweet Child o ' Mine '' at No. 1 on their list of `` The 100 Greatest Riffs '' in 2004 . During 2010 Gibson Guitar Corporation ranked Slash as No. 34 on their `` Top 50 Guitarists of All Time '' , while their readers landed him No. 9 on Gibson 's `` Top 25 Guitarists of All Time '' . In 2012 , he was inducted into the Rock and Roll Hall of Fame as a member of Guns N ' Roses ' classic line-up .",
"title": ""
},
{
"docid": "King_of_the_Delta_Blues_Singers",
"text": "King of the Delta Blues Singers is a compilation album by American blues musician Robert Johnson , released in 1961 on Columbia Records . It is considered one of the greatest and most influential blues releases ever . In 2003 , the album was ranked number 27 on Rolling Stone magazine 's list of the 500 greatest albums of all time .",
"title": ""
},
{
"docid": "Rakim",
"text": "William Michael Griffin ( born January 28 , 1968 ) , better known by his stage name Rakim , is an American rapper . One half of golden age hip hop duo Eric B. & Rakim , he is widely regarded as one of the most influential and most skilled MCs of all time . Eric B. & Rakim 's classic album Paid in Full was named the greatest hip hop album of all time by MTV in 2006 , while Rakim himself was ranked # 4 on MTV 's list of the Greatest MCs of All Time . Steve Huey of Allmusic stated that `` Rakim is near-universally acknowledged as one of the greatest MCs -- perhaps the greatest -- of all time within the hip-hop community . '' The editors of About.com ranked him # 2 on their list of the ` Top 50 MCs of Our Time ( 1987 -- 2007 ) ' . Rakim began his career as the emcee of the rap duo Eric B. & Rakim , who in 2011 were nominated for induction into the Rock and Roll Hall of Fame . In 2012 , The Source ranked him # 1 on their list of the ` Top 50 Lyricists of All Time ' .",
"title": ""
},
{
"docid": "Peter_Green_(musician)",
"text": "Peter Green ( born Peter Allen Greenbaum , 29 October 1946 ) is a British blues rock guitarist . As the founder of Fleetwood Mac , he was inducted into the Rock and Roll Hall of Fame in 1998 . Green 's songs , such as `` Albatross '' , `` Black Magic Woman '' , `` Oh Well '' , and `` Man of the World '' , appeared on the record charts , and several have been adapted by a variety of musicians . Green was a major figure in the `` second great epoch '' of the British blues movement . B.B. King commented , `` He has the sweetest tone I ever heard ; he was the only one who gave me the cold sweats . '' Eric Clapton and Jimmy Page have both praised his guitar playing ; he is noted for his use of string bending , vibrato , and economy of style . Rolling Stone Magazine ranked Green at number 38 in its list of the `` 100 Greatest Guitarists of All Time '' . His tone on the instrumental `` The Supernatural '' was rated as one of the 50 greatest of all time by Guitar Player . In June 1996 , Green was voted the third-best guitarist of all time in Mojo magazine .",
"title": ""
},
{
"docid": "George_Lynch_(musician)",
"text": "George Lynch ( born September 28 , 1954 ) is an American hard rock guitarist and songwriter . Lynch is best known for his work with 80 's `` hair metal '' band , Dokken , and his post-Dokken solo band , Lynch Mob . Lynch is considered to be one of the most influential and famous 1980s metal guitarists . He is known for his unique playing style and sound . He is ranked # 68 on `` 100 Greatest Guitarists Of All Time '' by Guitar World magazine and is also ranked # 10 on `` Top 10 Metal Guitarists Of All Time '' by Gibson .",
"title": ""
},
{
"docid": "All_in_the_Family",
"text": "All in the Family is an American sitcom TV-series that was originally broadcast on the CBS television network for nine seasons , from January 1971 to April 1979 . The following September , it was replaced by Archie Bunker 's Place , which picked up where All in the Family had ended and ran for four more seasons . Produced by Norman Lear and Bud Yorkin and starring Carroll O'Connor , Jean Stapleton , Sally Struthers , and Rob Reiner , All in the Family revolves around the life of a working-class bigot and his family . The show broke ground in its depiction of issues previously considered unsuitable for a U.S. network television comedy , such as racism , homosexuality , women 's liberation , rape , religion , miscarriage , abortion , breast cancer , the Vietnam War , menopause , and impotence . Through depicting these controversial issues , the series became arguably one of television 's most influential comedic programs , as it injected the sitcom format with more dramatic moments and realistic , topical conflicts . The show is often regarded in the United States as one of the greatest television series of all time . Following a lackluster first season , the show soon became the most watched show in the United States during summer reruns and afterwards ranked number one in the yearly Nielsen ratings from 1971 to 1976 . It became the first television series to reach the milestone of having topped the Nielsen ratings for five consecutive years . The episode `` Sammy 's Visit '' was ranked number 13 on TV Guide 's 100 Greatest Episodes of All Time . TV Guide 's 50 Greatest TV Shows of All Time ranked All in the Family as number four . Bravo also named the show 's protagonist , Archie Bunker , TV 's greatest character of all time . In 2013 , the Writers Guild of America ranked All in the Family the fourth-best written TV series ever , and TV Guide ranked it as the fourth-greatest show of all time .",
"title": ""
},
{
"docid": "Blonde_on_Blonde",
"text": "Blonde on Blonde is the seventh studio album by American singer-songwriter Bob Dylan , released on May 16 , 1966 , on Columbia Records . Recording sessions began in New York in October 1965 with numerous backing musicians , including members of Dylan 's live backing band , the Hawks . Though sessions continued until January 1966 , they yielded only one track that made it onto the final album -- `` One of Us Must Know ( Sooner or Later ) '' . At producer Bob Johnston 's suggestion , Dylan , keyboardist Al Kooper , and guitarist Robbie Robertson moved to the CBS studios in Nashville , Tennessee . These sessions , augmented by some of Nashville 's top session musicians , were more fruitful , and in February and March all the remaining songs for the album were recorded . Blonde on Blonde completed the trilogy of rock albums that Dylan recorded in 1965 and 1966 , starting with Bringing It All Back Home and Highway 61 Revisited . Critics often rank Blonde on Blonde as one of the greatest albums of all time . Combining the expertise of Nashville session musicians with a modernist literary sensibility , the album 's songs have been described as operating on a grand scale musically , while featuring lyrics one critic called `` a unique mixture of the visionary and the colloquial '' . It was one of the first double albums in rock music . The album peaked at number nine on the Billboard 200 chart in the US , where it eventually was certified double platinum , and it reached number three in the UK . Blonde on Blonde spawned two singles that were top-twenty hits in the US : `` Rainy Day Women # 12 & 35 '' and `` I Want You '' . Two additional songs -- `` Just Like a Woman '' and `` Visions of Johanna '' -- have been named as among Dylan 's greatest compositions and were featured in Rolling Stones 500 Greatest Songs of All Time list .",
"title": ""
},
{
"docid": "Ice_Cube",
"text": "O'Shea Jackson Sr. ( born June 15 , 1969 ) , known professionally as Ice Cube , is an American rapper and actor . He began his career as a member of the hip-hop group C.I.A. and later joined the seminal rap group N.W.A ( Niggaz With Attitudes ) . After leaving N.W.A in December 1989 , he built a successful solo career in music and films such as a role in drama Boyz n the Hood . Additionally , he has served as one of the producers of the Showtime television series Barbershop and the TBS series Are We There Yet ? , both of which are based upon films in which he portrayed the main character . Ice Cube is one of the founding artists of gangsta rap , and much of his musical output has contained harsh socio-political commentary . He was ranked number 8 on MTV 's list of the 10 Greatest MCs of All Time , while fellow rapper Snoop Dogg ranked Ice Cube as the greatest MC of all time . AllMusic has called him one of hip-hop 's best and most controversial artists , as well as `` one of rap 's greatest storytellers '' . In 2012 , The Source ranked him number 14 on their list of the Top 50 Lyricists of All Time . In 2014 , About.com ranked him number 11 on their list of the `` 50 Greatest MCs of All Time '' .",
"title": ""
},
{
"docid": "Ali_Farka_Touré",
"text": "Ali Ibrahim `` Ali Farka '' Touré ( October 31 , 1939 -- March 6 , 2006 ) was a Malian singer and multi-instrumentalist , and one of the African continent 's most internationally renowned musicians . His music is widely regarded as representing a point of intersection of traditional Malian music and its North American cousin , the blues . The belief that the latter is historically derived from the former is reflected in Martin Scorsese 's often quoted characterization of Touré 's tradition as constituting `` the DNA of the blues '' . Touré was ranked number 76 on Rolling Stones list of `` The 100 Greatest Guitarists of All Time '' and number 37 on Spin magazine 's `` 100 Greatest Guitarists of All Time '' .",
"title": ""
},
{
"docid": "Sex_Machine_(album)",
"text": "Sex Machine is a 1970 double album by James Brown . It showcases the playing of the original J.B. 's lineup featuring Bootsy and Catfish Collins , and includes an 11-minute rendering of the album 's title song , different from the original recording of the title song which was released as a two-part single in 1970 . Sex Machine purports to be a live recording . However , the first LP 's worth of material consists of tracks recorded in studio settings with added reverberation and overdubbed applause ( some of which subsequently were released in unadulterated mixes , most notably on the 1996 Funk Power compilation CD . ) . All but one track of the second LP apparently were recorded live in concert in Brown 's hometown of Augusta , Georgia , although this material , too , features added reverb and overdubbed applause . It charted # 4 R&B and # 29 Pop . Sex Machine is often considered to be one of the greatest and most important soul records of all time , and arguably the high point of Brown 's creative heyday from 1967-1971 . It was ranked 1st in SPIN magazine 's 25 greatest albums of all time in 1989 , and 96th in a 2005 survey held by British television 's Channel 4 to determine the 100 greatest albums of all time . Sex Machine was also voted the 34th greatest album of all time in a VH1 poll of over 700 musicians , songwriters , disc jockeys , radio programmers , and critics in 2003 .",
"title": ""
},
{
"docid": "James_Hetfield",
"text": "James Alan Hetfield ( born August 3 , 1963 ) is an American musician , singer , and songwriter known for being the co-founder , lead vocalist , rhythm guitarist , and main songwriter for the American heavy metal band Metallica . Hetfield is mainly known for his intricate rhythm playing , but occasionally performs lead guitar duties and solos , both live and in the studio . Hetfield co-founded Metallica in October 1981 after answering a classified advertisement by drummer Lars Ulrich in the Los Angeles newspaper The Recycler . Metallica has won nine Grammy Awards and released ten studio albums , three live albums , four extended plays and 24 singles . In 2009 , Hetfield was ranked at no. 8 in Joel McIver 's book The 100 Greatest Metal Guitarists , and ranked at no. 24 by Hit Parader on their list of the 100 Greatest Metal Vocalists of All Time . In Guitar World 's poll , Hetfield was placed as the 19th greatest guitarist of all time , as well as being placed second ( along with Metallica lead guitarist Kirk Hammett ) in The 100 Greatest Metal Guitarists poll of the same magazine . Rolling Stone placed Hetfield as the 87th greatest guitarist of all time .",
"title": ""
},
{
"docid": "Eddie_Van_Halen",
"text": "Edward Lodewijk Van Halen ( born January 26 , 1955 ) is a Dutch-American musician , songwriter and producer . He is best known as the lead guitarist , occasional keyboardist and co-founder of the American hard rock band Van Halen . He is considered one of the most influential guitarists in the history of rock music . In 2011 , Rolling Stone Magazine ranked Van Halen number eight in the list of the 100 Greatest Guitarists . In 2012 , he was voted number one in a Guitar World magazine reader 's poll for `` The 100 Greatest Guitarists of All Time '' .",
"title": ""
},
{
"docid": "Tony_Pizarro",
"text": "Tony Pizarro is an American entertainment executive , record producer listed as one of the `` Top 50 Hip Hop Producers '' of all time . Contributing to selling over 75 million albums as Tupac Shakur 's producer , songwriter , recording engineer , and mixing engineer . Tony Pizarro is one of Hip Hop 's most notable producers playing an instrumental part in Tupac achieving one of the Best-Selling Music Artists In The World . Memorable for co-writing & producing the hit single `` Dear Mama '' which was inducted into the Library of Congress . Making Tupac Shakur the 3rd American rapper to have a song honored in the National Recording Registry . Several years after Tupac 's death , Pizarro reemerged as one of DEF JAM RECORDS top performing executive A&R / Producers . Pizarro promoted prominent artists such as DMX , Scarface , MOP , WC , and Keith Murray . Facilitating DMX in the films Coach Carter and Cradle 2 The Grave . As well as , designing and delivering music for video games DEF JAMS Vendetta with EA sports . Tony Pizarro a multi talented musician catapulted to the top of urban music in the early 90s mixing a ( radio mix ) for the hit single `` I Wan na Sex You Up '' by R&B group COLOR ME BADD . Enjoying much success Pizarro continued working as a recording and mixing engineer for artists such as , Ice T , Teena Marie , Tevin Campbell , etc. .",
"title": ""
},
{
"docid": "The_Rise_and_Fall_of_Ziggy_Stardust_and_the_Spiders_from_Mars",
"text": "The Rise and Fall of Ziggy Stardust and the Spiders from Mars ( often shortened to Ziggy Stardust ) is the fifth studio album by English musician David Bowie , released on 16 June 1972 . It is a concept album telling the story of a fictional rock star named Ziggy Stardust . It peaked at No. 5 in the United Kingdom on the UK Albums Chart and No. 75 in the United States on the Billboard 200 , then improved to a No. 21 position in the wake of Bowie 's death . The album tells the story of Bowie 's alter ego Ziggy Stardust , a rock star who acts as a messenger for extraterrestrial beings . Bowie created Ziggy Stardust while in New York City promoting Hunky Dory and performed as him on a tour of the United Kingdom , Japan and North America . The album , and the character of Ziggy Stardust , was known for its glam rock influences and themes of sexual exploration and social commentary . These factors , coupled with the ambiguity surrounding Bowie 's sexuality and fuelled by a ground-breaking performance of `` Starman '' on Top of the Pops , led to the album being met with controversy and since hailed as a seminal work . The Rise and Fall of Ziggy Stardust and the Spiders From Mars has received critical acclaim and has been consistently considered one of the greatest albums of all time , with Rolling Stone magazine ranking it the 35th greatest ever . It was ranked the 20th greatest album ever in a 1997 British survey , the 41st greatest of all time by Q magazine and one of the 100 greatest releases ever by Time magazine . In 2017 , the album was selected for preservation in the National Recording Registry , being deemed `` culturally , historically , or artistically significant '' by the Library of Congress . A concert film of the same name , directed by D. A. Pennebaker , was recorded in 1973 and released a decade later in 1983 .",
"title": ""
},
{
"docid": "Duane_Allman",
"text": "Howard Duane Allman ( November 20 , 1946 -- October 29 , 1971 ) was an American guitarist , session musician , and co-founder and leader of the Allman Brothers Band until his death in a motorcycle crash in 1971 , at the age of 24 . The Allman Brothers Band was formed in Jacksonville , Florida , in 1969 . The band had great success in the early 1970s . Allman is best remembered for his brief but influential tenure in the band and in particular for his expressive slide guitar playing and inventive improvisational skills . In 2003 , he was ranked number 2 in Rolling Stone magazine 's list of the 100 greatest guitarists of all time , second only to Jimi Hendrix . In 2011 , he was ranked number 9 . His guitar tone ( achieved with a Gibson Les Paul and two 50-watt bass Marshall amplifiers ) was named one of the greatest of all time by Guitar Player . A sought-after session musician both before and during his tenure with the band , Duane Allman performed with such established stars as King Curtis , Aretha Franklin , Wilson Pickett , and Herbie Mann . He also contributed greatly to the 1970 album Layla and Other Assorted Love Songs , by Derek and the Dominos . Duane Allman 's skills as a guitarist were complemented by personal qualities such as his intensity , drive and ability to draw the best out of others in making music . He is still referred to by his nickname `` Skydog '' .",
"title": ""
},
{
"docid": "Al_Green's_Greatest_Hits",
"text": "Al Green 's Greatest Hits is a 1975 greatest hits release by soul singer Al Green . In 2003 , the album was ranked number 52 on Rolling Stone magazine 's list of the 500 greatest albums of all time . The release has consistently ranked as one of the best executed ` greatest hits ' albums in history .",
"title": ""
},
{
"docid": "The_100_Greatest_Slovak_Albums_of_All_Time",
"text": "The 100 Greatest Slovak Albums of All Time is a list of the best album releases issued by Slovak recording artists . As the first such list presented in Slovakia , it was published by Nový čas daily on 22 September 2007 . The list is entirely composed of Slovak , or else of formerly Czechoslovak artists , featuring all albums published in the country of origin from the 1960s onwards . Some of nominated full-length records could have been performed also in a different language ( occasionally in English but partially ) . Ranking itself was based on votes received from twenty-five selected native-born musicians , critics and/or industry figures . Each of them voted ten most significant Slovak LPs from the past four decades in the country . While the winning album became Zvoňte , zvonky ( 1969 ) by Prúdy band , the most-represented musical act on the list is female vocalist Marika Gombitová , having six out of her nine studio albums in total present . The final list also included two original motion picture soundtracks by various artists such as Neberte nám princeznú ( 1980 ) at number No. 27 and Fontána pre Zuzanu ( 1986 ) ranked at No. 90 , as well as one live recording Live ( 1973 ) by Collegium Musicum at number No. 89 .",
"title": ""
},
{
"docid": "Big_Pun",
"text": "Christopher Lee Rios ( November 10 , 1971 -- February 7 , 2000 ) , better known by his stage name Big Pun ( short for Big Punisher ) , was an American rapper . Emerging from the underground hip hop scene in The Bronx borough of New York City , in the early 1990s , he was the first Latino rapper to have an album certified platinum as a solo act . He first appeared on tracks from Fat Joe 's second album `` Jealous One 's Envy '' in 1995 , and The Beatnuts ' second album Stone Crazy in 1997 , prior to signing to Loud Records as a solo artist . Pun 's lyrics are notable for technical efficiency , having minimal pauses to take a breath , heavy use of alliteration as well as internal and multi-syllabic rhyming schemes . He is widely regarded as one of the greatest rappers of all time . About.com ranked him # 25 on its list of the 50 Greatest MCs of All Time , while MTV2 ranked him # 11 on its list of the `` 22 Greatest MCs '' . In 2012 , The Source ranked him # 19 on their list of the Top 50 Lyricists of All Time .",
"title": ""
},
{
"docid": "Friends",
"text": "Friends ( stylized as F • R • I • E • N • D • S ) is an American television sitcom , created by David Crane and Marta Kauffman , which aired on NBC from September 22 , 1994 , to May 6 , 2004 , lasting ten seasons . With an ensemble cast starring Jennifer Aniston , Courteney Cox , Lisa Kudrow , Matt LeBlanc , Matthew Perry and David Schwimmer , the show revolves around six 20-30 something friends living in Manhattan . The series was produced by Bright/Kauffman/Crane Productions , in association with Warner Bros. . Television . The original executive producers were Kevin S. Bright , Marta Kauffman , and David Crane . Kauffman and Crane began developing Friends under the title Insomnia Cafe between November and December 1993 . They presented the idea to Bright , and together they pitched a seven-page treatment of the show to NBC . After several script rewrites and changes , including a title change to Six of One and Friends Like Us , the series was finally named Friends . Filming took place at Warner Bros. . Studios in Burbank , California . All ten seasons of Friends ranked within the top ten of the final television season ratings ; ultimately reaching the No. 1 spot with its eighth season . The series finale on May 6 , 2004 , was watched by around 52.5 million American viewers , making it the fifth most watched series finale in television history , and the most watched television episode of the 2000s decade . Friends received acclaim throughout its run , becoming one of the most popular television shows of all time . The series was nominated for 62 Primetime Emmy Awards , winning the Outstanding Comedy Series award in 2002 for its eighth season . The show ranked no. 21 on -LSB- -LSB- TV Guide 's 50 Greatest TV Shows of All Time | TV Guide '' 's 50 Greatest TV Shows of All Time -RSB- -RSB- and no. 7 on Empire magazine 's The 50 Greatest TV Shows of All Time . In 1997 , the episode `` The One with the Prom Video '' was ranked no. 100 on TV Guide 's 100 Greatest Episodes of All-Time . In 2013 , Friends '' ranked no. 24 on the Writers Guild of America 's 101 Best Written TV Series of All Time and no. 28 on TV Guide 's 60 Best TV Series of All Time .",
"title": ""
},
{
"docid": "Alexi_Laiho",
"text": "Alexi `` Wildchild '' Laiho ( born Markku Uula Aleksi Laiho ; 8 April 1979 ) is a Finnish guitarist , composer , and vocalist . He is best known as the lead guitarist , lead vocalist and founding member of the melodic death metal band Children of Bodom , and is also the guitarist for Sinergy and Kylähullut . He has previously played with Thy Serpent and Impaled Nazarene on occasion , as well as Warmen and Hypocrisy . Laiho has received widespread acclaim for his guitar work . In 2004 he was ranked # 96 out of 100 Greatest Heavy Metal Guitarists of All Time by Guitar World . Guitar World magazine has also ranked him as one of the 50 fastest guitarists in the world . In addition , Roadrunner Records ranked Laiho at # 41 out of 50 of The Greatest Metal Frontmen of All Time . Furthermore , Total Guitar conducted a public voting poll to determine the greatest metal guitarist of all time ; Laiho was voted # 1 out of 20 metal guitarists , with over 20 % of the vote .",
"title": ""
},
{
"docid": "Whatever_People_Say_I_Am,_That's_What_I'm_Not",
"text": "Whatever People Say I Am , That 's What I 'm Not is the debut studio album by English rock band Arctic Monkeys , released on 23 January 2006 by Domino . The album surpassed Elastica 's self-titled album to become the fastest selling debut album in British music history , shifting over 360,000 copies in its first week , and remains the fastest selling debut album by a band . It has since gone quintuple platinum in the UK . The album includes both tracks from the band 's original EP , Five Minutes with Arctic Monkeys , as well as their first two singles and UK number ones , `` I Bet You Look Good on the Dancefloor '' and `` When the Sun Goes Down '' . It is often cited as one of the best rock albums of its decade . It received the 2006 Mercury Prize for Best Album , and was ranked number 371 on Rolling Stones 500 Greatest Albums of All Time . In 2013 Rolling Stone ranked it the 30th greatest debut album of all time . In October 2013 , music magazine NME also ranked the album at number 19 in their poll of the 500 greatest albums of all time .",
"title": ""
},
{
"docid": "Inner_City_Life",
"text": "Inner City Life is a 1994 single by British electronic musician Goldie . Its probably his best known track and features vocals by singer Diane Charlemagne . The single is taken from his acclaimed 1995 debut album Timeless . The song is one of the most iconic drum 'n' bass works of its era . In 2013 the song was ranked No. 30 in Mixmags list of 50 Greatest Dance Tracks of All Time ' .",
"title": ""
},
{
"docid": "Freddie_Mercury",
"text": "Farrokh `` Freddie '' Mercury ( née Bulsara ; 5 September 1946 -- 24 November 1991 ) was a British singer , songwriter and record producer , known as the lead vocalist and co-principal songwriter of the rock band Queen . He also became known for his flamboyant stage persona and four-octave vocal range . Mercury wrote and composed numerous hits for Queen ( including `` Bohemian Rhapsody '' , `` Killer Queen '' , `` Somebody to Love '' , `` Do n't Stop Me Now '' , `` Crazy Little Thing Called Love '' , and `` We Are the Champions '' ) ; occasionally served as a producer and guest musician ( piano or vocals ) for other artists ; and concurrently led a solo career while performing with Queen . Mercury was born of Parsi descent in the Sultanate of Zanzibar and grew up there and in India until his mid-teens , before moving with his family to Middlesex , England -- ultimately forming the band Queen in 1970 with Brian May and Roger Taylor . Mercury died in 1991 at age 45 due to complications from AIDS , having confirmed the day before his death that he had contracted the disease . In 1992 , Mercury was posthumously awarded the Brit Award for Outstanding Contribution to British Music , and had a tribute concert held at Wembley Stadium , London . As a member of Queen , he was inducted into the Rock and Roll Hall of Fame in 2001 , the Songwriters Hall of Fame in 2003 , the UK Music Hall of Fame in 2004 , and the band received a star on the Hollywood Walk of Fame in 2002 . In 2002 , he was placed at number 58 in the BBC 's poll of the 100 Greatest Britons . Consistently voted one of the greatest singers in the history of popular music , Mercury was voted best male singer of all time in a 2005 poll organised by Blender and MTV2 ; was elected in 2009 as the best rock singer of all time by Classic Rock readers ; was ranked at 18 on the 2008 Rolling Stone list of the 100 greatest singers ever ; -- and was described by Greg Prato of AllMusic as `` one of rock 's greatest all-time entertainers , '' with `` one of the greatest voices in all of music . ''",
"title": ""
},
{
"docid": "Frank_Zappa",
"text": "Frank Vincent Zappa ( December 21 , 1940 -- December 4 , 1993 ) was an American musician , activist and filmmaker . His work was characterized by nonconformity , free-form improvisation , sound experiments , musical virtuosity , and satire of American culture . In a career spanning more than 30 years , Zappa composed rock , pop , jazz , jazz fusion , orchestral and musique concrète works , and produced almost all of the 60-plus albums that he released with his band the Mothers of Invention and as a solo artist . Zappa also directed feature-length films and music videos , and designed album covers . He is considered one of the most innovative and stylistically diverse rock musicians of his generation . As a self-taught composer and performer , Zappa 's diverse musical influences led him to create music that was sometimes difficult to categorize . While in his teens , he acquired a taste for 20th-century classical composers such as Edgard Varèse , Igor Stravinsky , and Anton Webern , along with 1950s rhythm and blues and doo-wop music . He began writing classical music in high school , while at the same time playing drums in rhythm and blues bands ; later switching to electric guitar . His 1966 debut album with the Mothers of Invention , Freak Out ! , combined songs in conventional rock and roll format with collective improvisations and studio-generated sound collages . He continued this eclectic and experimental approach , irrespective of whether the fundamental format was rock , jazz or classical . Zappa 's output is unified by a conceptual continuity he termed `` Project/Object '' , with numerous musical phrases , ideas , and characters reappearing across his albums . His lyrics reflected his iconoclastic views of established social and political processes , structures and movements , often humorously so . He was a strident critic of mainstream education and organized religion , and a forthright and passionate advocate for freedom of speech , self-education , political participation and the abolition of censorship . Unlike many other rock musicians of his era , he personally disapproved of and seldom used drugs , but supported their decriminalization and regulation . During Zappa 's lifetime , he was a highly productive and prolific artist , earning widespread acclaim from critics and fellow musicians . He had some commercial success , particularly in Europe , and worked as an independent artist for most of his career . He remains a major influence on musicians and composers . His honors include an induction into the 1995 Rock and Roll Hall of Fame and the 1997 Grammy Lifetime Achievement Award . In 2000 , he was ranked number 36 on VH1 's 100 Greatest Artists of Hard Rock . In 2004 , Rolling Stone magazine ranked him at number 71 on its list of the `` 100 Greatest Artists of All Time '' , and in 2011 at number 22 on its list of the `` 100 Greatest Guitarists of All Time '' .",
"title": ""
},
{
"docid": "Sam_Langford",
"text": "Samuel `` Sam '' E. Langford , known as the Boston Tar Baby , Boston Terror , and Boston Bonecrusher ( March 4 , 1883 -- January 12 , 1956 ) was a Black Canadian boxing standout of the early part of the 20th century . Called the `` Greatest Fighter Nobody Knows '' , by ESPN , many boxing historians consider Langford to be one of the greatest fighters of all time . Originally from Weymouth Falls , a small community in Nova Scotia , Canada . He was known as `` The Boston Bonecrusher '' , `` The Boston Terror '' , and his most infamous nickname , `` The Boston Tar Baby '' . Langford stood 5 ft and weighed 185 lb in his prime . He fought from lightweight to heavyweight and defeated many world champions and legends of the time in each weight class . Considered a devastating puncher even at heavyweight , Langford was rated No. 2 by The Ring on their list of `` 100 greatest punchers of all time '' . One boxing historian described Langford as `` experienced as a heavyweight James Toney with the punching power of Mike Tyson '' . He was denied a shot at many World Championships , due to the color bar and by the refusal of Jack Johnson , the first African-American World Heavyweight Champion , to fight him . Langford was the World Colored Heavyweight Champion , a title vacated , by Johnson , after he won the World Championship , a record five times . Many boxing aficionados consider Langford to be the greatest boxer not to win a world title . BoxRec ranks him as the 2nd greatest heavyweight of all-time , the 12th greatest pound-for-pound fighter of all-time and the greatest Canadian boxer of all-time .",
"title": ""
},
{
"docid": "Purple_Rain_(album)",
"text": "Purple Rain is the sixth studio album by American recording artist Prince , the first to feature his backing band The Revolution , and is the soundtrack album to the 1984 film of the same name . It was released on June 25 , 1984 by Warner Bros. . Records . To date , it has sold over 25 million copies worldwide , making it the sixth-best-selling soundtrack album of all time . Purple Rain is regularly ranked among the best albums in music history , and is widely regarded as Prince 's magnum opus . Time magazine ranked it the 15th greatest album of all time in 1993 , and it placed 18th on VH1 's Greatest Rock and Roll Albums of All Time countdown . Rolling Stone ranked it the second-best album of the 1980s and 76th on their list of the `` 500 Greatest Albums of All Time '' . The first two singles from Purple Rain , `` When Doves Cry '' and `` Let 's Go Crazy '' , topped the US singles charts , and were hits around the world , while the title track went to number two on the Billboard Hot 100 . The album was certified thirteen-times platinum ( diamond ) by the RIAA . In 2007 , the editors of Vanity Fair labeled it the best soundtrack of all time , and Tempo magazine named it the greatest album of the 1980s . The 1,000 th issue of Entertainment Weekly dated July 4 , 2008 , listed Purple Rain at number one on their list of the top 100 best albums of the past 25 years . In 2013 , the magazine also listed the album at number two on their list of the 100 Greatest Albums ever . In 2012 , Slant Magazine listed the album at # 2 on its list of `` Best Albums of the 1980s '' behind only Michael Jackson 's Thriller . In the same year , the album was added to the Library of Congress 's National Recording Registry list of sound recordings that `` are culturally , historically , or aesthetically important '' .",
"title": ""
}
] |
109
|
An M2-like phenotype in brown adipose tissue macrophages is quickly induced by cold exposure.
|
[
{
"docid": "4319174",
"text": "All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue. Acting via the β(3)-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner. Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.",
"title": "Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis"
}
] |
[
{
"docid": "29381091",
"text": "Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a \"brite\" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with \"browning,\" as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes.",
"title": "Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice"
},
{
"docid": "43192375",
"text": "Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or \"alternatively activated\" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or \"classically activated\" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.",
"title": "Obesity induces a phenotypic switch in adipose tissue macrophage polarization."
},
{
"docid": "14865329",
"text": "Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.",
"title": "Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders"
},
{
"docid": "20532591",
"text": "White adipose tissue displays high plasticity. We developed a system for the inducible, permanent labeling of mature adipocytes that we called the AdipoChaser mouse. We monitored adipogenesis during development, high-fat diet (HFD) feeding and cold exposure. During cold-induced 'browning' of subcutaneous fat, most 'beige' adipocytes stem from de novo–differentiated adipocytes. During HFD feeding, epididymal fat initiates adipogenesis after 4 weeks, whereas subcutaneous fat undergoes hypertrophy for a period of up to 12 weeks. Gonadal fat develops postnatally, whereas subcutaneous fat develops between embryonic days 14 and 18. Our results highlight the extensive differences in adipogenic potential in various fat depots.",
"title": "Tracking adipogenesis during white adipose tissue development, expansion and regeneration"
},
{
"docid": "970012",
"text": "Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E(-/-) [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.",
"title": "Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis"
},
{
"docid": "36838958",
"text": "Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism.",
"title": "Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species."
},
{
"docid": "32955023",
"text": "The expansion of white adipose tissue (WAT) in obesity involves de novo differentiation of new adipocytes; however, the cellular origin of these cells remains unclear. Here, we utilize Zfp423(GFP) reporter mice to characterize adipose mural (Pdgfrβ(+)) cells with varying levels of the preadipocyte commitment factor Zfp423. We find that adipose tissue contains distinct mural populations, with levels of Zfp423 distinguishing adipogenic from inflammatory-like mural cells. Using our \"MuralChaser\" lineage tracking system, we uncover adipose perivascular cells as developmental precursors of adipocytes formed in obesity, with adipogenesis and precursor abundance regulated in a depot-dependent manner. Interestingly, Pdgfrβ(+) cells do not significantly contribute to the initial cold-induced recruitment of beige adipocytes in WAT; it is only after prolonged cold exposure that these cells differentiate into beige adipocytes. These results provide genetic evidence for a mural cell origin of white adipocytes in obesity and suggest that beige adipogenesis may originate from multiple sources.",
"title": "Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice."
},
{
"docid": "25687558",
"text": "The genetically obese (ob/ob) mouse exhibits defective thermoregulatory responses to cold exposure. Pathophysiological explanations for this phenomenon have focused on abnormalities in intracellular metabolism or insensitivity of peripheral tissues to the thermogenic effects of catecholamines. Because the sympathetic nervous system (SNS) is subject to feedback regulation, a peripheral impairment in thermogenesis should be associated with a compensatory increase in SNS activity. To examine SNS activity in the ob/ob mouse, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of ob/ob and lean mice. The results from studies utilizing radiolabeled NE or inhibition of NE biosynthesis with alpha-methyl-p-tyrosine to measure NE turnover demonstrated reductions in SNS activity of 33-56% in heart and of 45-73% in IBAT in ob/ob mice at ambient temperature (22 degrees C) compared with measurements in lean controls. During cold exposure (4 degrees C) NE turnover increased in heart and IBAT to a similar extent in both ob/ob and lean mice, but NE turnover rates in heart, and probably in IBAT as well, remained lower in the obese mice than in the lean despite the gradual development of hypothermia in the ob/ob mice during this period. Administration of naltrexone, a long-acting opiate antagonist, failed to reverse the suppression of SNS activity observed in the ob/ob mice. These data indicate that diminished SNS activity in ob/ob mice may be an additional factor contributing to the defective thermogenesis characteristic of these animals.",
"title": "Diminished sympathetic nervous system activity in genetically obese (ob/ob) mouse."
},
{
"docid": "8477699",
"text": "Studying the metabolism of immune cells in recent years has emphasized the tight link existing between the metabolic state and the phenotype of these cells. Macrophages in particular are a good example of this phenomenon. Whether the macrophage obtains its energy through glycolysis or through oxidative metabolism can give rise to different phenotypes. Classically activated or M1 macrophages are key players of the first line of defense against bacterial infections and are known to obtain energy through glycolysis. Alternatively activated or M2 macrophages on the other hand are involved in tissue repair and wound healing and use oxidative metabolism to fuel their longer-term functions. Metabolic intermediates, however, are not just a source of energy but can be directly implicated in a particular macrophage phenotype. In M1 macrophages, the Krebs cycle intermediate succinate regulates HIF1α, which is responsible for driving the sustained production of the pro-inflammatory cytokine IL1β. In M2 macrophages, the sedoheptulose kinase carbohydrate kinase-like protein is critical for regulating the pentose phosphate pathway. The potential to target these events and impact on disease is an exciting prospect.",
"title": "Metabolic Reprograming in Macrophage Polarization"
},
{
"docid": "34016987",
"text": "Monocytes are primary targets for human CMV (HCMV) infection and are proposed to be responsible for hematogenous dissemination of the virus. Monocytes acquire different functional traits during polarization to the classical proinflammatory M1 macrophage or the alternative antiinflammatory M2 macrophage. We hypothesized that HCMV induced a proinflammatory M1 macrophage following infection to promote viral dissemination because, biologically, a proinflammatory state provides the tools to drive infected monocytes from the blood into the tissue. To test this hypothesis of monocyte conversion from a normal quiescent phenotype to an inflammatory phenotype, we used Affymetrix Microarray to acquire a transcriptional profile of infected monocytes at a time point our data emphasized is a key temporal regulatory point following infection. We found that HCMV significantly up-regulated 583 (5.2%) of the total genes and down-regulated 621 (5.5%) of the total genes>or=1.5-fold at 4 h postinfection. Further ontology analysis revealed that genes implicated in classical M1 macrophage activation were stimulated by HCMV infection. We found that 65% of genes strictly associated with M1 polarization were up-regulated, while only 4% of genes solely associated with M2 polarization were up-regulated. Analysis of the monocyte chemokinome at the transcriptional level showed that 44% of M1 and 33% of M2 macrophage chemokines were up-regulated. Proteomic analysis using chemokine Ab arrays confirmed the secretion of these chemotactic proteins from HCMV-infected monocytes. Overall, the results identify that the HCMV-infected monocyte transcriptome displayed a unique M1/M2 polarization signature that was skewed toward the classical M1 activation phenotype.",
"title": "Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage."
},
{
"docid": "13000926",
"text": "Cold injury is a tissue trauma produced by exposure to freezing temperatures and even brief exposure to a severely cold and windy environment. Rewarming of frozen tissue is associated with blood reperfusion and the simultaneous generation of free oxygen radicals. In this review is discussed the current understanding of the mechanism of action of free oxygen radicals as related to cold injury during rewarming. Decreased energy stores during ischaemia lead to the accumulation of adenine nucleotides and liberation of free fatty acids due to the breakdown of lipid membranes. On rewarming, free fatty acids are metabolized via cyclo-oxygenase and adenine nucleotides are metabolized via the xanthine oxidase pathway. These may be the source of free oxygen radicals. Leukocytes may also play a major role in the pathogenesis of cold injury. Oxygen radical scavengers, such as superoxide dismutase and catalase, may help to reduce the cold induced injury but their action is limited due to the inability readily to cross the plasma membrane. Lipid soluble antioxidants are likely to be more effective scavengers because of their presence in membranes where peroxidative reactions can be arrested.",
"title": "The role of free radicals in cold injuries."
},
{
"docid": "24707550",
"text": "Macrophages play a pivotal role in innate and acquired immune responses to Schistosoma mansoni. Classical (M1) or alternative (M2) activation states of these cells further delineate their roles in tissue damage through innate immunity or fibrotic remodeling, respectively. In the present study, we addressed the following question: Does systemic Th2-type cytokine polarization evoked by S. mansoni affect macrophage differentiation and activation? To this end, we analyzed bone marrow-derived macrophages from mice with S. mansoni egg-induced pulmonary granulomas and unchallenged (or naïve) mice to determine their activation state and their response to specific TLR agonists, including S. mansoni egg antigens. Unlike naïve macrophages, macrophages from Th2-polarized mice constitutively expressed significantly higher \"found in inflammatory zone-1\" (FIZZ1) and ST2 (M2 markers) and significantly lower NO synthase 2, CCL3, MIP-2, TNF-alpha, and IL-12 (M1 markers). Also, compared with naïve macrophages, Th2-polarized macrophages exhibited enhanced responses to the presence of specific TLR agonists, which consistently induced significantly higher levels of gene and protein levels for M2 and M1 markers in these cells. Together, these data show that signals received by bone marrow precursors during S. mansoni egg-induced granuloma responses dynamically alter the development of macrophages and enhance the TLR responsiveness of these cells, which may ultimately have a significant effect on the pulmonary granulomatous response.",
"title": "A systemic granulomatous response to Schistosoma mansoni eggs alters responsiveness of bone-marrow-derived macrophages to Toll-like receptor agonists."
},
{
"docid": "52865789",
"text": "OBJECTIVE IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues. METHODS Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells. RESULTS Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues. CONCLUSIONS Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.",
"title": "Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues"
},
{
"docid": "17973161",
"text": "Uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes that are termed 'brite' (brown-in-white) or 'beige'. In humans, the presence of brite or beige (brite/beige) adipocytes is correlated with a lean, metabolically healthy phenotype, but whether a causal relationship exists is not clear. Here we report that human brite/beige adipocyte progenitors proliferate in response to pro-angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform in response to adenylate cyclase activation from being UCP1 negative to being UCP1 positive, which is a defining feature of the beige/brite phenotype, while displaying uncoupled respiration. When implanted into normal chow-fed, or into high-fat diet (HFD)-fed, glucose-intolerant NOD-scid IL2rg(null) (NSG) mice, brite/beige adipocytes activated in vitro enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Pro-angiogenic conditions therefore drive the proliferation of human beige/brite adipocyte progenitors, and activated beige/brite adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism.",
"title": "Human ‘brite / beige’ adipocytes develop from capillary networks and their implantation improves metabolic homeostasis in mice"
},
{
"docid": "79447",
"text": "OBJECTIVE The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. METHODS AND RESULTS In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Nonendothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase inhibition with N(ω)-nitro-l-arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. CONCLUSIONS Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.",
"title": "Arteriolar function in visceral adipose tissue is impaired in human obesity."
},
{
"docid": "26902591",
"text": "Cancer-associated cachexia (CAC) is a wasting syndrome characterized by systemic inflammation, body weight loss, atrophy of white adipose tissue (WAT) and skeletal muscle. Limited therapeutic options are available and the underlying mechanisms are poorly defined. Here we show that a phenotypic switch from WAT to brown fat, a phenomenon termed WAT browning, takes place in the initial stages of CAC, before skeletal muscle atrophy. WAT browning is associated with increased expression of uncoupling protein 1 (UCP1), which uncouples mitochondrial respiration toward thermogenesis instead of ATP synthesis, leading to increased lipid mobilization and energy expenditure in cachectic mice. Chronic inflammation and the cytokine interleukin-6 increase UCP1 expression in WAT, and treatments that reduce inflammation or β-adrenergic blockade reduce WAT browning and ameliorate the severity of cachexia. Importantly, UCP1 staining is observed in WAT from CAC patients. Thus, inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients.",
"title": "A switch from white to brown fat increases energy expenditure in cancer-associated cachexia."
},
{
"docid": "11428884",
"text": "Adipose tissue is an important metabolic organ, the dysfunction of which is associated with the development of obesity, diabetes mellitus, and cardiovascular disease. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is considered the master regulator of adipocyte differentiation and function. Although its cell-autonomous role in adipogenesis has been clearly demonstrated in cell culture, previous fat-specific knockouts of the murine PPARγ gene did not demonstrate a dramatic phenotype in vivo. Here, using Adipoq-Cre mice to drive adipose-specific recombination, we report a unique fat-specific PPARγ knockout (PPARγ FKO) mouse model with almost no visible brown and white adipose tissue at age 3 mo. As a consequence, PPARγ FKO mice had hugely enlarged pancreatic islets, massive fatty livers, and dramatically elevated levels of blood glucose and serum insulin accompanied by extreme insulin resistance. PPARγ FKO mice also exhibited delayed hair coat formation associated with absence of dermal fat, disrupted mammary gland development with loss of mammary fat pads, and high bone mass with loss of bone marrow fat, indicating the critical roles of adipose PPARγ in these tissues. Together, our data reveal the necessity of fat PPARγ in adipose formation, whole-body metabolic homeostasis, and normal development of fat-containing tissues.",
"title": "Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARγ."
},
{
"docid": "3984231",
"text": "Adverse remodeling following myocardial infarction (MI) leading to heart failure is driven by an imbalanced resolution of inflammation. The macrophage cell is an important control of post-MI inflammation, as macrophage subtypes secrete mediators to either promote inflammation and extend injury (M1 phenotype) or suppress inflammation and promote scar formation (M2 phenotype). We have previously shown that the absence of caveolin-1 (Cav1), a membrane scaffolding protein, is associated with adverse cardiac remodeling in mice, but the mechanisms responsible remain to be elucidated. We explore here the role of Cav1 in the activation of macrophages using wild type C57BL6/J (WT) and Cav1(tm1Mls/J) (Cav1(-/-)) mice. By echocardiography, cardiac function was comparable between WT and Cav1(-/-) mice at 3days post-MI. In the absence of Cav1, there were a surprisingly higher percentage of M2 macrophages (arginase-1 positive) detected in the infarcted zone. Conversely, restoring Cav1 function after MI in WT mice by adding back the Cav1 scaffolding domain reduced the M2 activation profile. Further, adoptive transfer of Cav1 null macrophages into WT mice on d3 post-MI exacerbated adverse cardiac remodeling at d14 post-MI. In vitro studies revealed that Cav1 null macrophages had a more pronounced M2 profile activation in response to IL-4 stimulation. In conclusion, Cav1 deletion promotes an array of maladaptive repair processes after MI, including increased TGF-β signaling, increased M2 macrophage infiltration and dysregulation of the M1/M2 balance. Our data also suggest that cardiac remodeling can be improved by therapeutic intervention regulating Cav1 function during the inflammatory response phase.",
"title": "Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2 macrophage activation in mice after myocardial infarction."
},
{
"docid": "6227220",
"text": "Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance.",
"title": "Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine"
},
{
"docid": "41790911",
"text": "Experimental studies have suggested that Wingless-related integration site 5A (WNT5A) is a proinflammatory secreted protein that is associated with metabolic dysfunction in obesity. Impaired angiogenesis in fat depots has been implicated in the development of adipose tissue capillary rarefaction, hypoxia, inflammation, and metabolic dysfunction. We have recently demonstrated that impaired adipose tissue angiogenesis is associated with overexpression of antiangiogenic factor VEGF-A165b in human fat and the systemic circulation. In the present study, we postulated that upregulation of WNT5A is associated with angiogenic dysfunction and examined its role in regulating VEGF-A165b expression in human obesity. We biopsied subcutaneous and visceral adipose tissue from 38 obese individuals (body mass index: 44 ± 7 kg/m2, age: 37 ± 11 yr) during planned bariatric surgery and characterized depot-specific protein expression of VEGF-A165b and WNT5A using Western blot analysis. In both subcutaneous and visceral fat, VEGF-A165b expression correlated strongly with WNT5A protein (r = 0.9, P < 0.001). In subcutaneous adipose tissue where angiogenic capacity is greater than in the visceral depot, exogenous human recombinant WNT5A increased VEGF-A165b expression in both whole adipose tissue and isolated vascular endothelial cell fractions (P < 0.01 and P < 0.05, respectively). This was associated with markedly blunted angiogenic capillary sprout formation in human fat pad explants. Moreover, recombinant WNT5A increased secretion of soluble fms-like tyrosine kinase-1, a negative regulator of angiogenesis, in the sprout media (P < 0.01). Both VEGF-A165b-neutralizing antibody and secreted frizzled-related protein 5, which acts as a decoy receptor for WNT5A, significantly improved capillary sprout formation and reduced soluble fms-like tyrosine kinase-1 production (P < 0.05). We demonstrated a significant regulatory nexus between WNT5A and antiangiogenic VEGF-A165b in the adipose tissue of obese subjects that was linked to angiogenic dysfunction. Elevated WNT5A expression in obesity may function as a negative regulator of angiogenesis. NEW & NOTEWORTHY Wingless-related integration site 5a (WNT5A) negatively regulates adipose tissue angiogenesis via VEGF-A165b in human obesity.",
"title": "WNT5A regulates adipose tissue angiogenesis via antiangiogenic VEGF-A165b in obese humans."
},
{
"docid": "2605032",
"text": "We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood.",
"title": "Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction"
},
{
"docid": "29691654",
"text": "Until recently, the mechanism of adaptive thermogenesis was ascribed to the expression of uncoupling protein 1 (UCP1) in brown and beige adipocytes. UCP1 is known to catalyze a proton leak of the inner mitochondrial membrane, resulting in uncoupled oxidative metabolism with no production of adenosine triphosphate and increased energy expenditure. Thus increasing brown and beige adipose tissue with augmented UCP1 expression is a viable target for obesity-related disorders. Recent work demonstrates an UCP1-independent pathway to uncouple mitochondrial respiration. A secreted enzyme, PM20D1, enriched in UCP1+ adipocytes, exhibits catalytic and hydrolytic activity to reversibly form N-acyl amino acids. N-acyl amino acids act as endogenous uncouplers of mitochondrial respiration at physiological concentrations. Administration of PM20D1 or its products, N-acyl amino acids, to diet-induced obese mice improves glucose tolerance by increasing energy expenditure. In short-term studies, treated animals exhibit no toxicity while experiencing 10% weight loss primarily of adipose tissue. Further study of this metabolic pathway may identify novel therapies for diabesity, the disease state associated with diabetes and obesity.",
"title": "Uncoupling Mitochondrial Respiration for Diabesity."
},
{
"docid": "10889845",
"text": "Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg(-/-)), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg(-/-) mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.",
"title": "Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance."
},
{
"docid": "12658073",
"text": "The gut microbiota has been proposed as an environmental factor that affects the development of metabolic and inflammatory diseases in mammals. Recent reports indicate that gut bacteria-derived lipopolysaccharide (LPS) can initiate obesity and insulin resistance in mice; however, the molecular interactions responsible for microbial regulation of host metabolism and mediators of inflammation have not been studied in detail. Hepatic serum amyloid A (SAA) proteins are markers and proposed mediators of inflammation that exhibit increased levels in serum of insulin-resistant mice. Adipose tissue-derived SAA3 displays monocyte chemotactic activity and may play a role in metabolic inflammation associated with obesity and insulin resistance. To investigate a potential mechanistic link between the intestinal microbiota and induction of proinflammatory host factors, we performed molecular analyses of germ-free, conventionally raised and genetically modified Myd88-/- mouse models. SAA3 expression was determined to be significantly augmented in adipose (9.9+/-1.9-fold; P<0.001) and colonic tissue (7.0+/-2.3-fold; P<0.05) by the presence of intestinal microbes. In the colon, we provided evidence that SAA3 is partially regulated through the Toll-like receptor (TLR)/MyD88/NF-kappaB signaling axis. We identified epithelial cells and macrophages as cellular sources of SAA3 in the colon and found that colonic epithelial expression of SAA3 may be part of an NF-kappaB-dependent response to LPS from gut bacteria. In vitro experiments showed that LPS treatments of both epithelial cells and macrophages induced SAA3 expression (27.1+/-2.5-fold vs. 1.6+/-0.1-fold, respectively). Our data suggest that LPS, and potentially other products of the indigenous gut microbiota, might elevate cytokine expression in tissues and thus exacerbate chronic low-grade inflammation observed in obesity.",
"title": "Regulation of Serum Amyloid A3 (SAA3) in Mouse Colonic Epithelium and Adipose Tissue by the Intestinal Microbiota"
},
{
"docid": "4854076",
"text": "The rising incidence of obesity and associated metabolic diseases has increased the urgency in understanding all aspects of adipose tissue biology. This includes the function of adipocytes, how adipose tissue expands in obesity, and how expanded adipose tissues in adults can impact physiology. Here, we highlight the growing appreciation for the importance of de novo adipocyte differentiation to adipose tissue expansion in adult humans and animals. We detail recent efforts to identify adipose precursor populations that contribute to the physiological postnatal recruitment of white, brown, and beige adipocytes in mice, and summarize new data that reveal the complexity of adipose tissue development in vivo.",
"title": "The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment."
},
{
"docid": "45153864",
"text": "Treatment with second-generation antipsychotic agents such as olanzapine frequently results in metabolic adverse effects, e.g. hyperphagia, weight gain and dyslipidaemia in patients of both genders. The molecular mechanisms underlying metabolic adverse effects are still largely unknown, and studies in rodents represent an important approach in their exploration. However, the validity of the rodent model is hampered by the fact that antipsychotics induce weight gain in female, but not male, rats. When administered orally, the short half-life of olanzapine in rats prevents stable plasma concentrations of the drug. We recently showed that a single intramuscular injection of long-acting olanzapine formulation yields clinically relevant plasma concentrations accompanied by several dysmetabolic features in the female rat. In the current study, we show that depot injections of 100-250 mg/kg olanzapine yielded clinically relevant plasma olanzapine concentrations also in male rats. In spite of transient hyperphagia, however, olanzapine resulted in weight loss rather than weight gain. The resultant negative feed efficiency was accompanied by a slight elevation of thermogenesis markers in brown adipose tissue for the highest olanzapine dose, but the olanzapine-related reduction in weight gain remains to be explained. In spite of the absence of weight gain, an olanzapine dose of 200mg/kg or above induced significantly elevated plasma cholesterol levels and pronounced activation of lipogenic gene expression in the liver. These results confirm that olanzapine stimulates lipogenic effects, independent of weight gain, and raise the possibility that endocrine factors may influence gender specificity of metabolic effects of antipsychotics in the rat.",
"title": "Olanzapine depot exposure in male rats: Dose-dependent lipogenic effects without concomitant weight gain."
},
{
"docid": "1568684",
"text": "The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans.",
"title": "The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity."
},
{
"docid": "40232172",
"text": "The research on mitochondrial functions in adipocytes has increasingly evidenced that mitochondria plays an important role in the onset and/or progression of obesity and related pathologies. Mitochondrial function in brown adipose tissue (BAT) has been classically assessed by measuring either the levels/activity of mitochondrial enzymes, or the respiration in isolated mitochondria. Isolation of mitochondria is not advantageous because it demands significant time and amount of tissue and, as tissue homogenates, disrupts biochemical and physical connections of mitochondria within the cell. Here, we described a new and efficient protocol to analyze the mitochondrial respiratory states in BAT biopsies that relies on intracellular triglyceride depletion followed by tissue permeabilization. In addition to minimizing tissue requirements to ∼17 mg wet weight, the proposed protocol enabled analysis of all mitochondrial respiratory states, including phosphorylation (OXPHOS), no-phosphorylation (LEAK), and uncoupled (ETS) states, as well as the use of substrates for complex I, complex II, and cytochrome c; together, these features demonstrated mitochondrial integrity and validated the preparation efficacy. Therefore, the protocol described here increases the possibilities of answering physiological questions related to small BAT regions of human and animal models, which shall help to unravel the mechanisms that regulate mitochondrial function in health and disease.",
"title": "Triglyceride depletion of brown adipose tissue enables analysis of mitochondrial respiratory function in permeabilized biopsies."
},
{
"docid": "18450716",
"text": "Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion.",
"title": "Noncanonical Wnt Signaling Promotes Obesity-Induced Adipose Tissue Inflammation and Metabolic Dysfunction Independent of Adipose Tissue Expansion"
},
{
"docid": "38023457",
"text": "Severe quantitative and qualitative brown adipocyte defects are common in obesity. To investigate whether aberrant expression of tumor necrosis factor alpha (TNF-alpha) in obesity is involved in functional brown fat atrophy, we have studied genetically obese (ob/ob) mice with targeted null mutations in the genes encoding the two TNF receptors. The absence of both TNF receptors or p55 receptor alone resulted in a significant reduction in brown adipocyte apoptosis and an increase in beta(3)-adrenoreceptor and uncoupling protein-1 expression in obese mice. Increased numbers of multilocular functionally active brown adipocytes, and improved thermoregulation was also observed in obese animals lacking TNF-alpha function. These results indicate that TNF-alpha plays an important role in multiple aspects of brown adipose tissue biology and mediates the abnormalities that occur at this site in obesity.",
"title": "Tumor necrosis factor alpha mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity."
}
] |
160230
|
Selene only serves as a minor character in the film Underworld: Evolution.
|
[
{
"docid": "Selene_(Underworld)",
"text": "Selene , portrayed by British actress Kate Beckinsale , is a fictional character and the main protagonist of the Underworld film series . More specifically , she serves as the central character in the films Underworld ( 2003 ) , Underworld : Evolution ( 2006 ) , Underworld : Awakening ( 2012 ) , and Underworld : Blood Wars ( 2016 ) . Beckinsale 's daughter , Lily Mo Sheen , plays the character as a child in a flashback in Underworld : Evolution . In Underworld : Endless War , Selene is voiced by Canadian voice actress Laura Harris .",
"title": ""
}
] |
[
{
"docid": "Underworld:_Evolution",
"text": "Underworld : Evolution is a 2006 American action horror film directed by Len Wiseman . The film is a sequel to the 2003 film , Underworld and the second installment in the Underworld franchise . In the film , Selene and Michael fight to protect the future of the Corvinus bloodline from its hidden past .",
"title": ""
},
{
"docid": "Underworld_(film_series)",
"text": "Underworld is a series of action horror films directed by Len Wiseman , Patrick Tatopoulos , Måns Mårlind , Björn Stein and Anna Foerster . The first film , Underworld , was released in 2003 . It tells the story of Selene ( Kate Beckinsale ) , a vampire who works as a Death Dealer , killing the lycans ( Werewolves ) who allegedly slaughtered her family . The second film , Underworld : Evolution , was released in 2006 . In this film , Selene takes Michael Corvin , a lycan/vampire hybrid , to a vampire safehouse and plans to return to Viktor 's estate to awaken another elder Markus , whom they discover is the first Vampire and a powerful enemy . The third film , Underworld : Rise of the Lycans , is the prequel to the series , chronicling the origins of the vampire-lycan war ( it was released on January 23 , 2009 ) . The fourth film , Underworld : Awakening , is the sequel to Underworld : Evolution and was released on January 20 , 2012 . In this film , humans have discovered the existence of the vampire and lycan clans , and are trying to eradicate both species . A fifth film titled Underworld : Blood Wars was released internationally on November 24 , 2016 , and in the United States on January 6 , 2017 . Despite receiving generally negative reviews from critics , the five films have grossed a total of $ 539 million , against a combined budget of $ 212 million .",
"title": ""
},
{
"docid": "Underworld_(2003_film)",
"text": "Underworld is a 2003 action horror film directed by Len Wiseman and written by Danny McBride , based on a story by McBride , Kevin Grevioux , and Wiseman . The film centers on the secret history of vampires and lycans ( an abbreviated form of lycanthrope , which means werewolf ) . It is the first installment in the Underworld franchise . The main plot revolves around Selene ( Kate Beckinsale ) , a vampire Death Dealer hunting Lycans . She finds herself attracted to a human , Michael Corvin ( Scott Speedman ) , who is being targeted by the Lycans . After Michael is bitten by a Lycan , Selene must decide whether to do her duty and kill him or go against her clan and save him . Alongside Beckinsale and Speedman , the film stars Michael Sheen , Shane Brolly , and Bill Nighy . An international co-production between companies from the United Kingdom , Germany , Hungary , and the United States , the film was released on September 19 , 2003 . Upon its release , the film received generally negative reviews from critics , but a smaller number of reviewers praised elements such as the film 's stylish Gothic visuals , the `` icy English composure '' in Kate Beckinsale 's performance , and the extensively worked-out vampire -- werewolf mythology that serves as the film 's backstory . A surprise hit , the film grossed $ 95 million against a production budget of $ 22 million . The film was followed by Underworld : Evolution , released three years later , and by three other films .",
"title": ""
},
{
"docid": "Underworld:_Awakening",
"text": "Underworld : Awakening is a 2012 American 3D action horror film directed by Måns Mårlind and Björn Stein . It is the fourth instalment in the Underworld franchise , with Kate Beckinsale reprising her role as Selene , joined by Theo James , Michael Ealy and India Eisley . Filming began in March 2011 in Vancouver , British Columbia and the film was released in Digital 3D , IMAX 3D and 2D theaters on January 20 , 2012 .",
"title": ""
},
{
"docid": "Underworld:_Blood_Wars",
"text": "Underworld : Blood Wars is a 2016 American action horror film directed by Anna Foerster ( in her feature film directorial debut ) . It is the fifth installment in the Underworld franchise and the sequel to Underworld : Awakening ( 2012 ) , with Kate Beckinsale reprising her role as Selene . The main cast also includes Theo James , Lara Pulver , James Faulkner and Charles Dance . Principal photography began on October 19 , 2015 , in Prague , Czech Republic . The film was released on November 24 , 2016 , in various countries and was subsequently released in the United States on January 6 , 2017 , by Screen Gems . It received generally negative reviews and has grossed over $ 81 million worldwide , against its production budget of $ 35 million .",
"title": ""
},
{
"docid": "Kate_Beckinsale",
"text": "Kathrin Romary Beckinsale ( born 26 July 1973 ) is an English actress . After some minor television roles , she made her film debut in Much Ado About Nothing ( 1993 ) while still a student at the University of Oxford . She then appeared in British costume dramas such as Prince of Jutland ( 1994 ) , Cold Comfort Farm ( 1995 ) , Emma ( 1996 ) , and The Golden Bowl ( 2000 ) , in addition to various stage and radio productions . She began to seek film work in the United States in the late 1990s and , after appearing in small-scale dramas The Last Days of Disco ( 1998 ) and Brokedown Palace ( 1999 ) , she had starring roles in the war drama Pearl Harbor and the romantic comedy Serendipity . She followed those with appearances in The Aviator ( 2004 ) and Click ( 2006 ) . Since being cast as Selene in the Underworld film series ( 2003-present ) , Beckinsale has become known primarily for her work in action films , including Van Helsing ( 2004 ) , Whiteout ( 2009 ) , Contraband ( 2012 ) , and Total Recall ( 2012 ) . She also continues to make appearances in smaller dramatic projects such as Snow Angels ( 2007 ) , Nothing but the Truth ( 2008 ) , and Everybody 's Fine ( 2009 ) . In 2016 , she appeared in Whit Stillman 's Jane Austen comedy Love & Friendship .",
"title": ""
},
{
"docid": "Underworld:_Rise_of_the_Lycans",
"text": "Underworld : Rise of the Lycans is a 2009 American action horror film directed by Patrick Tatopoulos . It is the third installment in the Underworld franchise and a prequel to the 2003 film Underworld . The film focuses primarily on the origins of the characters and the events that lead up to the Vampire -- Lycan war .",
"title": ""
},
{
"docid": "Scourge_of_the_Underworld",
"text": "The Scourge of the Underworld is the name of a series of fictional characters appearing in American comic books published by Marvel Comics . Writer/editor Mark Gruenwald originally created the Scourge in 1985 as a plot device intended to thin the criminal population of the Marvel Universe , in particular eliminating those supervillain characters he deemed to be too minor , redundant , or ill-conceived . Numerous other characters have used the name , often with differing motives and loyalties .",
"title": ""
},
{
"docid": "List_of_Mass_Effect_characters",
"text": "This article describes notable characters who appear in the Mass Effect fictional universe . This list describes only major protagonists , antagonists , squad members , and supporting characters that appear in the movies , games , novels , and comics , although these storylines feature much larger supporting casts consisting of dozens of minor characters . These characters are explored in the print novels Mass Effect : Revelation , Mass Effect : Ascension , Mass Effect : Retribution , and Mass Effect : Deception ; the graphic novels Mass Effect : Homeworlds , Mass Effect : Conviction , Mass Effect : Redemption , Mass Effect : Evolution ; the feature film Mass Effect : Paragon Lost ; and the video games Mass Effect , Mass Effect Galaxy , Mass Effect 2 , Mass Effect Infiltrator , Mass Effect 3 , Mass Effect 3 : Datapad and Mass Effect : Andromeda .",
"title": ""
},
{
"docid": "Raze",
"text": "Raze may refer to : Demolition Raze , Haute-Saône , a town in France Raze ( house-music group ) Raze ( Christian pop group ) Raze ( Underworld ) , a fictional character in the Underworld films Raze ( magazine ) , a videogame magazine published by Newsfield Publications from 1990-1991 . Raze ( film ) , a 2013 exploitation film Raze , a Marvel Comics character and Brotherhood of Mutants member",
"title": ""
},
{
"docid": "Don't_Shoot_the_Messenger",
"text": "Do n't Shoot the Messenger is an EP by Puscifer . Three of the tracks were previously released on soundtracks , `` Trekka '' ( Sean Beavan Mix ) being the only exception . `` REV 22:20 '' was released on the Underworld soundtrack , `` REV 22:20 '' ( 4:20 Mix ) was released on the Saw II soundtrack and `` The Undertaker '' ( Renholdër Mix ) was released on the Underworld : Evolution soundtrack .",
"title": ""
},
{
"docid": "Death_Dealer",
"text": "Death Dealer may refer to : Death Dealer ( painting ) , a fantasy painting , fictional character and book series created by Frank Frazetta The Death Dealers , a mystery novel by Isaac Asimov Death Dealer ( Underworld ) , the vampire warriors from the Underworld film series Vengeance Is a Dish Served Cold , also known as Death 's Dealer , a 1971 Italian Western film Death Dealer , a heavy metal band with ex-Manowar guitarist Ross Friedman Death Dealers , a 2011 album by Adept The Death Dealer , a paranormal romance novel by Heather Graham Pozzessere Death Dealer : the Memoirs of the SS Kommandant at Auschwitz , an autobiography by Rudolf Höss",
"title": ""
},
{
"docid": "580_Selene",
"text": "580 Selene is a minor planet orbiting the Sun in the asteroid belt . The name Selene is that of an ancient Greek goddess of the Moon . This body orbits the Sun nearly midway between the orbits of Mars and Jupiter . The orbital eccentricity is slightly lower than that of Mars . Based on its light curve , Selene has an estimated rotation period of 0.3947 ± 0.0004 days , or just under 9.5 hours . During each rotation , the apparent magnitude varies by 0.27 . The approximate diameter of this asteroid is 46 km . ( Some sources list a diameter of up to 56 km . ) The albedo is about 7 % , comparable to that of the Earth 's Moon .",
"title": ""
},
{
"docid": "Evolution:_The_Musical!",
"text": "Evolution : The Musical ! is a 2008 short musical comedy film depicting the struggle between Evolution and Creationism , through two groups of fictional characters : `` The Beasties '' and `` The Blesseds . '' As the film explores the struggle between these two groups , a love affair develops between two of the characters .",
"title": ""
},
{
"docid": "List_of_Top_Cat_characters",
"text": "This is a list of characters in the American animated television series Top Cat . Characters are listed only once , normally under the first applicable subsection in the list ; very minor characters are listed with a more regular character with whom they are associated . Characters that appear in only one episode are not listed . This also includes information and characters from the feature film Top Cat : The Movie and the prequel film Top Cat Begins .",
"title": ""
},
{
"docid": "Michael_Corvin",
"text": "Michael Corvin ( in Hungarian : Corvin Mihály ) is a fictional character from the Underworld series . He also appears in the novelizations of these films . He is portrayed by Scott Speedman in the first two films and by Trent Garrett through motion capture and prosthetics in Underworld : Blood Wars . He is the first Vampire/Lycan Hybrid from the mythos .",
"title": ""
},
{
"docid": "Pusher_(film_series)",
"text": "The Pusher films by Danish film director Nicolas Winding Refn illustrate and explore the criminal underworld of Copenhagen . Each of the three entries features a different character , with both sequels centered on a supporting character from the previous film .",
"title": ""
},
{
"docid": "Selene",
"text": "In Greek mythology , Selene ( -LSB- sᵻˈliːni -RSB- -LSB- selɛ̌ːnɛː -RSB- ` moon ' ;) is the goddess of the moon . She is the daughter of the Titans Hyperion and Theia , and sister of the sun-god Helios , and Eos , goddess of the dawn . She drives her moon chariot across the heavens . Several lovers are attributed to her in various myths , including Zeus , Pan , and the mortal Endymion . In classical times , Selene was often identified with Artemis , much as her brother , Helios , was identified with Apollo . Both Selene and Artemis were also associated with Hecate , and all three were regarded as lunar goddesses , although only Selene was regarded as the personification of the moon itself . Her Roman equivalent is Luna .",
"title": ""
},
{
"docid": "Bert_Selen",
"text": "Bert Selen ( Born Bert Jacobus Martinus Selen 30 August 1985 ) is a Multi Award-winning Music producer , TV/Film composer , Multi-Instrumentalist and songwriter based in Los Angeles . He is best known for his work on the primetime sitcom `` Rules of Engagement '' ( Sony/CBS ) . His music has been featured in a variety of films and TV shows , notably `` Parks and Recreation '' ( NBC ) , `` The Mentalist '' ( CBS ) , `` Lab Rats '' ( Disney ) and `` Mystery Girls '' ( ABC Family ) .",
"title": ""
},
{
"docid": "Hercules:_The_Legendary_Journeys",
"text": "Hercules : The Legendary Journeys is an American television series filmed in New Zealand . It was produced from January 16 , 1995 to November 22 , 1999 , and was based on the tales of the classical Greek culture hero Heracles ( Hercules was his Roman analogue ) . It ran for six seasons , producing action figures and other memorabilia as it became one of the highest rated syndicated television shows in the world at that time . It was preceded by several TV movies with the same major characters in 1994 as part of Universal Television 's Action Pack in order of appearance : Hercules and the Amazon Women , Hercules and the Lost Kingdom , Hercules and the Circle of Fire , Hercules in the Underworld , and Hercules in the Maze of the Minotaur , the last of which served mostly as a `` clip show '' of the previous movies as a lead up to the series . The show was cancelled midway through filming of the sixth season , and only a total of eight episodes were produced after Kevin Sorbo initially declined to renew a three-year extension contract to continue his role as Hercules .",
"title": ""
},
{
"docid": "Pafko_at_the_Wall",
"text": "`` Pafko at the Wall '' , subtitled `` The Shot Heard Round the World '' , was originally published as a folio in the October 1992 issue of Harper 's Magazine . It was later ( 1997 ) incorporated as the prologue in Don DeLillo 's magnum opus novel , Underworld , with minor changes from the original version , such as a new opening line . In 2001 , `` Pafko '' was re-released as a novella , by Scribner . This is the same version as printed in Underworld , where the section is titled `` The Triumph of Death '' , in reference to the painting by Pieter Brueghel the Elder . The title character is Andy Pafko , who , as the Dodgers ' left fielder , saw Bobby Thomson 's famous shot go over his head .",
"title": ""
},
{
"docid": "Japanese_Lunar_Exploration_Program",
"text": "The ( Japanese ) Lunar Exploration Program , is a program of robotic and human missions to the Moon undertaken by the Japanese Aerospace Exploration Agency ( JAXA ) , and its division , the Institute of Space and Astronautical Science ( ISAS ) . It is also one of the three major enterprises of the JAXA Space Exploration Center ( JSPEC ) . The main goal of the program is `` to elucidate the origin and evolution of the Moon and utilize the Moon in the future '' . The first spacecraft of the program , the unmanned lunar orbiter SELENE ( Kaguya ) , was launched from Tanegashima Space Center on September 14 , 2007 , after being delayed several times . SELENE-2 , Japan 's first lunar lander and rover , is expected to be launched in 2017 . The program also includes a lunar sample return mission ( SELENE-3 ) , a mission to Mars to collect data for future manned expeditions ( MELOS ) , participation in the Mars international sample return mission , and an advanced lander for future human missions to the Moon . The eventual goal is to participate in an international lunar outpost program , in which Japanese crews would stay on the lunar surface for a prolonged period of time and promote scientific research and environment utilization .",
"title": ""
},
{
"docid": "Selene_brevoortii",
"text": "Selene brevoortii ( the airfin lookdown , hairfin lookdown , Mexican lookdown , or Pacific lookdown ) , is a species of carangid native to the Pacific coast of the Americas where it is found from southernmost Baja California , Mexico to Ecuador . This species is generally found in shallow waters close to the coast . They grow to 42 cm in total length . It is of minor importance to local commercial fisheries , but is popular as a gamefish .",
"title": ""
},
{
"docid": "Bram_Stoker's_Dracula's_Curse",
"text": "Bram Stoker 's Dracula 's Curse ( also known simply as Dracula 's Curse ) is a 2006 horror film by The Asylum , written and directed by Leigh Scott . Despite featuring Bram Stoker 's name in the title , the film is not directly based on any of his writings or a mockbuster to the 1992 film Bram Stoker 's Dracula , but shares similarities to films such as Blade : Trinity , Dracula 2000 , Underworld : Evolution and Van Helsing . The film also shares some similarities with the 1971 Hammer horror film Countess Dracula , which also features a Dracula-esque femme fatale in the lead role .",
"title": ""
},
{
"docid": "Amanda_Young",
"text": "Amanda Young is a fictional character in the Saw franchise . She is portrayed by Shawnee Smith . At first a minor character in the original film , her role expanded in the sequels until she became one of the most important characters in the series , being the only character besides Jigsaw himself to have appeared in every Saw film .",
"title": ""
},
{
"docid": "Doraemon:_Nobita's_Great_Adventure_into_the_Underworld",
"text": ", also known as Doraemon , Nobita and the Underworld Adventure , is a feature-length Doraemon film which premiered on March 17 , 1984 . The fifth in series , it was the first to incorporate computer graphics technology . The movie was watched by 3,300,000 people and generated a revenue of 1,630,000,000 yen , making it became the highest grossing animated film of 1984 . By its release , Doraemon became the first and so far , the only franchise to have 2 back-to-back highest-grossing animated films of the year . A remake was released on March 10 , 2007 , entitled Doraemon : Nobita 's New Great Adventure into the Underworld .",
"title": ""
},
{
"docid": "Underworld_(comics)",
"text": "Underworld ( Jackie Dio ) is a fictional character , a supervillain in publications from Marvel Comics . The character first appeared in the Underworld limited series in 2006 .",
"title": ""
},
{
"docid": "Vaastav:_The_Reality",
"text": "Vaastav is a 1999 Indian crime drama written and directed by Mahesh Manjrekar and starring Sanjay Dutt and Namrata Shirodkar . It also features Sanjay Narvekar , Mohnish Behl , Paresh Rawal , Reema Lagoo and Shivaji Satam in supporting roles . `` The Reality '' as described by the film 's tagline , refers to the harsh realities of life in the Mumbai underworld . The film is said to be loosely based on the life of Mumbai underworld gangster Chhota Rajan . The film was very well received by both critics and audiences . It is the 14th highest grossing Bollywood film of 90 's decade and the amongst the highest grossing rated R certificate Hindi films of all time , ironically a scene of Sanjay Dutt 's character raghu shooting the parsi 's mans wife after she spits in his face was cut out in order for the film to get a 15 certificate for DVD and TV . Sanjay Dutt was nominated for the Filmfare best actor category for the fourth time in his then 18 year old film career and finally winning it , regarded by critics unanimusly amongst being one of Indian cinema 's most memorable and most quated onscreen characters . The film was extremely successful both in India and overseas . It was nominated for and won many awards . Over the years it has become a cult film . The film was followed by the 2002 sequel Hathyar .",
"title": ""
},
{
"docid": "On_the_Proteaceae:_the_evolution_and_classification_of_a_southern_family",
"text": "On the Proteaceae : the evolution and classification of a southern family is a highly influential monograph on the evolution , biogeography and taxonomy of the flowering plant family Proteaceae . Authored by Lawrie Johnson and Barbara Briggs , it appeared in Volume 70 of Botanical Journal of the Linnean Society in 1975 . Johnson and Briggs had presented what would become the paper at a meeting of the Linnaean Society on 6 December 1973 amid celebrations of 200 years since the birth of Robert Brown . One of its most important and long-lasting contributions was the establishment for a suprageneric classification of the Proteaceae , which was accepted with only minor modifications until 2006 , when Peter H. Weston and Nigel P. Barker presented a new arrangement based primarily upon molecular data . According to Weston and Barker , `` Johnson and Briggs ' classification has served as the systematic framework for a generation of researchers '' .",
"title": ""
},
{
"docid": "List_of_Saw_cast_members",
"text": "The list of Saw cast members is a list of actors who voiced or portrayed characters appearing in the Saw franchise created by James Wan and Leigh Whannell . The only actors to appear in all seven films are Tobin Bell ( Jigsaw ) , who is also the only actor to film scenes for every film in the series , and Shawnee Smith ( Amanda Young ) , who appears via archive footage in the three films she does not feature in prominently . Complementing them on screen are actors ranging from renowned status such as Danny Glover , Cary Elwes , and Donnie Wahlberg to lesser-known actors such as Dina Meyer and Lyriq Bent , among others . While many actors reprise their roles for cameos and minor appearances , the only actors besides Bell and Smith to appear with major roles in more than three films were Costas Mandylor ( Mark Hoffman ) and Betsy Russell ( Jill Tuck ) , both of whom appear in the latter five instalments of the series . In other Saw media , a significant number of actors have either been replaced or omitted from appearing . In the video game , Tobin Bell was the only actor to reprise his role from the films . Other characters such as Amanda Young , Obi Tate , and Jeff Thomas all returned but were voiced by other actors . Other characters , including Pamela Jenkins and Steven Sing were mentioned but did not make any appearance . For the Saw roller coaster , Billy the Puppet was the only character to appear , with no voice provided for him . The lack of characters present is attributed to the physical restraints of actors in a roller coaster . A prequel comic book , Saw : Rebirth , featured many recurring characters but little actor corresponding or likeness ' due to the comic not being supported by Twisted Pictures . Other actors likenesses were used in place of the films ' actors . While the films have not replaced any actors , their scripts have been altered to omit certain characters due to a number of conflicts . Cary Elwes ' character , Lawrence Gordon , did not appear in subsequent films after Saw due to a lawsuit from payment issues for Elwes , although his character has been referenced many times since . Elwes reprised his character in the final film , Saw 3D .",
"title": ""
}
] |
PLAIN-1281
|
gout
|
[
{
"docid": "MED-1292",
"text": "There has been enormous interest in the biologic activity of mushrooms and innumerable claims have been made that mushrooms have beneficial effects on immune function with subsequent implications for inhibition of tumor growth. The majority of these observations are anecdotal and often lack standardization. However, there remains considerable data on both in vitro and in vivo effects that reflect on the potential of mushroom compounds to influence human immunity. A number of these effects are beneficial but, unfortunately, many responses are still characterized based on phenomenology and there is more speculation than substance. With respect to tumor biology, although many neoplastic lesions are immunogenic, tumor antigens frequently are self antigens and induce tolerance and many patients with cancer exhibit suppressed immune responses, including defective antigen presentation. Therefore, if and when mushroom extracts are effective, they more likely function as a result of improved antigen presentation by dendritic cells than by a direct cytopathic effect. In this review we attempt to place these data in perspective, with a particular focus on dendritic cell populations and the ability of mushroom extracts to modulate immunity. There is, at present, no scientific basis for the use of either mushrooms or mushroom extracts in the treatment of human patients but there is significant potential for rigorous research to understand the potential of mushrooms in human disease and thence to focus on appropriate clinical trials to demonstrate effectiveness and/ or potential toxicity.",
"title": "The immunobiology of mushrooms."
},
{
"docid": "MED-4089",
"text": "Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.",
"title": "Antiproliferative effects of apple peel extract against cancer cells."
},
{
"docid": "MED-3153",
"text": "This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18-53 years, mean age: 36 ± 9, self-administered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP®) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon. Key points",
"title": "Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes"
},
{
"docid": "MED-1441",
"text": "Most ethnic foods and cooking practices have incorporated the use of spices and other food additives. Many common spices have crossed cultural boundaries and appear in multiple ethnic cuisines. Recent studies have demonstrated that many of these ingredients possess antimicrobial properties against common food spoilage microorganisms. We developed a laboratory exercise that promotes the use of scientific methodology to evaluate the effectiveness of salsa components at inhibiting the growth of undesirable microorganisms. Tomato, onion, garlic, cilantro, and jalapeño were tested for antimicrobial properties against a representative fungus, Saccharomyces cerevisiae, and the common food spoilage bacteria Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Each component was ethanol extracted and a modification of the Kirby-Bauer method of antimicrobial sensitivity was employed. Garlic demonstrated the greatest inhibitory effects against all organisms tested. Onion demonstrated a slight inhibition of all four organisms, while cilantro showed some inhibition of all three bacteria but no effect against the fungus. Jalapeño may have slightly inhibited E. coli and S. aureus, as evidenced by a consistently measured increase in the zone of inhibition that was not statistically significant when compared to that of the control. Following the initial exercise, students were given the opportunity to repeat the exercise using other spices such as cinnamon, clove, nutmeg, and coriander. Student learning outcomes were evaluated using preliminary and secondary surveys, mainly focusing on definitions of science and hypothesis as well as the process of science. Students enjoyed this exercise and met the learning goals of understanding the process and methodology of science, as well as the interdisciplinarity inherent in the sciences. Student learning was evidenced by an increase in the number of correct responses on the secondary survey in comparison to the preliminary.",
"title": "The Science of Salsa: Antimicrobial Properties of Salsa Components to Learn Scientific Methodology"
},
{
"docid": "MED-2781",
"text": "Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.",
"title": "Effect of different curcumin dosages on human gall bladder."
},
{
"docid": "MED-2788",
"text": "Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.",
"title": "Clinical utility of curcumin extract."
},
{
"docid": "MED-1987",
"text": "OBJECTIVE: Over the last 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guideline, \"Management of Type 2 Diabetes Mellitus in Children and Adolescents,\" and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline's recommendations. METHODS: A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary literature search was conducted relating to the screening and treatment of T2DM's comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treatment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were considered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. RESULTS: Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclusion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 studies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic review. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information.",
"title": "Management of type 2 diabetes mellitus in children and adolescents."
},
{
"docid": "MED-1994",
"text": "PURPOSE OF REVIEW: The prevalence of obesity in youth is increasing alarmingly among children and adolescents in the United States. The problem falls disproportionately on African-American and Hispanic children. Many of the metabolic and cardiovascular complications associated with obesity are already present during childhood and are closely linked to the concomitant insulin resistance/hyperinsulinemia and degree of obesity. Moreover, these co-morbidities persist into adulthood. RECENT FINDINGS: The progression from normal glucose tolerance to type 2 diabetes mellitus involves an intermediate stage known as prediabetes or impaired glucose regulation. Prediabetes is characterized by peripheral insulin-resistance and impaired glucose sensitivity of first-phase insulin secretion. On the other hand, in overt type 2 diabetes mellitus beta-cell failure becomes fully manifested. Progression from prediabetes to type 2 diabetes mellitus in youth is characterized by marked weight gain and further reduction in insulin secretion and insulin resistance. SUMMARY: Reverting obesity through lifestyle modification, that involves nutrition education, behavior modification and exercise, is an important step to prevent the progression to diabetes.",
"title": "Prediabetes and type 2 diabetes in youth: an emerging epidemic disease?"
},
{
"docid": "MED-3237",
"text": "The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",
"title": "Diet-induced metabolic acidosis."
},
{
"docid": "MED-3215",
"text": "The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.",
"title": "Excess dietary protein can adversely affect bone."
},
{
"docid": "MED-1998",
"text": "The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.",
"title": "The early treatment of type 2 diabetes."
},
{
"docid": "MED-3229",
"text": "High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.",
"title": "Protein intake, calcium balance and health consequences."
},
{
"docid": "MED-3535",
"text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.",
"title": "Cherries and health: a review."
},
{
"docid": "MED-1990",
"text": "BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.) 2009 Massachusetts Medical Society",
"title": "Intensive versus conventional glucose control in critically ill patients."
},
{
"docid": "MED-4092",
"text": "The relationship between uric acid and cardiovascular disease has been known since the 19th century, after that many authors reported the classical association of gout, hypertension, obesity and cardiovascular disease. With the exception of specific genetic defects in purine metabolism, increased uric acid is generally associated with important risk factors for atherosclerosis like hypertension, abdominal obesity, insulin resistance, the metabolic syndrome and renal failure. Studies have clearly shown an association between increased uric acid concentrations with oxidative stress, endothelial dysfunction, inflammation, subclinical atherosclerosis and an increased risk of cardiovascular events. Increased uric acid levels are independent markers of cardiovascular disease risk. Prospective studies are necessary to show that reduction of uric acid levels prevent cardiovascular events.",
"title": "Uric acid: A marker of increased cardiovascular risk."
},
{
"docid": "MED-3226",
"text": "Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.",
"title": "Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load"
},
{
"docid": "MED-3220",
"text": "Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.",
"title": "Alkaline diets favor lean tissue mass in older adults"
},
{
"docid": "MED-2787",
"text": "BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.",
"title": "The effect of curcumin and placebo on human gall-bladder function: an ultrasound study."
},
{
"docid": "MED-1997",
"text": "The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.",
"title": "Vegetarian diets and childhood obesity prevention."
},
{
"docid": "MED-2272",
"text": "To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.",
"title": "Consumption of cherries lowers plasma urate in healthy women."
},
{
"docid": "MED-2777",
"text": "BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.",
"title": "The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994."
},
{
"docid": "MED-4609",
"text": "Two pandemics of heart attack deaths have plagued the world's population during the past 130 years. The first pandemic, induced by beriberi, was caused by the industrial revolution altering the nutritional composition of rice. By 1892 a simple working knowledge, then at hand, could have terminated the beriberi plague; however, orthodox medicine being then enchanted with the false concept that all disease was caused by germs, permitted millions of Asians to die needlessly of beriberi by refusing to tell them to eat rice bran or to drink rice bran tea. A second pandemic of heart attack deaths, called myocardial infarction (MI), struck the developed nations of the Western World in full force after 1930. As a hypothesis, it is suggested that this MI pandemic, still raging today, was caused by a change in food processing that occurred after 1920, when the new oil seed industry introduced into our food three greatly harmful lipid substances. The unnatural trans-trans isomer of linoleic acid, which had never been in human food prior to 1920 and which entered our food in margarines and refined oils, blocked the conversion of natural cis-cis linoleic acid to prostaglandin E1, which tends to prevent MI, both by acting as a vasodilator and by minimizing platelet aggregation. Harmful lactones were also introduced into our food, increasing the risk of MI by decreasing the fibrinolytic activity of our blood. The oil seed industry also introduced into our diet free radical lipid peroxides that make the myocardium more vulnerable to infarction. It is suggested that except for the one in 500 of us who is afflicted by familial hypercholesterolemia, the cholesterol concept of MI is as false today as was the concept in 1900 that germs caused beriberi. It is further suggested that a working knowledge is at hand today that can make death from MI just as rare as death is now from a beriberi-induced heart attack.",
"title": "The beriberi analogy to myocardial infarction."
},
{
"docid": "MED-2273",
"text": "Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.",
"title": "Purine-rich foods intake and recurrent gout attacks"
},
{
"docid": "MED-1443",
"text": "SUMMARY BACKGROUND: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti-inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo. METHODS: 40 volunteers were enrolled in this monocentric,randomized,placebo-controlled double-blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV-B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place-bo.The effect of the test substances on the UV-induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non-irradiated skin. RESULTS: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV-induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent. CONCLUSIONS: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.",
"title": "Anti-inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test."
},
{
"docid": "MED-3231",
"text": "This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.",
"title": "The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health?"
},
{
"docid": "MED-1999",
"text": "Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.",
"title": "Strategies for preventing type 2 diabetes: an update for clinicians"
},
{
"docid": "MED-4093",
"text": "OBJECTIVE: The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. RESULTS: A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION: Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.",
"title": "Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study."
},
{
"docid": "MED-1295",
"text": "A number of polysaccharides with beta-glycosidic linkage are widespread in nature in a variety of sources. All have a common structure and the (1-->3)-beta-D-glucan backbone is essential. They have attracted attention over the years because of their bioactive and medicinal properties. In many cases their functional role is a mystery, in others it is well established. Because of their insoluble chemical nature, particulate (1-->3)-beta-D-glucans are not suitable for many medical applications. Various methods of changing or modifying the beta-D-glucan chemical structure and transforming it to a soluble form have been published. The beta-D-glucan bioactive properties can be affected positively or negatively by such modifications. This review examines beta-glucan sources in nature, health effects and structure-activity relationships. It presents the current state of beta-D-glucan solubilization methods and discusses their effectiveness and application possibilities for the future.",
"title": "Natural and modified (1-->3)-beta-D-glucans in health promotion and disease alleviation."
},
{
"docid": "MED-3230",
"text": "OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.",
"title": "Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores."
},
{
"docid": "MED-1300",
"text": "Purpose The effect of brewers’ yeast (1,3)-(1,6)-beta-d-glucan consumption on the number of common cold episodes in healthy subject was investigated. Methods In a placebo-controlled, double-blind, randomized, multicentric clinical trial, 162 healthy participants with recurring infections received 900 mg of either placebo (n = 81) or an insoluble yeast (1,3)-(1,6)-beta-d-glucan preparation (n = 81) per day over a course of 16 weeks. Subjects were instructed to document each occurring common cold episode in a diary and to rate ten predefined infection symptoms during an infections period, resulting in a symptom score. The subjects were examined by the investigator during the episode visit on the 5th day of each cold episode. Results In the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)-beta-glucan reduced the number of symptomatic common cold infections by 25 % as compared to placebo (p = 0.041). The mean symptom score was 15 % lower in the beta-glucan as opposed to the placebo group (p = 0.125). Beta-glucan significantly reduced sleep difficulties caused by cold episode as compared to placebo (p = 0.028). Efficacy of yeast beta-glucan was rated better than the placebo both by physicians (p = 0.004) participants (p = 0.012). Conclusion The present study demonstrated that yeast beta-glucan preparation increased the body’s potential to defend against invading pathogens.",
"title": "Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects"
},
{
"docid": "MED-2810",
"text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".",
"title": "Curcumin as \"Curecumin\": from kitchen to clinic."
},
{
"docid": "MED-1988",
"text": "PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.",
"title": "Pediatrician's role in screening and treatment: bullying, prediabetes, oral health."
},
{
"docid": "MED-1444",
"text": "Coriander (Coriandrum sativum L.), a herbal plant, belonging to the family Apiceae, is valued for its culinary and medicinal uses. All parts of this herb are in use as flavoring agent and/or as traditional remedies for the treatment of different disorders in the folk medicine systems of different civilizations. The plant is a potential source of lipids (rich in petroselinic acid) and an essential oil (high in linalool) isolated from the seeds and the aerial parts. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb, which include anti-microbial, anti-oxidant, anti-diabetic, anxiolytic, anti-epileptic, anti-depressant, anti-mutagenic, anti-inflammatory, anti-dyslipidemic, anti-hypertensive, neuro-protective and diuretic. Interestingly, coriander also possessed lead-detoxifying potential. This review focuses on the medicinal uses, detailed phytochemistry, and the biological activities of this valuable herb to explore its potential uses as a functional food for the nutraceutical industry. Copyright © 2012 John Wiley & Sons, Ltd.",
"title": "Coriander (Coriandrum sativum L.): a potential source of high-value components for functional foods and nutraceuticals--a review."
},
{
"docid": "MED-1985",
"text": "The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.",
"title": "Attained height of lacto-ovo vegetarian children and adolescents."
},
{
"docid": "MED-4091",
"text": "In this study, six common tests for measuring antioxidant activity were evaluated by comparing four antioxidants and applying them to beverages (tea and juices): Trolox equivalent antioxidant capacity assay (TEAC I-III assay), Total radical-trapping antioxidant parameter assay (TRAP assay), 2,2-diphenyl-l-picrylhydrazyl assay (DPPH assay), N,N-dimethyl-p-phenylendiamine assay (DMPD assay), Photochemiluminescence assay (PCL assay) and Ferric reducing ability of plasma assay (FRAP assay). The antioxidants included gallic acid representing the group of polyphenols, uric acid as the main antioxidant in human plasma, ascorbic acid as a vitamin widely spread in fruits and Trolox as water soluble vitamin E analogue. The six methods presented can be divided into two groups depending on the oxidising reagent. Five methods use organic radical producers (TEAC I-III, TRAP, DPPH, DMPD, PCL) and one method works with metal ions for oxidation (FRAP). Another difference between these tests is the reaction procedure. Three assays use the delay in oxidation and determine the lag phase as parameter for the antioxidant activity (TEAC I, TRAP, PCL). They determine the delay of radical generation as well as the ability to scavenge the radical. In contrast, the assays TEAC II and III, DPPH, DMPD and FRAP analyse the ability to reduce the radical cation (TEAC II and III, DPPH, DMPD) or the ferric ion (FRAP). The three tests acting by radical reduction use preformed radicals and determine the decrease in absorbance while the FRAP assay measures the formed ferrous ions by increased absorbance. Gallic acid was the strongest antioxidant in all tests with exception of the DMPD assay. In contrast, uric acid and ascorbic acid showed low activity in some assays. Most of the assays determine the antioxidant activity in the micromolar range needing minutes to hours. Only one assay (PCL) is able to analyse the antioxidant activity in the nanomolar range. Black currant juice showed highest antioxidant activity in all tests compared to tea, apple juice and tomato juice. Despite these differences, results of these in vitro assays give an idea of the protective efficacy of secondary plant products. It is strongly recommended to use at least two methods due to the differences between the test systems investigated.",
"title": "Assessment of antioxidant activity by using different in vitro methods."
},
{
"docid": "MED-4612",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "MED-2818",
"text": "Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.",
"title": "Curcumin: the story so far."
},
{
"docid": "MED-3216",
"text": "Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.",
"title": "Low protein intake: the impact on calcium and bone homeostasis in humans."
},
{
"docid": "MED-3236",
"text": "A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.",
"title": "Nutrient based estimation of acid-base balance in vegetarians and non-vegetarians."
},
{
"docid": "MED-5071",
"text": "Dietary intervention with anthocyanins may confer benefits in brain function, including vision. Research to date indicates that animals have only a limited capacity to absorb anthocyanins, compared to other types of flavonoids. Pigs, which are a suitable model for human digestive absorption, were used to examine the deposition of anthocyanins in tissues including the liver, eye, and brain tissue. Pigs were fed diets supplemented with 0, 1, 2, or 4% w/w blueberries ( Vaccinium corymbosum L. 'Jersey') for 4 weeks. Prior to euthanasia, pigs were fasted for 18-21 h. Although no anthocyanins were detected in the plasma or urine of the fasted animals, intact anthocyanins were detected in all tissues where they were sought. LC-MS/MS results are presented for the relative concentration of 11 intact anthocyanins in the liver, eye, cortex, and cerebellum. The results suggest that anthocyanins can accumulate in tissues, including tissues beyond the blood-brain barrier.",
"title": "Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs."
},
{
"docid": "MED-1296",
"text": "Natural immunomodulators are getting more and more popular. The popularity, however, often brings over-optimistic claims and mediocre effects. The purpose of the present study was to directly compare eleven most commonly used immunomodulators. Through testing both cellular and humoral branches of immune reactions, we found that most of the immunomodulators tested have limited, if any, effects, with glucan being consistently the most active molecule strongly stimulating every reaction evaluated. These data were also confirmed using a Lewis lung cancer model, where only glucan and resveratrol lowered the number of metastases.",
"title": "Natural immunomodulators and their stimulation of immune reaction: true or false?"
},
{
"docid": "MED-2278",
"text": "OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.",
"title": "Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats."
},
{
"docid": "MED-2780",
"text": "Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation.",
"title": "Total and soluble oxalate content of some Indian spices."
},
{
"docid": "MED-2816",
"text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.",
"title": "Plant-derived health: the effects of turmeric and curcuminoids."
},
{
"docid": "MED-1293",
"text": "In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.",
"title": "Immunity: plants as effective mediators."
},
{
"docid": "MED-3227",
"text": "Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.",
"title": "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women."
},
{
"docid": "MED-2815",
"text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin, a component of turmeric: from farm to pharmacy."
},
{
"docid": "MED-4722",
"text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.",
"title": "Dietary protein and bone health: a systematic review and meta-analysis."
},
{
"docid": "MED-3228",
"text": "A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.",
"title": "Dietary protein and bone health: harmonizing conflicting theories."
},
{
"docid": "MED-1992",
"text": "Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.",
"title": "Prediabetes: A high-risk state for developing diabetes"
},
{
"docid": "MED-1294",
"text": "Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.",
"title": "Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan"
},
{
"docid": "MED-1442",
"text": "We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h2 from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype–phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.",
"title": "Genetic Analysis of Chemosensory Traits in Human Twins"
},
{
"docid": "MED-1986",
"text": "BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up.",
"title": "Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935."
},
{
"docid": "MED-3464",
"text": "The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.",
"title": "Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women."
},
{
"docid": "MED-1996",
"text": "Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.",
"title": "Childhood obesity and type 2 diabetes mellitus."
},
{
"docid": "MED-2782",
"text": "BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.",
"title": "Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial."
},
{
"docid": "MED-2276",
"text": "A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.",
"title": "Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans."
},
{
"docid": "MED-2783",
"text": "Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Multitargeting by turmeric, the golden spice: From kitchen to clinic."
},
{
"docid": "MED-3221",
"text": "Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.",
"title": "Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid"
},
{
"docid": "MED-2785",
"text": "Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.",
"title": "Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells."
},
{
"docid": "MED-1291",
"text": "There is significant interest in the use of mushrooms and/or mushroom extracts as dietary supplements based on theories that they enhance immune function and promote health. To some extent, select mushrooms have been shown to have stimulatory action on immune responsiveness, particularly when studied in vitro. However, despite their widespread use for potential health benefits, there is a surprising paucity of epidemiologic and experimental studies that address the biologic activities of mushrooms after oral administration to animals or humans. There have been a number of studies that have addressed the ability of mushrooms to modulate mononuclear cell activation and the phenotypic expression of cytokines and their cognate receptors. There have also been a number of attempts to determine antitumor activities of mushrooms. Such studies are important because many of the components of mushrooms do potentially have significant biologic activity. All data, however, should be tempered by the possibility that there are toxic levels of metals, including arsenic, lead, cadmium, and mercury as well as the presence of radioactive contamination with 137Cs. In this review, we will present the comparative biology with respect to both immunological and antitumor activities of mushroom extracts and also highlight the need for further evidence-based research.",
"title": "Mushrooms, tumors, and immunity: an update."
},
{
"docid": "MED-2786",
"text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.",
"title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?"
},
{
"docid": "MED-4617",
"text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.",
"title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States"
},
{
"docid": "MED-1298",
"text": "Obesity-induced insulin resistance has been suggested to be a systemic inflammatory condition with activation of the innate immune system. Animal studies indicate that certain dietary fibers such as (1,3)(1,6)-beta-D-glycans (BDG) have potent effects on immune activity such as increasing the antiinflammatory cytokine interleukin-10 (IL-10) and reducing the secretion of inflammatory factors. Therefore, we hypothesized that BDG consumption improves inflammatory markers and insulin sensitivity in overweight and obese subjects with moderately increased levels of C-reactive protein, indicating subclinical inflammation. We screened 180 overweight and obese subjects for moderately increased C-reactive protein levels on 2 or more occasions, in the absence of any signs of acute infection. Twelve of the subjects met all inclusion criteria and were investigated in a randomized, double-blind, placebo-controlled, crossover design for 2 x 4 weeks (washout > or =4 weeks). Subjects ingested capsules containing 3 x 0.5 g of highly purified BDG or 3 x 0.5 g of placebo (waxy maize starch) daily. Maintenance of the normal diet of the participants and the correct intake of the capsules were monitored, using 6 x 3-day food recording and counting of the provided capsules. Predefined outcome measures were BDG-induced changes in pro and antiinflammatory markers in circulating blood and gene expression in adipose tissue and peripheral insulin sensitivity expressed as M value. The BDG consumption for 4 weeks significantly increased both circulating levels and adipose tissue messenger RNA (mRNA) expression of the antiinflammatory cytokine IL-10 in overweight and obese humans. Insulin sensitivity as well as circulating levels and mRNA expression of proinflammatory cytokines were unaffected by BDG treatment. Increased IL-10 after BDG consumption might be a contributing factor to the known beneficial effects of dietary fiber intake.",
"title": "Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-beta-glycan consumption in overweight humans."
},
{
"docid": "MED-3217",
"text": "To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.",
"title": "Age and systemic acid-base equilibrium: analysis of published data."
},
{
"docid": "MED-2274",
"text": "Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.",
"title": "Cherry Consumption and the Risk of Recurrent Gout Attacks"
},
{
"docid": "MED-1991",
"text": "The objective of this article is to review the epidemiologic literature examining the role of plant foods and plant-based diets in the prevention of childhood obesity. Available data suggest a protective effect of ready-to-eat cereal on risk of obesity, although prospective studies are still needed. Studies on fruit and vegetables; grains other than cereal; high-protein foods, including beans, legumes, and soy; fiber; and plant-based dietary patterns are inconsistent or generally null. The evidence base is limited, and most studies are fraught with methodologic limitations, including cross-sectional design, inadequate adjustment for potential confounders, and lack of consideration of reporting errors, stage of growth, and genetic influences. Well-designed prospective studies are needed. The lack of evidence showing an association between plant-based diets and childhood obesity does not mean that such diets should not be encouraged. Plant foods are highlighted in the Dietary Guidelines for Americans, and children do not meet the current recommendations for most plant foods. Although the advice to consume a plant-based, low-energy-dense diet is sound, ethical questions arise concerning the relatively high price of these diets in the United States and the way in which such diets are perceived in other parts of the world. Reducing the burden of childhood obesity, eliminating health disparities, and preventing the further spread of the disease around the globe will require not only policy interventions to ensure that plant foods are affordable and accessible to children of all income levels but also awareness of sociocultural norms that affect consumption.",
"title": "Plant foods and plant-based diets: protective against childhood obesity?"
},
{
"docid": "MED-3233",
"text": "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.",
"title": "A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m..."
},
{
"docid": "MED-1299",
"text": "OBJECTIVE: Several studies have shown a baker's yeast beta-1,3/1,6-d-glucan, extracted from Saccharomyces cerevisiae, is effective in reducing the incidence of cold and flu symptoms. This study evaluated the effect of a specific beta-glucan supplement (Wellmune) on upper respiratory tract symptoms and psychological well-being in women with moderate levels of psychological stress. METHODS: Healthy women (38 ± 12 years old) prescreened for moderate levels of psychological stress, self-administered a placebo (n = 38) or 250 mg of Wellmune (n = 39) daily for 12 weeks. We used the Profile of Mood States (POMS) psychological survey to assess changes in mental/physical energy levels (vigor) and overall well-being (global mood state). A quantitative health perception log was used to track upper respiratory symptoms. RESULTS: Subjects in the Wellmune group reported fewer upper respiratory symptoms compared to placebo (10% vs 29%), better overall well-being (global mood state: 99 ± 19 vs 108 ± 23, p < 0.05), and superior mental/physical energy levels (vigor: 19.9 ± 4.7 vs 15.8 ± 6.3, p < 0.05). CONCLUSIONS: These data show that daily dietary supplementation with Wellmune reduces upper respiratory symptoms and improves mood state in stressed subjects, and thus it may be a useful approach for maintaining immune protection against daily stressors.",
"title": "Baker's yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women."
},
{
"docid": "MED-4613",
"text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.",
"title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition."
},
{
"docid": "MED-2221",
"text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.",
"title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?"
},
{
"docid": "MED-1993",
"text": "Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.",
"title": "Type 2 diabetes mellitus in children and adolescents"
}
] |
[
{
"docid": "MED-1710",
"text": "Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.",
"title": "Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People"
},
{
"docid": "MED-3168",
"text": "Legumes and the polyphenolic compounds present in them have gained a lot of interest due to their beneficial health implications. Dietary polyphenolic compounds, especially flavonoids, exert antioxidant properties and are potent inhibitors of xanthine oxidase (XO) activity. XO is the main contributor of free radicals during exercise but it is also involved in pathogenesis of several diseases such as vascular disorders, cancer and gout. In order to discover new natural, dietary XO inhibitors, some polyphenolic fractions and pure compounds isolated from two legume plant extracts were tested for their effects on XO activity. The fractions isolated from both Vicia faba and Lotus edulis plant extracts were potent inhibitors of XO with IC50 values range from 40–135 µg/mL and 55–260 µg/mL, respectively. All the pure polyphenolic compounds inhibited XO and their Ki values ranged from 13–767 µM. Ten of the compounds followed the non competitive inhibitory model whereas one of them was a competitive inhibitor. These findings indicate that flavonoid isolates from legume plant extracts are novel, natural XO inhibitors. Their mode of action is under investigation in order to examine their potential in drug design for diseases related to overwhelming XO action.",
"title": "Flavonoid Glycosides Isolated from Unique Legume Plant Extracts as Novel Inhibitors of Xanthine Oxidase"
},
{
"docid": "MED-4040",
"text": "The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.",
"title": "Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man."
},
{
"docid": "MED-2099",
"text": "Water-soluble dietary fibers from apple peels and water-insoluble dietary fibers from wheat bran and soybean-seed hull were used to evaluate their binding capacities for four toxic elements (Pb, Hg, Cd, and As), lard, cholesterol, and bile acids. The water-soluble dietary fibers showed a higher binding capacity for three toxic cations, cholesterol, and sodium cholate; and a lower binding capacity for lard, compared to the water-insoluble ones. A mixture of the dietary fibers from all samples - apple peels, wheat bran, and soybean-seed hull - in the ratio 2:4:4 (w/w) significantly increased the binding capacity of water-insoluble dietary fibers for the three toxic cations, cholesterol, and sodium cholate; moreover, the mixture could lower the concentrations of Pb(2+) and Cd(+) in the tested solutions to levels lower than those occurring in rice and vegetables grown in polluted soils. However, all the tested fibers showed a low binding capacity for the toxic anion, AsO(3)(3-). Copyright © 2010. Published by Elsevier B.V.",
"title": "In vitro binding capacities of three dietary fibers and their mixture for four toxic elements, cholesterol, and bile acid."
},
{
"docid": "MED-3900",
"text": "Epidemiological studies examining potential associations between dried fruit consumption, diet quality, and weight status are lacking. The goal of this study was to examine the association of dried fruit consumption with nutrient intake, diet quality, and anthropometric indicators of overweight/obesity. A secondary analysis of dietary and anthropometric data collected from adult (19+ years) participants (n = 13 292) of the 1999-2004 National Health and Nutrition Examination Survey was conducted. Dried fruit consumers were defined as those consuming amounts ⅛ cup-equivalent fruit per day or more and identified using 24-hour recalls. Diet quality was measured using the Healthy Eating Index 2005. Covariate-adjusted means, SEs, prevalence rates, and odds ratios were determined to conduct statistical tests for differences between dried fruit consumers and nonconsumers. Seven percent of the population consumed dried fruit. Mean differences (P < .01) between consumers and nonconsumers in adult shortfall nutrients were dietary fiber (+6.6 g/d); vitamins A (+173 μg retinol activity equivalent per day), E (+1.5 mg α-tocopherol per day), C (+20 mg/d), and K (+20 mg/d); calcium (+103 mg/d); phosphorus (+126 mg/d); magnesium (+72 mg/d); and potassium (+432 mg/d). Dried fruit consumers had improved MyPyramid food intake, including lower solid fats/alcohol/added sugars intake, and a higher solid fats/alcohol/added sugars score (11.1 ± 0.2 vs 8.2 ± 0.1) than nonconsumers. The total Healthy Eating Index 2005 score was significantly higher (P < .01) in consumers (59.3 ± 0.5) than nonconsumers (49.4 ± 0.3). Covariate-adjusted weight (78.2 ± 0.6 vs 80.7 ± 0.3 kg), body mass index (27.1 ± 0.2 vs 28.1 ± 0.2), and waist circumference (94.0 ± 0.5 vs 96.5 ± 0.2 cm) were lower (P < .01) in consumers than nonconsumers, respectively. Dried fruit consumption was associated with improved nutrient intakes, a higher overall diet quality score, and lower body weight/adiposity measures. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Dried fruit consumption is associated with improved diet quality and reduced obesity in US adults: National Health and Nutrition Examination Survey..."
},
{
"docid": "MED-2577",
"text": "A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).",
"title": "Diet and colorectal cancer: a case-control study in Greece."
},
{
"docid": "MED-2754",
"text": "BACKGROUND: Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD. METHODS: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials. RESULTS: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment. CONCLUSION: Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease.",
"title": "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: ..."
},
{
"docid": "MED-3478",
"text": "Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 μM of HN and 32 μM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line--a comparative study."
},
{
"docid": "MED-2885",
"text": "OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.",
"title": "Ultraviolet phototoxicity to the retina."
},
{
"docid": "MED-2102",
"text": "The effects of the major human serum bile acid, glycochenodeoxycholic acid (GCDC), as well as unconjugated chenodeoxycholic acid (CDC), on the MCF-7 human breast cancer cell line have been studied in vitro under oestrogen and bile acid deprived culture conditions. GCDC increased the growth of the breast cancer cells over the range 10-300 microM. At concentrations in excess of the bile acid binding capacity of the medium cell growth was prevented. In contrast 10 microM CDC tended to reduce cell growth. Oestrogen (ER) and progesterone (PgR) receptors, pS2 and total cathepsin D were quantified by monoclonal antibody based immunoassays. Ten to 100 microM GCDC and 10 microM CDC down-regulated ER protein and this was accompanied by induction of the oestrogen-regulated proteins PgR, pS2 and possibly cathepsin D, including increased secretion of the latter two proteins into the culture medium. All these changes were quantitatively similar to those observed with 10 nM oestradiol. The bile acid effects on ER and PgR were not due to interference with the assay procedures. Cells incubated with 50 microM GCDC or 10 microM CDC had higher pmolar concentrations of the bile acids than controls. This study suggests that naturally occurring bile acids influence the growth and steroid receptor function of human breast cancer cells.",
"title": "Bile acids influence the growth, oestrogen receptor and oestrogen-regulated proteins of MCF-7 human breast cancer cells."
},
{
"docid": "MED-3930",
"text": "Studies that have addressed the association between the intake of coffee or caffeine and Parkinson's disease (PD) were conducted mainly in Western countries. Little is known about this relationship in an Asian population. Therefore, we performed an assessment of the association of the intake of coffee, other caffeine-containing beverages, and caffeine with the risk of PD in Japan. The study involved 249 PD cases and 368 control subjects. Information on dietary factors was obtained through a self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, educational level, pack-years of smoking, body mass index, the dietary glycemic index, and intake of cholesterol, vitamin E, β-carotene, vitamin B(6,) alcohol, and iron. Intake of coffee, black tea, and Japanese and Chinese teas was significantly inversely associated with the risk of PD: the adjusted odds ratios in comparison of the highest with the lowest quartile were 0.52, 0.58, and 0.59, respectively (95% confidence intervals = 0.30-0.90, 0.35-0.97, and 0.35-0.995, respectively). A clear inverse dose-response relationship between total caffeine intake and PD risk was observed. We confirmed that the intake of coffee and caffeine reduced the risk of PD. Furthermore, this is the first study to show a significant inverse relationship between the intake of Japanese and Chinese teas and the risk of PD. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Intake of Japanese and Chinese teas reduces risk of Parkinson's disease."
},
{
"docid": "MED-2352",
"text": "BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.",
"title": "Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose."
},
{
"docid": "MED-4456",
"text": "Broccoli sprouts are widely consumed in many parts of the world. There have been no reported concerns with respect to their tolerance and safety in humans. A formal phase I study of safety, tolerance, and pharmacokinetics appeared justified because these sprouts are being used as vehicles for the delivery of the glucosinolate glucoraphanin and its cognate isothiocyanate sulforaphane [1-isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have been designed to evaluate protective efficacy against development of neoplastic and other diseases. A placebo-controlled, double-blind, randomized clinical study of sprout extracts containing either glucosinolates (principally glucoraphanin, the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was conducted on healthy volunteers who were in-patients on our clinical research unit. The subjects were studied in three cohorts, each comprising three treated individuals and one placebo recipient. Following a 5-day acclimatization period on a crucifer-free diet, the broccoli sprout extracts were administered orally at 8-h intervals for 7 days (21 doses), and the subjects were monitored during this period and for 3 days after the last treatment. Doses were 25 micromol of glucosinolate (cohort A), 100 micromol of glucosinolate (cohort B), or 25 micromol of isothiocyanate (cohort C). The mean cumulative excretion of dithiocarbamates as a fraction of dose was very similar in cohorts A and B (17.8 +/- 8.6% and 19.6 +/- 11.7% of dose, respectively) and very much higher and more consistent in cohort C (70.6 +/- 2.0% of dose). Thirty-two types of hematology or chemistry tests were done before, during, and after the treatment period. Indicators of liver (transaminases) and thyroid [thyroid-stimulating hormone, total triiodothyronine (T3), and free thyroxine (T4)] function were examined in detail. No significant or consistent subjective or objective abnormal events (toxicities) associated with any of the sprout extract ingestions were observed.",
"title": "Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study."
},
{
"docid": "MED-3975",
"text": "Background In Japan, gargling is a generally accepted way of preventing upper respiratory tract infection (URTI). The effectiveness of gargling for preventing URTI has been shown in a randomized controlled trial that compared incidences of URTI between gargling and control groups. From the perspective of the third-party payer, gargling is dominant due to the fact that the costs of gargling are borne by the participant. However, the cost-effectiveness of gargling from a societal perspective should be considered. In this study, economic evaluation alongside a randomized controlled trial was performed to evaluate the cost-effectiveness of gargling for preventing URTI from a societal perspective. Methods Among participants in the gargling trial, 122 water-gargling and 130 control subjects were involved in the economic analysis. Sixty-day cumulative follow-up costs and effectiveness measured by quality-adjusted life days (QALD) were compared between groups on an intention-to-treat basis. Incremental cost-effectiveness ratio (ICER) was converted to dollars per quality-adjusted life years (QALY). The 95% confidence interval (95%CI) and probability of gargling being cost-effective were estimated by bootstrapping. Results After 60 days, QALD was increased by 0.43 and costs were $37.1 higher in the gargling group than in the control group. ICER of the gargling group was $31,800/QALY (95%CI, $1,900–$248,100). Although this resembles many acceptable forms of medical intervention, including URTI preventive measures such as influenza vaccination, the broad confidence interval indicates uncertainty surrounding our results. In addition, one-way sensitivity analysis also indicated that careful evaluation is required for the cost of gargling and the utility of moderate URTI. The major limitation of this study was that this trial was conducted in winter, at a time when URTI is prevalent. Care must be taken when applying the results to a season when URTI is not prevalent, since the ICER will increase due to decreases in incidence. Conclusion This study suggests gargling as a cost-effective preventive strategy for URTI that is acceptable from perspectives of both the third-party payer and society.",
"title": "Cost-effectiveness of gargling for the prevention of upper respiratory tract infections"
},
{
"docid": "MED-1834",
"text": "Observations of increasing allergy prevalence with decreasing distance from the Equator and positive associations with ambient ultraviolet radiation have contributed to a growing interest in the possible role of vitamin D in the etiology of allergy. The aims of this study were to describe any latitudinal variation in the prevalence of childhood allergy in Australia and to evaluate, in parallel, the individual associations between ultraviolet radiation (UVR)- and vitamin D-related measures and hayfever asthma and both conditions. Participants were population-based controls who took part in a multicenter case-control study, aged 18-61 yr and resident in one of four study regions ranging in latitude from 27°S to 43°S. Data were derived from a self-administered questionnaire, interview and examination by a research officer and biologic sampling. Latitude and longitude coordinates were geocoded from participants' residential locations and climatic data were linked to postcodes of current residence. Stored serum was analyzed for 25-hydroxyvitamin D concentrations and silicone rubber casts of the skin were used as an objective measure of cumulative actinic damage. There was an inverse latitude gradient for asthma (a 9% decrease per increasing degree of latitude); however, this pattern did not persist after adjusting for average daily temperature. There was no association between any of the UVR- or vitamin D-related measures and childhood asthma, but greater time in the sun in winter between the ages 6-15 yr was associated with an increase in the odds of having hayfever [adjusted odds ratios (OR) 1.29; 95% CI 1.01-1.63]. Oral supplementation with cod liver oil in childhood increased the odds of a history of having both asthma and hayfever (2.87; 1.00-8.32). Further investigation of the possible role of early vitamin D supplementation in the development of allergy is warranted. Our results also suggest that solar exposure during childhood may be important in allergic sensitization. Plausible explanations, including biologic mechanisms, exist for both observations. © 2010 John Wiley & Sons A/S.",
"title": "The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study."
},
{
"docid": "MED-4911",
"text": "Arsenic exposures contribute significantly to the burden of preventable disease worldwide, specifically related to increased risks of cancer, diabetes, and cardiovascular disease. Most exposures are associated with natural contamination of groundwater, which is difficult to mitigate when these sources are used for drinking water. An anthropogenic source of arsenic exposure stems from the widespread use of arsenical drugs in food-animal production in the United States and China, among many countries. This use results in residual contamination of food products from animals raised with the drugs, as well as environmental contamination associated with disposal of wastes from these animals. Land disposal of these wastes can contaminate surface and ground water, and the conversion of animal wastes into fertilizer pellets for home use as well as the introduction of animal waste incinerators may increase opportunities for exposure. As an intentional additive to animal feed, use of arsenical drugs is a preventable source of human exposure. The domestic practice of using these drugs in poultry production has been the subject of media attention and limited research, though the use of these drugs in domestic swine production and in the rapidly growing foreign animal production industry remains largely uncharacterized. This continued expansion of arsenical drug use may likely increase the burden of global human arsenic exposure and risk.",
"title": "The environmental and public health risks associated with arsenical use in animal feeds."
},
{
"docid": "MED-1351",
"text": "The relationship between psychiatry and pharmaceutical companies has come under scrutiny during the past decade. Concerns are growing that financial ties of psychiatrists to the pharmaceutical industry may unduly influence professional judgments involving the primary interests of patients. Such conflicts of interest threaten the public trust in psychiatry. The goal of conflict of interest policies is to protect the integrity of professional judgment and to preserve public trust. The disclosure of individual and institutional financial relationships is a critical but limited first step in the process of identifying and responding to conflicts of interest. Conflict of interest policies and procedures can be strengthened by engaged psychiatrists, researchers, institutions, and professional associations in developing policies and consensus standards. Research on conflicts of interest can provide a stronger evidence base for policy design and implementation. Society has traditionally granted the medical profession considerable autonomy and may be willing to continue do so in the case of conflicts of interest. Nevertheless, concern is growing that stronger measures are needed. To avoid undue regulatory burdens, psychiatrists can play a vital role in designing responsible and reasonable conflict of interest policies that reduce the risks of bias and the loss of trust. Psychiatrists and the institutions that carry out research, education, clinical care, and practice guideline development must recognize public concerns about conflicts of interest and take effective measures soon to maintain public trust with a cultural change in the practice of psychiatry, from reactive treatment-seeking for mental illness to proactive advocacy for patients. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.",
"title": "Conflicts of interest in psychiatry: strategies to cultivate literacy in daily practice."
},
{
"docid": "MED-5009",
"text": "OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.",
"title": "Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-3108",
"text": "The external surfaces of the body, such as the skin and the gastrointestinal mucosal membrane, are an important line of defence preventing the invasion of microorganisms and their products. Mucosal immune cells, especially intraepithelial lymphocytes, are involved in maintaining the integrity of these epithelial barriers. They contribute towards the tolerance to commensal organisms, which occupy these same sites, and to the immune responses against harmful organisms and their products. The composition of the microbiota is influenced by immune cells as well as external environmental factors, especially the use of antibiotics and diet. There is an increasing appreciation that the microbiota affects systemic immune responses in addition to local immunity. Failure to control the occupancy by microorganisms may result in the disruption of the delicate homeostasis between beneficial and harmful microorganisms and contribute to inflammatory pathologies. This review will discuss some of our current understanding of the impact of immune cells and diet on the microbiota.",
"title": "Epithelial barrier biology: good fences make good neighbours"
},
{
"docid": "MED-1695",
"text": "Fruits and vegetables have been thought to be beneficial in cardiovascular disease. The beneficial effects of fruits and vegetables may be explained by the antioxidants and other components contained therein. These nutrients may function individually or in concert to protect lipoproteins and vascular cells from oxidation, or by other mechanisms such as reducing plasma lipid levels (LDL cholesterol, triglycerides), and platelet aggregation response. Kiwi fruit which contains high amounts of vitamin C, vitamin E and polyphenols may be beneficial in cardiovascular disease; however very little is known about its cardioprotective effects. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. To this end, we evaluated whether consuming kiwi fruit modulated platelet activity and plasma lipids in human volunteers in a randomized cross-over study. We report that consuming two or three kiwi fruit per day for 28 days reduced platelet aggregation response to collagen and ADP by 18% compared with the controls (P < 0.05). In addition, consumption of kiwi fruit lowered blood triglycerides levels by 15% compared with control (P < 0.05), whereas no such effects were observed in the case of cholesterol levels. All these data indicate that consuming kiwi fruit may be beneficial in cardiovascular disease.",
"title": "Effects of kiwi fruit consumption on platelet aggregation and plasma lipids in healthy human volunteers."
},
{
"docid": "MED-825",
"text": "BACKGROUND: Some evidence has suggested that a diet with a higher ratio of protein to carbohydrates has metabolic advantages in the treatment of polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of this study was to compare the effect of a high-protein (HP) diet to a standard-protein (SP) diet in women with PCOS. DESIGN: A controlled, 6-mo trial was conducted in 57 PCOS women. The women were assigned through rank minimization to one of the following 2 diets without caloric restriction: an HP diet (>40% of energy from protein and 30% of energy from fat) or an SP diet (<15% of energy from protein and 30% of energy from fat). The women received monthly dietary counseling. At baseline and 3 and 6 mo, anthropometric measurements were performed, and blood samples were collected. RESULTS: Seven women dropped out because of pregnancy, 23 women dropped out because of other reasons, and 27 women completed the study. The HP diet produced a greater weight loss (mean: 4.4 kg; 95% CI: 0.3, 8.6 kg) and body fat loss (mean: 4.3 kg; 95% CI: 0.9, 7.6 kg) than the SP diet after 6 mo. Waist circumference was reduced more by the HP diet than by the SP diet. The HP diet produced greater decreases in glucose than did the SP diet, which persisted after adjustment for weight changes. There were no differences in testosterone, sex hormone-binding globulin, and blood lipids between the groups after 6 mo. However, adjustment for weight changes led to significantly lower testosterone concentrations in the SP-diet group than in the HP-diet group. CONCLUSION: Replacement of carbohydrates with protein in ad libitum diets improves weight loss and improves glucose metabolism by an effect that seems to be independent of the weight loss and, thus, seems to offer an improved dietary treatment of PCOS women.",
"title": "Effects of increased dietary protein-to-carbohydrate ratios in women with polycystic ovary syndrome."
},
{
"docid": "MED-868",
"text": "Adrenocortical carcinomas are rare but present with extremely poor prognosis. One of the approaches to control cancer progression and reduce cancer risk is prevention through diet. Bitter melon is widely consumed as a vegetable and especially as a traditional medicine in many countries. In this study, we have used human and mouse adrenocortical cancer cells as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. The protein concentrations of BME and other extracts were measured before use. First, BME treatment of adrenocortical cancer cells resulted in a significantly dose-dependent decrease in cell proliferation. However, we did not observe an antiproliferative effect in adrenocortical cancer cells treated with extracts from blueberry, zucchini, and acorn squash. Second, apoptosis of adrenocortical cancer cells was accompanied by increased caspase-3 activation and poly(ADP-ribose) polymerase cleavage. BME treatment enhanced cellular tumor antigen p53, cyclin-dependent kinase inhibitor 1A (also called p21), and cyclic AMP-dependent transcription factor-3 levels and inhibited G1/S-specific cyclin D1, D2, and D3, and mitogen-activated protein kinase 8 (also called Janus kinase) expression, suggesting an additional mechanism involving cell cycle regulation and cell survival. Third, BME treatment decreased the key proteins involved in steroidogenesis in adrenocortical cancer cells. BME treatment decreased the level of phosphorylation of cyclin-dependent kinase 7, which is required, at least in part, for steroidogenic factor 1 activation. Finally, we observed that BME treatment significantly reduced the level of insulin-like growth factor 1 receptor and its downstream signaling pathway as evidenced by lower levels of phosphorylated RAC-α serine/threonine-protein kinase. Taken together, these data illustrate the inhibitory effect of bitter melon on cell proliferation of adrenocortical cancer through modulation of diverse mechanisms.",
"title": "Bitter melon (Momordica charantia) extract suppresses adrenocortical cancer cell proliferation through modulation of the apoptotic pathway, steroid..."
},
{
"docid": "MED-1556",
"text": "Background: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. Objective: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. Design: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. Results: During 5–23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. Conclusions: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.",
"title": "Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease"
},
{
"docid": "MED-1497",
"text": "Traumatic brain injury (TBI) constitutes a major global health and socio-economic problem with neurobehavioral sequelae contributing to long-term disability. It causes brain swelling, axonal injury and hypoxia, disrupts blood brain barrier function and increases inflammatory responses, oxidative stress, neurodegeneration and leads to cognitive impairment. Epidemiological studies show that 30% of patients, who die of TBI, have Aβ plaques which are pathological features of Alzheimer's disease (AD). Thus TBI acts as an important epigenetic risk factor for AD. This review focuses on AD related genes which are expressed during TBI and its relevance to progression of the disease. Such understanding will help to diagnose the risk of TBI patients to develop AD and design therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Traumatic brain injury: a risk factor for Alzheimer's disease."
},
{
"docid": "MED-1803",
"text": "WHO has declared obesity to be a global epidemic. Obesity management strategies mainly target behavioural components of the disorder, but are only marginally effective. A comprehensive understanding of the causative factors of obesity might provide more effective management approaches. Several microbes are causatively and correlatively linked with obesity in animals and human beings. If infections contribute to human obesity, then entirely different prevention and treatment strategies and public health policies could be needed to address this subtype of the disorder. Ethical reasons preclude experimental infection of human beings with candidate microbes to unequivocally determine their contribution to obesity. As an alternative, the available information about the adipogenic human adenovirus Ad36 has been used to create a template that can be used to examine comprehensively the contributions of specific candidate microbes to human obesity. Clinicians should be aware of infectobesity (obesity of infectious origin), and its potential importance in effective obesity management. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A framework for identification of infections that contribute to human obesity."
},
{
"docid": "MED-4697",
"text": "Summary With the aging of the population, we are seeing a global increase in age-related disorders, especially in developed countries. Chronic diseases disproportionately affect the older segment of the population, contributing to disability, a diminished quality of life, and an increase in healthcare costs. Increased life expectancy reflects the success of contemporary medicine, which must now respond to the challenges created by this achievement, including the growing burden of chronic illnesses, injuries, and disabilities. A well-developed theoretical framework is required to understand the molecular basis of aging. This, in turn, is a prerequisite for developing the clinical interventions that will constitute an efficient response to the challenge of age-related health issues. This review critically analyzes the experimental evidence that supports and refutes the Free Radical/Mitochondrial Theory of Aging, which has dominated the field of aging research for almost half a century.",
"title": "Is there more to aging than mitochondrial DNA and reactive oxygen species?"
},
{
"docid": "MED-2980",
"text": "Background Inoxitol hexakisphosphate (IP6) has been found to have an important role in biomineralization and a direct effect inhibiting mineralization of osteoblasts in vitro without impairing extracellular matrix production and expression of alkaline phosphatase. IP6 has been proposed to exhibit similar effects to those of bisphosphonates on bone resorption, however, its direct effect on osteoclasts (OCL) is presently unknown. Methodology/Principal Findings The aim of the present study was to investigate the effect of IP6 on the RAW 264.7 monocyte/macrophage mouse cell line and on human primary osteoclasts. On one hand, we show that IP6 decreases the osteoclastogenesis in RAW 264.7 cells induced by RANKL, without affecting cell proliferation or cell viability. The number of TRAP positive cells and mRNA levels of osteoclast markers such as TRAP, calcitonin receptor, cathepsin K and MMP-9 was decreased by IP6 on RANKL-treated cells. On the contrary, when giving IP6 to mature osteoclasts after RANKL treatment, a significant increase of bone resorption activity and TRAP mRNA levels was found. On the other hand, we show that 1 µM of IP6 inhibits osteoclastogenesis of human peripheral blood mononuclear cells (PBMNC) and their resorption activity both, when given to undifferentiated and to mature osteoclasts. Conclusions/Significance Our results demonstrate that IP6 inhibits osteoclastogenesis on human PBMNC and on the RAW264.7 cell line. Thus, IP6 may represent a novel type of selective inhibitor of osteoclasts and prove useful for the treatment of osteoporosis.",
"title": "Inositol Hexakisphosphate Inhibits Osteoclastogenesis on RAW 264.7 Cells and Human Primary Osteoclasts"
},
{
"docid": "MED-2846",
"text": "OBJECTIVE: A cross-sectional institutional-based study was undertaken to know the prevalence of Gestational Diabetes Mellitus (GDM) among Indian pregnant women. SUBJECTS AND METHODS: 325 pregnant women were screened for evidence of diabetes who were previously not known to be diabetic. They underwent 75 g, 2 hour, oral glucose tolerance test (OGTT). Chi-square test was done for statistically association of variables in GDM. RESULTS AND CONCLUSIONS: The results of this study indicate that bad obstetrics history, obese patient on high calorie diet especially non vegetarian diet with less physical activity are highly prone to develop GDM.",
"title": "A hospital based study of prevalence of gestational diabetes mellitus in an urban population of India."
},
{
"docid": "MED-3534",
"text": "Background Numerous antioxidant and anti‐inflammatory agents have been identified in tart cherries. Objective To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage. Methods This was a randomised, placebo controlled, crossover design. Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions (2 × 20 maximum contractions) was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for four days after the eccentric exercise. The protocol was repeated two weeks later with subjects who took the placebo initially, now taking the cherry juice (and vice versa). The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect. Results Strength loss and pain were significantly less in the cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p = 0.017). Relaxed elbow angle (time by treatment p = 0.85) and muscle tenderness (time by treatment p = 0.81) were not different between trials. Conclusions These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.",
"title": "Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage"
},
{
"docid": "MED-1571",
"text": "One hundred and fifty-nine ichtyosarcotoxic outbreaks, including 477 people, were recorded in the island of Réunion (SW Indian ocean) between 1986 and 1994. Ciguatera outbreaks represented 78.6% of the total cases and its annual incidence rate was estimated to be 0.78/10,000 residents. Symptoms caused by ciguatera poisoning are not different from those reported in Pacific and Caribbean islands, except for the additional symptoms of hallucinatory poisoning in 16% of the patients. Serranidae fish, including species of great commercial value, were the most commonly incriminated accounting for 50% of the outbreaks.",
"title": "Ciguatera in Réunion Island (SW Indian Ocean): epidemiology and clinical patterns."
}
] |
2914
|
Can housing prices rise faster than incomes in the long run?
|
[
{
"docid": "517305",
"text": "In a strictly mathematical sense, no. Or rather, it depends what 'long run' means. Say today the home average is $200K, and payment is $900/mo. The $900 today happens to be about 20% of the median US monthly income (which is approximately $54,000/yr). Housing rises 4%/yr, income 3%/yr. In 100 years (long enough?) the house costs $10M but incomes are 'only' $1.03M/yr, and the mortgage, even at the same rate is $45K/month, or, to be clear, it rose to 52% of monthly income. My observation is that, long term, the median home costs what 25% of median income will support, in terms of the mortgage after downpayment. Long term. That means that if you graph this, you'll see trends above and below the long term line. You'll see a 25 year bubble form starting in the late 80's as rates dropped from near 18% to the Sub-4% in the early 00s. But once you normalize it to percent of income to pay the loan, much of the bubble is flattened out. At 18%, $1500/mo bought you a $100K mortgage, but at 3.5%, it bought $335K. This is in absolute dollars, wages also rose during that time. I am just clarifying how rates distort the long term trends and create the short term anomalies.",
"title": ""
},
{
"docid": "375606",
"text": "When over the long term housing costs in a area rise faster than wages rise, the demographic of who lives in the area changes. The size and income parameters change. A region that was full of young singles is now populated with couples with adult children, that means that the businesses and amenities have to change. At a national level it isn't sustainable unless other items change. The portion of monthly income that can be safely allocated to housing would have to change. One adjustment could be the the lengthening of home loan periods, thus dropping the monthly payment. This has been seen with car loans, over the last few decades the length of loans has increased. In interesting related event could be the change in deduction of mortgage interest and property tax. If this was to change abruptly, there could be an abrupt change the estimated value of housing, because the calculus of affordability would change.",
"title": ""
}
] |
[
{
"docid": "127597",
"text": "I don’t understand people’s obsession with inequality. As long as real wages are staying constant or rising then you are as good, or better off today than you were yesterday. This idea that “they” are getting “better” faster really doesn’t matter in the long run. It was only 60 years ago that multiple middle class houses shared a land line and you had to wait for your neighbor to finish before making a phone call. Today just about every individual in a low-income household has a cellphone. My point is, as long as things keep improving for everyone is it really that bad if it’s unequal improvement? [Freakonomics did an interesting podcast on the topic of spite a while back.](http://freakonomics.com/podcast/what-do-medieval-nuns-and-bo-jackson-have-in-common-a-new-freakonomics-radio-podcast/) The most interesting part to me is experiment where people were willing to accept less money just to ensure that the other person did not get more than them.",
"title": ""
},
{
"docid": "67816",
"text": "\"Even if the price of your home did match inflation or better — and that's a question I'll let the other answers address — I propose that owning a home, by itself, is not a sufficient hedge against inflation. Consider: Inflation will inflate your living expenses. If you're lucky, they'll inflate at the average. If you're unlucky, a change in your spending patterns (perhaps age-related) could result in your expenses rising faster than inflation. (Look at the sub-indexes of the CPI.) Without income also rising with inflation (or better), how will you cope with rising living expenses? Each passing year, advancing living expenses risk eclipsing a static income. Your home is an illiquid asset. Generally speaking, it neither generates income for you, nor can you sell only a portion. At best, owning your principal residence helps you avoid a rent expense and inflation in rents — but rent is only one of many living expenses. Some consider a reverse-mortgage an option to tap home equity, but it has a high cost. In other words: If you don't want to be forced to liquidate [sell] your home, you'll also need to look at ways to ensure your income sources rise with inflation. i.e. look at your cash flow, not just your net worth. Hence: investing in housing, as in your own principal residence, is not an adequate hedge against inflation. If you owned additional properties to generate rental income, and you retained pricing power so you could increase the rent charged at least in line with inflation, your situation would be somewhat improved — except you would, perhaps, be adopting another problem: Too high a concentration in a single asset class. Consequently, I would look at ways other than housing to hedge against inflation. Consider other kinds of investments. \"\"Safe as houses\"\" may be a cliché, but it is no guarantee.\"",
"title": ""
},
{
"docid": "374480",
"text": "They can't keep rising with respect to people's income because eventually you run out of buyers. If there's roughly one house for every five people, then you'd better make sure that the price you set to sell your house is affordable to people in the upper fifth of income scales, or else you are mathematically guaranteed not to have any customers. Now, it's true that the price of particular houses can get much higher, but they tended to be higher in the first place. Housing isn't exactly an efficient market, but for the most part you have to pay for the house that you get, or else someone else will outbid you. An individual area might, temporarily, buck these trends because it suddenly becomes popular and there are a lot of extra buyers putting money on the table. In the long run, someone is going to build for those buyers, even if it means moving up the chain from enormous rural lots to suburban single-family homes to low-density garden apartments to residential towers.",
"title": ""
},
{
"docid": "40865",
"text": "\"For most people \"\"home ownership\"\" is a long term lifestyle strategy (i.e. the intention is to own a home for several decades, regardless of how many times one particular house might be \"\"swapped\"\" for a different one. In an economic environment with steady monetary inflation, taking out a long-term loan backed by a tangible non-depreciating \"\"permanent\"\" asset (e.g. real estate) is in practice a form of investing not borrowing, because over time the monetary value of the asset will increase in line with inflation, but the size of the loan remains constant in money terms. That strategy was always at risk in the short term because of temporary falls in house prices, but long-term inflation running at say 5% per year would cancel out even a 20% fall in house prices in 4 years. Downturns in the economy were often correlated with rises in the inflation rate, which fixed the short-term problem even faster. Car and student loans are an essentially different financial proposition, because you know from the start that the asset will not retain its value (unless you are \"\"investing in a vintage car\"\" rather than \"\"buying a means of personal transportation\"\", a new car will lose most of its monetary value within say 5 years) or there is no tangible asset at all (e.g. taking out a student loan, paying for a vacation trip by credit card, etc). The \"\"scariness\"\" over home loans was the widespread realization that the rules of the game had been changed permanently, by the combination of an economic downturn plus national (or even international) financial policies designed to enforce low inflation rates - with the consequence that \"\"being underwater\"\" had been changed from a short term problem to a long-term one.\"",
"title": ""
},
{
"docid": "322825",
"text": "\"Here in the UK, the rule of thumb is to keep a lot of equity in your home if you can. I assume here that you have a lot of savings you're considering using. If you only have say 10% of the house price you wouldn't actually have a lot of choice in the matter, the mortgage lender will penalise you heavily for low deposits. The practical minimum is 5%, but for most people a 95% mortgage is just silly (albeit not as silly as the 100% or greater mortgages you could get pre-2008), and you should take serious individual advice before considering it. According to Which, the average in the UK for first-time buyers is 20% (not the best source for that data I confess, but a convenient one). Above 20% is not at all unusual. You'll do an affordability calculation to figure out how much you can borrow, which isn't at all the same as how much you should borrow, but does get you started. Basically you, decide how much a month you can spend on mortgage payments. The calculation will let you put every penny into this if you choose to, but in practice you'll want some discretionary income so don't do that. decide the term of the mortgage. For a young first-time buyer in the UK I think you'd typically take a 25-year term and consider early repayment options rather than committing to a shorter term, but you don't have to. Mortgage lenders will offer shorter terms as long as you can afford the payments. decide how much you're putting into a deposit make subtractions for cost of moving (stamp duty if applicable, fees, removals aka \"\"people to lug your stuff\"\"). receive back a number which is the house price you can pay under these constraints (and of course a breakdown of what the mortgage principle would be, and the interest rate you'll pay). This step requires access to lender information, since their rates depend on personal details, deposit percentage, phase of the moon, etc. Our mortgage advisor did multiple runs of the calculation for us for different scenarios, since we hadn't made up our minds entirely. Since you have not yet decided how much deposit to make, you can use multiple calculations to see the effect of different deposits you might make, up to a limit of your total savings. Putting up more deposit both increases the amount you can borrow for a given monthly payment (since mortgage rates are lower when the loan is a lower proportion of house value), and of course increases the house price you can afford. So unless you're getting a very high return on your savings, £1 of deposit gets you somewhat more than £1 of house, and the calculation will tell you how much more. Once you've chosen the house you want, the matter is even simpler: do you prefer to put your savings in the house and borrow less and make lower payments, or prefer to put your savings elsewhere and borrow more and make higher payments but perhaps have some additional income from the savings. Assuming you maintain a contingency fund, a lower mortgage is generally considered a good investment in the UK, but you need to check what's right for you and compare it to other investments you could make. The issue is complicated by the fact that residential property prices are rising quite quickly in most areas of the UK, and have been for a long time, meaning that highly-leveraged property investment appears to be a really good idea. This leads to the imprudent, but tempting, conclusion that you should buy the biggest house you can possibly afford and watch its value rises. I do not endorse this advice personally, but it's certainly true that in a sharply rising house market it's easier to get away with buying a bigger house than you need, than it is to get away with it in a flat or falling market. As Stephen says, an offset mortgage is a no-brainer good idea if the rate is the same. Unfortunately in the UK, the rate isn't the same (or anyway, it wasn't a couple of years ago). Offset mortgages are especially good for those who make a lot of savings from income and for any reason don't want to commit all of those savings to a traditional mortgage payment. Good reasons for not wanting to do that include uncertainty about your future income and a desire to have the flexibility to actually spend some of it if you fancy :-)\"",
"title": ""
},
{
"docid": "54945",
"text": "How can people afford 10% mortgage? Part of the history of housing prices was the non-bubble component of the bubble. To be clear, there was a housing bubble and crash. Let me offer some simple math to illustrate my point - This is what happened on the way down. A middle class earner, $60K/yr couple, using 25% of their income, the normal percent for a qualified mortgage, was able to afford $142K for the mortgage payment. At 10% fixed rate. This meant that after down payment, they were buying a house at $175K or so, which was above median home pricing. Years later, obviously, this wasn't a step function, with a rate of 4%, and ignoring any potential rise of income, as in real term, income was pretty stagnant, the same $1250/mo could pay for a $260K mortgage. If you want to say that taxes and insurance would push that down a bit, sure, drop the loan to $240K, and the house price is $300K. My thesis ('my belief' or 'proposal', I haven't written a scholarly paper, yet) is that the relationship between median home price and median income is easily calculated based on current 30 year fixed rate loans. For all the talk of housing prices, this is the long term number. Housing cannot exceed income inflation long term as it would creep up as a percent of income and slow demand. I'm not talking McMansion here, only the median. By definition, the median house targets the median earners, the middle class. The price increase I illustrate was just over 70%. See the famous Shiller chart - The index move from 110 to 199 is an 81% rise. I maintain, 70 of that 81 can be accounted for by my math. Late 80's, 1987 to be exact, my wife got a mortgage for 9%, and we thought that was ok, as I had paid over 13% just 3 years earlier.",
"title": ""
},
{
"docid": "463230",
"text": "\"There's too much here for one question. So no answer can possibly be comprehensive. I think little of gold for the long term. I go to MoneyChimp and see what inflation did from 1974 till now. $1 to $4.74. So $200 inflates to $950 or so. Gold bested that, but hardly stayed ahead in a real way. The stock market blew that number away. And buying gold anytime around the 1980 runup would still leave you behind inflation. As far as housing goes, I have a theory. Take median income, 25% of a month's pay each month. Input it as the payment at the going 30yr fixed rate mortgage. Income rises a bit faster than inflation over time, so that line is nicely curved slightly upward (give or take) but as interest rates vary, that same payment buys you far more or less mortgage. When you graph this, you find the bubble in User210's graph almost non-existent. At 12% (the rate in '85 or so) $1000/mo buys you $97K in mortgage, but at 5%, $186K. So over the 20 years from '85 to 2005, there's a gain created simply by the fact that money was cheaper. No mania, no bubble (not at the median, anyway) just the interest rate effect. Over the same period, inflation totaled 87%. So the same guy just keeping up with inflation in his pay could then afford a house that was 3.5X the price 20 years prior. I'm no rocket scientist, but I see few articles ever discussing housing from this angle. To close my post here, consider that homes have grown in size, 1.5%/yr on average. So the median new home quoted is actually 1/3 greater in size in 2005 than in '85. These factors all need to be normalized out of that crazy Schiller-type* graph. In the end, I believe the median home will always tightly correlate to the \"\"one week income as payment.\"\" *I refer here to the work of professor Robert Schiller partner of the Case-Schiller index of home prices which bears his name.\"",
"title": ""
},
{
"docid": "507029",
"text": "In general people make a few key mistakes with property: 1) Not factoring in depreciation properly. Houses are perpetually falling down, and if you are renting them perpetually being trashed by the tenants as well - particularly in bad areas. Accurate depreciation costs can often run in the 5-20% range per year depending on the property/area. Add insurance to this as well. 2) Related to 1), they take the index price of house price rises as something they can achieve, when in reality a lot of the house price 'rise' is just everyone having to spend a lot of money keeping them standing up. No investor can actually track a house price graph due to 1) so be careful to make reasonable assumptions about actual achievable future growth. 3) Failure to price in the huge transaction costs (often 5%+ per sale) and capital gains/other taxes (depends on the exact tax structure where you are). These add up very fast if you are buying and selling at all frequently. 4) Costs in either time or fees to real estate rental agents. Having to fill, check, evict, fix and maintain rental properties is a lot more work than most people realise, and you either have to pay this in your own time or someone else’s. Again, has to be factored in. 5) Liquidity issues. Selling houses in down markets is very, very hard. They are not like stocks where they can be moved quickly. Houses can often sit on the market for years before sale if you are not prepared to take low prices. As the bank owns your house if you fail to pay the mortgage (rents collapse, loss of job etc) they can force you to fire sale it leaving you in a whole world of pain depending on the exact legal system (negative equity etc). These factors are generally correlated if you work in the same cities you are buying in so quite a lot of potential long tail risk if the regional economy collapses. 6) Finally, if you’re young they can tie you to areas where your earnings potential is limited. Renting can be immensely beneficial early on in a career as it gives you huge freedom to up sticks and leave fast when new opportunities arise. Locking yourself into 20yr+ contracts/activities when young can be hugely inhibiting to your earnings potential – particularly in fast moving jobs like software development. Without more details on the exact legal framework, area, house type etc it’s hard to give more specific advise, but in general you need a very large margin of safety with property due to all of the above, so if the numbers you’re running are coming out close, it’s probably not worth it, and you’re better of sticking with more hands off investments like stocks and bonds.",
"title": ""
},
{
"docid": "73649",
"text": "It's always a good move for risk-averse person, expecially in Europe. Because houses are not represented by number in an index. Therefor if you are risk-adverse, you will suffer less pain when house prices go down because you won't have a number to look at everyday like the S&P500 index. Because houses in Europe (Germany, Italy, Spain) are almost all made by concrete and really well done (string real marble cover, hard ceramic covers, copper pipes, ...) compared to the ones in US. The house will still be almost new after 30 years, it will just need a repaint and really few/cheap fixings. Because on the long run (20/30 years) hosues are guaranteed to rise in price, expecially in dense places like big city, NY, San Francisco, etc. The reason is simple: the number of people is ever growing in this world, but the quantity of land is always the same. Moreover there is inflation, do you really think that 30 years from now building a concrete house will be less expensive than today??? Do you think the concrete will cost less? Do you think the gasoline that moves the trucks that bring the concrete will be less expensive than now? Do you think the labour cost will be less expensice than now? So, 30 years from now building an house will be much more expensive than today, and therefor your house wil be more expensive too. On the lomng run stock market do not guarantee you to always increase. The US stock market have always been growing in the long run, but Japan stock market today is at the same level of 30 years ago. Guess what happened to you if you invested your money in the Japan stock market, 30 years ago, whilest your friend bought an hosue in Japan 30 years ago. He would now be rich, and you would now be poor.",
"title": ""
},
{
"docid": "574616",
"text": "\"There are a few factors at work here, supply and demand being the main one. The Office for National Statistics has some good information: http://visual.ons.gov.uk/uk-perspectives-housing-and-home-ownership-in-the-uk/ Supply has historically struggled to compete with demand in the UK and this situation has been exacerpated since the 1980s when Margaret Thatcher was Prime Minister. She set up a variety of schemes to encourage people to own their own home, such as tax relief (MIRAS) and since then home ownership in the UK has increased dramatically. The then conservative government also set up the \"\"right to buy\"\" scheme (in 1980) that allowed council tenants to purchase their council houses at a discounted rate. The effect of this was to increase the number of home owners whilst reducing the amount of housing available for councils to rent to new tenants. Anecdotal evidence (I can't find a documented source to back this up) suggests that councils did not build sufficient new homes to replace those purchased by their ex-tenants. The population of the UK has also increased, by around 10 million since 1980 (around 20%) and this has pushed up demand for housing. House building in the UK has not kept pace with these factors that has led to a shortage of supply that has pushed up prices. http://www.ons.gov.uk/ons/rel/pop-estimate/population-estimates-for-uk--england-and-wales--scotland-and-northern-ireland/2013/sty-population-changes.html There's another factor at play here as well. If you go back to the 1970s around 53% of women would go out to work but in 2013 this figure increased to 67% as it became more common for households to have double incomes. This extra supply of cash also pushed up house prices. http://www.ons.gov.uk/ons/dcp171776_328352.pdf Your question regards a debt based monetary system is not entirely clear, but there are limitations put onto how much money people can borrow that are potentially limiting how much house prices can rise by. Today most lenders are more conservative in how much they will lend but this wasn't the case in the mid 2000s when house prices rose very quickly. Lenders are more cautious today after the crash of the late 2000s, but things are begining to relax again and they are starting to lend more which could in turn lead to further house price rises in line with what was seen in the 2000s. Recessions have coincided with house prices falling back or at least being stable. In the 1980s house prices trebled from 1980 to 1988 but then fell back a little as the recession hit, before starting to rise again in 1997. This rise was sustained until 2008 during which time prices trebled again. Based on this you could assume prices will treble again as we come out of the recession, as long as this is sustained for 8 years or so. However, as the potential for more households to become double income is reduced (high female employment already) and wages are unlikely to raise that quickly, this may not be realistic, unless the mortgage lenders become extremely lax, to the point of reckless! To answer your other question, about the affordability of housing, this will be based on the level of wages in the UK and how strict or lax the lenders are, also taking into effect the availability of housing for purchase. If wages rise, house prices will rise, if lenders are willing to lend more money, house prices will rise and if demand continues to outrstip supply, prices will rise. None of the major UK political parties are likely to solve the problems of population growth and not enough houses being built so it is likely prices will rise but you could argue that they are not far off a peak based on current wages and lenders attitudes. If the UK economy continues to recover from the recession, it is possible they will fuel another housing boom by lending ever increasing salary multiples as happened in the 2000s, unless there is government intervention, ie regulation of the lenders.\"",
"title": ""
},
{
"docid": "34844",
"text": "\"Yes, it's unreasonable to think the prices will drop 10-20% in that time frame. Housing prices are not an equation that can can be solved to \"\"home prices are X% overvalued.\"\" You have 3 answers so far, Quanty's \"\"prices are inversely proportional to rates,\"\" Rob's \"\"there's no strong correlation between interest rates and house prices,\"\" and MB's, \"\"rising interest rates create downward pressure on housing prices.\"\" Any research into price history had better take every other variable into account. Articles that look at rates vs price don't always address a key item, income. Say we agree that the data show your city to be 10% too high. But if sellers like their high price and have some 'dig my heels in' power, prices won't drop. The seller simply stays put, and the supply/demand curves result not in a lower price, but in less supply. And the effect is to change the demographic of that area, i.e. attracting higher income earners. Rob linked to an article with a nice set of charts. One chart showing the US30 yr fixed rate and 'Real House Prices'. What results is a chart that can refute the relationship between rates and prices. But that would ignore an historical point that's too important to forget. The tumble that started in Jan '06 had nothing to do with the 30 year rate. It was the result of a series of insane financial products including 'interest only option ARMs' which permitted buyers to get approved for a purchase based on a payment that wasn't fixed, and would change to a fully amortizing mortgage at a higher rate that was unaffordable. A product that was a financial time bomb. Canada Banks offered no such product, and when the US market got pneumonia, Canada experienced a mild cold. With respect to any answers that offer US centric data to prove any hypothesis, I don't feel such comparisons are appropriate. Correlations, and the data used to prove them are an interesting thing. I can suggest that you take the US 30 year rate, along with our median income, or rather 25% of monthly median income. Calculate the mortgage that results. This translates nicely to the home a median family can afford. And I claim that long term this is the equilibrium price of that median home. But supply/demand has another factor, 'stickyness' or the more technical term, 'inelasticity of demand.' This means that for example, a 10% increase in the price of cigarettes does not cause a 10% drop in consumption. Each and every good has its own elasticity, and in the case of housing, a rise in cost would certainly impact the marginal buyers, but others will simply adjust their budgets. Not all buyers were planning to hit the bank's limit on what they could afford, so the rise doesn't change their mind, just their budget. Last - I know that Canada does not have a 30 year mortgage, most common is a 5 year rate with 30 year amortization. (correction/clarification, anyone?) The effect of this is less volatility in the market, since I believe your rates are not poised for the 2.5% to 4% jump implied by another response. Small increases can be absorbed. In a beautiful coincidence, the Federal Reserve Board sent me a link to The Interest Rate Elasticity of Mortgage Demand: Evidence From Bunching at the Conforming Loan Limit. It's a bit long but a worthwhile look at how the correlation isn't as instant as some might think.\"",
"title": ""
},
{
"docid": "129149",
"text": "I wrote this in another thread but is also applicable here. In general people make some key mistakes with property: Not factoring in depreciation properly. Houses are perpetually falling down, and if you are renting them perpetually being trashed by the tenants as well - particularly in bad areas. Accurate depreciation costs can often run in the 5-20% range per year depending on the property/area. Add insurance to this as well or be prepared to lose the whole thing in a disaster. Related to 1), they take the index price of house price rises as something they can achieve, when in reality a lot of the house price 'rise' is just everyone having to spend a lot of money keeping them standing up. No investor can actually track a house price graph due to 1) so be careful to make reasonable assumptions about actual achievable future growth (in your example, they could well be lagging inflation/barely growing if you are not pricing in upkeep and depreciation properly). Failure to price in the huge transaction costs (often 5%+ per sale) and capital gains/other taxes (depends on the exact tax structure where you are). These add up very fast if you are buying and selling at all frequently. Costs in either time or fees to real estate rental agents. Having to fill, check, evict, fix and maintain rental properties is a lot more work than most people realise, and you either have to pay this in your own time or someone else’s. Again, has to be factored in. Liquidity issues. Selling houses in down markets is very, very hard. They are not like stocks where they can be moved quickly. Houses can often sit on the market for years before sale if you are not prepared to take low prices. As the bank owns your house if you fail to pay the mortgage (rents collapse, loss of job etc) they can force you to fire sale it leaving you in a whole world of pain depending on the exact legal system (negative equity etc). These factors are generally correlated if you work in the same cities you are buying in so quite a lot of potential long tail risk if the regional economy collapses. Finally, if you’re young they can tie you to areas where your earnings potential is limited. Renting can be immensely beneficial early on in a career as it gives you huge freedom to up sticks and leave fast when new opportunities arise. Locking yourself into 20 yr+ contracts/landlord activities when young can be hugely inhibiting to your earnings potential. Without more details on the exact legal framework, area, house type etc it’s hard to give more specific advise, but in general you need a very large margin of safety with property due to all of the above, so if the numbers you’re running are coming out close (and they are here), it’s probably not worth it, and you’re better of sticking with more hands off investments like stocks and bonds.",
"title": ""
},
{
"docid": "473765",
"text": "\"The three basic needs are food, clothing, and shelter. Housing falls into the third category. Because it is \"\"basic,\"\" housing takes up a large part of one's disposable income. The rule of thumb is that you shouldn't spend more than 25% of your income on rent or mortgages. And that is income BEFORE taxes. Anything much more than that takes up too much of one's budget. You simply CAN'T double housing's share of the budget from 25% to 50%. Whereas, it's easy to go from 1% to 2% for say, a cellphone upgrade. In the long run, housing prices are constrained by the size of people's housing budgets, which in turn are tied to incomes. Nowadays, that includes FOREIGN buyers. So there may be a case where west coast housing prices are driven up by Asian buyers, or Florida housing by buyers from Latin America, driving Americans out of local markets.\"",
"title": ""
},
{
"docid": "259777",
"text": "\"Indefinitely is easy to answer. Assume that the average house currently costs four times the average salary, and that house prices rise 1% faster than salaries indefinitely. Then in only 1,000 years' time, the average house will cost around 84,000 times the average salary. In 10,000 years, it will be 6.5*10E43 times the average salary. That doesn't seem plausible to me. If you want arguments about \"\"for the foreseeable future\"\", instead of \"\"indefinitely\"\", then that's harder.\"",
"title": ""
},
{
"docid": "118653",
"text": "As user14469 mentions you would have to decide what type of properties you would like to invest in. Are you after negatively geared properties that may have higher long term growth potential (usually within 15 to 20km from major cities), or after positive cash-flow properties which may have a lower long term growth potential (usually located more than 20km from major cities). With negative geared properties your rent from the property will not cover the mortgage and other costs, so you will have to supplement it through your income. The theory is that you can claim a tax deduction on your employment income from the negative gearing (benefits mainly those on higher tax brackets), and the potential long term growth of the property will make up for the negative gearing over the long term. If you are after these type of properties Michael Yardney has some books on the subject. On the other hand, positive cash-flow properties provide enough rental income to cover the mortgage and other costs. They put cash into your pockets each week. They don't have as much growth potential as more inner city properties, but if you stick to the outer regions of major cities, instead of rural towns, you will still achieve decent long term growth. If you are after these type of properties Margaret Lomas has some books on the subject. My preference is for cash-flow positive properties, and some of the areas user14469 has mentioned. I am personally invested in the Penrith and surrounding areas. With negatively geared properties you generally have to supplement the property with your own income and generally have to wait for the property price to increase so you build up equity in the property. This then allows you to refinance the additional equity so you can use it as deposits to buy other properties or to supplement your income. The problem is if you go through a period of low, stagnate or negative growth, you may have to wait quite a few years for your equity to increase substantially. With positively geared properties, you are getting a net income from the property every week so using none of your other income to supplement the property. You can thus afford to buy more properties sooner. And even if the properties go through a period of low, stagnate or negative growth you are still getting extra income each week. Over the long term these properties will also go up and you will have the benefit of both passive income and capital gains. I also agree with user14469 regarding doing at least 6 months of research in the area/s you are looking to buy. Visit open homes, attend auctions, talk to real estate agents and get to know the area. This kind of research will beat any information you get from websites, books and magazines. You will find that when a property comes onto the market you will know what it is worth and how much you can offer below asking price. Another thing to consider is when to buy. Most people are buying now in Australia because of the record low interest rates (below 5%). This is causing higher demand in the property markets and prices to rise steadily. Many people who buy during this period will be able to afford the property when interest rates are at 5%, but as the housing market and the economy heat up and interest rates start rising, they find it hard to afford the property when interest rate rise to 7%, 8% or higher. I personally prefer to buy when interest rates are on the rise and when they are near their highs. During this time no one wants to touch property with a six foot pole, but all the owners who bought when interest rates where much lower are finding it hard to keep making repayments so they put their properties on the market. There ends up being low demand and increased supply, causing prices to fall. It is very easy to find bargains and negotiate lower prices during this period. Because interest rates will be near or at their highs, the economy will be starting to slow down, so it will not be long before interest rates start dropping again. If you can afford to buy a property at 8% you will definitely be able to afford it at 6% or lower. Plus you would have bought at or near the lows of the price cycle, just before prices once again start increasing as interest rates drop. Read and learn as much as possible from others, but in the end make up your own mind on the type of properties and areas you prefer.",
"title": ""
},
{
"docid": "60001",
"text": "Yes, from the point-of-view to the end speculator/investor in stocks, it is ludicrous to take on liabilities when you don't have to. That's why single-stock options are far more liquid than single-stock futures. However, if you are a farmer with a huge mortgage depending upon the chaos of agricultural markets which are extremely volatile, a different structure might appeal to you. You could long your inputs while shorting your outputs, locking in a profit. That profit is probably lower than what one could expect over the long run without hedging, but it will surely be less volatile. Here's where the advantage of futures come in for that kind of structure: the margin on the longs and shorts can offset each other, forcing the farmer to have to put up much less of one's own money to hedge. With options, this is not the case. Also, the gross margin between the inputs rarely fluctuate to an unmanageable degree, so if your shorts rise faster than your longs, you'll only have to post margin in the amount of the change in the net of the longs and shorts. This is why while options on commodities exist to satisfy speculators, futures are the most liquid.",
"title": ""
},
{
"docid": "487354",
"text": "If there are a lot of houses for sale, can you be sure that in a year or two you can sell yours? How long does the average house in that area stay on the market before it is sold? What percentage of houses never get sold? If it can't be sold due to the crowded market you will be forced to rent the house. The question for you then is how much rental income can you get? Compare the rental income to your monthly cost of owning, and managing the house. One benefit to buying a house in a market that is easy to rent a house would be if you are forced to move quickly, then you aren't stuck being 3 months into a 12 month lease. Keep in mind that markets can change rather dramatically in just a few years. Housing costs were flat for much of the 90's, then rocketed up in the first half of the last decade, and after a big drop, they are one a slow climb back up. But the actual path they are on depends on the part of the US you are in. The rule of thumb in the past was based on the fact that over a few years the price would rise enough overcome the closing costs on the two transactions. Unfortunately the slow growth in the 90's meant that many had to bring checks to closing because the equity gained wasn't enough to overcome the closing costs due to low down payment loans. The fast growth period meant that people got into exotic loans to maximize the potential income when prices were going up 10-20% a year. When prices dropped some found that they bought houses they couldn't afford, but couldn't sell to break even on the transaction. They were stuck and had to default on the mortgage. In fact I have never seen a time frame when the rule of thumb ever applied.",
"title": ""
},
{
"docid": "507806",
"text": "\"Interestingly enough, \"\"strategic default\"\" seems to be more common than one might think in California and there is actually a lot of information available on it, to include a calculator that breaks down the numbers for you (although affiliated with a law office). Speaking from a purely financial standpoint, walking away only makes sense if it puts you in a better financial position than you were before while you had the mortgage. If you look at the downsides of walking away: The issues with the credit rating are will known but you need to take into account any open lines of credit you currently have as well as any need you might have to open a line of credit in the future. If you currently have credit cards, will the rates go up after the hit? On the housing side of things, you mortgage payment is currently a known quantity that will not change for the duration of the mortgage unless you do something to change it. However, it is fairly rare for rents to not change between years and if you want an apartment or house similar to what you currently have, you might find that the rent will fluctuate quite a bit between years and in the long run the rent might run higher than your current mortgage payment. Likewise, in the shorter term, if the landlord runs a credit check they might adjust what the rent is (or deny you the apartment) on the basis of the black mark on your history for reasons that other have mentioned. Another item to take into account is if you need to get a job in the future. Depending upon what you do for a living this might be a non-issue; however, if you are in a position of trust, walking away from a mortgage payment will reflect negatively upon your character unless you have a very good reason for it. This can lead to a loss of employment opportunities. Next, if you walk away from the mortgage you are walking away from the current value of the home and any future value that the home might have. If you like where you are living and aren't planning on moving to another part of the country, you are gambling that the market will not recover or that you would reach parity with what you owe by the time you need to sell the house. If you do plan on staying where you are and the house is in good repair, then in the long run you might be giving up quite a bit of money by walking away. These are a lot of factors to take into account though so its really hard to say one way or another if a strategic default is a good idea. In the long run you might come out ahead but knowing when that date is can be difficult to calculate. Likewise, in the long run it might adversely affect you and you might come to regret the decision. If the payments themselves are a bit too high, perhaps you can refinance or negotiate with the bank for a lower payment? If you get a better rate but keep your monthly payments the same then you might reach parity with the mortgage much faster which would also be to your advantage.\"",
"title": ""
},
{
"docid": "83543",
"text": "\"In the Netherlands specifically, there are several reasons to pay extra off on your mortgage. First, house prices have dropped significantly in the last several years. They are rising slowly now, but it's region specific and you can still borrow more than 100% of the price of the house. Under these conditions, if you choose to sell your house and the outstanding mortgage amount is greater than the value of your house, you are left with a gap (restschuld) to finance. I think the rules have changed recently around this, allowing you to finance this gap with a new mortgage, but this is not a good idea. The tax implications of this are likely to be complicated in the long run and your new house may not cover this gap for some time. Second, the less you owe on your house, the lower mortgage rates you can get. Mortgages in the Netherlands usually fall into categories based on percentage of the auction price at a foreclosure sale (executiewaarde). If you pay more of your mortgage off, you may qualify for a lower interest rate, possibly making refinancing interesting. This is especially important if interest rates continue to drop but the value of your house does not increase or even decreases. Third, if you choose to keep your house and rent it out, the banks in the Netherlands have very strict rules on this if you want to do it above board. I've read that some banks require the mortgage amount (NB not the value you may have built up in a linked savings or insurance account) to be less than 50% of the foreclosure auction price (executiewaarde). Also, related to point 2, if you have something other than a linear or annuity mortgage, you will need to refinance to do this as the tax advantages around savings mortgages ([bank]spaarhypotheken) do not apply if it is not used as your own residence. Finally, if you choose to sell and you are in the happy position of having the value of your house be greater than the value of your mortgage (you have an overwaarde), there may still be some obstacles. Any value you have accumulated in a linked savings or life insurance account is not available until after you sell your house. Extra value derived purely from the difference between mortgage value and sale price may be easier to deal with. EDIT: As a final note, I've made extra payments on both a \"\"Spaarhypotheek\"\" (linked life insurance) and a \"\"Bankspaarhypotheek\"\" (linked savings account). In one, the principal paid each month reduced and the mortgage lifetime stayed the same. In the other, the principal paid each month stayed the same and the lifetime reduced. In both cases, interest payments were less each month. I would contact your mortgage provider to understand what the expected impact of extra payments will be.\"",
"title": ""
},
{
"docid": "596834",
"text": "There's a few things going on here. If we fixed rates (and terms) over time we'd expect a pretty tight chart of home prices to income, almost lockstep. Add a layer of growth above that in boom times due to the wealth effect (when stocks are way up, we have extra money to blow on bigger houses) and the opposite when markets are down. Next, the effect of rates. With long term rates dropping from 14% in 1985 to 5% in 2003, the amount that can be bought for the same monthly payment rises dramatically as rates fall. Easy to lose site of that and the fact that the average size house has increased about 1.5% per year over the last 40 years, surely that can't continue. When you normalize all these factors, houses cost fewer hours-worked almost at the peak of the market than 25 years ago. Mike's logical example of extrapolating out is very clever, I like it. In the short term, we'll see periods that are booms and busts, but actual prices will straddle the line representing the borrowing power of a week's pay.",
"title": ""
},
{
"docid": "150607",
"text": "\"In England, currently and for most of the last fifty years, the standard length of the mortgage term is 25 years. A mortgage can be either a capital-and-interest mortgage, or interest-only. In the former, you pay off part of the original loan each month, plus the interest on the amount borrowed. In the latter, you only pay interest each month, and the original amount borrowed never reduces: you pay premiums on a life insurance policy, additionally, which is designed to pay off the original sum borrowed at the end of the 25 years. No one in England thinks that a 25 year loan has any drawbacks. The main point to appreciate is that the longer the period of the loan, the less you need to pay each month, because you are repaying the original loan - the capital - over a longer period of time. Thus, in principle, a mortgage is easier to repay the longer the term is, because the monthly payment is less. If you have a 12 year mortgage, you must pay back the original amount borrowed in half the time: the capital element in your payment each month is double what it would be if repaid over 25 years - i.e. if repaid over a period twice as long. Only if the borrower is less than 25 years away from retirement is a 25 years mortgage seen as a bad idea, by the lender - because, obviously, the lender relies on the borrower having an income sufficient to keep up the repayments. There are many complicating factors: an interest-only mortgage, where you pay back the original amount borrowed from the maturity proceeds from a life policy, puts you in a situation where the original capital sum never reduces, so you always pay the same each month. But on a straight repayment mortgage, the traditional type, you pay less and less each month as time goes by, for you are reducing the capital outstanding each month, and because that is reducing so is the amount of interest you pay each month (as this is calculated on the outstanding capital amount). There are snags to avoid, if you can. For example, some mortgage contracts impose penalties if the borrower repays more than the due monthly amount, hence in effect the borrower faces a - possibly heavy - financial penalty for early repayment of the loan. But not all mortgages include such a condition. If house prices are on a rising trend, the market value of the property will soon be worth considerably more than the amount owed on the mortgage, especially where the mortgage debt is reducing every month, as each repayment is made; so the bank or other lender will not be worried about lending over a 25 year term, because if it forecloses there should normally be no difficulty in recovering the outstanding amount from the sale proceeds. If the borrower falls behind on the repayments, or house prices fall, he may soon get into difficulties; but this could happen to anyone - it is not a particular problem of a 25 year term. Where a default in repayment occurs, the bank will often suggest lengthening the mortgage term, from 25 years to 30 years, in order to reduce the amount of the monthly repayment, as a means of helping the borrower. So longer terms than 25 years are in fact a positive solution in a case of financial difficulty. Of course, the longer the term the greater the amount that the borrower will pay in total. But the longer the term, the less he will pay each month - at least on a traditional capital-and-interest mortgage. So it is a question of balancing those two competing factors. As long as you do not have a mortgage condition that penalises the borrower for paying off the loan more quickly, it can make sense to have as long a term as possible, to begin with, which can be shortened by increasing the monthly repayment as fast as circumstances allow. In England, we used to have tax relief on mortgage payments, and so in times gone by it did make sense to let the mortgage run the full 25 years, in order to get maximum tax relief - the rules were very complex, but it tended to maximise your tax relief by paying over the longest possible period. But today, with no income tax relief given on mortgage payments, that is no longer a consideration in this country. The practical position is, of course, that you can never tell how long it might take you to pay off a mortgage. It is a gamble as to whether your income will rise in future years, and whether your job will last until your mortgage is paid off. You might fall ill, you might be made redundant, you might be demoted. Mortgage interest rates might rise. It is never possible to say that you \"\"can\"\" pay off the loan in a short time. If you hope to do so, the only matters that actually fall within your control are the conditions of the mortgage contract itself. Get a good lawyer. Tell him to watch out for early-redemption penalties. Get a good financial adviser. Tell him to work out what you will need to pay in additional premiums on your life policy if you are considering taking an interest-only mortgage. Try to fix your mortgage rate in the first few years, for as long as possible, so that in your most vulnerable period, with the greatest amount owing, you are insulated against unexpected interest rate fluctuations. Only the initial conditions can be controlled, so it might be prudent to take as long a term as possible, even though a prudent borrower will leave himself room to reduce that term, and a prudent lender will leave room to extend it, in case of unpredictable changes in the financial circumstances. In England, most lenders are, in my experience, reluctant to grant mortgages for less than 25 years. That is simply a policy. Rightly or wrongly, the borrower usually has no choice about the length of the mortgbage term. Hence, in the UK it can be difficult to find a choice of interest rates based on differing mortgage terms. I am aware that the situation in the USA is rather different, but if I personally were faced with the choice I would be uncomfortable about taking on a short term mortgage, because of the factors I have outlined above.\"",
"title": ""
},
{
"docid": "542024",
"text": "Will buying a flat which generates $250 rent per month be a good decision? Whether investing in real estate is a good decision or not depends on many things, including the current and future supply/demand for rental units in your particular area. There are many questions on this site about this topic, and another answer to this question which already addresses many risks associated with owning property (though there are also benefits to consider). I just want to focus on this point you raised: I personally think yes, because rent adjusts with inflation and the rise in the price of the property is another benefit. Could this help me become financially independent in the long run since inflation is getting adjusted in it? In my opinion, the fact that rental income general adjusts with 'inflation' is a hedge against some types of economic risk, not an absolute increase in value. First, consider buying a house to live in, instead of to rent: If you pay off your mortgage before your retire, then you have reduced your cost of accommodations to only utilities, property taxes, and repairs. This gives you a (relatively) known, fixed requirement of cash outflows. If the value of property goes up by the time you retire - it doesn't cost you anything extra, because you already own your house. If the value of property goes down by the time you retire, then you don't save anything, because you already own your house. If you instead rent your whole life, and save money each month (instead of paying off a mortgage), then when you retire, you will have a larger amount of savings which you can use to pay your monthly rental costs each month. By the time you retire, your cost of accommodations will be the market price for rent at that time. If the value of property goes up by the time you retire - you will have to pay more on rent. If the value of property goes down by the time you retire, you will save money on rent. You will have larger savings, but your cash outflow will be a little bit less certain, because you don't know what the market price for rent will be. You can see that, because you need to put a roof over your own head, just by existing you bear risk of the cost of property rising. So, buying your own home can be a hedge against that risk. This is called a 'natural hedge', where two competing risks can mitigate each-other just by existing. This doesn't mean buying a house is always the right thing to do, it is just one piece of the puzzle to comparing the two alternatives [see many other threads on buying vs renting on this site, or on google]. Now, consider buying a house to rent out to other people: In the extreme scenario, assume that you do everything you can to buy as much property as possible. Maybe by the time you retire, you own a small apartment building with 11 units, where you live in one of them (as an example), and you have no other savings. Before, owning your own home was, among other pros and cons, a natural hedge against the risk of your own personal cost of accommodations going up. But now, the risk of your many rental units is far greater than the risk of your own personal accommodations. That is, if rent goes up by $100 after you retire, your rental income goes up by $1,000, and your personal cost of accommodations only goes up by $100. If rent goes down by $50 after you retire, your rental income goes down by $500, and your personal cost of accommodations only goes down by $50. You can see that only investing in rental properties puts you at great risk of fluctuations in the rental market. This risk is larger than if you simply bought your own home, because at least in that case, you are guaranteeing your cost of accommodations, which you know you will need to pay one way or another. This is why most investment advice suggests that you diversify your investment portfolio. That means buying some stocks, some bonds, etc.. If you invest to heavily in a single thing, then you bear huge risks for that particular market. In the case of property, each investment is so large that you are often 'undiversified' if you invest heavily in it (you can't just buy a house $100 at a time, like you could a stock or bond). Of course, my above examples are very simplified. I am only trying to suggest the underlying principle, not the full complexities of the real estate market. Note also that there are many types of investments which typically adjust with inflation / cost of living; real estate is only one of them.",
"title": ""
},
{
"docid": "490057",
"text": "Unless some factor is pushing up home prices at a faster rate than apartment prices. Just guessing, but one reason might be that the increased potential to rent a home for AirBNB is higher than an apartment, and the increased value causes prices to rise faster in homes.",
"title": ""
},
{
"docid": "388571",
"text": "\"Number 2 cannot occur. You can buy the call back and sell the stock, but the broker won't force that #2 choice. To trade options, you must have a margin account. No matter how high the stock goes, once \"\"in the money\"\" the option isn't going to rise faster, so your margin % is not an issue. And your example is a bit troublesome to me. Why would a $120 strike call spike to $22 with only a month left? You've made the full $20 on the stock rise and given up any gain after that. That's all. The call owner may exercise at any time. Edit: @jaydles is right, there are circumstances where an option price can increase faster than the stock price. Options pricing generally follows the Black-Scholes model. Since the OP gave us the current stock price, option strike price, and time to expiration, and we know the risk free rate is <1%, you can use the calculator to change volatility. The number two scenario won't occur, however, because a covered call has no risk to the broker, they won't force you to buy the option back, and the option buyer has no motive to exercise it as the entire option value is time premium.\"",
"title": ""
},
{
"docid": "201736",
"text": "What is a good resource to learn about options trading strategies? Options are a quite advanced investment form, and you'd do well to learn a lot about them before attempting to dive into this fairly illiquid market. Yale's online course in financial markets covers the Options Market and is a good starting point to make sure you've got all the basics. You may be familiar with most of it, but it's a decent refresher on lingo and Black-Scholes. How can I use options to establish some cash flow from long standing investments while minimizing capital gains expenses? This question seems designed to get people to talk about covered calls. Essentially, you sell call contracts: you let people buy things you already have at a price in the future, at their whim. They pay you for this option, though usually not much if the options aren't in the money. You can think of this as trading any return above the call option for a bit of extra cash. I don't invest with taxable accounts, but there are significant tax consequences for options. Because they expire, there will be turnover in your portfolio, and up front income when you take the sell side. So if you trade in options with close expiration dates, you'll probably end up with a lot of short-term capital gains, which are treated as normal income. One strategy is to trade in broad-based stock index options, which have favorable tax treatments. Some people have abused this though to disguise normal income as capital gains, so it could go away. Obviously the easy approach is to just use a tax advantaged account for options trading. An ETF might also be able to handle the turnover on your behalf, for example VIX is a series of options on S&P500 options. A second strategy I've heard of is buying calls and puts at a given strike price. For example, if you bought Dec '13 calls and puts on SPX @ 115 today, it would cost you about $35 dollars. If the price moves more than 35 dollars away from 115 by DEC '13 (in either direction), you've made a profit. If you reflect on that for a bit, you'll see why VIX is considered a volatility index. I guess I should mention that shorting a stock and buying a put option at the market price are very similar, with the exception that your loss is limited to the price of the option. Is there ever an instance where options investing is not speculative? The term 'speculative' is not well defined. For many people, the answer is no. It's very easy to just buy put options and wait for prices to fall, or call options and wait for prices to rise. Moreover, the second strategy above essentially gives you similar performance to a stock without paying full price. These all fall under the headline of increasing a risk portfolio rather than decreasing it, which I figure is a decent definition of speculation. On the other hand, there are ways to use options minimize risk rather than increase it. You can buy underwater options as portfolio insurance, if your portfolio drops below a certain amount, you still have the right to sell it at a higher one. And the Case-Schiller index is run in part, on the hopes that one day there might be a thriving market for real estate options (or futures). When you buy a home or lend money to someone to buy one, you could buy regional Case-Schiller options to protect you if the regional market tanks. But in all of these cases, it's required for someone else to take the opposite trade. Risk isn't reduced, it's traded around. So technically, there is a speculative element to these as well. I think the proper question here is whether speculation is present, but whether speculation can be put to good ends. Without speculators, the already very thin market for options would shrivel faster.",
"title": ""
},
{
"docid": "117451",
"text": "Your question is a moving target. And my answer will be subject to revision. I disagree with the votes to close, as you are asking (imho) what role commodities and specifically oil, play in one's asset allocation. Right? How much may be opinion, but there's a place to ask if. I'm looking at this chart, and thinking, long term, the real return is zero. The discussion regarding gold has been pretty exhausted. For oil, it's not tough to make the case that it will fluctuate, but long term, there's no compelling reason to believe its price will rise any faster than inflation over the really long term.",
"title": ""
},
{
"docid": "599860",
"text": "The Shiller data is inflation adjusted. In effect, a flat line means that long term, housing rises with inflation, no more no less. There's no argument, just the underlying data to support his charts. This, among them. As much as I respect Nobel Prize winning Robert Shiller, his approach and analysis of the boom ignored interest rates. Say we look at a $50K earning couple. This is just below median income. At 9%, they qualify to borrow $145K. As rates fell to 4%, they qualify for $244K. Same fixed 30 term. Ignoring all other factors, the swing in rates will generate an oscillation around the long term trend. And my own data crunching suggests the equilibrium median home price will tend toward the price supported by the median income. A similar, but not identical question - Why can't house prices be out of tune with salaries? In response to Chan-Ho's comment - I'd imagine Shiller understood the interest impact. To clarify, the chart, as presented, ignores it.",
"title": ""
},
{
"docid": "285780",
"text": "When on this topic, you'll often hear general rules of thumb. And, similar to the 'only buy stocks if you plan to hold more than X years' there are going to be periods where if you buy at a bottom right before the market turns up, you might be ahead just months after you buy. I'd say that if you buy right, below market, you're ahead the day you close. Edit - I maintain, and have Schiller providing supporting data) that real estate goes up with inflation in the long term, no more, no less. If the rise were perfectly smooth, correlated 100% month to month, you'd find it would take X years to break even to the costs of buying, commission and closing costs. If we call that cost about 8%, and inflation averages 3, it points to a 3 year holding period to break even. But, since real estate rises and falls in the short term, there are periods longer than 4 years where real estate lags, and very short periods where it rises faster than the costs involved. The buy vs rent is a layer right on top of this. If you happen upon a time when the rental market is tight, you may buy, see the house decline 10% in value, and when the math is done, actually be ahead of the guy that rented.",
"title": ""
},
{
"docid": "589470",
"text": "Not only are absolute incomes (adjusted for inflation) not increasing, but purchasing power is also decreasing. Decades ago, the salary of one middle class worker can raise a family. Nowadays, you can't even buy a home with two salaries, especially in large metro areas. There are numerous factors why this is happening: 1. Globalization. Why pay an American more when something can be done or made in Vietnam for a fraction of the cost? Prices of non-renewable resources will increase as third-world countries modernize and their populations demand the same luxuries that we have. 2. Automation. Automation has eliminated many jobs further driving income inequality. There are people with very high salaries since automation are making them much more productive and then there are jobs that have been completely eliminated because of automation. I know of factories that laid off a large fraction of their operators because the machines are now automated (but they did a hire few more engineers and technicians to increase productivity). 3. Scarcity of land. Everyone wants to live in areas where the jobs are but you can only build so much housing in one area, so house prices go up faster than wages. People with good jobs in industries where jobs are clustered in one place (biotech, software, semiconductors, finance, etc.) actually can afford less real estate than one would think based on their income just because of their location. These issues will become even more relevant as technology continues to develop and globalization continues.",
"title": ""
},
{
"docid": "108399",
"text": "Some highly pessimistic things worth noting to go alongside all the stability and tax break upside that homes generally provide: Negative equity is no joke and basically the only thing that bankrupts the middle classes consistently en masse. The UK is at the end of a huge housing bull run where rents are extremely cheap relative to buying (often in the 1% range within the M25), Brexit is looming and interest rates could well sky rocket with inflation. Borrowing ~500k to buy a highly illiquid asset you might have to fire sale in case of emergency/job loss etc for 300k in a few years when lots of (relatively) cheap rental housing is available to rent risk free, could be argued to be a highly lopsided and dangerous bet vs the alternatives. Locking in 'preferential' mortgage rates can be a huge trap: low interest rates generally increase asset values. If/when they rise, assets fall in value as the demand shrinks, making you highly exposed to huge losses if you need to sell before it is paid off. In the case of housing this can be exceptionally vicious as the liquidity dramatically dries up during falls, meaning fire sales become much more severe than they are for more liquid assets like stock. Weirdly and unlike most products, people tend to buy the very best house they can get leverage for, rather than work out what they need/want and finding the best value equivalent. If a bank will lend you £20 a day to buy lunch, and you can just afford to pay it, do you hunt out the very best £20 lunch you can every day, or do you make some solid compromises so you can save money for other things etc? You seem to be hunting very close to the absolute peak amount you can spend on these numbers. Related to above, at that level of mortgage/salary you have very little margin for error if either of you lose jobs etc. Houses are much more expensive to maintain/trade than most people think. You spend ~2-5% every time you buy and sell, and you can easily spend 2-20k+ a year depending what happens just keeping the thing watertight, paid for, liveable and staying up. You need to factor this in and be pessimistic when you do. Most people don't factor in these costs to the apparent 'index' rise in house values and what they expect to sell for in x years. In reality no buy and hold investor can ever realise even close to the quoted house price returns as they are basically stocks you have to pay 5% each time you buy or sell and then 1-20% percent a year to own - they have to rise dramatically over time for you to even break even after all the costs. In general you should buy homes to make memories, not money, and to buy them at prices that don't cause you sleepless nights in case of disasters.",
"title": ""
}
] |
103874
|
Thinkin Bout You is an album.
|
[
{
"docid": "Thinkin_Bout_You",
"text": "`` Thinkin Bout You '' is a song by American singer Frank Ocean , released as the lead single from his debut studio album Channel Orange ( 2012 ) . The song was written by Ocean and produced by Shea Taylor . Originally to be featured on Bridget Kelly 's debut album , Ocean released his original version of the track for free on his Tumblr account in 2011 . In May 2012 , the song was officially sent to radio and released on iTunes as a single by Ocean . Kelly would later release her own version of the track entitled `` Thinking Bout Forever '' . Lyrically , the track is about a relationship just out of his reach and the turmoil that ensues . The track also explores feelings of regret and heartbreak . The song received highly positive reviews from music critics , who praised the atmospheric production , Ocean 's falsetto and writing ability . Some critics noted the possible bisexual undertones featured on the track . In September 2012 , the song peaked at position 32 on the Billboard Hot 100 , 94 on the UK Singles Chart , and 13 on the Heatseekers Songs chart . In 2011 , the song received a music video directed by visual art group High5Collective released on September 15 . Ocean appears in the violent clip revolving around an inter-dimensional love story and zombies . Ocean performed the track during his seven-show tour through North America and Europe in November 2011 , at the April 2012 Coachella Musical Festival , and his supporting tour for Channel Orange . `` Thinkin Bout You '' has been certified platinum by the Recording Industry Association of America ( RIAA ) and has sold more than one million units in the United States . The song was nominated for a Grammy Award in 2013 for Record of the Year .",
"title": ""
}
] |
[
{
"docid": "Still_Thinkin'_'bout_You",
"text": "Still Thinkin ' ` bout You is a country album by Billy `` Crash '' Craddock . It was released on ABC/Dot Records in 1975 . The album yielded two hit singles - `` I Love the Blues and the Boogie Woogie '' , which went to # 10 , and `` Still Thinkin ' ` bout You '' , which went to # 1 .",
"title": ""
},
{
"docid": "Still_Thinkin'_'bout_You_(song)",
"text": "`` Still Thinkin ' ` bout You '' is a single by American country music artist Billy `` Crash '' Craddock . Released in January 1975 , it was the first single from his album Still Thinkin ' ` bout You . The song peaked at number 4 on the Billboard Hot Country Singles chart . It also reached number 1 on the RPM Country Tracks chart in Canada .",
"title": ""
},
{
"docid": "Thinking_About_You",
"text": "Thinking About You may refer to : `` Thinking About You '' ( Whitney Houston song ) , 1985 `` Thinkin ' About You '' ( Mario song ) , 2009 `` Thinking About You '' ( Calvin Harris song ) , 2013 `` Thinking About You '' ( Norah Jones song ) , 2006 `` Thinking About You '' ( Hardwell song ) , a 2016 song by Hardwell featuring Jay Sean Thinkin ' About You , a 1995 album by Trisha Yearwood `` Thinkin ' About You '' ( Trisha Yearwood song ) `` Thinkin Bout You '' , a 2012 song by Frank Ocean `` Thinking About You '' , a 1993 song by Radiohead from Pablo Honey `` Thinking About You '' , a 2000 song by Screaming Jets from Scam `` Thinking About You '' , a 2005 song by Ivy from In the Clear `` Thinking About Ya '' , a 2008 song by Colby O'Donis from Colby O `` Thinking ` Bout You '' , a 2009 song by Yusuf Islam from Roadsinger `` Thinking Bout You '' , a 2015 song by Lil Wayne from Free Weezy Album `` Thinking About You '' , a 2016 song by Axwell Λ Ingrosso `` Mone Kori ( Thinking About You ) '' , a song by Mumzy Stranger from his 2008 mixtape",
"title": ""
},
{
"docid": "What_You_Leave_Behind_(album)",
"text": "What You Leave Behind is the third studio album by the American country music band Ricochet . It was released in 2000 on Columbia Records . The album , originally titled What a Ride , was to have been released in 1998 , and although three singles from the original album ( `` Honky Tonk Baby '' , `` Ca n't Stop Thinkin ' ` bout That '' and a cover of Steve Young 's `` Seven Bridges Road '' ) were all released from the original album , all three failed to make Top 40 . `` Honky Tonk Baby '' and `` Ca n't Stop Thinkin ' ` Bout That '' did not make the final cut , although `` You Beat All I 've Ever Seen '' , the final track on this album , is the B-side of `` Ca n't Stop Thinkin ' ` Bout That '' . `` Do I Love You Enough '' was released in 2000 , peaking at # 45 on the US country charts , followed by `` She 's Gone '' , the band 's last chart single , at # 48 . In between `` Seven Bridges Road '' and `` Do I Love You Enough '' , drummer Jeff Bryant and steel guitarist Teddy Carr both left the band as well . Also covered on the album is `` Why You Been Gone So Long '' , previously a hit in 1969 for Johnny Darrell .",
"title": ""
},
{
"docid": "Ain't_Thinkin'_'Bout_You",
"text": "`` Ai n't Thinkin ' ` Bout You '' is a song by rapper Bow Wow . This song features Chris Brown . An early version originally appeared on Brown 's collaborative mixtape with Tyga , Fan of a Fan .",
"title": ""
},
{
"docid": "Next_(Vanessa_Williams_album)",
"text": "Next is the fifth studio album by American singer and actress Vanessa Williams . It includes the singles `` Happiness '' ( # 36 on the Hot R&B / Hip-Hop Singles and Tracks chart ) , `` Who Were You Thinkin ' ` Bout '' , `` First Thing on Your Mind '' and `` Oh How the Years Go By '' ( # 6 on the Hot Adult Contemporary Tracks chart ) .",
"title": ""
},
{
"docid": "Thinkin'_About_You",
"text": "Thinkin ' About You is the fourth country studio album by country singer Trisha Yearwood . The album reached # 3 on the Billboard country albums chart . This album produced back-to-back Number One hits for Yearwood on the Billboard country charts in `` XXX 's and OOO 's ( An American Girl ) '' and `` Thinkin ' About You '' . Following these songs were `` You Can Sleep While I Drive '' ( # 23 ) , `` I Wan na Go Too Far '' ( # 9 ) , and `` On a Bus to St. Cloud '' ( # 59 ) . `` On a Bus to St. Cloud '' was also the first single of Yearwood 's career to miss Top 40 on the country charts . Allmusic gave the album a mediocre review , calling the arrangements `` too slick '' and one of Yearwood 's few albums that could be considered a disappointment .",
"title": ""
},
{
"docid": "ITunes_Session_(Jessica_Mauboy_EP)",
"text": "iTunes Session is the first extended play ( EP ) by Australian recording artist Jessica Mauboy , released through Sony Music Australia on 18 July 2014 . The seven-track EP was recorded in one take at 301 Studios in Sydney . It features rearranged live versions of Mauboy 's singles `` Running Back '' , `` Burn '' , `` Inescapable '' , `` Pop a Bottle ( Fill Me Up ) '' and `` Never Be the Same '' , as well as live cover versions of `` Who 's Loving You '' by The Miracles and `` Thinkin Bout You '' by Frank Ocean . Upon its release , iTunes Session debuted at number 25 on the ARIA Albums Chart .",
"title": ""
},
{
"docid": "Thinkin'_About_You_(Trisha_Yearwood_song)",
"text": "`` Thinkin ' About You '' is a song written by Tom Shapiro and Bob Regan , and recorded by American country music artist Trisha Yearwood . It was released in January 1995 as the second single and title track from her album Thinkin ' About You . The song became Yearwood 's third Number One country hit in April 1995 . Lee Roy Parnell plays slide guitar on the song .",
"title": ""
},
{
"docid": "Thinkin'_Problem",
"text": "Thinkin ' Problem is an album by American country music artist David Ball . It was released in 1994 ( see 1994 in country music ) on Warner Bros. . Records Nashville . Although he had recorded an eponymous album for RCA Nashville in 1988 prior to the release of Thinkin ' Problem , the RCA album was not released until later in 1994 . Thinkin ' Problem was certified platinum by the RIAA for sales of one million copies in the United States . It produced five singles for him on the Billboard Hot Country Singles & Tracks ( now Hot Country Songs ) charts between 1994 and 1995 . The first of these to chart was the title track , which reached number 2 on the country charts and number 40 on the Billboard Hot 100 . Following it were `` When the Thought of You Catches Up with Me '' ( number 7 on the country charts ) , `` Look What Followed Me Home '' ( number 11 ) , `` What Do You Want with His Love '' ( number 48 ) , and finally , `` Honky Tonk Healin ' '' at number 50 .",
"title": ""
},
{
"docid": "Darlin'_(The_Beach_Boys_song)",
"text": "`` Darlin ' '' is a song written by Brian Wilson and Mike Love , recorded by American rock band the Beach Boys with Carl Wilson on lead vocal . It opens the second side of their 1967 album Wild Honey and was also released as a single , backed with `` Here Today '' from their 1966 album Pet Sounds . The single peaked at No. 19 in the United States and No. 11 in the United Kingdom . The song is also known by different lyrics and structure as `` Thinkin ' ` Bout You Baby '' , also written by Wilson and Love , and first recorded by singer Sharon Marie in 1964 . It has twice returned to the US Billboard Hot 100 , reaching No. 51 for Paul Davis in 1978 , and two years later No. 68 for the Milwaukee-based band Yipes ! .",
"title": ""
},
{
"docid": "What_Were_You_Thinkin'",
"text": "`` What Were You Thinkin ' '' is a song recorded by American country music group Little Texas . It was released in October 1992 as the fourth single from the album First Time for Everything . The song reached # 17 on the Billboard Hot Country Singles & Tracks chart . The song was written by Porter Howell , Dwayne O'Brien , Brady Seals and Christy DiNapoli .",
"title": ""
},
{
"docid": "Frank_Ocean_discography",
"text": "American singer Frank Ocean has released two studio albums , one collaboration album , two mixtapes , nine singles and eight music videos . Following the flooding and destruction of his recording studio during Hurricane Katrina in 2005 , Ocean moved from his hometown of New Orleans to the Californian city of Los Angeles , where he sought to continue his musical career , eventually landing himself a songwriting contract . In 2008 , Ocean released his first independent mixtape Lonny Breaux , named after his former alter ego ; the following year , he signed to Def Jam Recordings as a solo artist . Ocean also formed a friendship with rapper Tyler , The Creator , leader of the Los Angeles-based hip hop collective Odd Future ( OFWGKTA ) and subsequently became a member of Odd Future , as well as making three guest appearances on the album Goblin , including the single `` She '' . In February 2011 , he released his first major project , his second mixtape Nostalgia , Ultra , which produced two singles : `` Novacane '' and `` Swim Good '' . `` Novacane '' became his first single to chart on the US Billboard Hot 100 , where it peaked at number 82 . Ocean also made two guest appearances on the Kanye West and Jay Z collaborative album Watch the Throne , including the single `` No Church in the Wild '' , which peaked at number 72 on the Billboard Hot 100 . Ocean has also written songs for several artists , such as Damienn Jones ( `` Cinderella '' and `` Summertime '' ) , Brandy Norwood ( `` 1st & Love '' and `` Scared of Beautiful '' ) , John Legend ( `` Quickly '' ) , Beyoncé ( `` I Miss You '' ) , Bridget Kelly ( `` Thinking About Forever '' ) , and Justin Bieber ( `` Bigger '' ) . Ocean started writing songs for his debut studio album in February 2011 with songwriter and producer James `` Malay '' Ho , his friend and creative partner since their start in the music industry as songwriters . The album , Channel Orange , was released on July 10 , 2012 . Upon release , the album received universal acclaim from music critics , who praised the album for its bold lyrical content . The album peaked at number 2 on both the US Billboard 200 and the UK Albums Chart , while it hit number one on the US Billboard Top R&B / Hip-Hop Albums chart . It also became the first album in chart history to chart within the UK Albums Chart top 20 solely based on digital sales . Five singles were released from the album : `` Thinkin Bout You '' , `` Pyramids '' , `` Sweet Life '' , `` Lost '' and `` Super Rich Kids '' . `` Thinkin Bout You '' peaked at number 32 on the Billboard Hot 100 , becoming Ocean 's first top 40 entry on the chart . `` Lost '' became a top five single in New Zealand and also achieved chart success in Australia and Denmark . After a four year hiatus , Ocean returned by releasing the Endless a visual album that also marked the end of contract with Def Jam . Endless was released on August 19 , 2016 , shortly followed by the release of the `` Nikes '' music video which would be the first single off of Blonde , his second studio album , release a day later on August 20 , 2016 . `` Endless '' was a 45 minute long album that intertwined the music with a video of Ocean eventually building a spiral staircase .",
"title": ""
},
{
"docid": "Frank_Ocean",
"text": "Christopher Francis `` Frank '' Ocean ( born Christopher Edwin Breaux ; October 28 , 1987 ) , is an American singer , songwriter , and rapper . Known for his idiosyncratic musical style , Ocean first embarked on a career as a ghostwriter , and in 2010 he became a member of hip hop collective Odd Future . He released his breakout mixtape , Nostalgia , Ultra , to critical acclaim in 2011 . It generated his first charting single `` Novacane '' . In 2012 , Ocean finished in second place in BBC 's Sound of 2012 poll . His debut studio album , Channel Orange , was released in July 2012 to critical acclaim and reached No. 2 on the Billboard 200 . It was promoted with three singles : `` Thinkin Bout You '' , `` Pyramids '' and `` Sweet Life '' . In 2016 , Ocean released the visual album Endless alongside his second studio album Blonde , following several years of delays . Blonde was acclaimed by critics , and debuted at number one in the United States and the United Kingdom .",
"title": ""
},
{
"docid": "Thinkin'_About_You_(Mario_song)",
"text": "`` Thinkin ' About You '' is a song performed by American R&B singer-songwriter Mario . It was written by Rico Love and produced by The Runners and The Monarch . It was released on September 4 , 2009 as the second single from his fourth studio album D.N.A. . The song debuted on the U.S. Billboard Hot R&B / Hip-Hop Songs , at number 96 . Since then , have reached number 45 on the charts .",
"title": ""
},
{
"docid": "Just_When_You're_Thinkin'_Things_Over",
"text": "`` Just When You 're Thinkin ' Things Over '' was a 1995 single by the English indie band The Charlatans , released from their self-titled fourth album . It charted at # 12 on the UK Singles Chart .",
"title": ""
},
{
"docid": "'Bout_It",
"text": "` Bout It is the second studio album from contemporary R&B singer Jesse Powell , released September 8 , 1998 , via Silas Records . It was his first album to chart on the Billboard 200 , peaking at # 63 . Three singles were released from the album : `` I Was n't with It '' , `` You '' ( which also appeared on his debut album ) and '' ` Bout It , ` Bout It '' . `` You '' is Powell 's only hit to date on the Billboard Hot 100 , peaking at # 10 in 1999 . The album was certified gold by the RIAA on June 8 , 1999 .",
"title": ""
},
{
"docid": "Tonight_(Silk_album)",
"text": "Tonight is the third studio album from R&B group Silk , released on March 23 , 1999 on Elektra Entertainment . It was their first album in four years and the reason for the break was due to the group wanting to be more involved in the creative process . Another reason for the hiatus was due to the lackluster performance of their previous album , which caused the group to seek new management after dealing with financial and legal issues . After severing ties with their former managers , they were managed by Sonja Norwood , mother of singer/actress Brandy . They were soon given the green light to record a new album by Elektra 's then-president Sylvia Rhone , who let them take their time to record the album until they had the right songs . Most of the production duties were split between group member Gary Jenkins and producer Darrell `` Delite '' Allamby . The latter was brought in due to his previous work with Gerald Levert ( `` Thinkin ' Bout It '' and `` Taking Everything '' ) , Busta Rhymes ( `` What 's It Gon na Be ?! '' ) and LSG ( `` My Body '' ) . They also have production from Maurice Wilcher , a singer that was formerly signed to Dr. Dre 's label Aftermath Entertainment . The album features the Hits `` If You '' , which peaked at # 13 on the Billboard Hot 100 ( their biggest hit since `` Freak Me '' in 1993 ) and `` Meeting In My Bedroom '' . Tonight proved to be their second most successful album , right behind their 1992 debut Lose Control . The album was certified platinum by the RIAA in 1999 .",
"title": ""
},
{
"docid": "You_Can_Sleep_While_I_Drive",
"text": "`` You Can Sleep While I Drive '' is a song recorded by American singer-songwriter Melissa Etheridge for her second album Brave and Crazy released in 1989 . Country music artist Trisha Yearwood covered the song and released it in April 1995 as the third single from her album Thinkin ' About You . The song reached # 23 on the Billboard Hot Country Singles & Tracks chart .",
"title": ""
},
{
"docid": "Love_&_Consequences",
"text": "Love & Consequences is the third studio album by American R&B singer Gerald Levert . It was released on July 21 , 1998 on East West Records . The album was a commercial success , peaking at # 17 on the Billboard 200 chart and at # 2 on the Top R&B Albums . In addition to his longtime collaborator , Edwin `` Tony '' Nicholas , Levert worked with more writers and producers including R. Kelly , Joe Little III of The Rude Boys ( whom Levert discovered ) and Darrell `` Delite '' Allamby . Singles included on the album were `` Thinkin ' Bout It '' , and `` Taking Everything '' . Both were top 5 R&B hits overall and Levert 's biggest crossover hits at # 12 and # 11 on the Hot 100 respectively .",
"title": ""
},
{
"docid": "First_Time_for_Everything",
"text": "First Time for Everything is the first studio album by country music band Little Texas . Released in 1992 on Warner Bros. . Records , the album was certified gold by the RIAA for sales of 500,000 copies . Five singles were released from it : `` Some Guys Have All the Love '' , the title track , `` You and Forever and Me '' , `` What Were You Thinkin ' '' , and `` I 'd Rather Miss You '' . Respectively , these reached # 8 , # 13 , # 5 , # 17 and # 16 on the Hot Country Songs charts .",
"title": ""
},
{
"docid": "Shea_Taylor",
"text": "Shea Taylor is a songwriter/producer/multi-instrumentalist based in New York City . He 's established a successful songwriting partnership with Def Jam 's R&B singer-songwriter phenom Ne-Yo , and has also worked with Rihanna , Beyoncé , Janet Jackson , Chris Brown , and Wyclef Jean . He has won an ASCAP Award , and has been nominated to the Grammy Awards . Taylor has songwriting credits on seven tracks off the Beyonce record entitled 4 . The album is certified platinum and debuted at number one on the Billboard 200 with first-week sales totaling over 300,000 . `` Love On Top '' made it to the top of the US Hot R&B / Hip-Hop Songs chart and Adult R&B Airplay chart in March 2012 . `` Run the World ( Girls ) '' also reached number one on the US Hot Dance Club Songs and is certified Gold in the US and New Zealand and Platinum in Australia and Canada . `` Best Thing I Never Had '' climbed to the top of Nielsen 's Urban airplay chart in September and peaked at number four on the Hot R&B / Hip-Hop Songs chart . Taylor co-wrote the lead single `` Thinkin Bout You '' and `` Pilot Jones '' on Frank Ocean 's debut channel ORANGE . The album debuted at number one on the US Billboard R&B / Hip-Hop Albums chart and number two on the UK R&B Albums chart . It also debuted at number two on the Billboard 200 . Shea is published by Downtown Music Publishing for the world .",
"title": ""
},
{
"docid": "Don't_You_Worry_'bout_a_Thing_(album)",
"text": "Do n't You Worry ` bout a Thing is a soul-jazz album by saxophonist Hank Crawford , released in 1975 on Kudu Records .",
"title": ""
},
{
"docid": "Used_to_Be_My_Girl",
"text": "`` Used to Be My Girl '' is a single by Brian McKnight , released in 2006 from Ten . It was written and produced by Tim & Bob . The song peaked at number 25 on the Billboard Hot R&B / Hip-Hop Songs chart . The album serves the first official single on October 17 , 2006 . The song , as McKnight states in the beginning , `` is not another love song '' . Instead , the song 's lyrics expresses dismay at what he perceives to be another man 's excessive pride in his relationship with an attractive girlfriend ; with whom the songwriter used to have a relationship . McKnight 's lyrics seemingly taunt the new love interest , going so far as to offer advice on dealing with the past relationship : See , I know what you 're thinkinYou 're feelin ' like a lucky guy I was the same waycause she was hard to come by I was on her so hard That I almost lost my hustle So go ` head , playboy , do your thing Do n't be mad if she calls my name The antagonist cautions the woman 's new boyfriend not to `` hate on '' him when she intimately mentions his name , and implies that the new relationship is really `` just a game '' , a theory that he argues is proven by her perceived inability to acknowledge his presence as he watches the new couple : <blockquote> She 's still thinkin ' ` bout me , And I 'll tell you why , She could n't even hold her head up when you walked by </blockquote> The song ends with the singer recounting and implying to the new boyfriend various intimate acts that the woman performed for him when `` she was my girl '' .",
"title": ""
},
{
"docid": "Don't_Worry_'bout_a_Thing",
"text": "Do n't Worry ` bout a Thing or Do n't Worry About a Thing may refer to : `` Do n't You Worry ` bout a Thing '' , a 1973 song by Stevie Wonder Do n't You Worry ` bout a Thing ( album ) , by Hank Crawford `` Do n't Worry ` bout a Thing '' ( SHeDAISY song ) , a 2005 song by SHeDAISY `` Feels Good ( Do n't Worry Bout a Thing ) '' , a 2002 song by Naughty by Nature `` Three Little Birds '' , a 1980 song by Bob Marley & The Wailers ( the chorus prominently features the phrase `` do n't worry about a thing '' )",
"title": ""
},
{
"docid": "What_You_Know_bout_Me?",
"text": "What You Know bout Me ? is studio album by Messy Marv in 2006 .",
"title": ""
},
{
"docid": "Look_What_Followed_Me_Home",
"text": "`` Look What Followed Me Home '' is a song co-written and recorded by American country music artist David Ball . It was released in January 1995 as the third single from the album Thinkin ' Problem . The song reached number 11 on the Billboard Hot Country Singles & Tracks chart . The song 's B-side , `` What Do You Want with His Love '' , was the album 's fourth single , released in May 1995 . `` What Do You Want with His Love '' peaked at number 48 on the same chart .",
"title": ""
},
{
"docid": "The_Secret_of_Life_(album)",
"text": "The Secret of Life is the debut studio album by singer-songwriter Gretchen Peters . It was released in 1996 , and featured a minor hit single in the track , `` When You Are Old '' . The song reached number 68 on the Hot Country Songs chart . The album was the first release for Imprint Records . Faith Hill covered the title track and took it to number 4 on the country chart in the States ( while also scraping into the top 50 on the Billboard Hot 100 ) . Trisha Yearwood recorded her own version of `` On a Bus to St. Cloud '' for her full-length Thinkin ' About You ( two years prior to the release of this album ) , while Martina McBride has recorded 3 songs : `` This Uncivil War '' , `` When You Are Old '' and `` Independence Day '' which she took to number 12 on the U.S. country chart .",
"title": ""
},
{
"docid": "Channel_Orange",
"text": "Channel Orange ( stylized as channel ORANGE ) is the 2012 debut studio album by American R&B singer and songwriter Frank Ocean . After releasing his mixtape Nostalgia , Ultra in 2011 , Ocean began writing new songs with Malay , a producer and songwriter who assisted him with recording the album at EastWest Studios in Hollywood . Rather than rely on samples as he had with his mixtape , Ocean wanted to approach sound and song structure differently on Channel Orange . He titled the album as a reference to the neurological phenomenon grapheme-color synesthesia and the color he claimed to have perceived during the summer he first fell in love . Channel Orange has an unconventional musical style , film-inspired segue tracks , and songs that draw on electro-funk , pop-soul , jazz-funk , and psychedelic music . Ocean 's songwriting touches on themes such as unrequited love , decadence , class , and drugs through the use of surrealistic imagery , conversational devices , and descriptive narratives depicting dark characters . His singing on the album exhibits free-form flow and alternating falsetto and tenor registers . To prevent Channel Orange from leaking onto the Internet , Ocean and Def Jam Recordings released the album digitally on July 10 , 2012 , one week earlier than its publicly announced date . It was promoted with five singles , including Ocean 's highest charting single `` Thinkin Bout You '' -- number 32 on the Hot 100 -- and a supporting concert tour in July 2012 . Channel Orange debuted at number two on the Billboard 200 and sold 131,000 copies in its first week . It received widespread critical acclaim and was named the best album of 2012 by numerous publications . By September 2014 , the album had sold 621,000 copies , according to Nielsen SoundScan .",
"title": ""
},
{
"docid": "When_the_Thought_of_You_Catches_Up_with_Me",
"text": "`` When the Thought of You Catches Up with Me '' is a song written and recorded by American country music singer David Ball . It was released in August 1994 as the second single from the album Thinkin ' Problem as the follow-up to the successful title track . This song reached number 7 on the Hot Country Singles & Tracks ( now Hot Country Songs ) chart , and number 6 on Canada 's RPM country chart .",
"title": ""
}
] |
3166
|
Why are credit cards preferred in the US?
|
[
{
"docid": "257916",
"text": "Your question is based on a false premise. Debit cards are more popular in the US than credit cards are. Indeed it seems to be the non-US part of the world that is big in credit cards. See here for example",
"title": ""
},
{
"docid": "481648",
"text": "For me, it is mostly for the fraud protection. If I have a debit card and someone makes a fraudulent charge the money is removed from my bank account. From my understanding, I can then file a fraud complaint with the bank to recover my money. However, for some period of time, the money is missing from my bank account. I've heard conflicting stories of money being returned quickly while the complaint is undergoing investigation as well as money being tied up for several days/weeks. It may depend on the bank. With a credit card, it is the banks money that is tied up.",
"title": ""
},
{
"docid": "467581",
"text": "\"There are two things I can think of that might be different in other countries: Until 2013, American Express, Visa and MasterCard prevented businesses from charging extra for credit card usage, and credit card surcharges still illegal in several states. Since credit card companies add a surcharge to credit card purchases, and merchants can't pass that onto credit card users, they just make everyone pay extra instead. Since everyone gets charged the credit card surcharge, you might as well use a credit card and recoup some of that via \"\"rewards\"\" points. Almost all credit cards here have grace periods, where you won't be charged interest if you pay back your loans in full within some period of time (at least 21 days). This makes credit cards attractive to people who don't need a loan, but like the convenience that credit cards provide (not carrying cash, extra insurance, better fraud protection). Apparently grace periods aren't required by law here, so this might be common in other countries as well.\"",
"title": ""
},
{
"docid": "5191",
"text": "Credit card fraud protection (by law), credit card cash back programs (provided by most CC issuers), and debit card fees (commonly imposed by the merchant). The crux is that with CC transactions, a small percentage is remitted to the issuing bank. Since the banks are already making money hand over fist on CC's, they incentivize people to use them. CC security is also lax because the merchant is responsible for fraudulent charges instead of the bank. If the merchant fails to check a signature, they are held liable for all charges if the card holder reports a fraudulent transaction.",
"title": ""
},
{
"docid": "30090",
"text": "There are several reasons why credit cards are popular in the US: On the other hand, debit cards do not have any of these going for them. A debit card doesn't make much money for the bank unless you overdraw or something, so banks don't have incentive to push you to use them as much. As a result they don't offer rewards other benefits. Some people say the ability to spend more than you have is a downside of a credit card. But it's really an upside. The behavior of doing that when it isn't needed is bad, but that's not the card's fault, it's the users'. You can get a credit card with a very small limit if this is an issue for you. The question I find interesting is why debit cards are more popular in your home country. I can't think of any advantage they offer besides free cash back. But most people in the US don't use cash much either. I have to think in your home country the banks have a different revenue model or perhaps your country isn't as eager to offer tons of easy credit to everyone as the US is.",
"title": ""
},
{
"docid": "486245",
"text": "",
"title": ""
},
{
"docid": "263965",
"text": "\"The real reason credit cards are so popular in the US is that Americans are lazy and broke, and the credit card companies know how to market to that. Have you ever heard of the $30k millionaires? These were individuals that purchased as if they were some of the wealthy elite, but had no real money to back it up. American society has pushed the idea of \"\"living on credit\"\" for quite some time now. An idea that is even furthered by watching the US government operate solely on credit. (Raise the debt ceiling much?) Live in America for more than six months and you will be bombarded with \"\"Pre-Approved Deals\"\" with low introductory rates that are designed to sucker the average consumer into opening multiple accounts that they don't need. Then, they try and get you to carry a balance by allowing low minimum payments that could take in the neighborhood of 20 years to pay off, depending on carried balance. This in turn pads the credit companies' pockets with all of the interest you now pay on the account. The few truly wealthy Americans do not purchase on credit.\"",
"title": ""
},
{
"docid": "85466",
"text": "\"Personally, I use my credit cards for everything because I get reward points (or, cash back, depending on the card), and I build credit history. I've had credit cards since I was 18 (now 22), and my credit score is in the higher end 700s which I'm told is pretty good for my age. Additionally, since I put my rent and large purchases on my credit card, I have a lot of reward points. I use these to buy things I wouldn't normally buy to try them out and see if they bring any value into my life. If not, I didn't really lose anything, but I have found value in some of those things. I realize most of this is gamification and consumerism at play, but getting that extra little thing once in a while for \"\"free\"\" which is pretty nice.\"",
"title": ""
}
] |
[
{
"docid": "585661",
"text": "\"Yes, merchants may charge a fee for using a credit card. For a credit card transaction, interchange fees flow from the merchant to the card issuer. This is why Australians are seeing a boom in \"\"Debit\"\" MasterCard/VISA cards - the issuing banks make income when you select \"\"Credit\"\". These costs can be passed from the merchant to the customer as a \"\"Credit Card Fee\"\". For an EFTPOS transaction, the interchange flows the other way, from the card issuer to the acquiring bank (The merchant's bank). As an aside, the setup of these fees is why some large supermarket chains in Australia restrict you from selecting \"\"Credit\"\" with a scheme debit card (MasterCard and VISA are 'schemes'). They are 'acquirers' in the payments networks and they make interchange fees when you hit \"\"Savings\"\" and pay if you hit \"\"Credit\"\" - therefore where you can hit either \"\"Credit\"\" or \"\"Savings\"\" they prefer (and may force) you to press \"\"Savings\"\".\"",
"title": ""
},
{
"docid": "22412",
"text": "That transaction probably cost the merchant $0.50 + 3% or close to $5. They should have refunded your credit card so they could have recouped some of the fees. (I imagine that's why big-box retailers like Home Depot always prefer to put it back on your card than give you store credit) Consider yourself lucky you made out with $0.15 this time. (Had they refunded your card, the 1% of $150 credit would have gone against next month's reward) Once upon a time folks were buying money from the US Mint by the tens of thousands $ range and receiving credit card rewards, then depositing the money to pay it off.. They figured that out and put a stop to it.",
"title": ""
},
{
"docid": "355592",
"text": "\"There absolutely is a specific model that makes this so popular with so many credit card companies, and that model is \"\"per transaction fees\"\". Card companies also receive cost-sharing incentives from certain merchants. There is also a psychological reasoning as an additional incentive. When you want to accept credit cards as a source of payment as a business, you generally have three kinds of fees to pay: monthly/yearly subscription fees, percentage of transaction fee, and per transaction fee. The subscription fees can be waived and sometimes are expressed as a \"\"minimum cost\"\", so the business pays a certain amount whether you actually have people use credit cards or not. Many of these fees don't actually make it to the credit card companies, as they just pay the service providers and middle-men processing companies. The percentage of transaction fee means that the business accepting payment via credit card must pay a percentage usually ranging from 1-3% of the total transactions they accept. So if they get paid $10,000 a month by customers in the form of credit cards, the business pays out $100-300 a month to the credit card processor - a good portion of which will make it back to the credit card issuing company, and is a major source of income for them. The per transaction fee means that every time a transaction is run involving a card, a set fee is incurred by the business (which is commonly anywhere from $0.05 to $0.30 per transaction). If that $10,000 a month business mentioned previously had 10 customers paying $1,000 each at $0.10 a transaction, that's only $1 in fees to the credit card processors/companies. But if instead that business was a grocery store with an average transaction of $40, that's $25 in fees. This system means that if you are a credit card company and want to encourage people to make a specific kind of purchase, you should encourage purchases that people make many times for relatively small amounts of money. In a perfect world you'd want them to buy $1 bottles of water 5 times a day with their credit card. If the card company had 50,000 card holders doing this, at the end of 1 year the company would have $91,250,000 spread across 91,250,000 transactions. The card company might reasonably make $0.05 per transaction and %1 of the purchase total. The Get Rewarded For Drinking More campaign might earn the card company $912,500 in percentage fees and over $4.5 million in transaction fees. Yet the company would only have to pay 3% in rewards from the percentage fees, or $2.7 million, back to customers. If the card company had encouraged using your credit card for large once-yearly purchases, they would actually pay out more money in rewards than they collect in card-use fees. Yet by encouraging people to make small transactions very often the card company earns a nice net-income even if absolutely every customer pays their balance in full, on time, and pays no annual/monthly fees for their card - which obviously does not happen in the real world. No wonder companies try so hard to encourage you to use your card all the time! For card companies to make real money they need you to use your credit card. As discussed above, the more often you use the card the better (for them), and there can be a built-in preference for small repeated transactions. But no matter what the size of transaction, they can't make the big bucks if you don't use the card at all! Selling your personal information isn't as profitable if they don't have in-depth info on you to sell, either. So how do they get you to make that plastic sing? Gas and groceries are a habit. Most people buy one or the other at least once a weak, and a very large number of us make such purchases multiple times a week. Some people even make such purchases multiple times a day! So how do people pay for such transactions? The goal of the card companies is to have you use their product to pay as much as possible. If you pay for something regularly you'll keep that card in your wallet with you, rather than it getting lost in a drawer at home. So the card companies want you to use your card as a matter of habit, too. If you use a card to buy for gas and groceries, why wouldn't you use it for other things too? Lunch, dinner, buying online? If the card company pays out more and makes less for large, less-regular purchases, then the ideal for them is to have you use the card for small regular purchase and yet still have you use the card for larger infrequent purchases even if you get reduced/no rewards. What better way to achieve all these goals than to offer special rewards on gas and groceries? And because it's not a one-time purchase, you aren't so likely to game the system; no getting that special 5% cash-back card, booking your once-per-decade dream vacation, then paying it off and cancelling it soon after - which would actually make the card company lose money on the deal. In the end, credit card companies as a whole have a business model that almost universally prefers customers who use their products regularly and preferably for small amounts a maximum number of times. They want to reduce their expenses (like rewards paid out) while maximizing their revenue. They haven't figured out a better way to do all of this so well as to encourage people to use their cards for gas and groceries - everything else seems like a losing proposition in comparison. The only time this preference differs is when they can avoid paying some or all of the cost of rewards, such as when the merchants themselves honor the rewards in exchange for reduced or zero payment from the card companies. So if you use an airline card that seems to give you 10% back in airline rewards? Well, that's probably a great deal for the card company if the airline provides that reward at their own expense to try to boost business. The card company keeps the transaction-related fees and pays out almost nothing in rewards - the perfect offer (for them)! And this assumes no shenanigans like black-out periods, \"\"not valid with any other offers\"\" rewards like on cars where only a fool pays full MSRP (and sometimes the rewards are tagged in this sort of way, like not valid on sale/clearance items, etc), expiring rewards, the fact that they know not everyone uses their rewards, annual fees that are greater than the rewards you'll actually be obtaining after accounting for all the other issues, etc. And credit card industries are known for their shenanigans!\"",
"title": ""
},
{
"docid": "335859",
"text": "As has been stated, you don't need to actively bank with a credit union to apply for one of their credit cards. That said, one benefit to having account activity, and significant capital with a CU, is to increase the likelihood of having a larger credit line granted to you, when you do apply. If you are going to use the card sparingly however, then this is a non issue. That said, if you really want to maximize card benefits, then you want to look for cards with large sign up bonuses (e.g. Chase Sapphire, or Ink Bold if you have a business) and sign up exclusively for those bonuses. These cards offer rewards in excessive value of $1000 in travel services (hotels/plane tickets), or $500 cash back if you prefer straight cash back redemptions. If you prefer to keep it really simple, you can sign up for a cash back card, like the Amex Fidelity, which offers 2% cash back everywhere, with no annual fee (albeit the cash back is through their investment account, which you don't actually have to 'invest' with). Personally, I have the Penfed card, and use it exclusively for gas (5% cash back). I also have a Charles Schwab bank account, which I keep funded exclusively for ATM withdrawals (free ATM usage, worldwide, 100% fee reimbursement). I use the accounts exclusively for the benefit they provide me, and no more and have never had an issue. I also have 3 dozen other credit cards which I signed up for exclusively for the sign up bonus, but that's outside the scope of this question. I only mention it because you seem to believe it is difficult to get approved for a new credit line. If your credit is good however, you won't have a problem. For a small idea, of how to maximize credit card bonus categories, I would advise you read this. As mentioned in the article, its possible to get rewards almost everywhere you shop. In short, anytime you use cash, you are missing out on a multitude of benefits a credit card offers you (e.g. see the benefits of a visa signature card) in addition to points/cash back.",
"title": ""
},
{
"docid": "408124",
"text": "When you start at a new job here in the U.S., the default means of payment is usually a paper check. Most folks will quickly set up direct deposit so that their employer deposits their paycheck directly into their personal bank account - the incentive to do so is that you receive your funds faster than if you deposit a paper check. Even if you set up direct deposit on your first day on the job, you may still receive your first paycheck as a paper check simply because the wheels of payroll processing turn slowly at some (large) companies. A counter example is a self-employed contractor - perhaps a carpenter or house painter. These folks are paid by their customers, homeowners and such. Many larger, well established contracters now accept credit card payments from customers, but smaller independents may be reluctant to set up a credit card merchant account to accept payment by card because of all the fees that are associated with accepting credit card payments. 3% transaction fees and monthly service fees can be scary to any businessman who already has very thin profit margins. In such cases, these contractors prefer to be paid by check or in cash for the simple reason that there are no fees deducted from cash payments. There are a few folks here who don't trust direct deposit, or more specifically, don't trust their employer to perform the deposit correctly and on time. Some feel uncomfortable giving their bank info to their employer, fearing someone at the company could steal money from their account. In my experience, the folks who prefer a paper paycheck are often the same folks who rush to the bank on payday to redeem their paychecks for cash. They may have a bank account (helps with check cashing) but they prefer to carry cash. I operate in a manner similar to you - I use a debit card or credit card (I only have one of each) for nearly all transactions in daily life, I use electronic payments through my bank to pay my regular bills and mortgage, and I receive my paycheck by direct deposit. There have been periods where I haven't written or received paper checks for so long that I have to hunt for where I put my checkbook! Even though I use a debit card for most store purchases, the bank account behind that debit card is actually a checking account according to the bank. Again, the system defaults to paper checks and you have the option of going electronic as well. Before we judge anyone who doesn't use direct deposit or who prefers to be paid in cold hard cash, consider that direct deposit is a luxury of stability. Steady job, home, etc. Direct deposit doesn't make sense for a contractor or day laborer who expect to work for a different person each day or week. I don't think this is all that unique to the US. There are people in every city and country who don't have long-term employment with a single employer and therefore prefer cash or paper check over electronic payments. I'd be willing to bet that this applies to the majority of people on the planet, actually.",
"title": ""
},
{
"docid": "490100",
"text": "\"The preferred accounts are designed to hope you do one of several things: Pay one day late. Then charge you all the deferred interest. Many people think If they put $X a month aside, then pay just before the 6 months, 12 moths or no-payment before 2014 period ends then I will be able to afford the computer, carpet, or furniture. The interest rate they will charge you if you are late will be buried in the fine print. But expect it to be very high. Pay on time, but now that you have a card with their logo on it. So now you feel that you should buy the accessories from them. They hope that you become a long time customer. They want to make money on your next computer also. Their \"\"Bill Me Later\"\" option on that site as essentially the same as the preferred account. In the end you will have another line of credit. They will do a credit check. The impact, both positive and negative, on your credit picture is discussed in other questions. Because two of the three options you mentioned in your question (cash, debit card) imply that you have enough cash to buy the computer today, there is no reason to get another credit card to finance the purchase. The delayed payment with the preferred account, will save you about 10 dollars (2000 * 1% interest * 0.5 years). The choice of store might save you more money, though with Apple there are fewer places to get legitimate discounts. Here are your options: How to get the limit increased: You can ask for a temporary increase in the credit limit, or you can ask for a permanent one. Some credit cards can do this online, others require you to talk to them. If they are going to agree to this, it can be done in a few minutes. Some individuals on this site have even been able to send the check to the credit card company before completing the purchase, thus \"\"increasing\"\" their credit limit. YMMV. I have no idea if it works. A good reason to use the existing credit card, instead of the debit card is if the credit card is a rewards card. The extra money or points can be very nice. Just make sure you pay it back before the bill is due. In fact you can send the money to the credit card company the same day the computer arrives in the mail. Having the transaction on the credit card can also get you purchase protection, and some cards automatically extend the warranty.\"",
"title": ""
},
{
"docid": "449131",
"text": "A retail revolving account is a more formal name for a general credit card. A revolving account is an account created by a lender to represent debts where the outstanding balance does not have to be paid in full every month by the borrower to the lender. The borrower may be required to make a minimum payment, based on the balance amount. Retail Revolving Account Wikipedia This is different from something like a car loan or mortgage or other more structured or secured debt. It used to be somewhat common for very large retailers to issue lines of credit to their customers in the form of a store card. This card was a lot like a credit card but only accepted at the specific retailer. These kinds of cards are all but extincted. Now major retailers will simply co-brand a credit card with a major bank, the differentiation being preferred rewards when used at the retailer.",
"title": ""
},
{
"docid": "557199",
"text": "\"I think they gave you the answer: You haven't previously shown that you can run that particular card up to (near) its existing maximum and then pay it off, so they don't have a strong indication that you can handle that large an unsecured loan. Generally, requests to have the limits raised when there isn't evidence that the customer is finding the current limit inconvenient are going to be considered suspicious. Remember, a great credit rating does not require that they consider you a good risk -- it's just one of the things they consider. Why do you need the limit raised? Have you tried contacting the bank's credit department directly and discussing what they will or won't let you do? Re paying off the card every month: Remember, they do get a processing fee from the vendor. They'd prefer that we paid interest (I'm told the term of art for those of us who don't is \"\"deadbeats\"\"), but they certainly don't lose money when we don't. And they'd generally rather have us be loyal customers who MIGHT someday pay interest, and who are bringing in fees, than have us go elsewhere.\"",
"title": ""
},
{
"docid": "266952",
"text": "\"As a rule of thumb, go in the order of proximity to the transaction. This would typically mean: Side note: I own a website that provides an online service that accepts PayPal and credit cards (via PayPal), and I personally have experience with all 3 of the above options. I can tell you from the merchant's point of view that I would also prefer the same order. I've had people contact my customer service department asking for a refund and we always immediately comply. Some people never contact us and just file a dispute directly with PayPal, and although refunding through the PayPal dispute is just as easy as refunding directly, it always makes me ask, \"\"Why didn't they just contact us first?\"\" One time we had a customer skip us and PayPal, and filed a dispute directly with their Credit Card. The CC company contacted PayPal and PayPal contacted us. The process was the same from my point of view, I just clicked a button saying issue refund. But my $5 refund cost me an additional $20 due to the CC dispute. Now that I know this I will never approve a CC dispute again. Anytime one happens I would just issue a refund directly, and then notify the dispute that their CC has already been refunded, which should end the dispute.\"",
"title": ""
},
{
"docid": "454412",
"text": "Unless a study accounts for whether the users are following a budget or not, it is irrelevant to those who are trying to take their personal finances seriously. I can certainly believe that those who have no budget will spend more on a credit card than they will on a debit card or with cash. Under the right circumstances spending with cards can actually be a tool to track and reduce spending. If you can see on a monthly and yearly basis where all of your money was spent, you have the information to make decisions about the small expenses that add up as well as the obvious large expenses. Debit cards and credit cards offer the same advantage of giving you an electronic record of all of your transactions, but debit cards do not come with the same fraud protection that credit cards have, so I (and many people like me) prefer to use credit cards for security reasons alone. Cash back and other rewards points bolster the case for credit cards over debit cards. It is very possible to track all of your spending with cash, but it is also more work. The frustration of accounting for bad transcriptions and rechecking every transaction multiple times is worth discussing too (as a reason that people get discouraged and give up on budgeting). My point is simply that credit cards and the electronic records that they generate can greatly simplify the process of tracking your spending. I doubt any study out there accounts for the people who are specifically using those benefits and what effect it has on their spending.",
"title": ""
},
{
"docid": "486419",
"text": "\"You don't need to have a bunch of credit cards lying around; just a couple is fine. Get a \"\"rewards\"\" card (without annual fee) that pays you back for use, and use it regularly to buy groceries, for example. Pay it off promptly each month, using the rewards, if you like, to reduce the amount you have to send in. Or you can use the rewards for other purchases; some merchants offer $25 worth of merchandise for $20 in rewards. It used to be the case that you could negotiate a discount for paying cash rather than use a credit card, but that is a lot harder to do now, in many cases because credit-card company contracts with merchants prohibit this practice. Also, merchants often prefer credit cards rather than cash because money-handling is an issue (pay for an armored car to come pick up the day's receipts, or risk getting mugged on the way to the bank, possible burglaries if you leave the money overnight in the store, daily balancing of cash-register trays, etc.) So, not being in debt and being rich enough to not need to be in debt are laudable goals, and you have my best wishes that you will reach them soon, but getting rid of all your credit cards as a part of not being in debt may be more trouble than it is worth. Keep a couple, pay them off promptly, and if you are concerned about being in debt, you can time your charges so that you are in debt at most 2 or 3 days each month.\"",
"title": ""
},
{
"docid": "483441",
"text": "If you keep going over budget with your credit card, then stop using the credit card. If you plan to pay off the card every month, then your balance should always be under whatever your budget is. For example, if you budget to spend $500, then even though your card has a limit of $5,000 you will never carry a balance of over $500. Most banks have an option to email and / or text message you when you pass a certain balance threshold; in this instance, you would set two notices, one when your balance exceeds $400 (warning you that you're close & need to start paying closer attention), and one when you exceed $500. Additionally, maybe you aren't ready to pay for everything with your credit card. I prefer to use mine just for groceries, and then pay it off at the end of the month. Whatever rewards you get for putting all of your purchases on the card are more than paid for when you cross your budget limit, costing you more in interest and fees. Perhaps starting with just one type of purchase (groceries or gas are good choices, as most consumers are fairly consistent in their purchases of both) would allow you to ease into using the card until you get used to managing your budget with it. Personal finances are all about behavior, not knowledge. Don't worry too much about slipping up right now and making a mistake; just keep practicing good behavior with your credit card, and soon managing your budget with it will be as natural for you as when you only used cash.",
"title": ""
},
{
"docid": "265427",
"text": "> Next time you call your bank (or credit card company), ask them some pointed questions: Do you have a financial or data sharing agreement with Equifax? If so, why? Next time you are deciding WHICH bank to use, preferably for a significant relationship (ie million dollar + loan, business relationship, etc), you ask them then. A bank teller has no power. If you are already a customer, they don't care. No one gets bonuses for customer retention, bonuses are for new business. That's when people will care about your questions.",
"title": ""
},
{
"docid": "89161",
"text": "\"You ask about the difference between credit and debit, but that may be because you're missing something important. Regardless of credit/debit, there is value in carrying two different cards associated with two different accounts. The reason is simply that because of loss, fraud, or your own mismanagement, or even the bank's technical error, any card can become unusable for some period of time. Exactly how long depends what happened, but just sending you a new card can easily take more than one business day, which might well be longer than you'd like to go without access to any funds. In that situation you would be glad of a credit card, and you would equally be glad of a second debit card on a separate account. So if your question is \"\"I have one bank account with one debit card, and the only options I'm willing to contemplate are (a) do nothing or (b) take a credit card as well\"\", then the answer is yes, take a credit card as well, regardless of the pros or cons of credit vs debit. Even if you only use the credit card in the event that you drop your debit card down a drain. So what you can now consider is the pros and cons of a credit card vs managing an additional bank account -- unless you seriously hate one or more of the cons of credit cards, the credit card is likely to win. My bank has given me a debit card on a cash savings account, which is a little scary, but would cover most emergencies if I didn't have a credit card too. Of course the interest rate is rubbish and I sometimes empty my savings account into a better investment, so I don't use it as backup, but I could. Your final question \"\"can a merchant know if I give him number of debit or credit card\"\" is already asked: Can merchants tell the difference between a credit card and embossed debit card? Yes they can, and yes there are a few things you can't (or might prefer not to) do with debit. The same could even be said of Visa vs. Mastercard, leading to the conclusion that if you have a Visa debit you should look for a Mastercard credit. But that seems to be less of an issue as time goes on and almost everywhere in Europe apparently takes both or neither. If you travel a lot outside the EU then you might want to be loaded down with every card under the sun, and three different kinds of cash, but you'd already know that without asking ;-)\"",
"title": ""
},
{
"docid": "58005",
"text": "Your practice of waiting until you can pay cash is a good one. It will certainly prevent you from getting into debt! Now, to be clear, your question puts a credit card in the same category as a loan, but it doesn't have to be. You could use a credit card almost like cash, if you are careful. I'm not familiar with the system in France, but in the US, even if you are paying cash all the time, there are some benefits to getting a credit card and paying it off in full every month, instead of simply paying with cash. Some of those benefits are: One pretty big downside of having a credit card depends on your personality. Some people, once they have credit, end up spending beyond their means, and end up getting into debt. Please look into whether credit cards work the same way in France before considering the above advice. As for your question regarding getting a loan vs paying cash, that will usually be personal preference, since with a loan you can buy expensive items (such as a house or car) much sooner than you otherwise could if you waited until you saved the money. For example, it might take 10 years or more to build up enough money to purchase a house with cash, so if you don't want to wait that long, you'll need to finance it.",
"title": ""
},
{
"docid": "361836",
"text": "You could conceivably open a few accounts. For example, a bank account and a credit card account. Then the accounts will be older when evaluated for credit when you return. This would look better than opening fresh accounts later. But don't expect a big difference in score. And you'll be stuck with those accounts in the future, otherwise you lose the benefit. I wouldn't worry about maintaining balances now. You can wait until you come back. Occasional purchases may be helpful. What they really want to see is a regular and sustained use of accounts without missing payments or overextending. But if you're not going to be here, you can't really do that. Note that good credit scores are based on seven years of data, preferably a lot of it. Opening a few accounts can't substitute for that, even if you put balances on them. If you're not here, you won't be paying rent or utilities. You won't have a proven payment history on the most common accounts. If money were no object, you could do something like purchase a house or condo that you could rent out, utilities included. That would build up a payment history. But if money were no object, you probably wouldn't be worried about your credit score. It's more practical to just live normally and be sure that you always live within your means so that you don't experience negative credit events. You might think about why you want a good credit score. Is it to borrow a lot of money? You might be able to spend money to achieve that. Is it to save money on future borrowing? If it costs money now, how much will you save total? Opening accounts now that you won't really use until you return is about the only thing that you can do that won't cost you money. Perhaps put a balance on the bank account--at least you'll get that money back some day. Maintaining a balance on the credit cards would cost you money in interest charges, and you don't really benefit from an improved credit score until you use your credit. So the interest fees aren't really buying you anything.",
"title": ""
},
{
"docid": "138645",
"text": "\"These are two different ways of processing payments. They go through different systems many times, and are treated differently by the banks, credit card issuers and the stores. Merchants pay different fees on transactions paid by debit cards and by credit cards. Debit transactions require PIN, and are deducted from your bank account directly. In order to achieve that, the transaction has to reach the bank in real time, otherwise it will be declined. This means, that the merchant has to have a line of communications open to the relevant processor, that in turn has to be able to connect to the bank and get the authorization - all that while on-line. The bank verifies the PIN, authorizes the transaction, and deducts the amount from your account, while you're still at the counter. Many times these transactions cannot be reversed, and the fraud protections and warranties are different from credit transactions. Credit transactions don't have to go to your card issuer at all. The merchant can accept credit payment without calling anyone, and without getting prior authorizations. Even if the merchant sends the transaction for authorization with its processor, if the processor cannot reach the issuing bank - they can still approve the transaction under certain conditions. This is, however, never true with debit cards (even if used as \"\"credit\"\"). They're not deducted from your bank account, but accumulated on your credit card account. They're posted there when the actual transaction reaches the card issuer, which may be many days (and even many months) after the transaction took place. Credit transactions can be reversed (in some cases very easily), and enjoy from a higher level of fraud protection. In some countries (and most, if not all, of the EU) fraudulent credit transactions are never the consumer's problem, always the bank's. Not so with debit transactions. Banks may be encouraging you to use debit for several reasons: Merchants will probably prefer credit because: Consumers will probably be better off with credit because:\"",
"title": ""
},
{
"docid": "9814",
"text": "\"Ever wonder why certain businesses won't accept certain credit cards? (The sign above the register saying \"\"Sorry, we don't accept AmericanExpress\"\"). It's because they don't want to pay that credit card company's transaction fees. One of the roles of the credit card company is to facilitate the transaction process between the customer (you) and the store. And now that using credit cards over cash or check is so ingrained in our culture, it creates extra work for the customer to make purchases at an establishment that is cash-only. Credit card companies know this, and so do businesses. So businesses will partner with credit card companies so that customers can use their cards. This way, everything is handled electronically (this can also benefit the business, since there's added security as they're not dealing with cash directly, and they don't have to manually count as much cash later). However a business may only budget a certain amount of their profits they want taken by credit card transactions. So if a company's fees are too high (say AmericanExpress, for example) and they are banking on you already having a Visa card, the company isn't going to go out of its way to provide the AmericanExpress option for you. If it were free for the business to use a credit card company's service at their stores, then they would all just provide the option for every card! So the credit card company making money is all contingent on you spending your money by using their credit card. You use the card, and the store pays the company for the transaction.\"",
"title": ""
},
{
"docid": "195207",
"text": "Do you have a separate bank account for your business? That is generally highly recommended. I have a credit card for my single-member LLC. I prefer it this way because it makes the separation of personal and business expenses very clear. Using a personal credit card, but using it for only business expenses seems to be a reasonable practice. You may be able to do one better though... For your sole proprietorship, you can file a DBA which establishes the business name. The details of this depend on your state. With a DBA, I believe you can open a bank account in the name of your business and you may also be able to open a credit card account in the name of the business. I'm not sure what practical difference it makes, but it does make the personal/business distinction clearer. Though, at that point, you might as well just do the LLC...",
"title": ""
},
{
"docid": "271472",
"text": "\"I have some experience with this. I have had fraudulent charges appear on my credit card statement and had to change my card number several times, despite (I believe) no carelessness on my part. Every time that this has happened, I have never lost a penny due to fraud on my credit card. The bank has ultimately removed the fraudulent charges in every instance. Given this, you'd think the consumer doesn't need to worry about this at all. But it seems like credit card companies beg to differ. Yes, because although I have never lost a penny to fraud, the bank (or the merchant) loses money every time it happens. The $0 liability protects you; the card security measures protect the bank. But... why should a consumer ever bother worrying about these in the first place, when he knows he legally can't be held responsible for fraudulent charges? What exactly is this new \"\"peace of mind\"\" that he supposedly gets by (say) using features like virtual account numbers that he doesn't already have? Although you shouldn't end up out any money when this happens, it is an inconvenience. The bank will cancel your card and issue you a new number. It may take a few days for you to receive your new card. If you have another card to use, this isn't a big deal. If you are out of state the day before you need to check out of a hotel and return a rental car with no backup credit card (as I have been), it is a big deal. (In my case, I had to have the credit card company talk to the hotel to give them the new card number, and they were able to overnight me a new credit card so I could get home. I now make sure I carry a backup credit card.) Should a consumer put any effort into worrying about this at all? (Why?) In my opinion, it makes sense to be careful what you do with your credit card number, if only to avoid the inconvenience. Don't type your credit card number into an e-mail message, for example, and only use it on websites that you trust. That having been said, it is not worth it to be paranoid about it, either. No matter how careful you are, eventually you will probably use it at a store that gets hacked, or your card will get skimmed somewhere, and you'll need to get a new credit card number. The best way to protect yourself is to make sure that you go over your credit card statement each month and look for any fraudulent charges that the bank didn't catch.\"",
"title": ""
},
{
"docid": "123549",
"text": "The question should be - do you need a debit card? Other than American Express I have to tell my other credit card issuers to not make my cards dual debit/credit. Using a debit card card can be summed up easily - It creates a risk of fraud, errors, theft, over draft, and more while providing absolutely no benefit. It was simply a marketing scheme for card companies to reduce risk that has lost favor, although they are still used. That is why banks put it on credit cards by default if they can. (I am talking about logical people who can control not overspending because of debit vs. credit - as it is completely illogical that you would spend more based on what kind of card you have.)",
"title": ""
},
{
"docid": "326094",
"text": "\"Yes, it can be a good idea to close unused credit cards. I am going to give some reasons why it can be a good idea to close unused accounts, and then I will talk about why it is NOT necessarily a bad idea. Why it can be a good idea to close unused accounts \"\"I'd like to close the cards.\"\" That is reason enough. Simplifying your financial life is a good thing. Fewer accounts let you focus your energy on the accounts that you actually use. Unused accounts still need to be monitored for fraud. You mentioned that you have high credit card balances that you are carrying. This may indicate that you have trouble using credit responsibly, and having more credit available to you might be a temptation for you. If these unused cards have annual fees, keeping them open will cost money. Unused cards sometimes get closed by the bank due to inactivity. As a result, the advice often given is that, in addition to not closing them, you are supposed to charge something to it every month. This, of course, takes more of your time and energy to worry about, as well as giving you another monthly bill to pay. Why it is NOT necessarily a bad idea to close unused accounts Other answers will tell you that it may hurt your credit score for two reasons: it would increase your utilization and lower your average account age. Before we talk about the validity of these two points, we need to discuss the importance of the credit score. Depending on what your credit score currently is, these actions may have minimal impact on your life. If you are in the mid 700's or higher, your score is excellent, and closing these cards will likely not impact anything for you in a significant way. If you aren't that high in your score yet, do you have an immediate need for a high score? Are you planning on getting more credit cards, or take out any more loans? I would suggest that, since you have credit card debt, you shouldn't be taking out any new loans until you get that cleaned up. So your score in the mean time is not very important. Are you currently working on eliminating this credit card debt? If so, your utilization number will improve, even after you close these accounts, when you get those paid off. Utilization has only a temporary effect on your score; when your utilization improves, your score improves immediately. Your average account age may or may not improve when you close these accounts, depending on how old they are compared to the accounts you are leaving open. However, the impact of this might not be as much as you think. I realize that this advice is different from other answers, or other things that you may read online. But in my own life, I do a lot of things that are supposedly bad for the credit score: I only have two credit cards, ages 2.5 and 1.5 years. (I closed my other cards when I got these.) My typical monthly utilization is around 25% on these cards, although I pay off the balance in full each month, never paying interest. I have no car loan anymore, and my mortgage is only 4 months old. No other debt. Despite those \"\"terrible\"\" credit practices, my credit score is very high. Conclusion Make your payments on time, get out of debt, and your score will be fine. Don't keep unwanted accounts open just because someone told you that you should.\"",
"title": ""
},
{
"docid": "502781",
"text": "My reason for not using direct debit is #4 on Dheer's list. I just don't know where exactly I'm going to have what balance on what day, because I usually don't leave more than $100-$200 on my checking, all my cash is in Savings. I also don't want to direct debit from Savings in order to not break the 6-withdrawals limit accidentally. I use direct debit to my credit card where its available, but most places charge for that and I don't want to pay the extra fee. So, I prefer to pay my bills manually. What I don't understand is the people who pay the credit card bills when the statement arrives. I haven't received a credit card statement in years. Don't they have on-line access? Can't they set reminders there? If so - throw the card away, and get a normal one. Same with mailing checks, by the way. I'm still not even half done with the free checks I got from Washington Mutual 5 years ago. I almost never write checks. All the bills are paid online, whether through bill-pay service or an ACH transfer.",
"title": ""
},
{
"docid": "219181",
"text": "Because even if you won the lottery, without at least some credit history you will have trouble renting cars and hotel rooms. I learned about the importance, and limitations of credit history when, in the 90's, I switched from using credit cards to doing everything with a debit card and checks purely for convenience. Eventually, my unused credit cards were not renewed. At that point in my life I had saved a lot and had high liquidity. I even bought new autos every 5 years with cash. Then, last decade, I found it increasingly hard to rent cars and sometimes even a hotel rooms with a debit card even though I would say they could precharge whatever they thought necessary to cover any expenses I might run. I started investigating why and found out that hotels and car rentals saw having a credit card as a proxy for low risk that you would damage the car or hotel room and not pay. So then I researched credit cards, credit reports, and how they worked. They have nothing about any savings, investments, or bank accounts you have. I had no idea this was the case. And, since I hadn't had cards or bought anything on credit in over 10 years there were no records in my credit files. Old, closed accounts had fallen off after 10 years. So, I opened a couple of secured credit cards with the highest security deposit allowed. They unsecured after a year or so. Then, I added several rewards cards. I use them instead of a debit card and always pay in full and they provide some cash back so I save money compared to just using a debit card. After 4 years my credit score has gone to 800+ even though I have never carried any debt and use the cards as if they were debit cards. I was very foolish to have stopped using credit cards 20 years ago but just had no idea of the importance of an established credit history. And note that establishing a great credit history does not require that you borrow money or take out loans for anything. just get credit cards and pay them in full each month.",
"title": ""
},
{
"docid": "106448",
"text": "If it's feasible, try to get one card down to zero balance, and preferably one of your cash-back cards. Then keep that at zero every month (pay it off in full), and use it for your purchases as you describe above. The idea would be to get it so that you are not paying interest on your month to month purchases. This not only reduces the 20% or whatever that you're paying on that balance, but also the 20% or whatever you're paying on those purchases - remember, a card you carry a balance on charges you interest on those purchases from the current month. If this isn't feasible (if these are all very high balance cards), then I suppose the way you're currently doing it would be okay, though I think you're overthinking things to some extent - but with 80% interest, if that's a significant pile of money, you may need to as clearly that needs to be tackled first. I think it's mostly better for you to pay your day to day stuff out of pocket and not use your cards the way you are suggesting, but with the 80% loan(s) you may need to. The reason I say it's better not to use your card the way you suggest is that it is difficult to do properly and never get it wrong (i.e., never go over a balance), and it's also leaving you in the habit of using credit. It doesn't help you budget necessarily, either. Instead, set up a fully developed budget that includes all of those minimum payments and pay them. Certainly once you have the > 50% debt handled, I would switch to this method (not using credit cards at all).",
"title": ""
},
{
"docid": "44802",
"text": "\"Some features to be aware of are: How you prioritize these features will depend on your specific circumstances. For instance, if your credit score is poor, you may have to choose among cards you can get with that score, and not have much choice on other dimensions. If you frequently travel abroad, a low or zero foreign transaction fee may be important; if you never do, it probably doesn't matter. If you always pay the balance in full, interest rate is less important than it is if you carry a balance. If you frequently travel by air, an airline card may be useful to you; if you don't, you may prefer some other kind of rewards, or cash back. Cards differ along numerous dimensions, especially in the \"\"extra benefits\"\" area, which is often the most difficult area to assess, because in many cases you can't get a full description of these extra benefits until after you get the card. A lot of the choice depends on your personal preferences (e.g., whether you want airline miles, rewards points of some sort, or cash back). Lower fees and interest rates are always better, but it's up to you to decide if a higher fee of some sort outweighs the accompanying benefits (e.g., a better rewards rate). A useful site for finding good offers is NerdWallet.\"",
"title": ""
},
{
"docid": "526106",
"text": "\"It is called \"\"Credit card installments\"\" or \"\"Equal pay installments\"\", and I am not aware of them being widely used in the USA. While in other countries they are supported by banks directly (right?), in US you may find this option only in some big stores like home improvement stores, car dealerships, cell phone operators (so that you can buy a new phone) etc. Some stores allow 0% financing for, say, 12 months which is not exactly the same as installments but close, if you have discipline to pay $250 each month and not wait for 12 months to end. Splitting the big payment in parts means that the seller gets money in parts as well, and it adds risks of customer default, introduces debt collection possibility etc. That's why it's usually up to the merchants to support it - bank does not care in this case, from the bank point of view the store just charges the same card another $250 every month. In other countries banks support this option directly, I think, taking over or dividing the risk with the merchants. This has not happened in US. There is a company SplitIt which automates installments if stores want to support it but again, it means stores need to agree to it. Here is a simple article describing how credit cards work: https://www.usbank.com/credit-cards/how-credit-cards-work.html In general, if you move to US, you are unlikely to be able to get a regular credit card because you will not have any \"\"credit history\"\" which is a system designed to track each customer ability to get & pay off debt. The easiest way to build the history - request \"\"secured credit card\"\", which means you have to give the bank money up front and then they will give you a credit card with a credit limit equal to that amount. It's like a \"\"practice credit card\"\". You use it for 6-12 months and the bank will report your usage to credit bureaus, establishing your \"\"credit score\"\". After that you should be able to get your money back and convert your secured card into a regular credit card. Credit history can be also built by paying rent and utilities but that requires companies who collect money to report the payments to credit bureaus and very few do that. As anything else in US, there are some businesses which help to solve this problem for extra money.\"",
"title": ""
},
{
"docid": "477853",
"text": "\"I would think it extremely unlikely that an issuer would cancel your card for having an ADB of approximately zero. The issuer charges the vendor that accepts a card a percentage of the transaction (usually up to ~3%, AMEX is generally higher) - so they are making money even if you carry no balance on your card (the specific language for various vendor-side (acceptor) credit card agreements boils down to \"\"we are essentially giving you, the vendor, a short-term loan and you will pay us for it). This why you see credit-card minimum purchase amounts at places like hot-dog stands - they're getting nailed on the percentage. This is also why, when given the choice between \"\"Debit or Credit\"\" for a particular card, I choose where to put the hit on the company I like less - the retailer or the bank.\"",
"title": ""
},
{
"docid": "85252",
"text": "\"In this answer, I won't elaborate on the possibilities of fraud (or pure human error), because something can always go wrong. I will, however, explain why I think you should always keep receipts. When the (monthly or so) time comes to pay your credit card bill, your credit card company sends you a list of transactions. That list has two primary purposes, both of which I would consider equally important: While for the former item, a receipt is not necessary (though it certainly does not hurt showing the receipt along with the bill to provide further proof that the payment was indeed connected to that bill), the latter point does require you to store the receipts so you can check, item-by-item, whether each of the sums is correct (and matched with a receipt at all). So, unless you can actually memorize all the credit card transactions you did throughout the past one or two months, the receipts are the most convenient way of keeping that information until the bill arrives. Yes, your credit card company probably has some safeguards in place to reveal fraud, which might kick in in time (the criteria are mostly heuristical, it seems, with credit cards or legitimate transactions here getting blocked every now and then simply because some travelling of the actual owner was misinterpreted as theft). However, it is your money, it is your responsibility to discover any issues with the bill, just as you would check the monthly transaction list from your bank account line by line. Ultimately, that is why you sign the vendor copy of the receipt when buying something offline; if you discover an issue in your list of transactions, you have to notify your credit card company that you dispute one of the charges, and then the charging vendor has to show that they have your signature for the respective transaction. So, to summarize: Do keep your receipts, use them to check the list of transactions before paying your credit card bill. EDIT: The receipt often cannot be replaced with the bill from the vendor. The bill is useful for seeing how the sum charged by the respective vendor was created, but in turn, such bills often do not contain any payment information, or (when payment was concluded before the bill was printed, as sometimes happens in pre-paid scenarios such as hotel booking) nondescript remarks such as \"\"- PAYMENT RECEIVED -\"\", without any further indication of which one of your credit cards, debit cards, bank accounts, stored value cards, or cash was used.\"",
"title": ""
},
{
"docid": "244133",
"text": "I've used PayPal for my business for a long time. Sometimes PayPal doesn't trust credit cards. Debit or direct bank transfer are reliable. There is also a charge for using a credit card but I don't think that is the reason. You may be trying to purchase a high value item. That would be a possible reason why PayPal allowed you to use credit cards in the past, but will not allow you to do so now, for these particular transactions.",
"title": ""
}
] |
139393
|
David Thewlis is an actor from England.
|
[
{
"docid": "David_Thewlis",
"text": "David Thewlis ( born David Wheeler ; born 20 March 1963 ) is an English actor , director , screenwriter , author . His most commercially successful role to date has been that of Remus Lupin in the Harry Potter film series . Other notable performances include the films Naked ( for which he won the Best Actor award at Cannes Film Festival ) , Dragonheart , Kingdom of Heaven , The Boy in the Striped Pyjamas , The Theory of Everything , Black Beauty , and Macbeth ( in which he played King Duncan ) . He will play Ares in Wonder Woman . He has also done voice work in the films James and the Giant Peach ( 1996 ) , The Miracle Maker ( 2000 ) , and Anomalisa ( 2015 ) , and is additionally known for the role of Cyrus Crabb in the TV mini series Dinotopia .",
"title": ""
}
] |
[
{
"docid": "David_Wheeler",
"text": "David Wheeler may refer to : David Wheeler ( actor ) ( active since 1990 ) , American television actor David Wheeler ( British computer scientist ) ( 1927 -- 2004 ) , British computer scientist David Wheeler ( footballer ) ( born 1992 ) , English footballer David Wheeler ( stage director ) ( c. 1925 -- 2012 ) , American director of theatre and film David A. Wheeler ( born 1965 ) , programmer and author David H. Wheeler ( 1829 -- 1902 ) , American academic , newspaperman and college president ; US ambassador to Italy David Thewlis ( David Wheeler , born 1963 ) , English actor and writer",
"title": ""
},
{
"docid": "Naked_(1993_film)",
"text": "Naked is a 1993 British black comedy-drama film written and directed by Mike Leigh and starring David Thewlis as Johnny , a motor-mouthed intellectual and conspiracy theorist . Stark and brutal in tone , Naked was a departure for Leigh , whose previous works were known for their subtle comedic dissections of middle-class and working-class manners . Leigh 's Naked screenplay relied heavily on lengthy improvisation during rehearsals , but little actual ad-libbing was filmed . Critically acclaimed , the film won a number of awards , including best director and best actor at Cannes . Naked marked a new career high for Leigh as a director and made the then-unknown Thewlis an internationally recognized star .",
"title": ""
},
{
"docid": "The_Late_Hector_Kipling",
"text": "The Late Hector Kipling is a novel written by English actor David Thewlis . The book was released in the UK in hardback on September 7 , 2007 and released on paperback July 4 , 2008 . In the US the book was released ( hardback version ) November 6 , 2007 .",
"title": ""
},
{
"docid": "The_Trial_(1993_film)",
"text": "The Trial is a 1993 film made by the British Broadcasting Corporation ( BBC ) based on Harold Pinter 's screenplay adaptation of Franz Kafka 's 1925 novel The Trial . Directed by David Jones and produced by Jan Balzer and Louis Marks , the film stars Kyle MacLachlan and has cameo appearances by several prominent British actors including Anthony Hopkins , Juliet Stevenson , Alfred Molina , David Thewlis , and Michael Kitchen . The film was shot in Prague and Kutná Hora .",
"title": ""
},
{
"docid": "John_Thewlis_junior",
"text": "John Thewlis junior ( 21 September 1850 -- 9 August 1901 ) was an English first-class cricketer , who played three matches for Yorkshire County Cricket Club in 1876 . Born in Lascelles Hall , Huddersfield , Yorkshire , England , Thewlis was a right-handed batsman , who hit 21 runs at 5.25 , with a best of ten against the MCC . His right and round-arm bowling was never employed in the first-class game . He was of considerable cricketing pedigree , his cousin , Ephraim Lockwood , playing 328 first-class games and a Yorkshire stalwart for many years , while his uncle , John Thewlis Senior , played over fifty matches for the county . Thewlis died in Huddersfield in August 1901 .",
"title": ""
},
{
"docid": "Michael_Thewlis",
"text": "Michael James Thewlis ( born 19 January 1970 ) was an English cricketer . He was a right-handed batsman and a right-arm medium-pace bowler who played for Northumberland . He was born in Ashington . Thewlis made a single List A appearance for the team , in the 1994 NatWest Trophy , against Nottinghamshire . He scored a duck in the match , and took just one wicket , that of former England Test cricketer Tim Robinson . Thewlis continued to play for Northumberland in the Minor Counties Championship until 1998 . He joined West Hertfordshire between 2002 and 2004 , and played for Winchmore Hill between 2005 and 2006 . Thewlis ' father Jim and uncle Joe both played cricket for Northumberland during the 1970s .",
"title": ""
},
{
"docid": "Herbert_Thewlis",
"text": "Herbert Thewlis ( 31 August 1865 -- 30 November 1920 ) was an English first-class cricketer , who played two matches for Yorkshire County Cricket Club in 1888 , against the MCC and Gloucestershire . Yorkshire lost by 103 runs at Lord 's , and drew the game at Clifton College . Born in Lascelles Hall , Huddersfield , Yorkshire , England , Thewlis was a right-handed batsman , who scored only four runs in four innings , one of them not out ( average of 1.33 ) . He took two catches in the field , but did not bowl . Thewlis died in Huddersfield in November 1920 .",
"title": ""
},
{
"docid": "Ares_(DC_Comics)",
"text": "Ares ( also sometimes referred to as Mars or War ) is a fictional character , a supervillain who appears in DC Comics publications and related media . Based upon the Greek mythological figure of the same name , he is the Greek god of war and a major adversary of the super-hero Wonder Woman . The character will make his cinematic debut in Wonder Woman portrayed by actor David Thewlis .",
"title": ""
},
{
"docid": "Malford_W._Thewlis",
"text": "Malford Wilcox Thewlis ( December 4 , 1889 -- June 3 , 1956 ) was an American physician and pioneer of gerontology , who co-founded the American Geriatrics Society in 1942 . He is commemorated by the annual Thewlis Lecture on Gerontology and Geriatrics , established at the University of Rhode Island . As a neuropsychiatrist , he attended US President Woodrow Wilson , following a stroke in 1919 . Thewlis was born on December 4 , 1889 in Wakefield , Rhode Island , the son of James E. Thewlis and Viola ( née Wilcox ) , and received his MD from the Bowdoin Medical School of Maine in 1911 . He married Miss Christiane Cherfils ( 1895 -- 1978 ) of Paris , France on December 10 , 1919 , and they had a son , Harold , who became a professor of politics at University of Rhode Island . Thewlis was one of the few physicians to take note of Ignatz Leo Nascher 's 1914 book , Geriatrics : The Diseases of Old Age and Their Treatment , and devoted his life 's work to care of the elderly and research into the diseases of old age . He authored `` The Care of the Aged : Geriatrics '' , first published in 1919 . Thewlis was also an accomplished amateur magician , and a member of the International Brotherhood of Magicians : he recommended the practice of conjuring tricks to keep the mind and hands supple . He died on June 3 , 1956 and was cremated .",
"title": ""
},
{
"docid": "The_Theory_of_Everything_(2014_film)",
"text": "The Theory of Everything is a 2014 British biographical romantic drama film directed by James Marsh and adapted by Anthony McCarten from the memoir Travelling to Infinity : My Life with Stephen by Jane Wilde Hawking , which deals with her relationship with her ex-husband , theoretical physicist Stephen Hawking , his diagnosis of amyotrophic lateral sclerosis ( ALS , also known as Lou Gehrig 's disease or motor neurone disease ) , and his success in physics . The film stars Eddie Redmayne and Felicity Jones with Charlie Cox , Emily Watson , Simon McBurney , Christian McKay , Harry Lloyd and David Thewlis featured in supporting roles . The film had its world premiere at the 2014 Toronto International Film Festival on 7 September 2014 . The film was acclaimed critically worldwide , with praise for the musical score , cinematography and the performance of Felicity Jones and especially Eddie Redmayne , which earned him nominations for a variety of accolades in award shows and film festivals , including the Academy Award for Best Actor . The film received four Golden Globe Award nominations , winning the Golden Globe Award for Best Actor -- Motion Picture Drama for Redmayne and Best Original Score for Jóhannsson . It received three Screen Actors Guild Awards nominations , winning one for the Screen Actors Guild Award for Outstanding Performance by a Male Actor in a Leading Role for Redmayne . It received 10 British Academy Film Awards nominations and won Outstanding British Film , Best Leading Actor ( for Redmayne ) and Best Adapted Screenplay ( for McCarten ) .",
"title": ""
},
{
"docid": "The_Street_(UK_TV_series)",
"text": "The Street is a British television drama series created by Jimmy McGovern and produced by Granada Television for the BBC . The series follows the lives of various residents of an unnamed street in Manchester and features an all-star cast including Timothy Spall , Jim Broadbent , Jane Horrocks , Bob Hoskins and David Thewlis . The Street won both the British Academy Television Award for Best Drama Series and RTS Television Award for Drama Series twice , in 2007 and 2008 . It also won two International Emmy Awards in November 2007 for Best Drama and Best Actor ( Jim Broadbent ) . The second series was nominated for the Best Drama prize at the 2008 Rose d'Or ceremony . Though it did not win , it received Special Mention from the jury . In November 2010 , the third series won the International Emmy Award for Best Drama and Best Actor ( Bob Hoskins ) . The third series began airing on 13 July 2009 and concluded on 17 August 2009 . This was the final series to be made due to cutbacks at ITV Studios in Manchester ( ITV produced the series , although it is shown by the BBC ) .",
"title": ""
},
{
"docid": "Gangster_No._1",
"text": "Gangster No. 1 ( pronounced Gangster Number One ) is a 2000 British crime drama film directed by Paul McGuigan and starring Paul Bettany in the title role . It also features Malcolm McDowell , David Thewlis and Saffron Burrows . It is based on the play Gangster No. 1 by Louis Mellis and David Scinto .",
"title": ""
},
{
"docid": "Road_(play)",
"text": "Road is the first play written by Jim Cartwright , and was first produced in 1986 . The play explores the lives of the people in a deprived , working class area of Lancashire during the government of Margaret Thatcher , a time of high unemployment in the north of England . Despite its explicit nature , it was considered extremely effective in portraying the desperation of people 's lives at this time , as well as containing a great deal of humour . The play won a number of awards and was voted the 36th best play of the 20th century in a poll by the Royal National Theatre . Set on a road on a busy night , the audience delve into the houses on the street and the characters lives . The play is often performed on a promenade , allowing the audience to follow the narrator ( Scullery ) along the road and visit different sets and the different homes of the characters . The play was initially performed at the Royal Court Theatre `` Upstairs '' , in 1986 with Edward Tudor-Pole as Scullery , moving `` Downstairs '' in 1987 with Ian Dury as the narrator . In 1995 Jim Cartwright directed a production at the Royal Exchange , Manchester with Bernard Wrigley and Matthew Dunster . It was later made for television by renowned director Alan Clarke and starred many young actors who later became well-known including Jane Horrocks , David Thewlis , Moya Brady and Lesley Sharp . Road was produced in New York by Lincoln Center Theater at La MaMa Etc. in 1988 , with a cast including Joan Cusack and Kevin Bacon .",
"title": ""
},
{
"docid": "Josh_Thewlis",
"text": "Josh Thewlis ( born 20 July 1984 ) is a former Australian rules footballer who played with Sydney in the Australian Football League ( AFL ) . Originally from the Victorian country town of Donald , Thewlis played with the Bendigo Pioneers in the elite junior championship the TAC Cup before being drafted at number 50 by Sydney at the 2002 AFL Draft . Thewlis made his senior debut against in the 2004 AFL season . He only played two games for Sydney , before he was delisted at the end of the 2004 season . However , he was recruited in the 2005 Rookie Draft by , but did not make his senior debut for them before he was delisted at the end of the 2005 season . After leaving the AFL , he continued to play football for South Adelaide in the South Australian National Football League , where he was included in the SANFL Team of the Year in 2011 .",
"title": ""
},
{
"docid": "The_Short_and_Curlies",
"text": "The Short and Curlies is a 1987 short film written and directed by Mike Leigh . It stars Alison Steadman , Wendy Nottingham , Sylvestra Le Touzel and David Thewlis . The hairdressers ` Cynthia 's ' was in Willesden and exterior locations were in nearby Harlesden . Channel Four put up money for the film and , pending the success of this project , agreed to co-produce with Portman Productions Leigh 's first feature film since Bleak Moments -- what became 1988 's feature movie High Hopes ( with music by Rachel Portman ) . The short , 18-minute film , made after three weeks of rehearsal , concerns a chatty hairdresser , Betty ( Alsion Steadman ) , her shy daughter , Charlene ( Wendy Nottingham ) , and one of her customers , Joy ( Sylvestra Le Touzel ) . Joy works in a chemist 's shop and is chatted up by Clive ( David Thewlis , in the first of his three Leigh roles ) over the Durex counter . `` On the one hand there is ritual , physical indignity , rubber , prevention ; on the other , new life , love , marriage . Charlene slips sadly and silently between two stools ... ''",
"title": ""
},
{
"docid": "Besieged_(film)",
"text": "Besieged ( Italian title : L'assedio ) is a 1998 film by Bernardo Bertolucci starring Thandie Newton and David Thewlis . The film is based on the short story `` The Siege '' by James Lasdun .",
"title": ""
},
{
"docid": "Divorcing_Jack",
"text": "Divorcing Jackmay refer to : Divorcing Jack ( novel ) , a 1994 novel by Colin Bateman Divorcing Jack ( film ) , a 1998 film , based on the novel , starring David Thewlis",
"title": ""
},
{
"docid": "Jonathan_Woodhouse",
"text": "Jonathan Woodhouse ( born 1987 ) is a British actor , director and producer . Woodhouse was born in London and attended school and college in the London Borough of Newham . He is of English and Filipino descent . He studied for a Master of Arts in Theatre at Royal Holloway , University of London before founding Encompass Productions , an artistic production company . He directed and produced Encompass ' first major project ` What It Feels Like ' , a new play that premiered at the 2011 Edinburgh Fringe festival to critical acclaim . His first major acting role was in the film The Lady directed by Luc Besson , playing ` Alexander Aris ' , the eldest son of Burmese opposition leader Aung San Suu Kyi ( played by Michelle Yeoh ) and Michael Aris ( David Thewlis ) . He is currently working in London on a number of theatre and short film projects .",
"title": ""
},
{
"docid": "David_Butler",
"text": "David Butler may refer to : David Butler ( Nebraska governor ) ( 1829 -- 1891 ) , American politician , governor of state of Nebraska David Butler ( basketball , born 1966 ) , UNLV Runnin ' Rebels basketball player who also played professionally Dave Butler ( basketball , born 1964/1965 ) , California Golden Bears basketball player who also played professionally David Butler ( director ) ( 1894 -- 1979 ) , American filmmaker , screenwriter and actor David Butler ( footballer , born 1945 ) , professional footballer in England David Butler ( footballer , born 1953 ) , professional footballer in England and the United States David Butler ( footballer , born 1962 ) , professional footballer in England David Butler ( general ) ( born 1928 ) , Australian Army officer Sir David Butler ( psephologist ) ( born 1924 ) , British social scientist and psephologist David Butler ( screenwriter ) ( 1927 -- 2006 ) , British writer of screenplays and teleplays David Butler ( author ) ( born 1964 ) , Irish author , playwright and poet David Butler ( hurler ) ( born 1992 ) , Irish hurler David Butler ( actor ) , silent film actor in Private Affairs ( 1925 film ) and others",
"title": ""
},
{
"docid": "Regression_(film)",
"text": "Regression is a 2015 Canadian-Spanish-American psychological thriller horror film directed , produced and written by Alejandro Amenábar . The film stars Ethan Hawke and Emma Watson with David Thewlis , Lothaire Bluteau , Dale Dickey , David Dencik , Peter MacNeill , Devon Bostick and Aaron Ashmore . The film had its world premiere at the San Sebastián International Film Festival on September 18 , 2015 .",
"title": ""
},
{
"docid": "A_Bit_of_a_Do",
"text": "A Bit of a Do is a British comedy-drama series based on the books by David Nobbs . The show starred David Jason and Gwen Taylor . It was produced by Yorkshire Television for two series and aired on the ITV network from 13 January to 1 December 1989 . The show was set in a fictional Yorkshire town . Each episode took place at a different social function and followed the changing lives of two families , the working-class Simcocks ( David Jason , Gwen Taylor , David Thewlis and Wayne Foskett ) and the middle-class Rodenhursts ( Nicola Pagett , Paul Chapman , Sarah-Jane Holm and Nigel Hastings ) , together with their respective friends , Rodney and Betty Sillitoe ( Tim Wylton and Stephanie Cole ) , and Neville Badger ( Michael Jayston ) . The series begins with the wedding of Ted and Rita Simcock 's son Paul to Laurence and Liz Rodenhurst 's daughter Jenny ; an event at which Ted and Liz begin an affair . The subsequent fallout from this affair forms the basis for most of the first series .",
"title": ""
},
{
"docid": "Veronika_Decides_to_Die_(film)",
"text": "Veronika Decides to Die is a 2009 psychological drama film directed by Emily Young and starring Sarah Michelle Gellar , Jonathan Tucker , Melissa Leo , David Thewlis and Erika Christensen , . The film is written by Larry Gross and Roberta Hanley and is adapted from the best-selling novel of the same name by Paulo Coelho . The setting of the movie is New York instead of the original location of the novel in Ljubljana , Slovenia .",
"title": ""
},
{
"docid": "Joe_Thewlis",
"text": "Joseph Thewlis ( 14 April 1939 -- 24 November 2010 ) was an English cricketer and footballer . In cricket , Thewlis was a right-handed batsman who bowled right-arm medium pace . He was born in Percy Main , Northumberland .",
"title": ""
},
{
"docid": "John_Thewlis_senior",
"text": "John Thewlis senior ( 30 June 1828 -- 29 December 1899 ) was an English first-class cricketer , active 1862 -- 75 , who played for Sheffield and Yorkshire . Thewlis was noted as a right-hand batsman with a full range of strokes .",
"title": ""
},
{
"docid": "David_Lodge_(actor)",
"text": "David William Frederick Lodge ( 19 August 1921 in Rochester , Kent , England -- 18 October 2003 in Northwood , Middlesex , England ) was an English character actor .",
"title": ""
},
{
"docid": "Paul_Cartledge_(music_producer)",
"text": "Paul Cartledge is a music producer specializing in media based projects including advertising , television , film , radio and digital . He grew up in the Punk scene in the North West of England , playing in various bands . He was taken under the wing of Tony Visconti , record producer to David Bowie among others , and became the studio manager of Visconti 's ` Good Earth Studios ' in London . There he worked with many rock and pop artists including The Moody Blues , Elaine Paige , Les Rita Mitsouko , The Alarm , Big Audio Dynamite , Paul Oakenfold & Steve Osbourne with Happy Mondays , Captain Sensible , The Jesus and Mary Chain , Hazel O'Connor , Bros , S'Express , Derek B , and Ed Buller . He went on to work for Joe & Co , the music production company owned by Joe Campbell & Paul Hart . He became house engineer and worked with many artists including Pink Floyd , Robert Plant , Dusty Springfield , Jon Secada , Roy Wood , Carl Wayne , Stephanie Lawrence , Ralph McTell , Georgie Fame , Charles Aznavour , Chrissie Hynde , Dead or Alive ; his highest profile engineering credits being on two records , produced by Phil Ramone , for Frank Sinatra . He pioneered ISDN recording techniques and used this in work on film soundtracks , including Steven Zaillian 's ` Searching For Bobby Fischer ' and Henry Selick 's ` James and the Giant Peach ' produced by Tim Burton . Notable actors he has recorded include James Coburn , Sir Robert Stephens , Sir Ben Kingsley , Pete Postlethwaite , and David Thewlis . At the beginning of the 21st century , Cartledge teamed up with Harrison Birtwistle protogé Philip Jewson to compose and produce music for the British cult drama Urban Gothic and has since worked with Jewson on an array of music for media projects . Together they own the Soho-based music production company ` Yellow Boat Music Limited ' . He has kept the connection with Visconti alive recording vocals on a duet ` No Other God ' between Placebo frontman Brian Molko And Kristeen Young , on the latter ' Visconti produced album ` X ' and is mentioned in his autobiography ` Bolan , Bowie and the boy from Brooklyn ' .",
"title": ""
},
{
"docid": "The_Lady_(2011_film)",
"text": "The Lady is a French-British biographical film directed by Luc Besson , starring Michelle Yeoh as Aung San Suu Kyi and David Thewlis as her late husband Michael Aris . Yeoh called the film `` a labour of love '' but also confessed it had felt intimidating for her to play the Nobel laureate .",
"title": ""
},
{
"docid": "David_Holt",
"text": "David or Dave Holt may refer to : David Holt ( American actor ) ( 1927 -- 2003 ) , American actor Dave Holt ( athlete ) ( born 1944 ) , English runner who competed in the 1972 Olympics David Holt ( cricketer ) ( born 1981 ) , Anglo-French cricketer David Holt ( footballer , born 1936 ) , Scottish international footballer David Holt ( footballer , born 1952 ) ( 1952 -- 2003 ) , English professional footballer David Holt ( musician ) ( born 1946 ) , American musician David Holt ( voice actor ) , British voice actor David Eldred Holt ( 1843 -- 1925 ) , American clergyman David Holt ( politician ) ( born 1979 ) , Oklahoma State Senator David Holt ( psychotherapist ) ( born 1926 ) , English psychotherapist David Holt ( bowls ) ( born 1966 ) , England international lawn and indoor bowler",
"title": ""
},
{
"docid": "Dora_Thewlis",
"text": "Dora Thewlis ( 1890 -- 1976 ) was a British suffragette .",
"title": ""
},
{
"docid": "List_of_Harry_Potter_cast_members",
"text": "Several actors of the United Kingdom and Ireland have voiced or portrayed characters appearing in the Harry Potter film series based on the book series by J. K. Rowling . Daniel Radcliffe , Rupert Grint and Emma Watson have played Harry Potter , Ron Weasley and Hermione Granger in all the films . When they were cast only Radcliffe had previously acted in a film . Complementing them on screen are such actors as Helena Bonham Carter , Jim Broadbent , John Cleese , Robbie Coltrane , Warwick Davis , Ralph Fiennes , Michael Gambon , Brendan Gleeson , Richard Griffiths , Richard Harris , John Hurt , Jason Isaacs , Miriam Margolyes , Helen McCrory , Gary Oldman , Alan Rickman , Fiona Shaw , Maggie Smith , Timothy Spall , Imelda Staunton , David Thewlis , Emma Thompson , and Julie Walters , among others . Thirteen actors have appeared as the same character in all eight films of the series . Some well-known British actors , who have not appeared in the series , were asked in jest why they had not been cast . When David Yates was directing the fifth film , Bill Nighy ( who knew Yates personally ) said that he hoped the director would cast him in Harry Potter . `` But nobody called '' , Nighy added . However , in 2009 , Yates cast Nighy as Minister of Magic Rufus Scrimgeour in the seventh film . Nighy said , `` I am no longer the only English actor not to be in Harry Potter and I am very pleased . '' Jude Law once quipped , `` Nobody 's asked me . I was a bit too old for Harry . '' When a reporter compared Potions professor Horace Slughorn 's obsession with famous names to the series ' connection to `` every notable British actor '' in 2009 , Jim Broadbent ( who plays Slughorn ) said , `` Well , not every actor gets invited . I know some who are still waiting . '' J.K. Rowling gave a speech during the world premiere of the final film in the series , Harry Potter and the Deathly Hallows -- Part 2 , on 7 July 2011 in London . Rowling praised the film series ' acting talent and announced that there are seven young Harry Potter cast members who she refers to as `` The Big Seven '' ; they are Daniel Radcliffe , Rupert Grint , Emma Watson , Tom Felton , Matthew Lewis , Evanna Lynch and Bonnie Wright . The list below is sorted by film and character since some characters have been portrayed by multiple actors . <center> Key <center> ( v ) indicates the actor or actress lent only his or her voice for his or her film character ( y ) indicates the actor or actress portrayed the role in a flashback scene or when the character was young . ( f ) indicates the actor or actress did not appear in any new footage for the film ; footage from an earlier film or films was used . A light grey cell ( such as the one in the `` Charity Burbage '' row in the `` Philosopher 's Stone '' column ) indicates the character was not in the film adaptation . __ TOC __",
"title": ""
}
] |
1054
|
Risk of cardiovascular events can be cut by a third by using antihypertensive drug therapy among hemodialysis patients.
|
[
{
"docid": "10072941",
"text": "Epidemiological studies demonstrate that a lower blood pressure and decline in blood pressure over months or years are associated with higher mortality in dialysis patients. In contrast, randomized, controlled trials lack power to establish benefits of antihypertensive therapy. Patients on long-term dialysis participating in randomized, controlled trials and receiving antihypertensive drug therapy were the subject of this meta-analysis. Outcomes assessed were the hazard ratio of cardiovascular events and all-cause mortality in treated group compared with controls. Among 1202 patients who we identified in 5 studies, the overall benefit of antihypertensive therapy compared with the control or placebo group had a combined hazard ratio for cardiovascular events of 0.69 (95% CI: 0.56 to 0.84) using a fixed-effects model and 0.62 (95% CI: 0.45 to 0.86) using a random-effects model. In a sensitivity analysis, we found that the hypertensive group had a pooled hazard ratio of 0.49 (95% CI: 0.35 to 0.67), but when normotensives were included in the trial, lesser cardiovascular protection was seen (pooled hazard ratio of 0.86 [95% CI: 0.67 to 1.12]). Test for heterogeneity between hypertensive and \"normotensive-included\" groups was significant (P<0.006). Similar results were seen for risk ratio for death and cardiovascular events. There was evidence of publication bias based on Egger's test and funnel plot. Randomized trials suggested a benefit of antihypertensive therapy among hemodialysis patients. Adequately powered randomized trials are required to confirm these observations, especially among those with hypertension.",
"title": "Cardiovascular protection with antihypertensive drugs in dialysis patients: systematic review and meta-analysis."
}
] |
[
{
"docid": "40790033",
"text": "BACKGROUND The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease. METHODS ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950. FINDINGS The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group. INTERPRETATION Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent. FUNDING Novartis.",
"title": "Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial."
},
{
"docid": "2522977",
"text": "The main purpose in hypertension treatment is the reduction of cardiovascular disease burden. Among different first-line antihypertensive drug classes, angiotensin-receptor blockers are characterized by their both good effectiveness and tolerability. Furthermore, the interruption of the renin-angiotensin cascade is related with several benefits in target organ protection and cardiovascular prevention. Among different angiotensin-receptor blockers, olmesartan has been examined in several trial of organ protection, showing improvements in several disease markers, such as microinflammation, regression of both plaque volume and vascular hypertrophy, as well as microalbuminuria prevention. Olmesartan has been also widely examined in combination of either hydrochlorothiazide or amlodipine, as well as with both drugs in a single-pill triple combination, showing improvements in antihypertensive efficacy without significant effects on tolerability. This treatment strategy based on a drug with such characteristics and the availability of different types of combinations with other first-line drug classes may represent an effective way for achieving blood pressure control in a majority of hypertensive patients and this could also be related with a better cardiovascular disease prevention.",
"title": "Olmesartan-based therapies: an effective way to improve blood pressure control and cardiovascular protection."
},
{
"docid": "6157837",
"text": "Angiotensin converting enzyme (ACE) inhibitors are now one of the most frequently used classes of antihypertensive drugs. Beyond their utility in the management of hypertension, their use has been extended to the long-term management of patients with congestive heart failure (CHF), as well as diabetic and nondiabetic nephropathies. Although ACE inhibitor therapy usually improves renal blood flow (RBF) and sodium excretion rates in CHF and reduces the rate of progressive renal injury in chronic renal disease, its use can also be associated with a syndrome of “functional renal insufficiency” and/or hyperkalemia. This form of acute renal failure (ARF) most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects. ARF is most likely to occur when renal perfusion pressure cannot be sustained because of substantial decreases in mean arterial pressure (MAP) or when glomerular filtration rate (GFR) is highly angiotensin II (Ang II) dependent. Conditions that predict an adverse hemodynamic effect of ACE inhibitors in patients with CHF are preexisting hypotension and low cardiac filling pressures. The GFR is especially dependent on Ang II during extracellular fluid (ECF) volume depletion, high-grade bilateral renal artery stenosis, or stenosis of a dominant or single kidney, as in a renal transplant recipient. Understanding the pathophysiological mechanisms and the common risk factors for ACE inhibitor–induced functional ARF is critical, because preventive strategies for ARF exist, and if effectively used, they may permit use of these compounds in a less restricted fashion. Under normal physiological conditions, renal autoregulation adjusts renal vascular resistance, so that RBF and GFR remain constant over a wide range of MAPs.1 The intrinsic renal autoregulation mechanism is adjusted by Ang II and the sympathetic nervous system. When renal perfusion pressure falls (as in …",
"title": "Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association."
},
{
"docid": "11254040",
"text": "Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Due to long duration of therapy and concurrent use of multiple second-line drugs, adverse drug events (ADEs) are regarded as the most important clinical consideration in patients undergoing anti-MDR-TB treatment. To evaluate the frequency and type of treatment-related ADEs owing to MDR-TB therapy. The Cochrane Library, MEDLINE, and EMBASE were searched from inception through October 1, 2012, with additional manual search of International Journal of Tuberculosis and Lung Disease. Studies with available ADEs were selected if MDR-TB patients were treated with regimen including second-line drugs. Pooled estimations of incidence for each specific type of ADEs were calculated with 95% confidence intervals using random-effects model. Of the 5346 patients included, 2602 (57.3%) experienced at least 1 kind of ADE. The 3 most common side effects were gastrointestinal disorders (32.1%), ototoxicity (14.6%), and psychiatric disorders (13.2%). Subgroup analyses based on each characteristic (study population, previous tuberculosis treated, human immunodeficiency virus prevalence, and length of treatment) did not show any significant difference between groups. Additionally, among 1519 patients who developed ADEs with available data of impact on MDR-TB therapy, 70.4% required change of MDR-TB treatment. Adverse events were common among MDR-TB cases, occurring in more than half of the cases, with over two-thirds requiring change of anti-MDR-TB treatment. MDR-TB patients should be monitored closely and managed aggressively for side effects during therapy, especially for ototoxicity and psychiatric disorders.",
"title": "Adverse Events Associated With the Treatment of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-analysis."
},
{
"docid": "39368721",
"text": "OBJECTIVE to investigate the role of glucose tolerance in the development of hypertension. DESIGN Retrospective analysis of the results of a health check up in a group of clinically healthy middle aged men in the late 1960s (median year 1968). The subjects were invited to enter into a primary prevention trial for cardiovascular disease in 1974, when they underwent clinical examination for risk factors. The trial was completed in 1979, when the men were re-examined. Follow up was in 1986. SETTING Institute of Occupational Health, Helsinki, Finland and second department of medicine, University of Helsinki. SUBJECTS In all, 3490 men born during 1919-34 participated in a health check up in the late 1960s. In 1974, 1815 of these men who were clinically healthy were entered into a primary prevention trial for cardiovascular disease. On clinical examination 1222 of the men were considered at high risk of cardiovascular disease. Of these, 612 received an intervention and were excluded from the study. A total of 593 men were without risk factors. The study comprised all of the men who did not have an intervention (n = 1203). In 1979, 1120 men were re-examined, and in 1986 945 men attended follow up. There were two groups for analysis: one comprising all subjects and the other comprising only men who were normotensive in 1968 and for whom complete information was available. INTERVENTIONS By 1979, 103 men were taking antihypertensive drugs, and by 1986, 131 were taking antihypertensive drugs and 12 were taking drugs for hyperglycaemia. MAIN OUTCOME MEASURES Blood glucose concentration one hour after a glucose load, blood pressure, and body weight were measured in 1968, 1974, and 1979. In 1986 blood pressure and body weight were recorded. RESULTS Men who were hypertensive in 1986 had significantly higher blood pressures (p less than 0.0001) and (after adjustment for body mass index and alcohol intake) significantly higher blood glucose concentrations one hour after a glucose load at all examinations than those who were normotensive in 1986. Regression analysis showed that the higher the blood glucose concentration after a glucose load in 1968 the higher the blood pressure during the following years. Those men between the second and third tertiles of blood glucose concentration in 1968 had a significantly higher risk of developing hypertension (odds ratio 1.71, 95% confidence interval 1.05 to 2.77) compared with those below the first tertile. CONCLUSION In this study men who developed hypertension tended to have shown an increased intolerance to glucose up to 18 years before the clinical manifestation of their disorder. Blood glucose concentration one hour after a glucose load was an independent predictor of future hypertension.",
"title": "Glucose tolerance and blood pressure: long term follow up in middle aged men."
},
{
"docid": "54490092",
"text": "Blood pressure variability is one of the characteristic features of hypertension in the elderly. However, its clinical significance remains to be determined. We therefore examined the impact of blood pressure variability on the development of cardiovascular events in elderly hypertensive patients. A total of 106 consecutive hypertensive patients aged more than 60 years old (mean age, 73.9 +/- 8.1 years old; male, 54%), all of whom underwent 24-h ambulatory blood pressure monitoring, were followed up (median, 34 months; range, 3-60 months). During the follow-up period, 39 cardiovascular events were observed, including 14 cases of cerebral infarction and 7 cases of acute myocardial infarction. The coefficient of variation (CV) of 24-h systolic blood pressure (SBP) values was used as an index of blood pressure variability. The patients showed a mean CV value of 10.6%, and were divided into two groups according to this mean value as a cut-off point: a high CV group (n = 46) and a low CV group (n = 60). Although baseline clinical characteristics were similar in the two groups, Kaplan-Meier plots for event-free survival revealed that the rate of cardiovascular events was significantly higher in high CV group than in low CV group (p < 0.05). Cox's proportional hazards analysis showed that increased blood pressure variability (a high CV value of 24-h SBP) was an independent predictive variable for cardiovascular events. The CV value of daytime SBP and the SD value of both 24-h SBP and daytime SBP also had positive correlations with the onset of cardiovascular events. These results suggest that increased blood pressure variability may be an independent risk factor for cardiovascular events in elderly hypertensive patients.",
"title": "Impact of blood pressure variability on cardiovascular events in elderly patients with hypertension."
},
{
"docid": "16760369",
"text": "CONTEXT Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear. OBJECTIVE To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors. DESIGN, SETTING, AND PATIENTS Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009. MAIN OUTCOME MEASURES Rates of cardiovascular death, myocardial infarction, and stroke. RESULTS A total of 45,227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15,264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P < .001 for all comparisons). In addition, in multivariable modeling, the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P < .001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P < .001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P < .001) each were associated with a significantly higher risk of the primary end point. CONCLUSION Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.",
"title": "Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis."
},
{
"docid": "11939159",
"text": "IMPORTANCE Among nontraditional cardiovascular risk factors, recent influenzalike infection is associated with fatal and nonfatal atherothrombotic events. OBJECTIVES To determine if influenza vaccination is associated with prevention of cardiovascular events. DATA SOURCES AND STUDY SELECTION A systematic review and meta-analysis of MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013) for randomized clinical trials (RCTs) comparing influenza vaccine vs placebo or control in patients at high risk of cardiovascular disease, reporting cardiovascular outcomes either as efficacy or safety events. DATA EXTRACTION AND SYNTHESIS Two investigators extracted data independently on trial design, baseline characteristics, outcomes, and safety events from published manuscripts and unpublished supplemental data. High-quality studies were considered those that described an appropriate method of randomization, allocation concealment, blinding, and completeness of follow-up. MAIN OUTCOMES AND MEASURES Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for composite cardiovascular events, cardiovascular mortality, all-cause mortality, and individual cardiovascular events. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization. RESULTS Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data. CONCLUSIONS AND RELEVANCE In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.",
"title": "Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis."
},
{
"docid": "10749308",
"text": "Placebo-controlled trials are used extensively in the development of new pharmaceuticals. They are sometimes challenged as unethical in settings in which patients could be treated with an existing therapy (1-7). The issues of when placebo controls are ethically acceptable and when they are scientifically necessary are important and worthy of discussion. The Ethics of Placebo Controls The Declaration of Helsinki The Declaration of Helsinki (8) is an international document that describes ethical principles for clinical investigation. Those who contend that placebo controls are unethical whenever known effective therapy exists for a condition usually cite the following sentence in the Declaration as support for that position: In any medical study, every patientincluding those of a control group, if anyshould be assured of the best proven diagnostic and therapeutic method. We believe that an interpretation of this sentence as barring placebo controls whenever an effective treatment exists is untenable. First, the requirement that all patients receive the best proven diagnostic and therapeutic method would bar not only placebo-controlled trials but also active-control and historically controlled trials. When effective treatment exists, the patient receiving the investigational treatment instead of the established therapy is clearly not getting the best proven treatment. Second, it does not seem reasonable to consider as equivalent all failures to use known effective therapy. Historically, concerns about placebo use have usually arisen in the context of serious illness. There is universal agreement that use of placebo or otherwise untreated controls is almost always unethical when therapy shown to improve survival or decrease serious morbidity is available. But in cases in which the treatment does not affect the patient's long-term health, an ethical imperative to use existing therapy is not plausible. Can it be, for example, that because topical minoxidil or oral finasteride can grow hair, a placebo-controlled trial of a new remedy for baldness is unethical? Is it really unethical to use placebos in short-term studies of drugs for allergic rhinitis, insomnia, anxiety, dermatoses, heartburn, or headaches in fully informed patients? We do not believe that there is a reasonable basis for arguing that such studies and many other placebo-controlled studies of symptom relief are unethical and that an informed patient cannot properly be asked to participate in them. Third, there is good reason to doubt that the cited phrase was intended to discourage placebo-controlled trials. The phrase under discussion was not part of the original 1964 Declaration but was added in 1975 to reinforce the idea that the physicianpatient relationship must be respected just as it would be in a purely therapeutic situation not involving research objectives (8). In the explanation accompanying the 1975 change, the issue of placebo-controlled trials was not even mentioned (9). The American Medical Association (10), the World Health Organization (11), and the Council for International Organizations of Medical Sciences (12) have rejected the position that the Declaration uniformly bars placebo-controlled trials when proven therapy is available. Informed Consent in Placebo-Controlled Trials Patients asked to participate in a placebo-controlled trial must be informed of the existence of any effective therapy, must be able to explore the consequences of deferring such therapy with the investigator, and must provide fully informed consent. Concern about whether consent to participate in trials is as informed as we would like to believe is valid, but these concerns apply as much to the patient's decision to forgo known effective treatment and risk exposure to a potentially ineffective or even harmful new agent in an active-control trial as to a decision to accept possible persistence of symptoms in a placebo-controlled trial. Thus, this problem is not unique to placebo-controlled trials. For the above reasons, we conclude that placebo-controlled trials may be ethically conducted even when effective therapy exists, as long as patients will not be harmed by participation and are fully informed about their alternatives. Although in many cases application of this standard will be fairly straightforward, in others it will not, and there may be debate about the consequences of deferring treatment (13). Assessment of Effectiveness with Active-Control Trials Clinical trials that, because of deficiencies in study design or conduct, are unlikely to provide scientifically valid and clinically meaningful results raise their own ethical concerns (12, 14). The remainder of this paper will address the inability of commonly proposed alternatives to placebo-controlled trials to evaluate the effectiveness of new treatments in many medical settings. Active-Control Equivalence Trials (Noninferiority Trials) The ability to conduct a placebo-controlled trial ethically in a given situation does not necessarily mean that placebo-controlled trials should be carried out when effective therapy exists. Patients and physicians might still prefer a trial in which every participant is given an active treatment. What remains to be examined is why placebo-controlled trials (or, more generally, trials intended to show an advantage of one treatment over another) are frequently needed to demonstrate the effectiveness of new treatments and often cannot be replaced by active-control trials showing that a new drug is equivalent or noninferior to a known effective agent. The limitations of active-control equivalence trials (ACETs) that are intended to show the effectiveness of a new drug have long been recognized and are well described (15-33) but are perhaps not as widely appreciated as they should be. A recent proposed international guideline on choice of control group addresses this issue in detail (33). The Fundamental Problem: Need for Assay Sensitivity There are two distinct ways to show that a new therapy is effective. One can show that the new therapy is superior to a control treatment, or one can show that the new therapy is equivalent to or not worse by some defined amount than a known effective treatment. Each method can be valid, but each requires entirely different inferential approaches. A well-designed study that shows superiority of a treatment to a control (placebo or active therapy) provides strong evidence of the effectiveness of the new treatment, limited only by the statistical uncertainty of the result. No information external to the trial is needed to support the conclusion of effectiveness. In contrast, a study that successfully shows equivalencethat is, little difference between a new drug and known active treatmentdoes not by itself demonstrate that the new treatment is effective. Equivalence could mean that the treatments were both effective in the study, but it could also mean that both treatments were ineffective in the study. To conclude from an ACET that a new treatment is effective on the basis of its similarity to the active control, one must make the critical (and untestable within the study) assumption that the active control had an effect in that particular study. In other words, one must assume that if a placebo group had been included, the placebo would have been inferior to the active control (15-33). Support for this assumption must come from sources external to the trial. Although it might appear reasonable to expect a known active agent to be superior to placebo in any given appropriately designed trial, experience has shown that this is not the case for many types of drugs. The ability of a study to distinguish between active and inactive treatments is termed assay sensitivity. If assay sensitivity cannot be assumed, then even if the new and standard treatments appear virtually identical and the confidence interval for their comparison is exquisitely narrow, the study cannot demonstrate effectiveness of the new drug. (Note that in practice, ACETs are not designed simply to show lack of a statistically significant difference between treatments. Rather, such trials are designed to show noninferioritythat the new treatment is not inferior to the control by more than a specified margin. This approach is described in the Appendix.) The best evidence that an active drug would have an effect superior to that of placebo in a given study would be a series of trials of similar design in which the active drug has reliably outperformed placebo. The ACET thus requires information external to the trial (the information about past placebo-controlled studies of the active control) to interpret the results. In this respect, an ACET is similar to a historically controlled trial. In some settings, such as highly responsive cancers, most infectious diseases, and some cardiovascular conditions, such external information is available and ACETs can and do provide a valid and reliable basis for evaluating new treatments. In many cases, however, the historically based assumption of assay sensitivity cannot be made; for many types of effective drugs, studies of apparently adequate size and design do not regularly distinguish drugs from placebo (16-18, 25, 34). More than 20 years ago, Lasagna (19) described this difficulty particularly well (reflecting long recognition of the problem among analgesiologists): a comparison between new drug and standard is convincing only when the new remedy is superior to standard treatment. If it is inferior, or even indistinguishable from a standard remedy, the results are not readily interpretable. In the absence of placebo controls, one does not know if the inferior new medicine has any efficacy at all, and equivalent performance may reflect simply a patient population that cannot distinguish between two active treatments that differ considerably from each other, or between active drug and placebo. Certain clinical conditions, such as seri",
"title": "Placebo-Controlled Trials and Active-Control Trials in the Evaluation of New Treatments. Part 1: Ethical and Scientific Issues"
},
{
"docid": "6158879",
"text": "BACKGROUND Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38. METHODS AND RESULTS We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05). CONCLUSIONS Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM.",
"title": "Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38."
},
{
"docid": "45447613",
"text": "OBJECTIVE Previous studies have shown increases in ambulatory short-term blood pressure (BP) variability to be related to cardiovascular disease. In this study, we examined whether an angiotensin II type 1 receptor blocker losartan would improve ambulatory short-term BP variability in hypertensive patients on hemodialysis. METHODS Forty hypertensive patients on hemodialysis therapy were randomly assigned to the losartan treatment group (n=20) or the control treatment group (n=20). At baseline and 6 and 12 months after the treatment, 24-h ambulatory BP monitoring was performed. Echocardiography and measurements of brachial-ankle pulse wave velocity (baPWV) and biochemical parameters were also performed before and after therapy. RESULTS After 6- and 12-months of treatment, nighttime short-term BP variability, assessed on the basis of the coefficient of variation of ambulatory BP, was significantly decreased in the losartan group, but remained unchanged in the control group. Compared with the control group, losartan significantly decreased left ventricular mass index (LVMI), baPWV, and the plasma levels of brain natriuretic peptide and advanced glycation end products (AGE). Furthermore, multiple regression analysis showed significant correlations between changes in LVMI and changes in nighttime short-term BP variability, as well as between changes in LVMI and changes in the plasma levels of AGE. CONCLUSION These results suggest that losartan is beneficial for the suppression of pathological cardiovascular remodeling though its inhibitory effect on ambulatory short-term BP variability during nighttime.",
"title": "Effect of losartan on ambulatory short-term blood pressure variability and cardiovascular remodeling in hypertensive patients on hemodialysis."
},
{
"docid": "14121786",
"text": "BACKGROUND Epidemiologic analysis of family data on blood pressure (BP) is often compromised by the effects of antihypertensive medications. A review of numerous clinical trials that investigated the effects of BP-lowering medications is summarized here. METHODS Published clinical trials, including 137 clinical trials with monodrug therapies and 28 clinical trials of combination drug therapies with a total of 11,739 participants, were reviewed from PubMed. Six major classes/groups of antihypertensive medications were categorized by ethnicity, including angiotensin-converting enzyme (ACE) inhibitors, alpha1-blockers, cardioselective beta-blockers (beta1-blockers), calcium channel blockers, thiazide and thiazide-like diuretics, and loop diuretics. RESULTS Using sitting or supine BP, for ethnic groups combined, monodrug therapy with ACE inhibitors showed a weighted average effect of lowering the systolic and diastolic BP by 12.5/9.5 mm Hg; alpha1-blockers by 15.5/11.7 mm Hg; beta1-blockers by 14.8/12.2 mm Hg; calcium channel blockers by 15.3/10.5 mm Hg; thiazide diuretics by 15.3/9.8 mm Hg; and loop diuretics by 15.8/8.2 mm Hg. However, ACE inhibitors, alpha1-blockers, and beta1-blockers were less effective in African Americans than in non-African Americans, whereas calcium channel blockers, thiazide diuretics, and loop diuretics were more effective in African Americans than in non-African Americans. For two-drug combination therapy with ethnic groups combined, the BP-lowering effect of the second medication, when compared to its effect as monodrug therapy, was 84% and 65% for systolic and diastolic BP, respectively. CONCLUSIONS The BP-lowering effects reported here may be used to impute the pretreatment BP levels, which can improve the information content and hence the power of epidemiologic analysis in studies where use of antihypertensive medications is a confounding factor in the BP measurements.",
"title": "A summary of the effects of antihypertensive medications on measured blood pressure."
},
{
"docid": "32463364",
"text": "OBJECTIVES Prevention of cognitive decline and dementia with blood pressure lowering treatments has shown inconsistent results. We compared the effects of different classes of antihypertensive drugs on the incidence of dementia, and on cognitive function. METHODS We conducted a systematic review and included 19 randomized trials (18 515 individuals) and 11 studies (831 674 individuals) analysing the effects of antihypertensive treatment on cognition and on the incidence of dementia, respectively, in hypertensive patients without prior cerebrovascular disorders. Network meta-analysis was used for the comparison of antihypertensive classes. RESULTS Antihypertensive treatment, regardless of the drug class, had benefits on overall cognition [effect size 0.05, 95% confidence interval (CI) 0.02-0.07] and all cognitive functions except language. Antihypertensive treatment reduced the risk of all-cause dementia by 9%, with reference to the control group (hazard ratio 0.91, 95% CI 0.89-0.94), when randomized trials and observationnal studies were combined (n = 15). Result was not significant with randomized trials alone (n = 4). Angiotensin II receptor blockers (ARBs) had larger benefits than placebo on overall cognition (adjusted effect size 0.60 ± 0.18, P = 0.02). ARBs were more effective than β-blockers (0.67 ± 0.18, P = 0.01), diuretics (0.54 ± 0.19, P = 0.04) and angiotensin-converting enzyme inhibitors (0.47 ± 0.17, P = 0.04) in rank. The mean change in blood pressure did not differ significantly between the different antihypertensive drug classes. CONCLUSION Our results support the notion that antihypertensive treatment has beneficial effects on cognitive decline and prevention of dementia, and indicate that these effects may differ between drug classes with ARBs possibly being the most effective.",
"title": "Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis."
},
{
"docid": "10984005",
"text": "CONTEXT More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND PARTICIPANTS Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). MAIN OUTCOME MEASURES Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias. RESULTS During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.",
"title": "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults."
},
{
"docid": "21590125",
"text": "Data of prescribing practices for antipsychotics are of great interest with respect to quality of care. Consequently, we analysed all prescriptions under the statutory health insurance redeemed at pharmacies in Southern Germany between July 1999 and December 2001. The database covers prescriptions for approximately 25 million people. Up to 6% of the population were prescribed an antipsychotic at least once during the study period. Most prescriptions were for conventional antipsychotics and written by non-specialists. Patients receiving second generation antipsychotics were more likely to receive continuous antipsychotic therapy. For a large proportion of patients, antipsychotic polypharmacy, as well as comedication for somatic illnesses, were observed. In particular, drugs for the treatment of cardiovascular and metabolic disorders were frequently co-prescribed. Physicians should consider patients' cardiovascular and metabolic risk profile when making treatment choices. The data suggest that the majority of antipsychotics are used for the treatment of disorders other than schizophrenia. It is important to raise awareness among non-specialists about the indications, efficacy and side-effects of the antipsychotics because these physicians account for the majority of antipsychotic prescriptions.",
"title": "Antipsychotic prescribing patterns in Germany: a retrospective analysis using a large outpatient prescription database."
},
{
"docid": "3578380",
"text": "Importance Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. Objectives To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Design and Setting Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Exposures Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time. Main Outcomes and Measures A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. Results From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near–regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Conclusions and Relevance Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near–regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.",
"title": "Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010"
},
{
"docid": "9498458",
"text": "UNLABELLED Rociletinib is a third-generation EGFR inhibitor active in lung cancers with T790M, the gatekeeper mutation underlying most first-generation EGFR drug resistance. We biopsied patients at rociletinib progression to explore resistance mechanisms. Among 12 patients with T790M-positive cancers at rociletinib initiation, six had T790-wild-type rociletinib-resistant biopsies. Two T790-wild-type cancers underwent small cell lung cancer transformation; three T790M-positive cancers acquired EGFR amplification. We documented T790-wild-type and T790M-positive clones coexisting within a single pre-rociletinib biopsy. The pretreatment fraction of T790M-positive cells affected response to rociletinib. Longitudinal circulating tumor DNA (ctDNA) analysis revealed an increase in plasma EGFR-activating mutation, and T790M heralded rociletinib resistance in some patients, whereas in others the activating mutation increased but T790M remained suppressed. Together, these findings demonstrate the role of tumor heterogeneity when therapies targeting a singular resistance mechanism are used. To further improve outcomes, combination regimens that also target T790-wild-type clones are required. SIGNIFICANCE This report documents that half of T790M-positive EGFR-mutant lung cancers treated with rociletinib are T790-wild-type upon progression, suggesting that T790-wild-type clones can emerge as the dominant source of resistance. We show that tumor heterogeneity has important clinical implications and that plasma ctDNA analyses can sometimes predict emerging resistance mechanisms.",
"title": "Heterogeneity Underlies the Emergence of EGFRT790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor."
},
{
"docid": "195680777",
"text": "BACKGROUND Moderate differences in efficacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could affect treatment choices. We sought any such differences. METHODS We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plus-anthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44,000); one anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide, methotrexate, and fluorouracil (CMF; n=18,000); and polychemotherapy versus no chemotherapy (n=32,000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported. FINDINGS In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided significance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no significant difference (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little affected by age, nodal status, tumour diameter or differentiation (moderate or poor; few were well differentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality differences paralleled breast cancer mortality differences, despite taxane, anthracycline, and other toxicities. INTERPRETATION 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute benefit, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both. FUNDING Cancer Research UK; British Heart Foundation; UK Medical Research Council.",
"title": "Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials."
},
{
"docid": "31942055",
"text": "BACKGROUND Being overweight is often cited as a relative contraindication to peritoneal dialysis. Our primary objective was to determine whether actual mortality rates support this opinion. METHODS Retrospective cohort study of United States Medicare patients initiating dialysis between 1995 and 2000 (N = 418,021; 11% peritoneal dialysis). RESULTS Seven percent were underweight [body mass index (BMI) < 18.5 kg/m2], 27% were overweight (BMI 25.0 to 29.9 kg/m2), and 23% were obese (BMI> 29.9 kg/m2) at dialysis initiation. Compared to those with normal BMI, the adjusted odds of initiating peritoneal dialysis were 0.70 (P < 0.05) in underweight, 1.12 (P < 0.05) in overweight, and 0.87 (P < 0.05) in obese subjects. Among peritoneal dialysis patients, adjusted mortality hazard ratios in the first, second, and third year were 1.45 (P < 0.05), 1.28 (P < 0.05), and 1.17 for the underweight, respectively; 0.84 (P < 0.05), 0.89 (P < 0.05), and 0.98 for the overweight, respectively; and 0.89 (P < 0.05), 0.99, and 1.00 for the obese, respectively. Apart from higher third-year mortality in the obese, associations were similar after censoring at a switch to hemodialysis. For transplantation, the corresponding results were 0.76 (P < 0.05), 0.90 (P < 0.05), and 0.88 for the underweight, respectively; 0.95, 1.06, and 0.93 for the overweight, respectively; and 0.62 (P < 0.05), 0.68, and 0.71 for the obese, respectively. For switching to hemodialysis, hazards ratios were 0.92, 0.97, and 0.80 for the underweight, respectively; 1.07, 1.11 (P < 0.05), and 1.03 for the overweight, respectively; and 1.28 (P < 0.05), 1.29 (P < 0.05), and 1.36 (P < 0.05) for the obese, respectively. CONCLUSION Although less likely to initiate peritoneal dialysis, overweight and obese peritoneal dialysis patients have longer survival than those with lower BMI, not adequately explained by lower transplantation and technique survival rates.",
"title": "Body size and outcomes on peritoneal dialysis in the United States."
},
{
"docid": "25451374",
"text": "BACKGROUND More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown. METHODS We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years. RESULTS The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P=0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001). CONCLUSIONS Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. (Funded by the Population Health Research Institute and others.).",
"title": "Cardiovascular risk and events in 17 low-, middle-, and high-income countries."
},
{
"docid": "6793674",
"text": "Circulating trimethylamine N-oxide (TMAO), a canonical metabolite from gut flora, has been related to the risk of cardiovascular disorders. However, the association between circulating TMAO and the risk of cardiovascular events has not been quantitatively evaluated. We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating TMAO and subsequent cardiovascular events. Embase and PubMed databases were searched for relevant cohort studies. The overall hazard ratios for the developing of cardiovascular events (CVEs) and mortality were extracted. Heterogeneity among the included studies was evaluated with Cochran's Q Test and I2 statistics. A random-effect model or a fixed-effect model was applied depending on the heterogeneity. Subgroup analysis and meta-regression were used to evaluate the source of heterogeneity. Among the 11 eligible studies, three reported both CVE and mortality outcome, one reported only CVEs and the other seven provided mortality data only. Higher circulating TMAO was associated with a 23% higher risk of CVEs (HR = 1.23, 95% CI: 1.07-1.42, I2 = 31.4%) and a 55% higher risk of all-cause mortality (HR = 1.55, 95% CI: 1.19-2.02, I2 = 80.8%). Notably, the latter association may be blunted by potential publication bias, although sensitivity analysis by omitting one study at a time did not significantly change the results. Further subgroup analysis and meta-regression did not support that the location of the study, follow-up duration, publication year, population characteristics or the samples of TMAO affect the results significantly. Higher circulating TMAO may independently predict the risk of subsequent cardiovascular events and mortality.",
"title": "Circulating trimethylamine N‐oxide and the risk of cardiovascular diseases: a systematic review and meta‐analysis of 11 prospective cohort studies"
},
{
"docid": "13619127",
"text": "OBJECTIVE To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones). DESIGN Open cohort study in primary care. SETTING 1243 practices contributing data to the QResearch database in England. PARTICIPANTS 469,688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015. EXPOSURES Hypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination. MAIN OUTCOME MEASURES First recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records. Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders. RESULTS 21,308 (4.5%) and 32,533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively. Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10,000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74). We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94). CONCLUSIONS We have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness. These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs.",
"title": "Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care"
},
{
"docid": "6525844",
"text": "BACKGROUND Damage to large arteries is a major factor in the high cardiovascular morbidity and mortality of patients with end-stage renal disease (ESRD). Increased arterial stiffness and intima-media thickness, together with increased pulse pressure, are the principal arterial alterations. Whether increased aortic pulse-wave velocity (PWV), a classic marker of increased arterial stiffness, may predict all-cause and/or cardiovascular mortality has never been investigated. METHODS AND RESULTS A cohort of 241 patients with ESRD undergoing hemodialysis was studied between April 1987 and April 1998. The mean duration of follow-up was 72+/-41 months (mean+/-SD). Mean age at entry was 51.5+/-16.3 years. Seventy-three deaths occurred, including 48 cardiovascular and 25 noncardiovascular fatal events. At entry, together with standard clinical and biochemical analyses, patients underwent echocardiography and aortic PWV measured by Doppler ultrasonography. On the basis of Cox analyses, 2 factors emerged as predictors of all-cause and cardiovascular mortality: age and aortic PWV. Hemoglobin and low diastolic pressure interfered to a smaller extent. After adjustment for all the confounding factors, an OR for PWV >12. 0 versus <9.4 m/s was 5.4 (95% CI, 2.4 to 11.9) for all-cause mortality and 5.9 (95% CI, 2.3 to 15.5) for cardiovascular mortality. For each PWV increase of 1 m/s in our study population, all-cause mortality-adjusted OR was 1.39 (95% CI, 1.19 to 1.62). CONCLUSIONS These results provide the first direct evidence that in patients with ESRD, increased aortic stiffness determined by measurement of aortic PWV is a strong independent predictor of all-cause and mainly cardiovascular mortality.",
"title": "Impact of aortic stiffness on survival in end-stage renal disease."
},
{
"docid": "1287809",
"text": "IMPORTANCE The American College of Cardiology and the American Heart Association (ACC/AHA) cholesterol treatment guidelines have wide-scale implications for treating adults without history of atherosclerotic cardiovascular disease (ASCVD) with statins. OBJECTIVE To estimate the cost-effectiveness of various 10-year ASCVD risk thresholds that could be used in the ACC/AHA cholesterol treatment guidelines. DESIGN, SETTING, AND PARTICIPANTS Microsimulation model, including lifetime time horizon, US societal perspective, 3% discount rate for costs, and health outcomes. In the model, hypothetical individuals from a representative US population aged 40 to 75 years received statin treatment, experienced ASCVD events, and died from ASCVD-related or non-ASCVD-related causes based on ASCVD natural history and statin treatment parameters. Data sources for model parameters included National Health and Nutrition Examination Surveys, large clinical trials and meta-analyses for statin benefits and treatment, and other published sources. MAIN OUTCOMES AND MEASURES Estimated ASCVD events prevented and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS In the base-case scenario, the current ASCVD threshold of 7.5% or higher, which was estimated to be associated with 48% of adults treated with statins, had an incremental cost-effectiveness ratio (ICER) of $37,000/QALY compared with a 10% or higher threshold. More lenient ASCVD thresholds of 4.0% or higher (61% of adults treated) and 3.0% or higher (67% of adults treated) had ICERs of $81,000/QALY and $140,000/QALY, respectively. Shifting from a 7.5% or higher ASCVD risk threshold to a 3.0% or higher ASCVD risk threshold was estimated to be associated with an additional 161,560 cardiovascular disease events averted. Cost-effectiveness results were sensitive to changes in the disutility associated with taking a pill daily, statin price, and the risk of statin-induced diabetes. In probabilistic sensitivity analysis, there was a higher than 93% chance that the optimal ASCVD threshold was 5.0% or lower using a cost-effectiveness threshold of $100,000/QALY. CONCLUSIONS AND RELEVANCE In this microsimulation model of US adults aged 45 to 75 years [corrected], the current 10-year ASCVD risk threshold (≥7.5% risk threshold) used in the ACC/AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (ICER, $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0% risk threshold) or $150,000/QALY (≥3.0% risk threshold). The optimal ASCVD threshold was sensitive to patient preferences for taking a pill daily, changes to statin price, and the risk of statin-induced diabetes.",
"title": "Cost-effectiveness of 10-Year Risk Thresholds for Initiation of Statin Therapy for Primary Prevention of Cardiovascular Disease."
},
{
"docid": "32850528",
"text": "OBJECTIVE To evaluate serum amylase and lipase levels and the rate of acute pancreatitis in patients with type 2 diabetes and high cardiovascular risk randomized to liraglutide or placebo and observed for 3.5-5.0 years. RESEARCH DESIGN AND METHODS A total of 9,340 patients with type 2 diabetes were randomized to either liraglutide or placebo (median observation time 3.84 years). Fasting serum lipase and amylase were monitored. Acute pancreatitis was adjudicated in a blinded manner. RESULTS Compared with the placebo group, liraglutide-treated patients had increases in serum lipase and amylase of 28.0% and 7.0%, respectively. Levels were increased at 6 months and then remained stable. During the study, 18 (0.4% [1.1 events/1,000 patient-years of observation] [PYO]) liraglutide-treated and 23 (0.5% [1.7 events/1,000 PYO]) placebo patients had acute pancreatitis confirmed by adjudication. Most acute pancreatitis cases occurred ≥12 months after randomization. Liraglutide-treated patients with prior history of pancreatitis (n = 147) were not more likely to develop acute pancreatitis than similar patients in the placebo group (n = 120). Elevations of amylase and lipase levels did not predict future risk of acute pancreatitis (positive predictive value <1.0%) in patients treated with liraglutide. CONCLUSIONS In a population with type 2 diabetes at high cardiovascular risk, there were numerically fewer events of acute pancreatitis among liraglutide-treated patients (regardless of previous history of pancreatitis) compared with the placebo group. Liraglutide was associated with increases in serum lipase and amylase, which were not predictive of an event of subsequent acute pancreatitis.",
"title": "Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial."
},
{
"docid": "5698494",
"text": "OBJECTIVES To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. DESIGN Meta-analysis of randomised trials. DATA SOURCES Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I(2) statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. RESULTS 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to 0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. CONCLUSION In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.",
"title": "The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials"
},
{
"docid": "12470783",
"text": "PURPOSE There is a need for valid and reliable short scales that can be used to assess social networks and social supports and to screen for social isolation in older persons. DESIGN AND METHODS The present study is a cross-national and cross-cultural evaluation of the performance of an abbreviated version of the Lubben Social Network Scale (LSNS-6), which was used to screen for social isolation among community-dwelling older adult populations in three European countries. Based on the concept of lack of redundancy of social ties we defined clinical cut-points of the LSNS-6 for identifying persons deemed at risk for social isolation. RESULTS Among all three samples, the LSNS-6 and two subscales (Family and Friends) demonstrated high levels of internal consistency, stable factor structures, and high correlations with criterion variables. The proposed clinical cut-points showed good convergent validity, and classified 20% of the respondents in Hamburg, 11% of those in Solothurn (Switzerland), and 15% of those in London as at risk for social isolation. IMPLICATIONS We conclude that abbreviated scales such as the LSNS-6 should be considered for inclusion in practice protocols of gerontological practitioners. Screening older persons based on the LSNS-6 provides quantitative information on their family and friendship ties, and identifies persons at increased risk for social isolation who might benefit from in-depth assessment and targeted interventions.",
"title": "Performance of an abbreviated version of the Lubben Social Network Scale among three European community-dwelling older adult populations."
},
{
"docid": "5402581",
"text": "CONTEXT Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease and other dementia; however, concerns have arisen about the increased risk for cerebrovascular adverse events, rapid cognitive decline, and mortality with their use. OBJECTIVE To assess the evidence for increased mortality from atypical antipsychotic drug treatment for people with dementia. DATA SOURCES MEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register (2005, Issue 1), meetings presentations (1997-2004), and information from the sponsors were searched using the terms for atypical antipsychotic drugs (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial. STUDY SELECTION Published and unpublished randomized placebo-controlled, parallel-group clinical trials of atypical antipsychotic drugs marketed in the United States to treat patients with Alzheimer disease or dementia were selected by consensus of the authors. DATA EXTRACTION Trials, baseline characteristics, outcomes, all-cause dropouts, and deaths were extracted by one reviewer; treatment exposure was obtained or estimated. Data were checked by a second reviewer. DATA SYNTHESIS Fifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis. CONCLUSIONS Atypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.",
"title": "Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials."
},
{
"docid": "44384384",
"text": "AIMS While randomized clinical trials have compared clopidogrel with higher potency adenosine diphosphate (ADP) receptor inhibitors among patients with acute myocardial infarction, little is known about the frequency, effectiveness and safety of switching between ADP receptor inhibitors in routine clinical practice. METHODS AND RESULTS We studied 11,999 myocardial infarction patients treated with percutaneous coronary intervention at 230 hospitals from April 2010 to October 2012 in the TRANSLATE-ACS study. Multivariable Cox regression was used to compare six-month post-discharge risks of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, or unplanned revascularization) and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-defined bleeding between in-hospital ADP receptor inhibitor switching versus continuation of the initially selected therapy. Among 8715 patients treated initially with clopidogrel, 994 (11.4%) were switched to prasugrel or ticagrelor; switching occurred primarily after percutaneous coronary intervention (60.9%) and at the time of hospital discharge (26.7%). Among 3284 patients treated initially with prasugrel or ticagrelor, 448 (13.6%) were switched to clopidogrel; 48.2% of switches occurred after percutaneous coronary intervention and 48.0% at hospital discharge. Switching to prasugrel or ticagrelor was not associated with increased bleeding when compared with continuation on clopidogrel (2.7% vs. 3.3%, adjusted hazard ratio 0.96, 95% confidence interval 0.64-1.42, p=0.82). Switching from prasugrel or ticagrelor to clopidogrel was not associated with increased MACE (8.9% vs. 7.7%, adjusted hazard ratio 1.06, 95% confidence interval 0.75-1.49, p=0.76) when compared with continuation on the higher potency agent. CONCLUSIONS In-hospital ADP receptor inhibitor switching occurs in more than one in 10 myocardial infarction patients in contemporary practice. In this observational study, ADP receptor inhibitor switching does not appear to be significantly associated with increased hazard of MACE or bleeding.",
"title": "In-hospital switching between adenosine diphosphate receptor inhibitors in patients with acute myocardial infarction treated with percutaneous coronary intervention: Insights into contemporary practice from the TRANSLATE-ACS study."
},
{
"docid": "6085365",
"text": "BACKGROUND Few studies have examined whether physician knowledge, attitudes, or practice patterns might contribute to gender disparities in the primary prevention of coronary heart disease (CHD), including among physicians caring for the largest number of reproductive-age women, obstetricians and gynecologists (OB/GYNs). We sought to identify barriers affecting the provision of recommended coronary risk factor therapies in women. METHODS We surveyed internists and OB/GYNs who attended Grand Rounds presentations developed for the New York State Women and Heart Disease Physician Education Initiative. This program was designed to improve screening and management of coronary risk factors in women. Attendees were asked to complete a 7-minute questionnaire. RESULTS The mean age of the 529 respondents was 40.3 years (standard deviation = 12.3), 75.1% were internists (n=378), and 42.7% (n=226) were women. Physicians correctly responded to 71.5% of the 13 questions assessing knowledge of coronary risk prevention (range, 4-13). Almost one third of internists and half of the OB/GYNs did not know that tobacco use was the leading cause of myocardial infarction in young women. For patients who smoked tobacco, only two thirds of internists and 55.4% of OB/GYNs reported suggesting a quit date (p=.007). After controlling for covariates, physicians who did not perceive time as a barrier were more likely to discuss smoking cessation (odds ratio=1.7 [1.1-2.7]). CONCLUSIONS Among the internists and OB/GYNs surveyed, time was perceived as a barrier to implementing risk prevention. These physicians also underestimated the impact of tobacco use as a risk factor for CHD in young women. To lessen gender disparities in CHD prevention, both specialties need time-efficient educational programs that reflect specialty differences.",
"title": "Physician knowledge levels and barriers to coronary risk prevention in women: survey results from the Women and Heart Disease Physician Education Initiative."
}
] |
8501
|
The 2016 Summer Olympics is played at Royal Birkdale.
|
[
{
"docid": "2017_Open_Championship",
"text": "The 2017 Open Championship will be the 146th Open Championship , held 20 -- 23 July 2017 at Royal Birkdale Golf Club in Southport , England.It will be the 10th Open Championship played at Royal Birkdale .",
"title": ""
}
] |
[
{
"docid": "Birkdale_(disambiguation)",
"text": "Places named Birkdale include : Birkdale in Southport , Merseyside , England . Royal Birkdale Golf Club , Southport , one of the rotating hosts of the Open Championship Birkdale , New Zealand , a suburb of Auckland Birkdale , North Yorkshire , a dale in the Yorkshire Dales National Park , England Birkdale , Queensland in Australia Birkdale School , Sheffield , United Kingdom Birkdale Village , near Huntersville , North Carolina , USA",
"title": ""
},
{
"docid": "Birkdale",
"text": "Birkdale is an area of Southport , within the Metropolitan Borough of Sefton , Merseyside , though historically in Lancashire , in the north-west of England . The area is located on the Irish Sea coast , approximately a mile away from the centre of Southport . From 1894 to 1912 , Birkdale and the adjoining suburb/village of Ainsdale were administered by Birkdale Urban District Council before becoming part of the county borough of Southport . Until 1 April 1974 , Birkdale lay in the traditional borders of the county of Lancashire . At the 2001 census , the local government ward called Birkdale had a population of 12,265 . The population of the area at the 2011 Census is shown under Birkdale ( Ward ) ( qv ) . Other parts of Birkdale are included in Dukes Ward-which contains a significant part of the village centre and the Royal Birkdale Golf Club , - Kew Ward and Ainsdale ward . Birkdale also inspired the name for a new urban mixed use community twelve miles north of Charlotte , North Carolina in Huntersville , North Carolina called Birkdale Village .",
"title": ""
},
{
"docid": "Royal_Birkdale_Golf_Club",
"text": "Royal Birkdale Golf Club is a golf course in the United Kingdom in North West England , located in Southport , Merseyside , north of Liverpool . It is one of the clubs in the rotation for both the Open Championship and Women 's British Open and has hosted the Open Championship nine times from 1954 through 2008 , with a tenth scheduled in 2017 . Winners of the Open at the course include Pádraig Harrington , Mark O'Meara , Ian Baker-Finch , Tom Watson , Johnny Miller , Lee Trevino , Arnold Palmer and Peter Thomson ( twice ) . Royal Birkdale hosted the women 's tournament for a sixth time in 2014 , and was the site of the Senior Open Championship in 2013 . It has also hosted the Ryder Cup ( 1965 , 1969 ) , the Walker Cup ( 1951 ) , and the Curtis Cup ( 1948 ) . Other courses in the Open rota near Liverpool are Royal Liverpool Golf Club ( Hoylake ) and Royal Lytham & St Annes Golf Club .",
"title": ""
},
{
"docid": "2014_Women's_British_Open",
"text": "The 2014 Ricoh Women 's British Open was played 10 -- 13 July at the Royal Birkdale Golf Club in Southport , England . It was the 39th Women 's British Open , and the 14th as a major championship on the LPGA Tour . It was the sixth Women 's British Open at Royal Birkdale , the most recent was four years earlier in 2010 . ESPN and BBC Sport televised the event from Royal Birkdale . Mo Martin won her first major , one shot ahead of runners-up Shanshan Feng and Suzann Pettersen . Martin led after 36 holes at 138 ( − 6 ) after consecutive rounds of 69 , but fell three shots back with a 77 ( +5 ) on Saturday , tied with six others for seventh place . An hour ahead of the final pair on a clear and breezy Sunday , she shot even par , capped by an eagle at the final hole . Her second shot from the fairway on the par 5 nearly holed out for an albatross ( double eagle ) ; it rolled onto the green and struck the flagstick , stopping six feet ( 1.8 m ) away . She sank the putt and waited for the others to finish , preparing for a potential playoff . It was Martin 's first win on the LPGA Tour , and moved her from 99 to 26 in the women 's world rankings .",
"title": ""
},
{
"docid": "Rugby_sevens_at_the_2016_Summer_Olympics",
"text": "Rugby sevens at the 2016 Summer Olympics was held in August in Rio de Janeiro . The competition took six days . The 2016 Summer Olympics marked the debut for rugby sevens at the Summer Olympics , though rugby union was last played at the 1924 Summer Olympics . The usual laws of rugby sevens applied .",
"title": ""
},
{
"docid": "Golf_at_the_2016_Summer_Olympics",
"text": "Golf at the 2016 Summer Olympics in Rio de Janeiro , Brazil , was held in August at the new Olympic Golf Course ( Campo Olímpico de Golfe ) , built within the Reserva de Marapendi in the Barra da Tijuca zone . The 2016 Summer Olympics was the first time for golf to be played at the Olympics since the 1904 Summer Olympics and featured two events , the men 's and women 's individual events .",
"title": ""
},
{
"docid": "Football_at_the_2016_Summer_Olympics_CONCACAF–CONMEBOL_play-off",
"text": "The CONCACAF -- CONMEBOL play-off for the 2016 Summer Olympics was a men 's under-23 international football play-off between a team from CONCACAF ( North , Central America and Caribbean ) and a team from CONMEBOL ( South America ) , with the winner qualifying for the final berth in the 2016 Summer Olympics men 's football tournament . Colombia qualified to the Olympics with a 3 -- 2 aggregate win over the United States , after a 1 -- 1 draw in the first leg and a 1 -- 2 win in the second leg .",
"title": ""
},
{
"docid": "1983_Open_Championship",
"text": "The 1983 Open Championship was the 112th Open Championship held 14 -- 17 July at Royal Birkdale Golf Club in Southport , England . It was the sixth time the course had hosted , with the first in 1954 . Tom Watson won his fifth Open Championship , one stroke ahead of runners-up Andy Bean and Hale Irwin . It was his second consecutive Open win and third in the last four . At age 33 , this was Watson 's eighth and final major title ; he had won three of the last six majors . Watson was the fifth to win five Open Championships , last accomplished in 1965 by Peter Thomson , also at Royal Birkdale . He was the first to successfully defend the title in over a decade , since Lee Trevino in 1972 at Muirfield . Of his five Open wins , this was the only one outside of Scotland . Seven years earlier at Royal Birkdale in 1976 , defending champion Watson posted an 80 in the third round , finishing with a pair of sixes , and missed the 54-hole cut by a stroke .",
"title": ""
},
{
"docid": "Rugby_sevens_at_the_2016_Summer_Olympics_–_Men's_tournament",
"text": "The men 's rugby sevens tournament at the 2016 Summer Olympics was held in Brazil . It was hosted at the Deodoro Stadium , a temporary outdoor stadium constructed as part of the Deodoro Modern Pentathlon Park in Rio de Janeiro . The tournament was held from 9 August to 11 August 2016 , starting with group matches before finishing with the medal ceremony on 11 August . The 2016 Games marked the first time that rugby sevens has played at the Olympics , and the first time since 1924 that any form of rugby has played at the Olympics . The gold medal for Fiji represented the first ever Olympic medal earned by Fiji at any Olympics . Great Britain won silver and South Africa defeated Japan to win the bronze medal .",
"title": ""
},
{
"docid": "Hillside_railway_station",
"text": "Hillside railway station serves the southern half of the Birkdale area of Southport , England . It is located on the Southport branch of the Merseyrail network 's Northern Line . It is the closest station to the Royal Birkdale golf course , and is extremely busy when major events ( such as the Open Championship ) are held there .",
"title": ""
},
{
"docid": "Basketball_at_the_2016_Summer_Olympics",
"text": "Basketball at the 2016 Summer Olympics in Rio de Janeiro , Brazil was held from 6 to 21 August 2016 . The preliminary and knockout matches for men were played inside the Carioca Arena 1 in Olympic Park which seats up to 16,000 spectators , and the matches for women were played in Youth Arena . This marked the first time that the men 's and women 's Olympic tournaments were played in multiple/separate venues . Hosting country , Brazil , failed to make it to the quarterfinals of both the men 's and women 's division after being eliminated from the group stage . Three countries in both categories took all of the medals : United States ( who took both gold medals ) , Serbia and Spain .",
"title": ""
},
{
"docid": "Baseball_at_the_Summer_Olympics",
"text": "Baseball at the Summer Olympics unofficially debuted at the 1904 Summer Games , and became an official Olympic sport at the 1992 Summer Olympics . The event was last played in the 2008 Olympics in Beijing with South Korea taking the gold . In 2016 it was confirmed that Baseball would return for the 2020 games in Tokyo . Olympic baseball is governed by the International Baseball Federation ( IBAF ) .",
"title": ""
},
{
"docid": "1961_Open_Championship",
"text": "The 1961 Open Championship was the 90th Open Championship , played 12 -- 15 July at Royal Birkdale Golf Club in Southport , England . Arnold Palmer won the first of two consecutive Open Championships , one stroke ahead of Dai Rees . It was the second Open for Palmer , the runner-up in his first in 1960 , and the fourth of his seven major titles . He was the first American to win the Claret Jug since Ben Hogan in 1953 . This was the second Open Championship at Royal Birkdale , which hosted in 1954 . Qualifying took place on 10 -- 11 July . Entries played 18 holes on the Championship course and 18 holes at Hillside Golf Club . The number of qualifiers was limited to a maximum of 120 . Ties for 120th place would not qualify . The qualifying score was 151 and 108 players qualified . There were 22 players on 152 . Bob Charles led the qualifiers on 136 , two ahead of Gary Player . A maximum of 50 players could make the cut after 36 holes . Ties for 50th place did not make the cut . Gale-force winds caused scores to soar during the second round on Thursday , followed by heavy rains which washed out both rounds on Friday . Cancellation was a possibility , but the weather cooperated enough to play the third and fourth rounds in showers on Saturday . 1959 Open champion and reigning Masters champion Gary Player withdrew early in the third round due to a stomach ailment .",
"title": ""
},
{
"docid": "Evgenia_Ukolova",
"text": "Evgenia Nikolayevna Ukolova ( Евгения Николаевна Уколова born 17 May 1989 ) is a Russian beach volleyball player . As of 2012 , she plays with Ekaterina Khomyakova . They have qualified for 2012 Summer Olympics in London and for the 2016 Summer Olympics in Rio de Janeiro . She will play with Ekaterina Birlova in Rio 2016",
"title": ""
},
{
"docid": "Barbados_at_the_2016_Summer_Olympics",
"text": "Barbados competed at the 2016 Summer Olympics in Rio de Janeiro , Brazil , from 5 to 21 August 2016 . This was the nation 's twelfth appearance at the Summer Olympics , with the exception of the 1980 Summer Olympics in Moscow , because of its partial support to the United States-led boycott . The Barbados Olympic Association registered a total of 12 athletes , 7 men and 5 women , to compete in five different sports at these Games , doubling the nation 's roster size from London 2012 . Among the sports played by the athletes , Barbados marked its Olympic debut in tennis and triathlon , and the return of females to the team for the first time after sending only men to the previous Games . The Barbadian team featured only two returning Olympians ; skeet shooter Michael Maskell , who staged a comeback in Rio for his fifth Olympic appearance as the most experienced member after a twelve-year absence , and sprinter Ramon Gittens , who became the nation 's flag bearer in the opening ceremony . Barbados , however , failed to win a single Olympic medal since the 2000 Summer Olympics in Sydney , where sprinter Obadele Thompson took the bronze in the men 's 100 metres .",
"title": ""
},
{
"docid": "Chris_Wood_(golfer)",
"text": "Christopher James Wood ( born 26 November 1987 ) is an English professional golfer who currently plays on the European Tour . He was the low amateur in the 2008 Open Championship at Royal Birkdale and tied for third in the following year 's tournament held at Turnberry .",
"title": ""
},
{
"docid": "Southport_and_Ainsdale_Golf_Club",
"text": "Southport and Ainsdale Golf Club is an 18-hole championship golf course in North West England , situated near the Merseyside ( formerly Lancashire ) towns of Southport and Ainsdale , north of Liverpool . The course is near the coast of the Irish Sea , set amongst ranges of tall sandhills and smaller sand dunes , just south of Royal Birkdale Golf Club . Founded in 1906 , the club hosted the Ryder Cup in 1933 and 1937 . It has also staged many other notable tournaments , including the 2005 Amateur Championship with Royal Birkdale , and is on the roster for Final Qualifying tournaments for The Open Championship . As of 2009 , the club professional is former European Tour golfer Jim Payne .",
"title": ""
},
{
"docid": "Heather_Stanning",
"text": "Heather Mary Stanning MBE ( born 26 January 1985 ) is a retired British professional rower , a member of the Great Britain Rowing Team , and Royal Artillery officer . Ranked number 1 female rower in the world since 2016 , she is a double Olympic champion , double World champion , quadruple World Cup champion and double European champion . As of May 2015 she and her partner Helen Glover are the World , Olympic , World Cup and European record holders , plus the reigning Olympic , World , and European champions in the women 's coxless pairs . She has also been a British champion in both women 's fours and quad sculls . She was a Captain , now a Major , in the Royal Artillery but had been given dispensation from the army to pursue an Olympic career with the British team at both the 2012 Summer Olympics in London and the 2016 Olympics in Rio de Janeiro . Paired with Helen Glover in 2012 she won an Olympic gold medal , the first for their country of the 2012 Games and the first ever British Olympic gold medal in women 's rowing . She set the world record time in partnership with Helen Glover at the 2014 World Rowing Championships in Amsterdam , and they retained their World title at the 2015 World Rowing Championships in Lac d'Aiguebelette , France . In 2016 they retained their European title at Brandenburg an der Havel , and set the World Rowing Cup record time at Poznan . She announced her retirement from rowing in November 2016 . In September 2016 , Stanning was awarded the freedom of the Scottish region of Moray .",
"title": ""
},
{
"docid": "Juan_Pedro_de_Miguel",
"text": "Juan Pedro de Miguel Rubio ( January 13 , 1958 -- August 12 , 2016 ) was a Spanish handball player who competed in the 1980 Summer Olympics and in the 1984 Summer Olympics . In 1980 he was part of the Spanish team which finished fifth in the Olympic tournament . He played all six matches as goalkeeper . Four years later he finished eighth with the Spanish team in the 1984 Olympic tournament . He played five matches as goalkeeper . Rubio died on August 12 , 2016 from a heart attack . He was 58 .",
"title": ""
},
{
"docid": "Football_at_the_2016_Summer_Olympics_–_Men's_tournament_–_Group_A",
"text": "Group A of the men 's football tournament at the 2016 Summer Olympics was played from 4 to 10 August 2016 , and included hosts Brazil , Denmark , Iraq and South Africa . The top two teams advanced to the knockout stage . All times are BRT ( UTC − 3 ) .",
"title": ""
},
{
"docid": "Football_at_the_2016_Summer_Olympics_–_Men's_tournament_–_Group_D",
"text": "Group D of the men 's football tournament at the 2016 Summer Olympics was played from 4 to 10 August 2016 , and included Algeria , Argentina , Honduras and Portugal . The top two teams advanced to the knockout stage . All times are BRT ( UTC − 3 ) .",
"title": ""
},
{
"docid": "Golf_at_the_2016_Summer_Olympics_–_Women's_individual",
"text": "The women 's golf tournament at the 2016 Summer Olympics placed at the Olympic Golf Course ( Campo Olímpico de Golfe ) , built within the Reserva de Marapendi in the Barra da Tijuca zone , between 17 and 20 August 2016 . It was the first women 's golf tournament at the Olympics since 1900 . Sixty players played four rounds of stroke play . The field included 57 professionals and three amateurs . The event was won by Inbee Park of South Korea with a score -16 , defeating Lydia Ko from New Zealand and China 's Shanshan Feng who won silver and bronze respectively . The medals were presented by Dick Pound , IOC member , Canada and Antony Scanlon , Secretary General of the IGF .",
"title": ""
},
{
"docid": "Rugby_sevens_at_the_Summer_Olympics",
"text": "Rugby sevens is a Summer Olympics sport . It was played for the first time at the 2016 Summer Olympics with both men 's and women 's contests . Rugby sevens was added to the Olympics following the decision of the 121st IOC Session in Copenhagen in October 2009 .",
"title": ""
},
{
"docid": "Football_at_the_2016_Summer_Olympics_–_Men's_tournament_–_Group_C",
"text": "Group C of the men 's football tournament at the 2016 Summer Olympics was played from 4 to 10 August 2016 , and included Fiji , Germany , Mexico and South Korea . The top two teams advanced to the knockout stage . All times are BRT ( UTC − 3 ) .",
"title": ""
},
{
"docid": "Football_at_the_2016_Summer_Olympics_–_Men's_tournament_–_Knockout_stage",
"text": "The knockout stage of the men 's football tournament at the 2016 Summer Olympics was played from 13 to 20 August 2016 . The top two teams from each group in the group stage qualified for the knockout stage . All times are local , BRT ( UTC − 3 ) .",
"title": ""
},
{
"docid": "Aurelia_Brădeanu",
"text": "Aurelia Brădeanu ( née Stoica ; born 5 May 1979 ) is a Romanian handballer who last played for CSM Bucharest . She participated at the 2000 Summer Olympics in Sydney , at the 2008 Summer Olympics in Beijing and at the 2016 Summer Olympics in Rio de Janeiro . She is among the top 5 all-time league goalscorers of Győri Audi ETO KC , with 656 goals in 155 appearances . Brădeanu was the captain of Romania and retired from the national team on 27 November 2016 .",
"title": ""
},
{
"docid": "Panagiotis_Gionis",
"text": "Panagiotis Gionis ( born January 7 , 1980 ) is a Greek table tennis player and a dentist . He is a member of the Greek National Team and has competed in 4 Olympics and many World and European Championships . He has been playing professionally in Germany and France since 2001 . Currently , he is playing for German club Borussia Düsseldorf . and is being sponsored by TAMASU BUTTERFLY In May 2011 , he qualified directly for the London 2012 Summer Olympics based on his ITTF world ranking . At the 2012 Summer Olympics , he lost in the third round to Japan 's Seiya Kishikawa . He placed 3rd in the men 's single 2013 LIEBHERR European Championships and second in the team event . He is currently ranked 21st in the world and 7th in Europe . In Aug 2014 he was invited to participate in the mixed European team that will compete in Asia vs. Europe All Star Challenge on November 1 -- 2 , 2014 in Zhang Jia Gang , China . In April 2016 , he secured his spot at the 2016 Summer Olympics by winning the group final match at the ITTF European Olympic Games Qualification Tournament in Halmstad , Sweden . At the 2016 Summer Olympics , he defeated Padasak Tanviriyavechakul of Thailand in the second round . He was defeated by Jun Mizutani of Japan in the third round .",
"title": ""
},
{
"docid": "Football_at_the_2016_Summer_Olympics_–_Women's_tournament_–_Knockout_stage",
"text": "The knockout stage of the women 's football tournament at the 2016 Summer Olympics was played from 12 to 19 August 2016 . The top two teams from each group in the group stage and the two best third-placed teams qualified for the knockout stage . All times are local , BRT ( UTC − 3 ) .",
"title": ""
},
{
"docid": "Nadezhda_Glyzina-Fedotova",
"text": "Nadezhda Sergeyevna Glyzina-Fedotova ( Надежда Сергеевна Глызина , born 20 May 1988 ) is a Russian female water polo player . She was a member of the Russia women 's national water polo team , playing as a driver . She was a part of the team at the 2008 Summer Olympics , 2012 Summer Olympics and 2016 Summer Olympics . On club level she played for Kinef Kirishi in Russia .",
"title": ""
},
{
"docid": "List_of_The_Open_Championship_venues",
"text": "The Open Championship is an annual golf competition that was established in 1860 . It is played on the weekend of the third Friday in July , and is the third of the four major championships to be played each year . In addition , this championship is conducted by The Royal and Ancient Golf Club of St Andrews ( R&A ) . The championship is currently held on a different course each year , of the 14 that have been used , 9 are currently used in the rota . All the courses on the rota are links . Prestwick Golf Club hosted the first championship in 1860 and remained the sole venue until 1873 , when the Old Course at St Andrews hosted the event . Prestwick hosted a further 12 championships , the last in 1925 . Musselburgh Links became the third course to host the championship in 1874 . The three courses rotated the hosting of the championship until 1892 when Muirfield hosted the event . The Honourable Company of Edinburgh golfers built their own course at Muirfield and Musselburgh , which was removed from the rota as a result . Royal St George 's Golf Club became the first course outside Scotland to host the championship in 1894 . Royal Liverpool Golf Club hosted the event for the first time in 1897 . Royal Cinque Ports Golf Club became the next course to host the event in 1909 . The course hosted a further championship in 1920 , but further attempts to host the Championship in 1938 and 1949 were thwarted by bad weather and the course was dropped from the rota . Royal Troon , Royal Lytham & St Annes and Carnoustie held the Open Championship for the first time in 1923 , 1926 and 1931 respectively . The following year Prince 's Golf Club hosted the event for the only time . The course was requisitioned by the military during the Second World War and was extensively damaged . Royal Birkdale was chosen as the host course in 1940 , however , due to the Second World War the event did not go ahead . It was not until 1954 that Royal Birkdale hosted the Open . The Old Course at St Andrews has hosted the most championships with 29 in total , most recently with the 2015 Open Championship . The championship has only been held outside Scotland and England once , in 1951 when Royal Portrush Golf Club in Northern Ireland was the venue . Turnberry became the most recent course to have hosted the Championship for the first time , when it held the 1977 Open Championship .",
"title": ""
}
] |
8103
|
How long can a company keep the money raised from IPO of its stocks?
|
[
{
"docid": "347348",
"text": "You realize that most of the money raised through the IPO process doesn't go into the company's bank account? Those shares were shares that were held by the investors and original owners and it's those prior pre-IPO shareholders that got their money back along with a tidy profit. The cash on its books was there before the IPO, and after. The IPO process was more about a change in stock owners ship than anything else. Edit - as the SEC disclosure mentioned in comments below states, the Facebook IPO raised $6.7B for facebook's use, the rest of the transaction was from the investors selling their shares. Mark Zuckerberg still owns more than 55% of shares outstanding. The $6.7B is still about 10% of the company value. Nothing to ignore, but clearly, 'most' of the money from the IPO didn't go to the company.",
"title": ""
},
{
"docid": "119505",
"text": "Yes, that is correct. There is no limit. An initial public offering of common stock by a company means that these shares remain outstanding for as long as the company wishes. The exceptions are through corporate actions, most commonly either",
"title": ""
},
{
"docid": "332657",
"text": "Is it correct that there is no limit on the length of the time that the company can keep the money raised from IPO of its stocks, unlike for the debt of the company where there is a limit? Yes that is correct, there is no limit. But a company can buy back its shares any time it wants. Anyone else can also buy shares on the market whenever they want.",
"title": ""
}
] |
[
{
"docid": "44461",
"text": "\"Yes, you could buy a stock on the day of its IPO. I'm a college student, and I wonder if I can buy stock from a company right after it finishes its IPO? Yes, you can. However, unless you are friends or family of an employee, chances are you'll be paying a higher price than you think as there is generally a fair bit of hype on most IPOs that allows some people to \"\"flip them\"\" which means someone is buying at a higher price. If I am not allowed to buy its stocks immediately after they go on sell, how long do I have to wait? Generally I'd wait until the hype dies down as if you look at most historical IPOs the stock could be bought cheaper later but that's just my perspective. And also who are allowed to buy the stocks at the first minute they are on sell? Anyone but keep in mind that while an IPO may be priced at $x, the initial trades may be a few times that value and the stock may come down over time. Facebook could be an example to consider of a company that had an IPO at one price and then came down for a little while on its chart over the past couple of years.\"",
"title": ""
},
{
"docid": "11311",
"text": "\"Why only long term investments? What do they care if I buy and sell shares in a company in the same year? Simple, your actually investing when you hold it for a long term. If you hold a stock for a week or a month there is very little that can happen to change the price, in a perfect market the value of a company should stay the same from yesterday to today so long as there is no news(a perfect market cannot exist). When you hold a stock for a long term you really are investing in the company and saying \"\"this company will grow\"\". Short term investing is mostly speculation and speculation causes securities to be incorrectly valued. So when a retail investor puts money into something like Facebook for example they can easily be burned by speculation whether its to the upside or downside. If the goal is to get me to invest my money, then why not give apply capital gains tax to my savings account at my local bank? Or a CD account? I believe your gains on these accounts are taxed... Not sure at what rate. If the goal is to help the overall health of business, how does it do that? During an IPO, the business certainly raises money, but after that I'm just buying and selling shares with other private shareholders. Why does the government give me an incentive to do this (and then hold onto it for at least a year)? There are many reasons why a company cares about its market price: A companies market cap is calculated by price * shares outstanding. A market cap is basically what the market is saying your company is worth. A company can offer more shares or sell shares they currently hold in order to raise even more capital. A company can offer shares instead of cash when buying out another company. It can pay for many things with shares. Many executives and top level employees are payed with stock options, so they defiantly want to see there price higher. these are some basic reasons but there are more and they can be more complex.\"",
"title": ""
},
{
"docid": "499154",
"text": "\"The offering price is what the company will raise by selling the shares at that price. However, this isn't usually what the general public sees as often there will be shows to drive up demand so that there will be buyers for the stock. That demand is what you see on the first day when the general public can start buying the stock. If one is an employee, relative or friend of someone that is offered, \"\"Friends and Family\"\" shares they may be able to buy at the offering price. Pricing of IPO from Wikipedia states around the idea of pricing: A company planning an IPO typically appoints a lead manager, known as a bookrunner, to help it arrive at an appropriate price at which the shares should be issued. There are two primary ways in which the price of an IPO can be determined. Either the company, with the help of its lead managers, fixes a price (\"\"fixed price method\"\"), or the price can be determined through analysis of confidential investor demand data compiled by the bookrunner (\"\"book building\"\"). Historically, some IPOs both globally and in the United States have been underpriced. The effect of \"\"initial underpricing\"\" an IPO is to generate additional interest in the stock when it first becomes publicly traded. Flipping, or quickly selling shares for a profit, can lead to significant gains for investors who have been allocated shares of the IPO at the offering price. However, underpricing an IPO results in lost potential capital for the issuer. One extreme example is theglobe.com IPO which helped fuel the IPO \"\"mania\"\" of the late 90's internet era. Underwritten by Bear Stearns on November 13, 1998, the IPO was priced at $9 per share. The share price quickly increased 1000% after the opening of trading, to a high of $97. Selling pressure from institutional flipping eventually drove the stock back down, and it closed the day at $63. Although the company did raise about $30 million from the offering it is estimated that with the level of demand for the offering and the volume of trading that took place the company might have left upwards of $200 million on the table. The danger of overpricing is also an important consideration. If a stock is offered to the public at a higher price than the market will pay, the underwriters may have trouble meeting their commitments to sell shares. Even if they sell all of the issued shares, the stock may fall in value on the first day of trading. If so, the stock may lose its marketability and hence even more of its value. This could result in losses for investors, many of whom being the most favored clients of the underwriters. Perhaps the best known example of this is the Facebook IPO in 2012. Underwriters, therefore, take many factors into consideration when pricing an IPO, and attempt to reach an offering price that is low enough to stimulate interest in the stock, but high enough to raise an adequate amount of capital for the company. The process of determining an optimal price usually involves the underwriters (\"\"syndicate\"\") arranging share purchase commitments from leading institutional investors. Some researchers (e.g. Geoffrey C., and C. Swift, 2009) believe that the underpricing of IPOs is less a deliberate act on the part of issuers and/or underwriters, than the result of an over-reaction on the part of investors (Friesen & Swift, 2009). One potential method for determining underpricing is through the use of IPO Underpricing Algorithms. This may be useful for seeing the difference in that \"\"theglobe.com\"\" example where the offering price is $9/share yet the stock traded much higher than that initially.\"",
"title": ""
},
{
"docid": "386278",
"text": "how do they turn shares into cash that they can then use to grow their business? Once a Company issues an IPO or Follow-On Public Offer, the company gets the Money. Going over the list of question tagged IPO would help you with basics. Specifically the below questions; How does a company get money by going public in an IPO? Why would a company care about the price of its own shares in the stock market? Why would a stock opening price differ from the offering price? From what I've read so far, it seems that pre-IPO an investment bank essentially buys the companies public shares, and that bank then sells them on the open market. Is the investment bank buying 100% of the newly issued public shares? And then depositing the cash equivalent into the companies bank account? Additionally, as the stock price rises and falls over the lifetime of the company how does that actually impact the companies bank balance? Quite a bit on above is incorrect. Please read the answers to the question tagged IPO. Once an IPO is over, the company does not gain anything directly from the change in shareprice. There is indirect gain / loss.",
"title": ""
},
{
"docid": "35252",
"text": "You are right that Facebook really doesn't get impacted as they got their $38. However it would make it slightly more difficult for Facebook to raise more money in future as large investors would be more cautious. This can keep the price lowers than it actually needs to be. Quite a few companies try to list the IPO at lower price so that it keeps going up and have more positive effect overall there by making it easier for future borrowings. See related question Why would a company care about the price of its own shares in the stock market?",
"title": ""
},
{
"docid": "245834",
"text": "In short, thanks to the answers and comments posted so far. No actual money is magically disappeared when the stock price goes down but the value is lost. The value changes of a stock is similar to the value changes of a house. The following is the long answer I came up with based on the previous answers and comments alone with my own understandings. Any experts who find any of the following is 200% out of place and wrong, feel free to edit it or make comments. Everything below only applies if the following are true: The stock price is only decreasing since the IPO because the company has been spending the money but not making profits after the IPO. The devaluation of the stock is not the result of any bad news related to the company but a direct translation of the money the company has lost by spending on whatever the company is doing. The actual money don’t just disappear into the thin air when the stock price goes down. All the money involved in trading this stock has already distributed to the sellers of this stock before the price went down. There is no actual money that is literally disappeared, it was shifted from one hand to another, but again this already happened before the price went down. For example, I bought some stocks for $100, then the price went down to $80. The $100 has already shifted from my hand to the seller before the price went down. I got the stock with less value, but the actual money $100 did not just go down to $80, it’s in the hand of the seller who sold the stock to me. Now if I sell the stock to the same seller who sold the stock to me, then I lost $20, where did the $20 go? it went to the seller who sold the stock to me and then bought it back at a lower price. The seller ended up with the same amount of the stocks and the $20 from me. Did the seller made $20? Yes, but did the seller’s total assets increased? No, it’s still $100, $80 from the stocks, and $20 in cash. Did anyone made an extra $20? No. Although I did lost $20, but the total cash involved is still there, I have the $80 , the seller who sold the stock to me and then bought it back has the $20. The total cash value is still $100. Directly, I did lost $20 to the guy who sold me the stock when the stock has higher value and then bought it back at a lower price. But that guy did not increased his total assets by $20. The value of the stock is decreased, the total money $100 did not disappear, it ended up from one person holding it to 2 people holding it. I lost $20 and nobody gained $20, how is that possible? Assume the company of the stock never made any profit since it’s IPO, the company just keeps spending the money, to really track down where the $20 I lost is going, it is the company has indirectly spent that money. So who got that $20 I lost? It could be the company spent $20 for a birthday cake, the $20 went to the cake maker. The company never did anything to make that $20 back, so that $20 is lost. Again, assume the stock price only goes down after its IPO, then buying this stock is similar to the buying a sport car example from JoeTaxpayer (in one of the answers), and buying an apple example from BrenBarn(in one of the comments from JoeTaxpayer’s answer). Go back to the question, does the money disappears into the thin air when the value of the stock goes down? No, the money did not disappear, it switched hands. It went from the buyer of the stock to the company, and the company has spent that money. Then what happens when the stock price goes down because bad news about the company? I believe the actual money still did not just disappear. If the bad news turn out to be true that the company had indeed lost this much money, the money did not disappear, it’s been spent/lost by the company. If the bad news turn out to be false, the stock price will eventually go up again, the money is still in the hand of the company. As a summary, the money itself did not disappear no matter what happens, it just went from one wallet to another wallet in many different ways through the things people created that has a value.",
"title": ""
},
{
"docid": "408695",
"text": "its the best investment you can have specially with the company you work for and IPO, if i was you i would invest in more then just the minimum since its IPO. ask you your manager or supervisor how much are they buying the stocks for if they are doing it the go for it you'll be okay just keep track of it regular sometime you can invest more as time go by. You can get the idea by how much production your company is doing, if your company's profit going up chances are you need to buy more.",
"title": ""
},
{
"docid": "340791",
"text": "\"It appears that the company in question is raising money to invest in expanding its operations (specifically lithium production but that is off topic for here). The stock price was rising on the back of (perceived) increases in demand for the company's products but in order to fulfil demand they need to either invest in higher production or increase prices. They chose to increase production by investing. To invest they needed to raise capital and so are going through the motions to do that. The key question as to what will happen with their stock price after this is broken down into two parts: short term and long term: In the short term the price is driven by the expectation of future profits (see below) and the behavioural expectations from an increase in interest in the stock caused by the fact that it is in the news. People who had never heard of the stock or thought of investing in the company have suddenly discovered it and been told that it is doing well and so \"\"want a piece of it\"\". This will exacerbate the effect of the news (broadly positive or negative) and will drive the price in the short run. The effect of extra leverage (assuming that they raise capital by writing bonds) also immediately increases the total value of the company so will increase the price somewhat. The short term price changes usually pare back after a few months as the shine goes off and people take profits. For investing in the long run you need to consider how the increase in capital will be used and how demand and supply will change. Since the company is using the money to invest in factors of production (i.e. making more product) it is the return on capital (or investment) employed (ROCE) that will inform the fundamentals underlying the stock price. The higher the ROCE, the more valuable the capital raised is in the future and the more profits and the company as a whole will grow. A questing to ask yourself is whether they can employ the extra capital at the same ROCE as they currently produce. It is possible that by investing in new, more productive equipment they can raise their ROCE but also possible that, because the lithium mines (or whatever) can only get so big and can only get so much access to the seams extra capital will not be as productive as existing capital so ROCE will fall for the new capital.\"",
"title": ""
},
{
"docid": "407911",
"text": "Rather than take anyone's word for it (including and especially mine) you need to do think very carefully about your company; you know it far better than almost anyone else. Do you feel that the company values its employees? If it values you and your immediate colleagues then its likely that it not only values its other employees but also its customers which is a sign that it will do well. Does the company have a good relationship with its customers? Since you are a software engineer using a web stack I assume that it is either a web consultancy or has an e-commerce side to it so you will have some exposure to what the customers complain about, either in terms of bugs or UX difficulties. You probably even get bug reports that tell you what customer pain points are. Are customers' concerns valid, serious and damaging? If they are then you should think twice about taking up the offer, if not then you may well be fine. Also bear in mind how much profit is made on each item of product and how many you can possibly sell - you need to be able to sell items that have been produced. Those factors indicate how the future of the company looks currently, next you need to think about why the IPO is needed. IPOs and other share offerings are generally done to raise capital for the firm so is your company raising money to invest for the future or to cover losses and cashflow shortfalls? Are you being paid on time and without issues? Do you get all of the equipment and hiring positions that you want or is money always a limiting factor? As an insider you have a better chance to analyse these things than outsiders as they effect your day-to-day work. Remember that anything in the prospectus is just marketing spiel; expecting a 4.5 - 5.3% div yield is not the same as actually paying it or guaranteeing it. Do you think that they could afford to pay it? The company is trying to sell these shares for the maximum price they can get, don't fall for the hyped up sales pitch. If you feel that all of these factors are positive then you should buy as much as you can, hopefully far more than the minimum, as it seems like the company is a strong, growing concern. If you have any concerns from thinking about these factors then you probably shouldn't buy any (unless you are getting a discount but that's a different set of considerations) as your money would be better utilized elsewhere.",
"title": ""
},
{
"docid": "496921",
"text": "\"The hardest part seems to be knowing exactly when to sell the stock. Well yes, that's the problem with all stock investing. Reports come out all the time, sometimes even from very smart people with no motivation to lie, about expected earnings for this company, or for that industry. Whether those predictions come true is something you will only find out with time. What you are considering is using financial information available to you (and equally available to the public) to make investment choices. This is called 'fundamental analysis'; that is, the analysis of the fundamentals of a business and what it should be worth. It forms the basis of how many investment firms decide where to put their money. In a perfectly 'efficient' market, all information available to the public is immediately factored into the market price for that company's stock. ie: if a bank report states with absolute certainty (through leaked documents) that Coca-Cola is going to announce 10% revenue growth tomorrow, then everyone will immediately buy Coca-Cola stock today, and then tomorrow there would be no impact. Even if PwC is 100% accurate in its predictions, if the rest of the market agrees with them, then the price at the time of IPO would equal the future value of the cashflows, meaning there would be no gain unless results surpassed expectations. So what you are proposing is to take one sliver of the information available to the public (have you also read all publicly available reports on those businesses and their industries?), and using that to make a high risk investment. Are you going to do better than the investment firms that have teams of researchers and years of experience in the investment world? You can do quite well by picking individual stocks, but you can also lose a lot of money if you do it haphazardly. Be aware that there is risk in doing any type of investing. There is higher than average risk if you invest in equities ('the stock market'). There is higher risk still, if you pick individual stocks. There is yet even higher risk, if you pick small startup companies. There are some specific interesting side-elements with your proposal to purchase stock about to have an IPO - those are better dealt with in a separate question if you want more information; search this site for 'IPO' and you should find a good starting point. In short, the company about to go public will hire a firm of analysts who will try to calculate the best price the public will accept for an offering of shares. Stock often goes up after IPO, but not always. Sometimes the company doesn't even fill its full IPO order, adding a new type of risk to a potential investor, that the stock will drop on day 1. Consider an analogy outside the investing world: Let's say Auto Trader magazine prints an article that says \"\"all 2015 Honda Civics are worth $15,000 if they have less than 50,000 Miles.\"\" Assume you have no particular knowledge about cars. If you read this article, and you see an ad in the paper the next day for a Honda Civic with 40k miles, should you buy it for $14k? The answer is not without more research. And even if you determine enough about cars to find one for $14k that you can reasonably sell for $15k, there's a whole world of mechanics out there who buy and sell cars for a living, and they have an edge both because they can repair the cars themselves to sell for more, and also because they have experience to spot low-offers faster than you. And if you pick a clunker (or a stock that doesn't perform even when everyone expected it would), then you could lose some serious money. As with buying and selling individual stocks, there is money to be made from car trading, but that money gets made by people who really know what they're doing. People who go in without full information are the ones who lose money in the long run.\"",
"title": ""
},
{
"docid": "90519",
"text": "\"IPO is \"\"Initial Public Offering\"\". Just so you know. The valuations are done based on the company business model, intellectual property, products, market shares, revenues and profits, assets, and future projections. You know, the usual stuff. Yes, it is. And very frequently done. In fact, I can't think of any company that is now publicly traded, that didn't start this way. The first investor, the one who founds the company, is the first one who invests in it after raising the capital (even if it is from his own bank account to pay the fees for filing the incorporation papers). What is the difference between \"\"normal\"\" investor and \"\"angel\"\"? What do you refer to as \"\"angel\"\"? How is it abnormal to you? Any investor can play a role, depending on the stake he/she has in the company. If the stake is large enough - the role will be significant. If the stake is the majority - the investor will in fact be able major decisions regarding the company. How he bought the stocks, whether through a closed offering, initial investment or on a stock exchange - doesn't matter at all. You may have heard of the term \"\"angels\"\" with regards to high-tech start up companies. These are private investors (not funds) that invest their own money in start ups at very early stages. They're called \"\"angels\"\" because they invest at stages at which it is very hard for entrepreneurs to raise money: there's no product, no real business, usually it is a stage of just an idea or a patent with maybe initial prototype and some preliminary business analysis. These people gamble, in a sense, and each investment is very small (relatively to their wealth) - tens of thousands of dollars, sometimes a hundred or two thousands, and they make a lot of these. Some may fail and they lose the money, but those that succeed - bring very high returns. Imagine investing 10K for 5% stake at Google 15 years ago. Those people are as investors as anyone else, and yes, depending on their stake in the company, they can influence its decisions.\"",
"title": ""
},
{
"docid": "433806",
"text": "\"1) Are the definitions for capital market from the two sources the same? Yes. They are from two different perspectives. Investopedia is looking at it primarily from the perspective of a trader and they lead-off with the secondary market. This refers to the secondary market: A market in which individuals and institutions trade financial securities. This refers to the primary market: Organizations/institutions in the public and private sectors also often sell securities on the capital markets in order to raise funds. Also, the Investopedia definition leaves much to be desired, but it is supposed to be pithy. So, you are comparing apples and oranges, to some extent. One is an article, as short as it may be, this other one is an entry in a dictionary. 2) What is the opposite of capital market, according to the definition in investopedia? It's not quite about opposites, this is not physics. However, that is not the issue here. The Investopedia definition simply does not mention any other possibilities. The Wikipedia article defines the term more thoroughly. It talks about primary/secondary markets in separate paragraph. 3) According to the Wikipedia's definition, why does stock market belong to capital market, given that stocks can be held less than one year too? If you follow the link in the Wikipedia article to money market: As money became a commodity, the money market is nowadays a component of the financial markets for assets involved in short-term borrowing, lending, buying and selling with original maturities of one year or less. The key here is original maturities of one year or less. Here's my attempt at explaining this: Financial markets are comprised of money markets and capital markets. Money is traded as if it were a commodity on the money markets. Hence, the short-term nature in its definition. They are more focused on the money itself. Capital markets are focused on the money as a means to an end. Companies seek money in these markets for longer terms in order to improve their business in some way. A business may go to the money markets to access money quickly in order to deal with a short-term cash crunch. Meanwhile, a business may go to the capital markets to seek money in order to expand its business. Note that capital markets came first and money markets are a relatively recent development. Also, we are typically speaking about the secondary (capital) market when we are talking about the stock or bond market. In this market, participants are merely trading among themselves. The company that sought money by issuing that stock/bond certificate is out of the picture at that point and has its money. So, Facebook got its money from participants in the primary market: the underwriters. The underwriters then turned around and sold that stock in an IPO to the secondary market. After the IPO, their stock trades on the secondary market where you or I have access to trade it. That money flows between traders. Facebook got its money at the \"\"beginning\"\" of the process.\"",
"title": ""
},
{
"docid": "195455",
"text": "\"The company gets the proceeds from the sales of shares on the open market. If a company is selling 1,000,000 shares at $12/share then they will receive $12,000,000 from the underwriter minus some fees that the underwriter will collect. The part that ties into valuation is to consider what percentage is the company selling of itself that is coming from its own holdings. If the company is putting out 10% of its shares in the IPO from treasury holdings on a $10B valuation then it will get $1B minus the fees I'd suspect. Where I worked in late 1990s/early 2000s had an IPO where the underwriter did a bridge loan and the IPO so that the company didn't get all the money raised but did get enough to run operations for a while before ending operations. Public Offering notes that after an IPO other offerings would be called \"\"seasoned equity offering\"\" that may or may not be dilutive as they could come from new or existing shares.\"",
"title": ""
},
{
"docid": "576564",
"text": "It would be very unusual (and very erroneous) to have a company's stock be included in the Long Term Investments on the balance sheet. It would cause divergent feedback loops which would create unrepresentative financial documents and stock prices. That's how your question would be interpreted if true. This is not the case. Stock prices are never mentioned on the financial documents. The stock price you hear being reported is information provided by parties who are not reporting as part of the company. The financial documents are provided by the company. They will be audited internally and externally to make sure that they can be presented to the market. Stock prices are quoted and arbitrated by brokers at the stock exchange or equivalent service. They are negotiated and the latest sale tells you what it has sold for. What price this has been reported never works its way onto the financial document. So what use are stock prices are for those within the company? The stock price is very useful for guessing how much money they can raise by issuing stock or buying back stock. Raising money is important for expansion of the company or to procure money for when avenues of debt are not optimal; buying back stock is important if major shareholders want more control of the company.",
"title": ""
},
{
"docid": "332323",
"text": "Stock trading (as opposed to IPO) doesn't directly benefit the company. But it affects their ability to raise additional funds; if they're valued higher, they don't need to sell as many shares to raise a given amount of money. And the stockholders are part owners of the company; their votes in annual corporate meetings and the like can add up to a substantial influence on the company's policies, so the company has an interest in keeping them (reasonably) happy. Dividends (distributing part of the company's profits to the stockholders) are one way of doing so. You're still investing in the company. The fact that you're buying someone else's share just means you're doing so indirectly, and they're dis-investing at the same time.",
"title": ""
},
{
"docid": "534870",
"text": "Why do companies exist? Well, the corporate charter describes why the company exists. Usually the purpose is to enrich the shareholders. The owners of a company want to make money, in other words. There are a number of ways that a shareholder can make money off a stock: As such, maintaining the stock price and dividend payouts are generally the number one concern for any company in the long term. Most of the company's business is going to be directed towards making the company more valuable for a future buyout, or more valuable in terms of what it can pay its shareholders directly. Note that the company doesn't always need to be worried about the specifics of the day-to-day moves of the stock. If it keeps the finances in line - solid profits, margins, earnings growth and the like - and can credibly tell people that it's generally a valuable business, it can usually shrug off any medium-term blips as market craziness. Some companies are more explicitly long-term about things than others (e.g. Berkshire Hathaway basically tells people that it doesn't care all that much about what happens in the short term). Of course, companies are abstractions, and they're run by people. To make the people running the company worry about the stock price, you give them stock. Or stock options, or something like that. A major executive at a big company is likely to have a significant amount of stock. If the company does well, he does well; if it does poorly, he does poorly. Despite a few limitations, this is really a powerful incentive. If a company is losing a lot of money, or if its profits are falling so it's just losing a lot of its value as a business, the owners (stockholders) tend to get upset, and may vote in new management, or launch some sort of shareholder lawsuit. And, as previously noted, to raise funds, a company can also issue new shares to the market as a secondary offering as well (and they can issue fewer shares if the price is high - meaning that whatever the company is worth afterward, the existing owners own proportionally more of it).",
"title": ""
},
{
"docid": "459392",
"text": "\"Just skimming through the Wikipedia article on airberlin, I notice there is more to the story than simply \"\"airberlin's IPO failed, so they postponed it and did it anyways.\"\" 3 points to keep in mind about IPOs: 1) An IPO is the mechanism for taking a private company and setting it up for shares to be owned by \"\"the public\"\". 2) The process of selling shares to the public often allows original owners and/or early investors to \"\"cash out\"\". Most countries (including member nations of the EU) limit some transactions like pre-IPO companies to \"\"accredited investors\"\". 3) Selling shares to the public also can allow the company to access more funds for growth. This is particularly important in a capital-intensive business like an airline; new B737-MAX costs >$110M. New A320neo costs >$105M USD. Ultimately, the question of a successful IPO depends on how you define success. Initially, there was a lot of concern that the IPO was set up with too much focus on goal #2... allowing the management & owners to cash out. It looks like the first approach was not meeting good opinions in the market during 2006. A major concern was that the initial approach focused on management only cashing out its shares and no money actually going to the company to support its future. The investment bankers restructured the IPO, including the issuance of more new shares so that more $ could end up in the company's accounts, not just in the accounts of the management. If anything, it's still a pretty successful IPO given that the shares were successfully listed, the company collected the money it needed to invest and grow, and the management still cashed out.\"",
"title": ""
},
{
"docid": "138178",
"text": "That's because they literally could not help you. It's not that they were just unwilling to. A hedge fund manager might be able to do it, because the person who bet on Facebook would be willing to let him borrow their shares. An IPO in explain like I'm five: A bank helps underwrite the shares pre offering. This means they buy the shares wholesale. They buy a large majority of the company in order to offer them to the public when the stock goes public. The bank does this for profit, the company does this become it helps raise their price. The bank that underwrites the stock is legally prohibited from short selling that stock for ***at least*** 30 days before the IPO. This is to prevent the bank from trying to commit fraud by selling stock out the front door and betting against it out the back. *** So, now let's jump forward to the day of the IPO. The bank is offering stock to everyone who wants to buy it (other banks who will cut it up and sell it to more people). In order to short the stock someone must be willing to let you borrow their shares. Only the bank that underwrote it prohibited from short selling. It's possible but hard. The underwriter has the majority of the shares for the first thirty days anyways. They're just going to release enough of them to raise volume on the ticker symbol (volume is the amount of people buying and selling). The others the underwriter sold to are unwilling to let someone borrow their stock because they want to ride the price hike and shares are in short supply. So while it's possible to short shares, it's very hard. The underwriters limit the supply of shares to prevent that from happening. The underwriters can't just let you short their own shares because they are legally prohibited from it. Basically, you're left with the fact that the only person who has enough supply to let you short, is prohibited by law from letting you do it. I'm sure Morgan Stanley would have been happy to let their customers short Facebook (as long as you did it through them) to hedge their bets. But they can't.",
"title": ""
},
{
"docid": "555176",
"text": "\"Working for a lot of startups, I have seen this cycle. Really it has little to do with making the IPO look good because of number of employees, and is more about making the IPO look good because of planning for the future. Many times an IPO is released, it will be valued at $1.00 (made up) and the market will soar and spike. Now stock shares are valued at $3.00. Great. Till after the dust settles a bit, and stocks are valued at $0.85. This is \"\"normal\"\" and good. It would be better if the stocks ended a little higher than their initial value, but... such is life. Now the initial value of the stock is made up of basically the value of the company's assets, and employees are part of those assets and its earning power. They are also a liability, but that has less impact on initial value than assets. Sales right after IPO are based on how well a company will do. Part of that is growth. So it looks nicer to say: \"\"We have 500 employees and have been growing by 20% per month.\"\" than to say \"\"We have 100 employees\"\". In other words, before IPO, employees may be hired to make the company look like it is growing. They may be hired because the budget is projected based on expected growth and expected valuation. After IPO, you get a concrete number. You have your budget. It may be more than you thought, or it may be less. In our example, the real budget (from capital), is only 28% of the entire projected budget, and 85% of the initial value. It's time to make some budget cuts. Also, normally, there is a period of adjustment, company wide, as a company goes from VC funding, \"\"here, have as much money as you want\"\", to \"\"real world\"\" funding, with stricter limits and less wiggle room.\"",
"title": ""
},
{
"docid": "400713",
"text": "\"I actually tend to disagree. This was one of the most watched IPOs in history. Facebook would have benefited greatly from a pop. People would have thought \"\"wow, they really can do no wrong\"\". Instead there are endless negative articles about how this is a horrible failure. Sure, financially savvy people look at this and think FB did a beautiful job. They maximized their take from the IPO. But the price of the bad press can't be accurately measured. The benefit in terms of publicity of being seen as a stock/company on the move UP is hard to measure too. Suppose they had priced it at $25 and limited the number of shares they would have gotten less money but they'd also be looking at a massively successful pop on their share price. The halo effect on their business of THAT reality seems to me to have had the potential to be significant. So I'm not so sure, in the long term, whether it would have made more sense for them to get less money up front and get a successful IPO rather than go for the max dollars and have a PR disaster. I think the way things turned out made FB go from an unstoppable juggernaut into a company that can fail just like any other.\"",
"title": ""
},
{
"docid": "334162",
"text": "Here is an example for you. We have a fictional company. It's called MoneyCorp. Its job is to own money, and that's all. Right now it owns $10,000. It doesn't do anything special with that $10,000 - it stores it in a bank account, and whenever it earns interest gives it to the shareholders as a dividend. Also, it doesn't have any expenses at all, and doesn't pay taxes, and is otherwise magic so that it doesn't have to worry about distractions from its mathematical perfection. There are 10,000 shares of MoneyCorp, each worth exactly $1. However, they may trade for more or less than $1 on the stock market, because it's a free market and people trading stock on the stock market can trade at whatever price two people agree on. Scenario 1. MoneyCorp wants to expand. They sell 90,000 shares for $1 each. The money goes in the same bank account at the same interest rate. Do the original shareholders see a change? No. 100,000 shares, $100,000, still $1/share. No problem. This is the ideal situation. Scenario 2: MoneyCorp sells 90,000 shares for less than the current price, $0.50 each. Do the original shareholders lose out? YES. It now has something like $55,000 and 100,000 shares. Each share is now worth $0.55. The company has given away valuable equity to new shareholders. That's bad. Why didn't they get more money from those guys? Scenario 3: MoneyCorp sells 90,000 shares for more than the current price, $2 each, because there's a lot of hype about its business. MoneyCorp now owns $190,000 in 100,000 shares and each share is worth $1.90. Existing shareholders win big! This is why a company would like to make its share offering at the highest price possible (think, Facebook IPO). Of course, the new shareholders may be disappointed. MoneyCorp is actually a lot like a real business! Actually, if you want to get down to it, MoneyCorp works very much like a money-market fund. The main difference between MoneyCorp and a random company on the stock market is that we know exactly how much money MoneyCorp is worth. You don't know that with a real business: sales may grow, sales may drop, input prices may rise and fall, and there's room for disagreement - that's why stock markets are as unpredictable as they are, so there's room for doubt when a company sells their stock at a price existing shareholders think is too cheap (or buys it at a price that is too expensive). Most companies raising capital will end up doing something close to scenario 1, the fair-prices-for-everyone scenario. Legally, if you own part of a company and they do something a Scenario-2 on you... you may be out of luck. Consider also: the other owners are probably hurt as much as you are. Only the new shareholders win. And unless the management approving the deal is somehow giving themselves a sweetheart deal, it'll be hard to demonstrate any malfeasance. As an individual, you probably won't file a lawsuit either, unless you own a very large stake in the company. Lawsuits are expensive. A big institutional investor or activist investor of some sort may file a suit if millions of dollars are at stake, but it'll be ugly at best. If there's nothing evil going on with the management, this is just one way that a company loses money from bad management. It's probably not the most important one to worry about.",
"title": ""
},
{
"docid": "231268",
"text": "Companies do not support their stock. Once the security is out on the wild (market), its price fluctuates according to what investors think they are worth. Support is a whole different concept, financially speaking: Support or support level refers to the price level below which, historically, a stock has had difficulty falling. It is the level at which buyers tend to enter the stock. So it is the lowest assumed price for that stock. Once it reaches its price, buyers will rush to the stock, raising its price. The company wants to keep the stock price at acceptable levels, as it can be seen as the general view of the company's health. Also several employees/executives in the company have stock or stock options, so it is in their interest to keep their stock price up. A bond that goes down in value may indicate a believe the bond issuer (government in this case) won't honor the bond when it matures. As for bonds, there is a wealth of reading in this site: Can someone explain how government bonds work? Who sets the prices on government bonds? Basic understanding of bonds, values, rates and yields",
"title": ""
},
{
"docid": "566553",
"text": "The other answer has some good points, to which I'll add this: I believe you're only considering a company's Initial Public Offering (IPO), when shares are first offered to the public. An IPO is the way most companies get a public listing on the stock market. However, companies often go to market again and again to issue/sell more shares, after their IPO. These secondary offerings don't make as many headlines as an IPO, but they are typical-enough occurrences in markets. When a company goes back to the market to raise additional funds (perhaps to fund expansion), the value of the company's existing shares that are being traded is a good indicator of what they may expect to get for a secondary offering of shares. A company about to raise money desires a higher share price, because that will permit them to issue less shares for the amount of money they need. If the share price drops, they would need to issue more shares for the same amount of money – and dilute existing owners' share of the overall equity further. Also, consider corporate acquisitions: When one company wants to buy another, instead of the transaction being entirely in cash (maybe they don't have that much in the bank!), there's often an equity component, which involves swapping shares of the company being acquired for new shares in the acquiring company or merged company. In that case, the values of the shares in the public marketplace also matter, to provide relative valuations for the companies, etc.",
"title": ""
},
{
"docid": "21975",
"text": "\"In an IPO (initial public offering) or APO (additional public offering) situation, a small group of stakeholders (as few as one) basically decide to offer an additional number of \"\"shares\"\" of equity in the company. Usually, these \"\"shares\"\" are all equal; if you own one share you own a percentage of the company equal to that of anyone else who owns one share. The sum total of all shares, theoretically, equals the entire value of the company, and so with N shares in existence, one share is equivalent to 1/Nth the company, and entitles you to 1/Nth of the profits of the company, and more importantly to some, gives you a vote in company matters which carries a weight of 1/Nth of the entire shareholder body. Now, not all of these shares are public. Most companies have the majority (51%+) of shares owned by a small number of \"\"controlling interests\"\". These entities, usually founding owners or their families, may be prohibited by agreement from selling their shares on the open market (other controlling interests have right of first refusal). For \"\"private\"\" companies, ALL the shares are divided this way. For \"\"public\"\" companies, the remainder is available on the open market, and those shares can be bought and sold without involvement by the company. Buyers can't buy more shares than are available on the entire market. Now, when a company wants to make more money, a high share price at the time of the issue is always good, for two reasons. First, the company only makes money on the initial sale of a share of stock; once it's in a third party's hands, any profit from further sale of the stock goes to the seller, not the company. So, it does little good to the company for its share price to soar a month after its issue; the company's already made its money from selling the stock. If the company knew that its shares would be in higher demand in a month, it should have waited, because it could have raised the same amount of money by selling fewer shares. Second, the price of a stock is based on its demand in the market, and a key component of that is scarcity; the fewer shares of a company that are available, the more they'll cost. When a company issues more stock, there's more shares available, so people can get all they want and the demand drops, taking the share price with it. When there's more shares, each share (being a smaller percentage of the company) earns less in dividends as well, which figures into several key metrics for determining whether to buy or sell stock, like earnings per share and price/earnings ratio. Now, you also asked about \"\"dilution\"\". That's pretty straightforward. By adding more shares of stock to the overall pool, you increase that denominator; each share becomes a smaller percentage of the company. The \"\"privately-held\"\" stocks are reduced in the same way. The problem with simply adding stocks to the open market, getting their initial purchase price, is that a larger overall percentage of the company is now on the open market, meaning the \"\"controlling interests\"\" have less control of their company. If at any time the majority of shares are not owned by the controlling interests, then even if they all agree to vote a certain way (for instance, whether or not to merge assets with another company) another entity could buy all the public shares (or convince all existing public shareholders of their point of view) and overrule them. There are various ways to avoid this. The most common is to issue multiple types of stock. Typically, \"\"common\"\" stock carries equal voting rights and equal shares of profits. \"\"Preferred stock\"\" typically trades a higher share of earnings for no voting rights. A company may therefore keep all the \"\"common\"\" stock in private hands and offer only preferred stock on the market. There are other ways to \"\"class\"\" stocks, most of which have a similar tradeoff between earnings percentage and voting percentage (typically by balancing these two you normalize the price of stocks; if one stock had better dividends and more voting weight than another, the other stock would be near-worthless), but companies may create and issue \"\"superstock\"\" to controlling interests to guarantee both profits and control. You'll never see a \"\"superstock\"\" on the open market; where they exist, they are very closely held. But, if a company issues \"\"superstock\"\", the market will see that and the price of their publicly-available \"\"common stock\"\" will depreciate sharply. Another common way to increase market cap without diluting shares is simply to create more shares than you issue publicly; the remainder goes to the current controlling interests. When Facebook solicited outside investment (before it went public), that's basically what happened; the original founders were issued additional shares to maintain controlling interests (though not as significant), balancing the issue of new shares to the investors. The \"\"ideal\"\" form of this is a \"\"stock split\"\"; the company simply multiplies the number of shares it has outstanding by X, and issues X-1 additional shares to each current holder of one share. This effectively divides the price of one share by X, lowering the barrier to purchase a share and thus hopefully driving up demand for the shares overall by making it easier for the average Joe Investor to get their foot in the door. However, issuing shares to controlling interests increases the total number of shares available, decreasing the market value of public shares that much more and reducing the amount of money the company can make from the stock offering.\"",
"title": ""
},
{
"docid": "306149",
"text": "Fully Paid up Partly Paid up: A company may issue stock to you which is only partly paid up, for example, a company may issue a stock of face value 10 to you and ask you to pay 5 now and other 5 will be adjusted later by some other mechanism. This stock shall be partly paid up. Usually, these stocks are issued in different circumstances, for example as part payment for debentures, preference shares or other capital structuring. On the other hand for a fully paid up share no more money needs to be paid by you or no other adjustments need to be made. So, above, the company is issuing you with stocks for which you will need to pay no further money, they are fully paid for. Authorized Capital: Authorized capital of a company is the amount of money a company can raise by selling stock (not debt, equity). This number is registered when the company is incorporated, subsequently, this number can be revised upward by applying to the registrar of companies. Now, this means that at max. the company is authorized to raise this much capital and no more. However, a company may raise less than this, which is called Issued Capital. In your case, the company is raising its authorized capital by applying to the registrar of companies, though in this case they are looking at their full authorized capital to be issued capital, it was not necessary to do so. Increase of Authorized capital: The main benefit is that the company can get more money in form of equity and utilize the same, perhaps, for expansion of business etc., that is the primary benefit. Bonus Share: Usually, companies keep some surplus as reserve, this money comes out of the profit the company makes and is essentially money of the shareholders. This reserve surplus is maintained for situations, when the money may be required for exigencies. However, this surplus grows over a few years and the company usually the company plans for an expansion of business. However, this money cannot be just taken, as it belongs to the shareholder, so shareholders are issued extra equity in proportion to their current holding and this surplus is capitalized i.e. used as part of the company's equity capital. Bonus declaration does not add t o the value of the company and the share prices fall in proportion (but not quite) to the bonus.",
"title": ""
},
{
"docid": "371720",
"text": "Most of stock trading occurs on what is called a secondary market. For example, Microsoft is traded on NASDAQ, which is a stock exchange. An analogy that can be made is that of selling a used car. When you sell a used car to a third person, the maker of your car is unaffected by this transaction and the same goes for stock trading. Still within the same analogy, when the car is first sold, money goes directly to the maker (actually more complicated than that but good enough for our purposes). In the case of stock trading, this is called an Initial Public Offering (IPO) / Seasoned Public Offering (SPO), for most purposes. What this means is that a drop of value on a secondary market does not directly affect earning potential. Let me add some nuance to this. Say this drop from 20$ to 10$ is permanent and this company needs to finance itself through equity (stock) in the future. It is likely that it would not be able to obtain as much financing in this matter and would either 1) have to rely more on debt and raise its cost of capital or 2) obtain less financing overall. This could potentially affect earnings through less cash available from financing. One last note: in any case, financing does not affect earnings except through cost of capital (i.e. interest paid) because it is neither revenue nor expense. Financing obtained from debt increases assets (cash) and liabilities (debt) and financing obtained from stock issuance increases assets (cash) and shareholder equity.",
"title": ""
},
{
"docid": "420046",
"text": "You should be worried. You have made the mistake of entering an investment on the recommendation of family/friend. The last think you should do is make another mistake of just leaving it and hoping it will go up again. Your stock has dropped 37.6% from its high of $74.50. That means it has to go up over 60% just to reach the high of $74.50. You are correct this may never happen or if it does it could take a long, long time to get up to its previous highs. What is the company doing to turn its fortunes around? Take a look at some other examples: QAN.AX - Qantas Airways This stock reached a high of around $6 in late 2007 after a nice uptrend over a year and a half, it then dropped drastically at the start of the GFC, and has since kept falling and is now priced at just $1.15. QAN reported its first ever loss earlier this year, but its problems were evident much earlier. AAPL - Apple Inc. AAPL reach a high of just over $700 in September 2013, then dropped to around $400 and has recovered a bit to about $525 (still 25% below its highs) and looks to be at the start of another downtrend. How long will it take AAPL to get back to $700, more than 33% from its current price? TEN.AX - Ten Network Holdings Limited TEN reached a high of $4.26 in late 2004 after a nice uptrend during 2004. It then started a steep journey downwards and is still going down. It is now priced at just $0.25, a whopping 94% below its high. It will have to increase by 1600% just to reach its high of $4.26 (which I think will never happen). Can a stock come back from a drastic downtrend? Yes it can. It doesn't always happen, but a company can turn around and can reach and even surpass it previous highs. The question is how and when will this happen? How long will you keep your capital tied up in a stock that is going nowhere and has every chance of going further down? The most important thing with any investment is to protect your current capital. If you lose all your capital you cannot make any new investments until you build up more capital. That is why it is so important to have a risk management strategy and decide what is your get out point if things go against you before you get into any new investment. Have a stop loss. I would get out of your investment before you lose more capital. If you had set a stop loss at 20% off the stock's last highs, you would have gotten out at about $59.60, 28% higher than the current share price of $46.50. If you do further analysis on this company and find that it is improving its prospects and the stock price breaks up through its current ranging band, then you can always buy back in. However, do you still want to be in the stock if it breaks the range band on the downside? In this case who knows how low it can continue to go. N.B. This is my opinion, as others would have theirs, and what I would do in your current situation with this stock.",
"title": ""
},
{
"docid": "457294",
"text": "You also need to remember that stock options usually become valueless if not exercised while an employee of the company. So if there is any chance that you will leave the company before an IPO, the effective value of the stock options is zero. That is the safest and least risky valuation of the stock options. With a Google or Facebook, stock options can be exercised and immediately sold, as they are publicly traded. In fact, they may give stock grants where you sell part of the grant to pay tax withholding. You can then sell the remainder of the grant for money at any time, even after you leave the company. You only need the option/grant to vest to take advantage of it. Valuing these at face value (current stock price) makes sense. That's at least a reasonable guess of future value. If you are absolutely sure that you will stay with the company until the IPO, then valuing the stock based on earnings can make sense. A ten million dollar profit can justify a hundred million dollar IPO market capitalization easily. Divide that by the number of shares outstanding and multiply by how many you get. If anything, that gives you a conservative estimate. I would still favor the big company offers though. As I said, they are immediately tradeable while this offer is effectively contingent on the IPO. If you leave before then, you get nothing. If they delay the IPO, you're stuck. You can't leave the company until then without sacrificing that portion of your compensation. That seems a big commitment to make.",
"title": ""
},
{
"docid": "25195",
"text": "\"If you participate in an IPO, you specify how many shares you're willing to buy and the maximum price you're willing to pay. All the investors who are actually sold the shares get them at the same price, and the entity managing the IPO will generally try to sell the shares for the highest price they can get. Whether or not you actually get the shares is a function of how many your broker gets and how your broker distributes them - which can be completely arbitrary if your broker feels like it. The price that the market is willing to pay afterward is usually a little higher. To a certain extent, this is by design: a good deal for the shares is an incentive for the big (million/billion-dollar) financiers who will take on a good bit of risk buying very large positions in the company (which they can't flip at the higher price, because they'd flood the market with their shares and send the price down). If the stock soars 100% and sticks around that level, though, the underwriting bank isn't doing its job very well: Investors were willing to give the company a lot more money. It's not \"\"stealing\"\", but it's definitely giving the original owners of the company a raw deal. (Just to be clear: it's the existing company's owners who suffer, not any third party.) Of course, LinkedIn was estimated to IPO at $30 before they hiked it to $45, and plenty of people were skeptical about it pricing so high even then, so it's not like they didn't try. And there's a variety of analysis out there about why it soared so much on the first day - fewer shares offered, wild speculative bubbles, no one could get a hold of it to short-sell, et cetera. They probably could have IPO'd for more, but it's unlikely there was, say, $120/share financing available: just because one sucker will pay the price doesn't mean you can move all 7.84 million IPO shares for it.\"",
"title": ""
},
{
"docid": "480967",
"text": "\"Aganju has mentioned put options, which are one good possibility. I would suggest considering an even easier strategy: short selling. Technically you are borrowing the stock from someone and selling it. At some point you repurchase the stock to return to the lender (\"\"covering your short\"\"). If the stock price has fallen, then when you repurchase it, it will be cheaper and you keep the profit. Short selling sounds complicated but it's actually very easy--your broker takes care of all the details. Just go to your brokerage and click \"\"sell\"\" or \"\"sell short.\"\" You can use a market or limit order just like you were selling something you own. When it sells, you are done. The money gets credited to your account. At some point (after the price falls) you should repurchase it so you don't have a negative position any more, but your brokerage isn't going to hassle you for this unless you bought a lot and the stock price starts rising. There will be limits on how much you can short, depending on how much money is in your account. Some stocks (distressed and small stocks) may sometimes be hard to short, meaning your broker will charge you a kind of interest and/or may not be able to complete your transaction. You will need a margin account (a type of brokerage account) to either use options or short sell. They are easy to come by, though. Note that for a given amount of starting money in your account, puts can give you a much more dramatic gain if the stock price falls. But they can (and often do) expire worthless, causing you to lose all money you have spent on them. If you want to maximize how much you make, use puts. Otherwise I'd short sell. About IPOs, it depends on what you mean. If the IPO has just completed and you want to bet that the share price will fall, either puts or short selling will work. Before an IPO you can't short sell and I doubt you would be able to buy an option either. Foreign stocks? Depends on whether there is an ADR for them that trades on the domestic market and on the details of your brokerage account. Let me put it this way, if you can buy it, you can short sell it.\"",
"title": ""
}
] |
12247
|
Jimmy Carter was a president.
|
[
{
"docid": "Carter_Center",
"text": "The Carter Center is a nongovernmental , not-for-profit organization founded in 1982 by former U.S. President Jimmy Carter . He and his wife Rosalynn Carter partnered with Emory University just after his defeat in the 1980 U.S. Presidential elections . The center is located in a shared building adjacent to the Jimmy Carter Library and Museum on 37 acre of parkland , on the site of the razed neighborhood of Copenhill , two miles ( 3 km ) from downtown Atlanta , Georgia . The library and museum are owned and operated by the United States National Archives and Records Administration , while the Center is governed by a Board of Trustees , consisting of business leaders , educators , former government officials , and philanthropists . The Carter Center 's goal is to advance human rights and alleviate human suffering , including helping improve the quality of life for people in more than 80 countries . The center has many projects including election monitoring , supporting locally led state-building and democratic institution-building in various countries , mediating conflicts between warring states , and intervening with heads of states on behalf of victims of human rights abuses . It also leads disease eradication efforts , spearheading the campaign to eradicate Guinea worm disease , as well as controlling and treating onchocerciasis , trachoma , lymphatic filariasis , and malaria through awareness campaigns . In 2002 , President Carter received the Nobel Peace Prize for his work `` to find peaceful solutions to international conflicts , to advance democracy and human rights , and to promote economic and social development '' through the Carter Center . In 2007 , he wrote an autobiography entitled Beyond the White House : Waging Peace , Fighting Disease , Building Hope , which chronicles the first 25 years of The Carter Center .",
"title": ""
},
{
"docid": "Camp_David_Accords",
"text": "The Camp David Accords were signed by Egyptian President Anwar El Sadat and Israeli Prime Minister Menachem Begin on 17 September 1978 , following twelve days of secret negotiations at Camp David . The two framework agreements were signed at the White House , and were witnessed by United States President Jimmy Carter . The second of these frameworks ( A Framework for the Conclusion of a Peace Treaty between Egypt and Israel ) led directly to the 1979 Egypt -- Israel Peace Treaty . Due to the agreement , Sadat and Begin received the shared 1978 Nobel Peace Prize . The first framework ( A Framework for Peace in the Middle East ) , which dealt with the Palestinian territories , was written without participation of the Palestinians and was condemned by the United Nations .",
"title": ""
},
{
"docid": "United_States_presidential_election,_1980",
"text": "The United States presidential election of 1980 was the 49th quadrennial presidential election . It was held on Tuesday , November 4 , 1980 . The contest was between the Democratic national ticket of incumbent President Jimmy Carter from Georgia and Vice President Walter Mondale from Minnesota , and the Republican national ticket of Ronald Reagan , a former Hollywood actor and former Governor from California with his running mate George H.W. Bush , a former Congressman and CIA Director from Texas who would eventually win the presidency eight years later , as well as Republican Congressman John B. Anderson , who ran as an independent . Reagan , aided by the Iran hostage crisis and a worsening economy at home marked by high unemployment and inflation , won the election by a landslide , receiving the highest number of electoral votes ever won by a non-incumbent presidential candidate . Aged 69 at the time , Reagan became the oldest person to ever take the oval office , a record that was later surpassed by Republican Donald Trump , aged 70 , 36 years later . Carter , after defeating Edward M. `` Ted '' Kennedy , the long-time U.S. Senator from Massachusetts and brother of former president John F. Kennedy for the Democratic nomination , attacked Reagan as a dangerous right-wing extremist . For his part , Reagan pledged to uplift the pessimistic mood of the nation , and won a decisive victory ; in the simultaneous Congressional elections , Republicans won control of the United States Senate for the first time since 1955 . This election marked the beginning of what is called the `` Reagan Revolution '' or Reagan Era , and signified a conservative realignment in national politics .",
"title": ""
},
{
"docid": "Jimmy_Carter",
"text": "James Earl Carter Jr. ( born October 1 , 1924 ) is an American politician who served as the 39th President of the United States from 1977 to 1981 . A member of the Democratic Party , he served as the Governor of Georgia prior to his election as president . Carter has remained active in public life during his post-presidency , and in 2002 he was awarded the Nobel Peace Prize for his work with the Carter Center . Carter joined the United States Navy after graduating high school , serving on nuclear submarines . He left the Navy in 1953 to return to Georgia , where he worked as a peanut farmer . From 1963 to 1967 , Carter served in the Georgia State Senate . In 1970 , Carter won election as Governor of Georgia , defeating former Governor Carl Sanders in the Democratic primary . He served as governor from 1971 to 1975 . Despite being little-known outside of Georgia at the start of the campaign , Carter won the 1976 Democratic presidential nomination . In the general election , Carter defeated incumbent Republican President Gerald Ford in a relatively close election . On his second day in office , Carter pardoned all evaders of the Vietnam War drafts . During Carter 's term as President , two new cabinet-level departments , the Department of Energy and the Department of Education , were established . He established a national energy policy that included conservation , price control , and new technology . In foreign affairs , Carter pursued the Camp David Accords , the Panama Canal Treaties , the second round of Strategic Arms Limitation Talks ( SALT II ) , and the return of the Panama Canal Zone to Panama . On the economic front he confronted persistent `` stagflation '' , a combination of high inflation , high unemployment and slow growth . The end of his presidential tenure was marked by the 1979 -- 1981 Iran hostage crisis , the 1979 energy crisis , the Three Mile Island nuclear accident , and the Soviet invasion of Afghanistan . In response to the invasion , Carter ended détente , escalated the Cold War , and led the international boycott of the 1980 Summer Olympics in Moscow . In 1980 , Carter faced a primary challenge from Senator Ted Kennedy , but Carter won re-nomination at the 1980 Democratic National Convention . Carter lost the general election in an electoral landslide to Republican nominee Ronald Reagan . Polls of historians and political scientists usually rank Carter as a below average president . In 2012 , he surpassed Herbert Hoover as the longest-retired president in U.S. history , and he is also the first president to mark the 40th anniversary of his inauguration . He set up the Carter Center in 1982 as his base for advancing human rights . He has also traveled extensively to conduct peace negotiations , observe elections , and advance disease prevention and eradication in developing nations . Additionally , Carter is a key figure in the Habitat for Humanity project and he has written several books about various topics . In reference to current political views , he has criticized some of Israel 's actions and policies in regards to the Israeli -- Palestinian conflict and has advocated for a two-state solution . He has vigorously opposed the Supreme Court 's decision in Citizens United v. FEC to strike down limits on campaign spending by corporations and unions , saying that the U.S. is `` no longer a functioning democracy '' and now has a system of `` unlimited political bribery . ''",
"title": ""
}
] |
[
{
"docid": "Timeline_of_the_presidency_of_Jimmy_Carter",
"text": "The presidency of Jimmy Carter began on January 20 , 1977 when Jimmy Carter was inaugurated as President of the United States , and ended on January 20 , 1981 .",
"title": ""
},
{
"docid": "USS_Jimmy_Carter",
"text": "USS Jimmy Carter ( SSN-23 ) is the third and last Seawolf-class submarine in the United States Navy . She is named for Jimmy Carter , the 39th President of the United States ; Carter is the only President who had qualified in submarines , having served as a Communications Officer , Sonar Officer , Electronics Officer , Weapons Officer , and Supply Officer while on board . Jimmy Carter is one of the few ships of the United States Navy ( and only the third submarine ) to have been named for a person who was alive at the time of the ship 's naming , and the only submarine to be named for a living former president .",
"title": ""
},
{
"docid": "Inauguration_of_Jimmy_Carter",
"text": "The Inauguration of Jimmy Carter as the 39th President of the United States was held on Thursday , January 20 , 1977 , on the East Portico of the United States Capitol in Washington D.C. . The inauguration marked the commencement of the only four-year term of Jimmy Carter as President and of Walter Mondale as Vice President . Chief Justice Warren E. Burger administered the presidential oath of office to Carter , and Speaker of the House Tip O'Neill administered the vice presidential oath of office to Mondale . This was the last inauguration held on the East Portico of the Capitol building to date .",
"title": ""
},
{
"docid": "Jimmy_&_Rosalynn_Carter_Work_Project",
"text": "The Jimmy & Rosalynn Carter Work Project - formerly the Jimmy Carter Work Project ( JCWP ) - is an annual home building blitz organized by Habitat for Humanity International and its affiliates . It generally takes place in the United States one year , and an international location the next . President Jimmy Carter and Rosalynn Carter helped Habitat volunteers renovate the 19-unit building , and media coverage brought attention to Habitat , which had been founded in 1976 in Americus , Georgia , a short distance from Carter 's hometown of Plains , Georgia . Even though President Carter has said repeatedly he never intended to start an annual project , the following year the Carters returned to the same site to finish the renovation work . On Oct. 10 , 2013 , as part of the 30th annual project , the Carters returned to the building and met with families living there . By 2013 , the Jimmy & Rosalynn Carter Work Project had helped more than 3,800 families move into safe , affordable shelter in 14 countries . Over the years , more than 89,000 volunteers from all over the world have signed up to build alongside the Carters . The Carter Work Projects started modestly and built slowly . Early projects were held in the United States , and were relatively small compared to later years .",
"title": ""
},
{
"docid": "Mary_Prince_(nanny)",
"text": "Mary Prince is a woman convicted of murder who then became the nanny for Amy Carter , the daughter of Jimmy Carter and Rosalynn Carter . Prince became Amy 's nanny in 1971 while Jimmy Carter was governor of Georgia and she was a prisoner assigned to the governor 's mansion . She had been convicted of murdering another woman 's boyfriend in 1970 . In 1975 , when Jimmy Carter 's term as governor ended , she was sent back to prison ; however , in January , 1977 Prince was able to travel to Washington for Carter 's inauguration as U.S. president . With a letter from the White House to Georgia prison officials , she was reprieved , and Prince was able to work at the White House . Jimmy Carter was designated as her parole officer , and she lived in the White House for the four years of his presidency . Jimmy Carter dedicated his 2005 book , Sharing Good Times , to Prince , and discusses her in his 2006 book , Our Endangered Values : America 's Moral Crisis . Prince is also featured in the 2015 Kate Anderson Brower book The Residence : Inside the Private World of the White House .",
"title": ""
},
{
"docid": "Jimmy_Carter_National_Historic_Site",
"text": "The Jimmy Carter National Historic Site , located in Plains , Georgia , preserves sites associated with James Earl `` Jimmy '' Carter , Jr. ( 1924 -- present ) , 39th President of the United States . These include his residence , boyhood farm , school , and the town railroad depot , which served as his campaign headquarters during the 1976 election . The building which used to be Plains High School ( opened in 1921 and closed in 1979 ) serves as the park 's museum and visitor center . As President Carter lives in Plains , the area surrounding the residence is under the protection of the United States Secret Service and is not open to the public . The Carters returned to Plains in January 1981 . The former President and First Lady Rosalynn Carter pursue many of the goals of his administration through the Carter Center in Atlanta , which has programs to alleviate human suffering and to promote human rights and world peace . When they are in Plains , Carter teaches Sunday school at Maranatha Baptist Church , which is open to the public .",
"title": ""
},
{
"docid": "Jimmy_Carter_Library_and_Museum",
"text": "The Jimmy Carter Library and Museum in Atlanta , Georgia houses U.S. President Jimmy Carter 's papers and other material relating to the Carter administration and the Carter family 's life . The library also hosts special exhibits , such as Carter 's Nobel Peace Prize and a full-scale replica of the Oval Office , including a reproduction of the Resolute desk . The Carter Library and Museum includes some parts that are owned and administered by the federal government , and some that are privately owned and operated . The library and museum are run by the National Archives and Records Administration and are part of the Presidential Library system of the federal government . Privately owned areas house Carter 's offices and the offices of the Carter Center , a non-profit human rights agency . The building housing the library and museum makes up 69,750 square feet ( 6480 m ² ) , with 15,269 square feet ( 1419 m ² ) of space for exhibits and 19,818 square feet ( 1841 m ² ) of archive and storage space . The library stacks house 27 million pages of documents ; 500,000 photos , and 40,000 objects , along with films , videos , and audiotapes . These collections cover all areas of the Carter administration , from foreign and domestic policy to the personal lives of President and Mrs. Carter . The complex lies next to Freedom Parkway , which was originally called `` Presidential Parkway '' ( and at one point , `` Jimmy Carter Parkway '' ) in its planning stages .",
"title": ""
},
{
"docid": "Jimmy_Carter_Supreme_Court_candidates",
"text": "During President Jimmy Carter 's term in office , no vacancy occurred on the Supreme Court of the United States . Carter thus became the first president since Andrew Johnson and the fourth president overall ( after William Henry Harrison , Zachary Taylor and Johnson ) to complete his term without making any appointments to the Supreme Court .",
"title": ""
},
{
"docid": "Jimmy_Carter_rabbit_incident",
"text": "The Jimmy Carter rabbit incident , dubbed the `` killer rabbit '' attack by the media , involved a swamp rabbit that swam toward then -- U.S. President Jimmy Carter 's fishing boat on April 20 , 1979 . The incident caught press imagination after Carter 's press secretary mentioned the event to a correspondent months later .",
"title": ""
},
{
"docid": "List_of_federal_judges_appointed_by_Jimmy_Carter",
"text": "Following is a list of all United States federal judges appointed by President Jimmy Carter during his presidency . In total Carter appointed 259 federal judges , including 56 judges to the courts of appeals and 203 judges to the United States district courts . Although Carter made no appointments to the Supreme Court of the United States , two of his Court of Appeals appointees - Stephen Breyer and Ruth Bader Ginsburg - were later appointed to the Supreme Court by Bill Clinton . Later presidents have exceeded Carter 's total , itself which surpassed the previous record of 231 set by Richard Nixon , but Carter retains the record for the largest number of judicial appointments in a single term .",
"title": ""
},
{
"docid": "Presidency_of_Jimmy_Carter",
"text": "The presidency of Jimmy Carter began on January 20 , 1977 at noon Eastern Standard Time , when Jimmy Carter was inaugurated as President of the United States , and ended on January 20 , 1981 . A Democrat , he took office after defeating Republican incumbent President Gerald Ford in the 1976 presidential election . His presidency ended with his defeat in the 1980 presidential election by Republican Ronald Reagan . Carter , the 39th United States president , sought to make the government `` competent and compassionate '' but , in the midst of an economic crisis produced by rising energy prices and stagflation , met with difficulty in achieving its objectives . At the end of his administration , Carter had seen a substantial decrease in unemployment and a partial reduction of the deficit , but the recession ultimately continued . Carter created the United States Department of Education and United States Department of Energy , established a national energy policy and pursued civil service and social security reform . In foreign affairs , Carter strongly emphasized human rights throughout his career . He signed the second round of the Strategic Arms Limitation Talks ( SALT II ) with the Soviet Union and , in an effort to end the Arab -- Israeli conflict , initiated the Camp David Accords . With the Torrijos -- Carter Treaties , he guaranteed the transfer of the Panama Canal to Panama in 1999 . His administration also established official diplomatic relations with the People 's Republic of China , while he signed the Taiwan Relations Act to define relations with Taiwan . The final year of his presidential tenure was marked by several major crises , including the 1979 takeover of the American embassy in Iran and holding of hostages by Iranian students , an unsuccessful rescue attempt of the hostages , serious fuel shortages , and the Soviet invasion of Afghanistan . In the 1980 election , Carter defeated a primary challenge from Ted Kennedy , a prominent liberal Democrat . However , Carter lost the general election in a landslide to Reagan . In polls of historians and political scientists , Carter is usually ranked as a below-average president .",
"title": ""
},
{
"docid": "United_States_presidential_election_in_Missouri,_1976",
"text": "The 1976 United States presidential election in Missouri took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose twelve representatives , or electors , to the Electoral College , who voted for President and Vice President . Missouri was won by Jimmy Carter ( D -- Georgia ) , with 51.10 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 47.47 % of the popular vote . Jimmy Carter went on to become the 39th President of the United States .",
"title": ""
},
{
"docid": "Amy_Carter",
"text": "Amy Lynn Carter ( born October 19 , 1967 ) is the only daughter of former U.S. President Jimmy Carter and his wife Rosalynn Carter . Carter entered the limelight as a child when she lived in the White House during the Carter presidency .",
"title": ""
},
{
"docid": "Jimmy_Carter_UFO_incident",
"text": "The Jimmy Carter UFO incident was an incident in which Jimmy Carter ( US President 1977 -- 1981 ) reported seeing an unidentified flying object while at Leary , Georgia , in 1969 . While governor of Georgia , Carter was asked to file a report of the sighting by the International UFO Bureau in Oklahoma City , Oklahoma , which he did in September 1973 . Since its writing , the report has been discussed several times by both ufologists and by members of the mainstream media .",
"title": ""
},
{
"docid": "United_States_presidential_election_in_Rhode_Island,_1976",
"text": "The 1976 United States presidential election in Rhode Island took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose four representatives , or electors , to the Electoral College , who voted for President and Vice President . Rhode Island was won by Jimmy Carter ( D -- Georgia ) , with 55.36 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 44.08 % of the popular vote . No third party candidate received any votes . Jimmy Carter went on to become the 39th President of the United States .",
"title": ""
},
{
"docid": "List_of_executive_actions_by_Jimmy_Carter",
"text": "Executive Orders 11967 -- 12286 ( Presidency of Jimmy Carter )",
"title": ""
},
{
"docid": "United_States_presidential_election_in_Delaware,_1976",
"text": "The 1976 United States presidential election in Delaware took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose three representatives , or electors , to the Electoral College , who voted for President and Vice President . Delaware was won by Jimmy Carter ( D -- Georgia ) , with 51.98 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 46.57 % of the popular vote . No third party candidate amounted 1 % of the vote , but Eugene McCarthy ( Independent -- Minnesota ) finished third in Delaware with 1.03 % of the statewide popular vote . Jimmy Carter went on to become the 39th President of the United States .",
"title": ""
},
{
"docid": "United_States_presidential_election_in_Louisiana,_1976",
"text": "The 1976 United States presidential election in Louisiana took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose ten representatives , or electors , to the Electoral College , who voted for President and Vice President . Louisiana was won by Jimmy Carter ( D -- Georgia ) , with 51.73 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 45.95 % of the popular vote . No third party candidate amounted 1 % of the vote ; American Independent Party candidate Lester Maddox cane the closest with 0.79 % . Jimmy Carter went on to become the 39th President of the United States .",
"title": ""
},
{
"docid": "Bibliography_of_Jimmy_Carter",
"text": "Books authored by Jimmy Carter , the 39th President of the United States ( 1977 -- 1981 ) . A historical novel about the American Revolution , and the first work of fiction written by a U.S. President . Won a Grammy Award for best spoken-word album . UK edition of Our Endangered Values .",
"title": ""
},
{
"docid": "Ruth_Clusen",
"text": "Ruth Chickering Clusen ( 1922 -- 2005 ) was an American conservationist , politician , civil rights activist , and government official . She is remembered for serving as the president of the League of Women Voters , for hosting the debates between Jimmy Carter and Gerald Ford , and for serving as the Assistant Secretary of Energy under President Jimmy Carter .",
"title": ""
},
{
"docid": "United_States_presidential_election_in_Kentucky,_1976",
"text": "The 1976 United States presidential election in Kentucky took place on November 2 , 1976 , as part of the 1976 United States presidential election . Voters chose nine representatives , or electors , to the Electoral College , who voted for President and Vice President . Kentucky was won by Jimmy Carter ( D -- Georgia ) , with 52.75 % of the popular vote . Carter defeated incumbent President Gerald Ford ( R -- Michigan ) , who finished with 45.57 % of the popular vote , and did so by winning all major demographic groups in the Commonwealth . No third party candidate amounted 1 % of the vote ; American Party candidate Thomas Anderson cane the closest with 0.71 % . Jimmy Carter went on to become the 39th President of the United States .",
"title": ""
},
{
"docid": "Chip_Carter",
"text": "Chip Carter may refer to : James Earl `` Chip '' Carter III , son of former president Jimmy Carter Chip Carter , Former sports director of WTVT",
"title": ""
},
{
"docid": "Amy_Carter_(politician)",
"text": "Amy Carter is a Republican member of the Georgia House of Representatives , representing the 175th district since 2007 . Her district includes part of Lowndes County , primarily the city of Valdosta . Carter bears no relation to former President Jimmy Carter , who has a daughter of the same name . Her legislative district is about 120 mi south of President Carter 's hometown of Plains .",
"title": ""
},
{
"docid": "Lillian_Gordy_Carter",
"text": "Bessie Lillian Gordy Carter ( August 15 , 1898 -- October 30 , 1983 ) was the mother of former President of the United States , Jimmy Carter . She was also known for her contribution to nursing in her home state of Georgia and as a Peace Corps volunteer in India as well as writing two books during the Carter presidency .",
"title": ""
},
{
"docid": "List_of_honors_and_awards_received_by_Jimmy_Carter",
"text": "U.S. President Jimmy Carter ( born 1924 ) has received numerous accolates , awards , and honorary degrees . Several places , institutions , and other things have been named for him .",
"title": ""
},
{
"docid": "Jimmy_Carter_judicial_appointment_controversies",
"text": "During President Jimmy Carter 's presidency , he nominated four people for four different federal appellate judgeships who were not processed by the Democratic-controlled Senate Judiciary Committee before Carter 's presidency ended . None of the four nominees were renominated by Carter 's successor , President Ronald Reagan . Three of the nominees who were not processed ( Eugene Nickerson , Nicholas Bua and Howard F. Sachs ) were nominated after July 1 , 1980 , the traditional start date of the unofficial Thurmond Rule during a presidential election year . All four seats eventually were filled by appointees of President Ronald Reagan . The four nominees were blocked in committee ; no committee hearings ever were held for any of the three . The nominees were held up at the same time that in an unprecedented move , the Senate chose to take up Carter 's November 13 , 1980 , nomination -- after he already had lost the 1980 presidential election to Ronald Reagan -- of Stephen Breyer to an appellate judgeship on the United States Court of Appeals for the First Circuit . The Senate wound up confirming Breyer ( whom President Bill Clinton appointed to the United States Supreme Court in 1994 ) during the lame-duck session of the 96th Congress the following month . ( Breyer 's appellate court confirmation in 1980 , which was the result of support from both Democrats and Republicans on the Senate Judiciary Committee , often is cited as evidence disproving the existence of the Thurmond Rule . ) During his presidency , Carter also nominated 16 people for 15 different federal district judgeships who were never confirmed by the United States Senate .",
"title": ""
},
{
"docid": "Gerald_Ford_judicial_appointment_controversies",
"text": "During President Gerald Ford 's presidency , he nominated two people for two different federal appellate judgeships who were not processed by the Democratic-controlled Senate Judiciary Committee before Ford 's presidency ended . Neither of the two nominees was renominated by Ford 's successor , President Jimmy Carter . Both nominees were nominated after July 1 , 1976 , the traditional start date of the unofficial Thurmond Rule during a presidential election year . Both seats eventually were filled by appointees of President Jimmy Carter . The two nominees were blocked in committee ; no committee hearings ever were held for either one .",
"title": ""
},
{
"docid": "Jason_Carter",
"text": "Jason Carter may refer to : Jason Carter ( gridiron football ) ( born 1982 ) , American football player Jason Carter ( actor ) ( born 1960 ) , English actor Jason Carter ( fiddler ) Jason Carter ( harp-guitarist ) and documentary filmmaker Jason Carter ( politician ) ( born 1975 ) , state senator of Georgia and grandson of former U.S. President Jimmy Carter",
"title": ""
},
{
"docid": "Jack_Carter_(politician)",
"text": "John William `` Jack '' Carter ( born July 3 , 1947 ) is an American businessman and politician who unsuccessfully ran for the United States Senate in Nevada in 2006 . Carter is the eldest child of former President Jimmy Carter and former First Lady Rosalynn Carter .",
"title": ""
},
{
"docid": "Gloria_Carter_Spann",
"text": "Gloria Carter Spann ( October 22 , 1926 -- March 5 , 1990 ) was a sister of former United States President Jimmy Carter .",
"title": ""
}
] |
168685
|
Jane Lynch is an American comedian.
|
[
{
"docid": "Jane_Lynch",
"text": "Jane Marie Lynch ( born July 14 , 1960 ) is an American actress , singer , and comedian . She is best known as Sue Sylvester on Glee . She also gained fame in Christopher Guest 's improv mockumentary pictures such as Best in Show . Lynch 's television cameos include an appearance in the Nickelodeon situation comedy iCarly and the Showtime dark comedy series Weeds . Lynch had a recurring role in the Warner Bros. situation comedy Two and a Half Men from 2004 to 2014 and was nominated for a Primetime Emmy Award for her performance in 2010 . She has also had other notable roles in numerous mainstream comedies , such as Talladega Nights : The Ballad of Ricky Bobby , The 40-Year-Old Virgin , Role Models and The Three Stooges . Her portrayal of Sue Sylvester in Glee has won numerous awards , including the Primetime Emmy Award , Golden Globe Award , Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Comedy Series , TCA Award for Individual Achievement in Comedy , Satellite Award for Best Supporting Actress -- Series , Miniseries , or Television Film , and the People 's Choice Award for Favorite TV Comedy Actress . On September 4 , 2013 , Lynch received the 2,505 th star on the Hollywood Walk of Fame in the category of television located at 6640 Hollywood Blvd. . Lynch has lent her voice to multiple animated films , including Space Chimps , Ice Age : Dawn of the Dinosaurs , Shrek Forever After and Wreck-It Ralph . Since 2013 , she has hosted the NBC game show Hollywood Game Night , for which she has won two Emmy Awards .",
"title": ""
}
] |
[
{
"docid": "List_of_works_by_Jane_Lynch",
"text": "This is a list of works by American actress , singer , and comedian Jane Lynch .",
"title": ""
},
{
"docid": "Ron_Lynch",
"text": "Ron Lynch may refer to : Ron Lynch ( cricketer ) ( 1923-2012 ) , English cricketer Ron Lynch ( American football ) ( born 1940 ) , American football coach Ron Lynch ( comedian ) ( born 1951 ) , American stand-up comedian and actor Ron Lynch ( rugby league ) , Australian rugby league footballer",
"title": ""
},
{
"docid": "Stephen_Lynch",
"text": "Stephen Lynch may refer to : Stephen Lynch ( musician ) ( born 1971 ) , American musician and comedian Stephen Lynch fitz Dominick Dubh ( fl . 1504 -- 1523 ) , mayor of Galway Stephen Lynch ( English cricketer ) ( born 1951 ) Stephen Lynch ( New Zealand cricketer ) ( born 1976 ) Stephen Lynch ( Franciscan ) , a member of the Order of Saint Francis Stephen Lynch ( professor ) , Australian liver transplant surgeon Stephen Andrew Lynch ( 1882 -- 1969 ) , motion picture industry pioneer Stephen F. Lynch ( born 1955 ) , United States Representative from Massachusetts Steve Lynch ( born 1955 ) , original lead guitarist for the band Autograph",
"title": ""
},
{
"docid": "Ron_Lynch_(comedian)",
"text": "Ron Lynch is an American stand-up comedian , actor , and writer . He has appeared in a number of movies and television shows . He has worked as a voice actor for several animated shows , including Home Movies , Bob 's Burgers , and Tom Goes to the Mayor , and has made guest appearances on Dr. Katz , Professional Therapist , The Sarah Silverman Program , Andy Richter Controls the Universe , Adventure Time , and Comedy Bang ! Bang ! . Lynch hosts a weekly musical and comedic variety show called Tomorrow ! comedy show , every Saturday night at midnight at The Steve Allen Theater in Hollywood , California . Other live shows he has performed in include a show called The Idiots , performed with co-writer and co-actor Craig Anton and a rotating cast of characters .",
"title": ""
},
{
"docid": "Carmen_Lynch",
"text": "Carmen Lynch ( born 1988 ) is a Spanish-American comedian , actress , and writer based in New York City . She has performed in English and Spanish in the United States and Spain . She has appeared on Conan , Inside Amy Schumer , Last Comic Standing , The Late Show with David Letterman , and The Late Show with Stephen Colbert .",
"title": ""
},
{
"docid": "Stephen_Lynch_(musician)",
"text": "Stephen Andrew Lynch ( born July 28 , 1971 ) , is an American comedian , musician and Tony Award-nominated actor who is known for his songs mocking daily life and popular culture . Lynch has released three studio albums and three live albums along with a live DVD . He has appeared in two Comedy Central Presents specials and starred in the Broadway adaptation of The Wedding Singer . Stephen released a new double-disc ( Studio & Live ) album , Lion , on November 13 , 2012 . Most recently , Stephen released a live concert video called `` Hello Kalamazoo '' available on Vimeo .",
"title": ""
},
{
"docid": "Casey_Jane_Ellison",
"text": "Casey Jane Ellison ( born March 29 , 1988 ) is an American stand-up comedian , writer and multimedia artist .",
"title": ""
},
{
"docid": "Lion_(Stephen_Lynch_album)",
"text": "Lion is the fifth album by American comedian Stephen Lynch , released in 2012 . The first half of the album was recorded at Studio G ! ( Nashville , Tennessee ) and the second half of the album was recorded live from Symphony Space ( New York City ) . Lynch told interviewer Dylan Gadino , `` I wanted this album to have the Americana flavor to it that I love so much in the music of , say , Neil Young or Patty Griffin or Ray LaMontagne . I think it does ... And , I 'm confident the songs are still funny , if a bit subtler than some of my earlier work . Astute listeners will detect a slight shift of direction , comedy-wise . Musically , it 's the best work I 've ever done . I 'm a little bit in love with it . ''",
"title": ""
},
{
"docid": "Afternoon_Delight_(film)",
"text": "Afternoon Delight is a 2013 American comedy-drama film written and directed by Jill Soloway . The film stars Kathryn Hahn , Juno Temple , Josh Radnor , and Jane Lynch .",
"title": ""
},
{
"docid": "The_Late_Bloomer",
"text": "The Late Bloomer is an American comedy-drama film directed by Kevin Pollak and written by Gary Rosen , Joe Nussbaum , Paul A. Kaplan & Mark Torgove , and Kyle Cooper & Austyn Jeffs . It is based on journalist Ken Baker 's autobiographical Man Made : A Memoir of My Body . It stars Johnny Simmons , Maria Bello , Brittany Snow , Jane Lynch , J. K. Simmons , Kumail Nanjiani , Beck Bennett and Paul Wesley . The film had its world premiere at the San Diego Film Festival on September 30 , 2016 . The film was scheduled to be released in a limited release and through video on demand on October 7 , 2016 , by Momentum Pictures . The film was met with general dislike , the Hollywood Reporter saying that while Johnny Simmons fits his role perfectly , many secondary actors such as J.K. Simmons , Jane Lynch , Laraine Newman , Illeana Douglas , Maria Bello and Brian Doyle-Murray have fun in their stereotypical roles , but J.K. Simmons and Maria Bello , in particular , seem severely overqualified for their roles .",
"title": ""
},
{
"docid": "Reno_(comedian)",
"text": "Reno is an American stand-up comedian and actress known for such films as Quiz Show , The Manchurian Candidate , The Hard Way and Kinsey . She also hosted her own 2001 reality documentary television series on Bravo called Citizen Reno which was produced by Lily Tomlin and Jane Wagner .",
"title": ""
},
{
"docid": "Keavy_Lynch",
"text": "Keavy-Jane Elizabeth Annie Lynch ( born 15 December 1979 ) is an Irish singer . She is best known for being a member of the girl group B * Witched , of which her twin sister Edele is also a member .",
"title": ""
},
{
"docid": "From_Method_to_Madness",
"text": "`` From Method to Madness '' is the 18th episode of the third season of the American television show Family Guy . It features the guest performances of Chris Cox , Ralph Garman , Mike Henry , Jane Lynch , Rachael MacFarlane , Denis Martell , Mark Peredes , and Fred Willard .",
"title": ""
},
{
"docid": "Sleepover_(film)",
"text": "Sleepover is a 2004 American teen film directed by Joe Nussbaum and starring Alexa Vega , Sara Paxton , Mika Boorem , Scout Taylor-Compton , Kallie Flynn Childress , Sean Faris , Steve Carell , Jane Lynch , Sam Huntington , Brie Larson and Evan Peters .",
"title": ""
},
{
"docid": "Janeite",
"text": "The term Janeite has been both embraced by devotees of the works of Jane Austen and used as a term of opprobrium . According to Austen scholar Claudia Johnson Janeitism is `` the self-consciously idolatrous enthusiasm for ` Jane ' and every detail relative to her '' . Janeitism did not begin until after the publication of J. E. Austen-Leigh 's A Memoir of Jane Austen in 1870 , when the literary elite felt that they had to separate their appreciation of Austen from that of the masses . The term Janeite was originally coined by the literary scholar George Saintsbury in his 1894 introduction to a new edition of Pride and Prejudice . As Austen scholar Deidre Lynch explains , `` he meant to equip himself with a badge of honor he could jubilantly pin to his own lapel '' . In the early twentieth century , Janeitism was `` principally a male enthusiasm shared among publishers , professors , and literati '' . Rudyard Kipling even published a short story entitled `` The Janeites '' about a group of World War I soldiers who were secretly fans of Austen 's novels . During the 1930s and 1940s , when Austen 's works were canonized and accepted within the academy , the term began to change meaning . It was used to signify those who appreciated Austen in the `` wrong '' way and the term , according to Lynch , is `` now used almost exclusively about and against other people '' ( emphasis in original ) . Modern Janeites are described by their most fervent detractors in the same tones as Trekkies ; academically speaking , the Janeite phenomenon can be seen as the very first `` subculture '' with all the attendant aspects , including pejorative but also positive . Johnson noted Janeites are `` derided and marginalized by dominant cultural institutions bent on legitimizing their own objects and protocols of expertise '' . It remains a popular interest however , with such recent books as 2013 's Among the Janeites : A Journey through the World of Jane Austen Fandom and Global Jane Austen : Pleasure , Passion , and Possessiveness in the Jane Austen Community . At the same time , Austen remains a topic of serious academic inquiry at top global universities in a way to which very recent subcultures are only just beginning to aspire . Scholars such as Johnson and Lynch study `` the ludic enthusiasm of -LSB- the -RSB- amateur reading clubs , whose ` performances ' include teas , costume balls , games , readings , and dramatic representations , staged with a campy anglophilia in North America , and a brisker antiquarian meticulousness in England , and whose interests range from Austenian dramatizations , to fabrics , to genealogies , and to weekend study trips '' . Lynch has described committed Janeites as members of a cult , comparing their travels to places Austen lived or places described in her novels or their adaptations as pilgrimages , for example . She argues that such activities provide `` a kind of time-travel to the past , because they preserve an all but vanished Englishness or set of ` traditional ' values ... This may demonstrate the influence of a sentimental account of Austen 's novels that presents them as means by which readers might go home again -- to a comfortable , soothingly normal world . ''",
"title": ""
},
{
"docid": "Sue_Sylvester",
"text": "Susan `` Sue '' Sylvester is a fictional character of the Fox musical comedy-drama series , Glee . The character is portrayed by actress Jane Lynch , and has appeared in Glee from its pilot episode , first broadcast on May 19 , 2009 . Sue was developed by Glee creators Ryan Murphy , Brad Falchuk , and Ian Brennan . For the show 's first four seasons , Sue is the track-suit wearing coach of the William McKinley High School cheerleading squad , and a ruthless bully to both students and faculty members alike . Because her cheerleading squad competes with the glee club for the school 's limited funding , she is often at odds with the club and more particularly its director Will Schuester ( Matthew Morrison ) . Sue is the main antagonist throughout the series ' run . In the show 's fifth season , Sue is made the school 's new principal . Due to Lynch 's initial limited availability , Sue was originally set to be a recurring character while Lynch was working on a Damon Wayans pilot for the American Broadcasting Company ( ABC ) . When that pilot fell through , Sue became a starring role . The character has been acclaimed by critics . Mary McNamara for the Los Angeles Times has written that `` Lynch alone makes Glee worth watching '' , while Entertainment Weekly Ken Tucker has called Sue `` the greatest Broadway-musical villain to ever co-star in a TV series '' . In recognition of her portrayal of Sue , Lynch won an Emmy and a Golden Globe Award .",
"title": ""
},
{
"docid": "Mary_Jane's_Last_Dance",
"text": "`` Mary Jane 's Last Dance '' is a song written by Tom Petty and recorded by American rock band Tom Petty and the Heartbreakers . It was recorded on July 22 , 1993 , while Petty was recording his Wildflowers album , and was produced by Rick Rubin , guitarist Mike Campbell , and Tom Petty . The sessions would prove to be the last to include drummer Stan Lynch before his eventual departure in 1994 . This song was first released as part of the Greatest Hits album in 1993 . It rose to # 14 on the Billboard Hot 100 , becoming his first Billboard Top 20 hit of the 1990s , and also topped the Billboard Album Rock Tracks chart for two weeks .",
"title": ""
},
{
"docid": "Jane_Kennedy",
"text": "Jane Kennedy may refer to : Jane Kennedy ( courtier ) ( died 1589 ) , Scottish courtier Jane Kennedy ( actress ) ( born 1964 ) , Australian actress and comedian Jane Kennedy ( politician ) ( born 1958 ) , British Labour Party Member of Parliament",
"title": ""
},
{
"docid": "Trevor_Dwyer-Lynch",
"text": "Trevor Dwyer-Lynch 1968 , is a Black British actor , presenter , and stand up comedian . Born and raised in Moss Side and Salford , calls himself a `` Mossfordian '' trained in Drama and Performing Arts at City College / Arden School of Theatre Manchester in 1990 , Dwyer-Lynch has appeared in numerous television and theatre productions , merging both serious roles -- such as `` Gloucester '' in Shakespeare 's King Lear -- to his best known comedic role in Coronation Street as Patrick Tussell the taxi-driver working for Steve McDonald ( 2002 -- 2005 ) . A dog lover , his 15-stone , Old English Mastiff also appeared with him in an episode , his dog spoiling `` Patrick 's '' attempt to win over love interest Janice Battersby . Lynch achieved one of his wishes working for the Ken Loach in `` Looking for Eric '' , he publicly expresses a desire to work with Directors Shane Meadows , Mike Leigh and Steve McQueen A keen sportsman , Ex Part-time professional footballer , boxing , golf and squash are amongst the sports he has been involved in . Dwyer-Lynch is also a professional qualified Uefa ` B ' licence football coach , having worked on both Manchester United and City 's Community Football and Centre of Excellence Schemes . He merges acting and coaching together . When available , Dwyer-Lynch plays for a celebrity football team , consisting of actors and ex-professional footballers , raising money for various charities , including Cancer , NSPCC , Drugs and Drink addiction , Terminally ill children and Sickle Cell . Some of the many grounds he has played at include Wembley stadium and Old Trafford . Desmond Tutu and Pelé managed him in an International celebrity match at Stoke Citys ground `` Brazil v England '' with Gordan Banks being the England boss . On meeting Pele , Dwyer-Lynch commented to him , that although the greatest footballer in the world , Dwyer-Lynch had achieved something Pele had n't , by playing at Wembley 3 times , Pele never played there in his career . Dwyer-Lynch established , alongside his '' brother from another universe '' The brilliant stand up comic Justin Moorhouse ( `` Kenny Junior '' from Phoenix Nights and Key 103 D.J. ) the first and only Smoke Free Comedy Zone in Manchester at The Circle Club some 18 months before the official smoke-free ban came into force and where many stand up comedians appeared including John Bishop , Jason Manford and Tony Hendriks .",
"title": ""
},
{
"docid": "Carla_Lynch",
"text": "Carla Jade Lynch ( born 19 May 1984 , Newcastle upon Tyne ) is a British comedian and model who plays the `` Scummy Mummy '' in Channel 4 's comedy show Balls of Steel . Carla got her first break in television as a presenter on Channel 4 's Whatever in 2006 .",
"title": ""
},
{
"docid": "Laura_Silverman",
"text": "Laura Jane Silverman ( born June 10 , 1966 ) is an American actress and voice actress , and the older sister of comedian Sarah Silverman . She is best known for portraying a fictionalized version of herself alongside her sister in Sarah Silverman : Jesus is Magic and The Sarah Silverman Program . She also stars as Jane Benson on The Comeback with Lisa Kudrow and voiced Laura , the sarcastic receptionist on the animated comedy television series Dr. Katz , Professional Therapist .",
"title": ""
},
{
"docid": "The_Power_of_Madonna",
"text": "`` The Power of Madonna '' is the fifteenth episode of the American television series Glee . The episode premiered on the Fox network on April 20 , 2010 . When cheerleading coach Sue Sylvester ( Jane Lynch ) demands that Madonna 's music be played over the school intercom system , glee club director Will Schuester ( Matthew Morrison ) sets the club a Madonna-themed assignment , hoping to empower the female club members . `` The Power of Madonna '' was written and directed by series creator Ryan Murphy , and serves as a musical tribute to Madonna , featuring cover versions of eight of her songs , with the singer having granted Glee the rights to her entire catalogue of music . Glee : The Music , The Power of Madonna , an album containing studio recordings of songs performed in the episode , was released on April 20 , 2010 . The episode was watched by 12.98 million American viewers , and was generally well received by critics . Tim Stack of Entertainment Weekly and Aly Semigran of MTV both deemed it the best episode of the show thus far , and the Houston Chronicle Bobby Hankinson called it potentially `` the most-enjoyable hour of television of all time . '' Other reviews were more mixed , with Todd VanDerWerff of The A.V. Club criticizing the increasing number of musical performances for disrupting the tonal balance of the show , and IGN 's Eric Goldman questioning the series ' writing . Madonna herself approved of the episode , calling it `` brilliant on every level '' . The episode won `` Outstanding Sound Mixing For A Comedy Or Drama Series ( One Hour ) '' at the Creative Arts Emmy Awards , while Jane Lynch won the Primetime Emmy Award for Outstanding Supporting Actress in a Comedy Series for her performance in this episode .",
"title": ""
},
{
"docid": "Jane_Hajduk",
"text": "Jane Hajduk ( born October 26 , 1966 ) is an American television and voice actress . She is known for playing the role of Researcher Taylor in the film Zoom . Hajduk is married to actor and comedian Tim Allen , with whom she also appeared in Zoom , Joe Somebody and The Shaggy Dog . They were married in October 2006 , and have a daughter together , Elizabeth ( b. 2009 ) . She is also stepmother to Allen 's child , Katherine ( b. 1989 ) by his first wife .",
"title": ""
},
{
"docid": "Drew_Lynch",
"text": "Drew Lynch is a stand-up comedian known for his severe stutter . He appeared on the tenth season of America 's Got Talent and finished in second place . He is a regular content contributor to YouTube -- often featuring his service dog Stella in his videos -- with his channel having over 700,000 subscribers and 28 million views .",
"title": ""
},
{
"docid": "George_Lynch",
"text": "George Lynch may refer to : George Lynch ( basketball ) ( born 1970 ) , American NCAA champion and NBA player George Lynch ( musician ) ( born 1954 ) , American member of the heavy metal band Dokken the ESP George Lynch , any of various customized guitars based on those used by George Lynch George Lynch ( racing driver ) ( 1918 -- 1997 ) , American Indianapolis 500 competitor George Lynch-Staunton , Canadian politician . George Edward Lynch , American bishop",
"title": ""
},
{
"docid": "Count_Patrick_D'Arcy",
"text": "Count Patrick D'Arcy was an Irish mathematician and soldier . Born at Kiltullagh House , County Galway , D'Arcy was a descendant of the Irish Confederate Patrick D'Arcy ( 1598 -- 1668 ) , his parents were John D'Arcy and Jane ( née Lynch ; a daughter of Sir Robert Blosse Lynch ) , both members of the Tribes of Galway . At age fourteen he was sent to France under the care of an uncle , Martin D'Arcy , a banker in Paris . He studied mathematics under Clairaut , and resided in his house for some time . He joined the French Army , being Colonel in the Irish Brigade at the Battle of Rossbach in 1757 . He married his cousin Jane D'Arcy , who became a lady-in-waiting to Marie Antoinette . In 1749 , D'Arcy was elected a member of the French Academy of Sciences , and had the title of Count conferred upon him . He died in Paris in 1779 , aged 54 , and was buried in the Church of Saint-Philippe du Roule .",
"title": ""
},
{
"docid": "Dino_Time",
"text": "Dino Time is a 2012 South Korean computer-animated fantasy comedy adventure film produced by CJ Entertainment and distributed by Clarius Entertainment . The film was released on November 30 , 2012 in South Korea . The English dub ( titled Back to the Jurassic for American audiences ) was released in June 2 , 2015 with the English dub voices led by Melanie Griffith , Jane Lynch , William Baldwin , Stephen Baldwin , and Rob Schneider .",
"title": ""
},
{
"docid": "List_of_Galway_people",
"text": "Thomas Arthur , comte de Lally -RSB- -RSB- , Baron de Tollendal ( 1702 -- 1766 ) Margaret Athy , founder of St. Augustine 's Convent , Galway Nora Barnacle , wife of James Joyce Francis Barrett , professional boxer Joseph Henry Blake ( 1797 -- 1849 ) , 3rd Baron Wallscourt Ken Bruen , author Sister Mary Bonaventure Browne , Poor Clares nun and historian Peadar de Burca , actor , playwright , comedian Robert Malachy Burke , Christian Socialist development worker Eamon Casey , ex-Roman Catholic bishop James Cole , Professional Gamer J. J. Clancy , MP Anthony Daly ( Whiteboy ) ( ex .1820 ) Fr . Peter Daly Patrick D'Arcy , lawyer and Confederate Ireland leader Richard Donovan , long distance runner Anthony Duane ( 1679 -- 1747 ) Luke Duffy , trade unionist ; Senator Jim Fahy , RTÉ reporter Mickey Finn , fiddler David Forde , soccer player Pat Gibson , a top prize winner on Who Wants to Be a Millionaire ? Julian Gough , writer and former lead singer of Toasted Heretic Lady Gregory ( 1852 -- 1932 ) James Hardiman Frank Harris Michael D. Higgins , politician Rita Ann Higgins ( born 1955 ) Dolores Keane , musician Richard Kirwan Gerard Lally ( fl . 1689 -- 1737 ) Graham Lee , jockey Tony Lundon ( b. 1979 ) , pop singer Angela Lynch Patrick Lynch , Roman Catholic bishop of Charleston , South Carolina Patrick Lynch , Irish emigrant to Argentina ; ancestor of Che Guevara Peirce Lynch ( fl . 1485 ) Walter Macken ( 1915 -- 1967 ) Richard Martin fitz Oliver ( 1602 -- 1648 ) , father of Richard Martin ( `` Humanity Dick '' ) Thomas Barnwall Martin ( 1784-1847 ) Violet Florence Martin ( 1862 -- 1915 ) Edward Martyn ( 1859 -- 1923 ) Gerard A. Hays McCoy ( 1911 -- 1975 ) Pat McDonagh Bishop James McLoughlin Pauline McLynn , actress Tom Molloy , electro and house music producer Aoife Mulholland , musical actress Ronan Mullen , columnist with the Irish Daily Mail Nora Jane Noone , actress Brendan O'Brien , cricketer Pádraic Ó Conaire , Irish language author Éamon Ó Cuív , Fianna Fáil politician Liam O'Flaherty Dessie O'Halloran William O'Halloran , trade union pioneer Gideon Ouseley Marc Roberts John Sealy Townsend ( 1869 -- 1967 ) , mathematical physicist Alexander Young",
"title": ""
},
{
"docid": "Greatest_Comedy_Hits",
"text": "Greatest Comedy Hits is the first compilation album by American comedian Eddie Murphy . The album was released on May 27 , 1997 for Columbia Records , produced by Vernon ` Vas ' Lynch Jr and Murphy himself . Greatest Comedy Hits featured his greatest stand-up comedy sketches as well as recordings from his films , Coming to America , The Nutty Professor and Eddie Murphy Raw .",
"title": ""
},
{
"docid": "Hollywood_Game_Night",
"text": "Hollywood Game Night is an American television game show hosted by Jane Lynch currently airing on NBC . The program premiered on July 11 , 2013 and follows two contestants who take part in a casual game night with celebrities , with the winning contestant taking home up to $ 25,000 in cash prizes . On May 15 , 2016 , NBC renewed the series for a fifth season , which is set to premiere on June 22 , 2017 .",
"title": ""
}
] |
685
|
Lamins are associated with nuclear membrane structure maintenance.
|
[
{
"docid": "4452659",
"text": "Macroautophagy (hereafter referred to as autophagy) is a catabolic membrane trafficking process that degrades a variety of cellular constituents and is associated with human diseases. Although extensive studies have focused on autophagic turnover of cytoplasmic materials, little is known about the role of autophagy in degrading nuclear components. Here we report that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8, which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS. Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevents activated RAS-induced lamin B1 loss and attenuates oncogene-induced senescence in primary human cells. Our study suggests that this new function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis.",
"title": "Autophagy mediates degradation of nuclear lamina"
}
] |
[
{
"docid": "25036988",
"text": "Nuclear lamin B1 (LMNB1) constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of LMNB1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion. In addition, we observed telomere attrition and an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrated that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that LMNB1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S phase due to activation of Chk1. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.",
"title": "Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories."
},
{
"docid": "34747208",
"text": "Mutations in the nuclear structural protein lamin A cause the premature aging syndrome Hutchinson-Gilford progeria (HGPS). Whether lamin A plays any role in normal aging is unknown. We show that the same molecular mechanism responsible for HGPS is active in healthy cells. Cell nuclei from old individuals acquire defects similar to those of HGPS patient cells, including changes in histone modifications and increased DNA damage. Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS. Inhibition of this splice site reverses the nuclear defects associated with aging. These observations implicate lamin A in physiological aging.",
"title": "Lamin A-dependent nuclear defects in human aging."
},
{
"docid": "22544171",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A. Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS.",
"title": "Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome"
},
{
"docid": "37362689",
"text": "The bulk of ATP consumed by various cellular processes in higher eukaryotes is normally produced by five multimeric protein complexes (I-V) embedded within the inner mitochondrial membrane, in a process known as oxidative phosphorylation (OXPHOS). Maintenance of energy homeostasis under most physiological conditions is therefore contingent upon the ability of OXPHOS to meet cellular changes in bioenergetic demand, with a chronic failure to do so being a frequent cause of human disease. With the exception of Complex II, the structural subunits of OXPHOS complexes are encoded by both the nuclear and the mitochondrial genomes. The physical separation of the two genomes necessitates that the expression of the 13 mitochondrially encoded polypeptides be co-ordinated with that of relevant nuclear-encoded partners in order to assemble functional holoenzyme complexes. Complex biogenesis is a highly ordered process, and several nuclear-encoded factors that function at distinct stages in the assembly of individual OXPHOS complexes have been identified.",
"title": "Oxidative phosphorylation: synthesis of mitochondrially encoded proteins and assembly of individual structural subunits into functional holoenzyme complexes."
},
{
"docid": "834336",
"text": "Hutchinson–Gilford progeria syndrome (HGPS; OMIM 176670) is an extremely rare but devastating disorder that mimics premature aging.1–3 Affected children appear normal at birth but typically develop failure to thrive in the first two years. Other features include alopecia, micrognathia, loss of subcutaneous fat with prominent veins, abnormal dentition, sclerodermatous skin changes, and osteolysis of the clavicles and distal phalanges. The mean age of death is at age 13 years, most commonly due to atherosclerosis. HGPS is mainly sporadic in occurrence, but a genetic cause has now been implicated following the identification of de novo heterozygous mutations in the LMNA gene in the majority of HGPS patients.4,5 A single family showing autosomal recessive inheritance of homozygous LMNA mutations has also been reported.6 LMNA encodes lamins A and C, components of the nuclear lamina, a meshwork underlying the nuclear envelope that serves as a structural support and is also thought to contribute to chromatin organisation and the regulation of gene expression.7,8 Interestingly, mutations in LMNA have recently been associated with at least eight inherited disorders, known as laminopathies, with differential dystrophic effects on a variety of tissues including muscle, neurones, skin, bone, and adipose tissue (reviewed in Mounkes et al 9). However, the realisation that these disorders share common genetic defects has led to clinical re-evaluation, with emerging evidence of significant phenotypic overlap.10 Hence the laminopathies might reasonably be considered as a spectrum of related diseases. HGPS has phenotypic similarities to several other laminopathies, in particular the atypical Werner’s syndrome11 and mandibuloacral dysplasia (MAD; OMIM 248370 and 608612).12 These diseases are associated with lipodystrophy,3,13 which is the most prominent feature of another laminopathy, familial partial lipodystrophy of the Dunnigan variety (OMIM 151660).14 MAD has been further classified as two …",
"title": "Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype."
},
{
"docid": "7468449",
"text": "Ever since the first demonstration of their repetitive sequence and unique replication pathway, telomeres have beguiled researchers with how they function in protecting chromosome ends. Of course much has been learned over the years, and we now appreciate that telomeres are comprised of the multimeric protein/DNA shelterin complex and that the formation of t-loops provides protection from DNA damage machinery. Deriving their name from D-loops, t-loops are generated by the insertion of the 3' overhang into telomeric repeats facilitated by the binding of TRF2. Recent studies have uncovered novel forms of chromosome end-structure that may implicate telomere organization in cellular processes beyond its essential role in telomere protection and homeostasis. In particular, we have recently described that t-loops form in a TRF2-dependent manner at interstitial telomere repeat sequences, which we termed interstitial telomere loops (ITLs). These structures are also dependent on association of lamin A/C, a canonical component of the nucleoskeleton that is mutated in myriad human diseases, including human segmental progeroid syndromes. Since ITLs are associated with telomere stability and require functional lamin A/C, our study suggests a mechanistic link between cellular aging (replicative senescence induced by telomere shortening) and organismal aging (modeled by Hutchinson Gilford Progeria Syndrome). Here we speculate on other potential ramifications of ITL formation, from gene expression to genome stability to chromosome structure.",
"title": "A beginning of the end: new insights into the functional organization of telomeres"
},
{
"docid": "37608303",
"text": "Cristae, the organized invaginations of the mitochondrial inner membrane, respond structurally to the energetic demands of the cell. The mechanism by which these dynamic changes are regulated and the consequences thereof are largely unknown. Optic atrophy 1 (OPA1) is the mitochondrial GTPase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA1's role in mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA1 was required for resistance to starvation-induced cell death, for mitochondrial respiration, for growth in galactose media and for maintenance of ATP synthase assembly, independently of its fusion activity. We identified mitochondrial solute carriers (SLC25A) as OPA1 interactors and show that their pharmacological and genetic blockade inhibited OPA1 oligomerization and function. Thus, we propose a novel way in which OPA1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC25A protein-dependent manner.",
"title": "OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand."
},
{
"docid": "935034",
"text": "Publisher Summary The classification of cell death can be based on morphological or biochemical criteria or on the circumstances of its occurrence. Currently, irreversible structural alteration provides the only unequivocal evidence of death; biochemical indicators of cell death that are universally applicable have to be precisely defined and studies of cell function or of reproductive capacity do not necessarily differentiate between death and dormant states from which recovery may be possible. It has also proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances. One of these patterns is the swelling proceeding to rupture of plasma and organelle membranes and dissolution of organized structure—termed “coagulative necrosis. ” It results from injury by agents, such as toxins and ischemia, affects cells in groups rather than singly, and evokes exudative inflammation when it develops in vivo. The other morphological pattern is characterized by condensation of the cell with maintenance of organelle integrity and the formation of surface protuberances that separate as membrane-bounded globules; in tissues, these are phagocytosed and digested by resident cells, there being no associated inflammation.",
"title": "Cell death: the significance of apoptosis."
},
{
"docid": "30835854",
"text": "We have recently isolated SMAP (Smg GDS-associated protein; Smg GDS: small G protein GDP dissociation stimulator) as a novel Smg GDS-associated protein, which has Armadillo repeats and is phosphorylated by Src tyrosine kinase. SMAP is a human counterpart of mouse KAP3 (kinesin superfamily-associated protein) that is associated with mouse KIF3A/B (a kinesin superfamily protein), which functions as a microtubule-based ATPase motor for organelle transport. We isolated here a SMAP-interacting protein from a human brain cDNA library, identified it to be a human homolog of Xenopus XCAP-E (Xenopus chromosome-associated polypeptide), a subunit of condensins that regulate the assembly and structural maintenance of mitotic chromosomes, and named it HCAP (Human chromosome-associated polypeptide). Tissue and subcellular distribution analyses indicated that HCAP was ubiquitously expressed and highly concentrated in the nuclear fraction, where SMAP and KIF3B were also present. SMAP was extracted as a ternary complex with HCAP and KIF3B from the nuclear fraction in the presence of Mg-ATP. The results suggest that SMAP/KAP3 serves as a linker between HCAP and KIF3A/B in the nucleus, and that SMAP/KAP3 plays a role in the interaction of chromosomes with an ATPase motor protein.",
"title": "Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein, with a human chromosome-associated polypeptide."
},
{
"docid": "4701662",
"text": "As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria.",
"title": "A phospholipid transfer function of ER-mitochondria encounter structure revealed in vitro"
},
{
"docid": "15692098",
"text": "Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cognitive development is normal. Data on 10 of our own cases and 132 cases from literature are presented. The incidence in the last century in the Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy (20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed than growth in height, and growth delay started already prenatally. Mean height > 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but not expressed, except in the viscerocranium, and remained limited to membranous formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions remain present. Cardiovascular problems are extremely variable, both in age of onset and nature. Stroke and coronary dysfunctioning are most frequent. Pathologic findings in coronaries and aorta resemble sometimes the findings in elderly persons, but can also be much more limited. Loss of smooth muscle cells seems the most important finding. Mean age of demise was 12.6 years. Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, (almost) all cases representing spontaneous mutations, and in non-classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood is not uncommon. Pattern of inheritance of non-classical progeria is most probably autosomal recessive. The cause of HGPS is an abnormally formed Lamin A, either directly by a mutated LMNA gene, or through abnormal posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations found in progeria patients, there were 26 classical p. G608G mutations (76%). Pathogenesis is most likely to follow several different pathways. Potential therapeutic strategies are developed along these lines and include RNA interference techniques and inhibition of the dominant-negative influence of abnormally formed Lamin A on polymerization with normally formed Lamin A.",
"title": "Hutchinson-Gilford progeria syndrome: review of the phenotype"
},
{
"docid": "8247597",
"text": "Mutations and deletions in the mitochondrial genome (mtDNA), as well as instability of the nuclear genome, are involved in multiple human diseases. Here, we report that in Saccharomyces cerevisiae, loss of mtDNA leads to nuclear genome instability, through a process of cell-cycle arrest and selection we define as a cellular crisis. This crisis is not mediated by the absence of respiration, but instead correlates with a reduction in the mitochondrial membrane potential. Analysis of cells undergoing this crisis identified a defect in iron-sulfur cluster (ISC) biogenesis, which requires normal mitochondrial function. We found that downregulation of nonmitochondrial ISC protein biogenesis was sufficient to cause increased genomic instability in cells with intact mitochondrial function. These results suggest mitochondrial dysfunction stimulates nuclear genome instability by inhibiting the production of ISC-containing protein(s), which are required for maintenance of nuclear genome integrity. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.",
"title": "Mitochondrial Dysfunction Leads to Nuclear Genome Instability via an Iron-Sulfur Cluster Defect"
},
{
"docid": "14446279",
"text": "In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex (NPC) has been proposed to serve a role in chromatin organization. Here, using fluorescence microscopy in living cells, we show that nuclear pore proteins of the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor telomere XI-L at the nuclear periphery. The integrity of this complex is shown to be required for repression of a URA3 gene inserted in the subtelomeric region of this chromosome end. Furthermore, altering the integrity of this complex decreases the efficiency of repair of a DNA double-strand break (DSB) only when it is generated in the subtelomeric region, even though the repair machinery is functional. These effects are specific to the Nup84 complex. Our observations thus confirm and extend the role played by the NPC, through the Nup84 complex, in the functional organization of chromatin. They also indicate that anchoring of telomeres is essential for efficient repair of DSBs occurring therein and is important for preserving genome integrity.",
"title": "Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region"
},
{
"docid": "5914739",
"text": "The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide--MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.",
"title": "Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain"
},
{
"docid": "25787749",
"text": "The evolutionarily conserved G-quadruplexes (G4s) are faithfully inherited and serve a variety of cellular functions such as telomere maintenance, gene regulation, DNA replication initiation, and epigenetic regulation. Different from the Watson-Crick base-pairing found in duplex DNA, G4s are formed via Hoogsteen base pairing and are very stable and compact DNA structures. Failure of untangling them in the cell impedes DNA-based transactions and leads to genome instability. Cells have evolved highly specific helicases to resolve G4 structures. We used a recombinant nuclear form of Saccharomyces cerevisiae Pif1 to characterize Pif1-mediated DNA unwinding with a substrate mimicking an ongoing lagging strand synthesis stalled by G4s, which resembles a replication origin and a G4-structured flap in Okazaki fragment maturation. We find that the presence of G4 may greatly stimulate the Pif1 helicase to unwind duplex DNA. Further studies reveal that this stimulation results from G4-enhanced Pif1 dimerization, which is required for duplex DNA unwinding. This finding provides new insights into the properties and functions of G4s. We discuss the observed activation phenomenon in relation to the possible regulatory role of G4s in the rapid rescue of the stalled lagging strand synthesis by helping the replicator recognize and activate the replication origin as well as by quickly removing the G4-structured flap during Okazaki fragment maturation.",
"title": "G-quadruplexes significantly stimulate Pif1 helicase-catalyzed duplex DNA unwinding."
},
{
"docid": "14178995",
"text": "The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their early replication arrest. Treatment of patient cells with a protein farnesyltransferase inhibitor (FTI) did not result in reduction of DNA double-strand breaks and damage checkpoint signaling, although the treatment significantly reversed the aberrant shape of their nuclei. This suggests that DNA damage accumulation and aberrant nuclear morphology are independent phenotypes arising from prelamin A accumulation in these progeroid syndromes. Since DNA damage accumulation is an important contributor to the symptoms of HGPS, our results call into question the possibility of treatment of HGPS with FTIs alone.",
"title": "Summary"
},
{
"docid": "6969753",
"text": "Metastatic tumor cells that actively migrate and invade surrounding tissues rely on invadopodia to degrade extracellular matrix (ECM) barriers. Invadopodia are membrane protrusions that localize enzymes required for ECM degradation. Little is known about the formation, function, and regulation of invadopodia. Here, we show that invadopodia have two distinct aspects: (a) structural for organizing the cellular actin cytoskeleton to form membrane protrusions and (b) functional for using proteolytic enzyme(s) for ECM degradation. Small interfering RNA (siRNA) inhibition established that organization of invadopodia structure requires cortactin, whereas protease inhibitor studies identified membrane type 1 matrix metalloproteinase (MT1-MMP) as the key invadopodial enzyme responsible for gelatin matrix degradation in the breast carcinoma cell line MDA-MB-231. The inhibition of invadopodial structure assembly by cortactin depletion resulted in a block of matrix degradation due to failure of invadopodia formation. Either protease inhibition or MT1-MMP siRNA depletion moderately decreased the formation of invadopodial structures that were identified as actin-cortactin accumulations at the ventral cell membrane adherent to matrix. The invadopodia that were able to form upon MT1-MMP inhibition or depletion retained actin-cortactin accumulations but were unable to degrade matrix. Examination of cells at different time points as well as live-cell imaging revealed four distinct invadopodial stages: membrane cortactin aggregation at membranes adherent to matrix, MT1-MMP accumulation at the region of cortactin accumulation, matrix degradation at the invadopodia region, and subsequent cortactin dissociation from the area of continued MT1-MMP accumulation associated with foci of degraded matrix. Based on these results, we propose a stepwise model of invadopodia formation and function.",
"title": "Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function."
},
{
"docid": "9539753",
"text": "RNA interference (RNAi) is heritable in Caenorhabditis elegans; the progeny of C. elegans exposed to dsRNA inherit the ability to silence genes that were targeted by RNAi in the previous generation. Here we investigate the mechanism of RNAi inheritance in C. elegans. We show that exposure of animals to dsRNA results in the heritable expression of siRNAs and the heritable deposition of histone 3 lysine 9 methylation (H3K9me) marks in progeny. siRNAs are detectable before the appearance of H3K9me marks, suggesting that chromatin marks are not directly inherited but, rather, reestablished in inheriting progeny. Interestingly, H3K9me marks appear more prominently in inheriting progeny than in animals directly exposed to dsRNA, suggesting that germ-line transmission of silencing signals may enhance the efficiency of siRNA-directed H3K9me. Finally, we show that the nuclear RNAi (Nrde) pathway maintains heritable RNAi silencing in C. elegans. The Argonaute (Ago) NRDE-3 associates with heritable siRNAs and, acting in conjunction with the nuclear RNAi factors NRDE-1, NRDE-2, and NRDE-4, promotes siRNA expression in inheriting progeny. These results demonstrate that siRNA expression is heritable in C. elegans and define an RNAi pathway that promotes the maintenance of RNAi silencing and siRNA expression in the progeny of animals exposed to dsRNA.",
"title": "Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans."
},
{
"docid": "43752562",
"text": "Subcellular membranes of Saccharomyces cerevisiae, including mitochondria, microsomes, plasma membranes, secretory vesicles, vacuoles, nuclear membranes, peroxisomes, and lipid particles, were isolated by improved procedures and analyzed for their lipid composition and their capacity to synthesize phospholipids and to catalyze sterol delta 24-methylation. The microsomal fraction is heterogeneous in terms of density and classical microsomal marker proteins and also with respect to the distribution of phospholipid-synthesizing enzymes. The specific activity of phosphatidylserine synthase was highest in a microsomal subfraction which was distinct from heavier microsomes harboring phosphatidylinositol synthase and the phospholipid N-methyltransferases. The exclusive location of phosphatidylserine decarboxylase in mitochondria was confirmed. CDO-diacylglycerol synthase activity was found both in mitochondria and in microsomal membranes. Highest specific activities of glycerol-3-phosphate acyltransferase and sterol delta 24-methyltransferase were observed in the lipid particle fraction. Nuclear and plasma membranes, vacuoles, and peroxisomes contain only marginal activities of the lipid-synthesizing enzymes analyzed. The plasma membrane and secretory vesicles are enriched in ergosterol and in phosphatidylserine. Lipid particles are characterized by their high content of ergosteryl esters. The rigidity of the plasma membrane and of secretory vesicles, determined by measuring fluorescence anisotropy by using trimethylammonium diphenylhexatriene as a probe, can be attributed to the high content of ergosterol.",
"title": "Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae."
},
{
"docid": "8093935",
"text": "Sec7-related guanine nucleotide exchange factors (GEFs) initiate vesicle budding from the Golgi membrane surface by converting the GTPase ARF to a GTP-bound, membrane-associated form. Here we report the crystal structure of the catalytic Sec7 homology domain of Arno, a human GEF for ARF1, determined at 2.2 angstroms resolution. The Sec7 domain is an elongated, all-helical protein with a distinctive hydrophobic groove that is phylogenetically conserved. Structure-based mutagenesis identifies the groove and an adjacent conserved loop as the ARF-interacting surface. The sites of Sec7 domain interaction on ARF1 have subsequently been mapped, by protein footprinting experiments, to the switch 1 and switch 2 GTPase regions, leading to a model for the interaction between ARF GTPases and Sec7 domain exchange factors.",
"title": "Structure of the Guanine Nucleotide Exchange Factor Sec7 Domain of Human Arno and Analysis of the Interaction with ARF GTPase"
},
{
"docid": "19138874",
"text": "The biogenesis of the many functional compartments contained in the mammalian cell nucleus is poorly understood. More specifically, little is known regarding the initial nucleation step required for nuclear body formation. Here we show that RNA can function as a structural element and a nucleator of nuclear bodies. We find that several types of coding and noncoding RNAs are sufficient to de novo assemble, and are physiologically enriched in, histone locus bodies (with associated Cajal bodies), nuclear speckles, paraspeckles and nuclear stress bodies. Formation of nuclear bodies occurs through recruitment and accumulation of proteins resident in the nuclear bodies by nucleating RNA. These results demonstrate that transcription is a driving force in nuclear body formation and RNA transcripts can function as a scaffold in the formation of major nuclear bodies. Together, these data suggest that RNA-primed biogenesis of nuclear bodies is a general principle of nuclear organization.",
"title": "Nucleation of nuclear bodies by RNA"
},
{
"docid": "11844826",
"text": "MURR1 is a multifunctional protein that inhibits nuclear factor kappaB (NF-kappaB), a transcription factor with pleiotropic functions affecting innate and adaptive immunity, apoptosis, cell cycle regulation, and oncogenesis. Here we report the discovery of a new family of proteins with homology to MURR1. These proteins form multimeric complexes and were identified in a biochemical screen for MURR1-associated factors. The family is defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions. Like MURR1, several of these factors also associate with and inhibit NF-kappaB. The proteins designated as COMMD or COMM domain containing 1-10 are extensively conserved in multicellular eukaryotic organisms and define a novel family of structural and functional homologs of MURR1. The prototype of this family, MURR1/COMMD1, suppresses NF-kappaB not by affecting nuclear translocation or binding of NF-kappaB to cognate motifs; rather, it functions in the nucleus by affecting the association of NF-kappaB with chromatin.",
"title": "COMMD proteins, a novel family of structural and functional homologs of MURR1."
},
{
"docid": "22495397",
"text": "The Tat protein of human immunodeficiency virus type 1 (HIV-1) plays a key role as inducer of viral gene expression. We report that Tat function can be potently inhibited in human microglial cells by the recently described nuclear receptor cofactor chicken ovalbumin upstream promoter transcription factor-interacting protein 2 (CTIP2). Overexpression of CTIP2 leads to repression of HIV-1 replication, as a result of inhibition of Tat-mediated transactivation. In contrast, the related CTIP1 was unable to affect Tat function and viral replication. Using confocal microscopy to visualize Tat subcellular distribution in the presence of the CTIPs, we found that overexpression of CTIP2, and not of CTIP1, leads to disruption of Tat nuclear localization and recruitment of Tat within CTIP2-induced nuclear ball-like structures. In addition, our studies demonstrate that CTIP2 colocalizes and associates with the heterochromatin-associated protein HP1alpha. The CTIP2 protein harbors two Tat and HP1 interaction interfaces, the 145-434 and the 717-813 domains. CTIP2 and HP1alpha associate with Tat to form a three-protein complex in which the 145-434 CTIP2 domain interacts with the N-terminal region of Tat, while the 717-813 domain binds to HP1. The importance of this Tat binding interface and of Tat subnuclear relocation was confirmed by analysis of CTIP2 deletion mutants. Our findings suggest that inhibition of HIV-1 expression by CTIP2 correlates with recruitment of Tat within CTIP2-induced structures and relocalization within inactive regions of the chromatin via formation of the Tat-CTIP2-HP1alpha complex. These data highlight a new mechanism of Tat inactivation through subnuclear relocalization that may ultimately lead to inhibition of viral pathogenesis.",
"title": "Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells."
},
{
"docid": "26071782",
"text": "Latent membrane protein 1 (LMP1), an oncoprotein encoded by Epstein–Barr virus (EBV), is an integral membrane protein, which acts like a constitutively active receptor. LMP1 is critical for some facet of EBV's induction and maintenance of proliferation of infected B cells. It, in part, mimics signaling by the CD40 receptor and has been implicated in regulating proliferation, survival, or both properties of EBV-infected cells. We established a conditional LMP1 allele in the context of the intact EBV genome to define the immediate-early cellular target genes regulated by LMP1 in order to assess its contributions to infected human B cells. The functional analysis of this conditional system indicated that LMP1 specifically induces mitogenic B-cell activation through c-myc and Jun/AP1 family members and confirms its direct role in upregulating expression of multiple genes with opposing activities involved in cell survival. LMP1's signals were found to be essential for the G1/S transition in human B cells; cells lacking LMP1's signals are cell cycle arrested and survive quiescently. LMP1's activities are therefore not required to maintain survival in nonproliferating cells. LMP1 does induce both pro- and antiapoptotic genes whose balance seems to permit survival during LMP1's induction and maintenance of proliferation.",
"title": "Latent membrane protein 1 of Epstein–Barr virus coordinately regulates proliferation with control of apoptosis"
},
{
"docid": "43054703",
"text": "Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.",
"title": "A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus."
},
{
"docid": "28271439",
"text": "Completion of genome duplication is challenged by structural and topological barriers that impede progression of replication forks. Although this can seriously undermine genome integrity, the fate of DNA with unresolved replication intermediates is not known. Here, we show that mild replication stress increases the frequency of chromosomal lesions that are transmitted to daughter cells. Throughout G1, these lesions are sequestered in nuclear compartments marked by p53-binding protein 1 (53BP1) and other chromatin-associated genome caretakers. We show that the number of such 53BP1 nuclear bodies increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. Conversely, 53BP1 nuclear bodies are partially suppressed by knocking down SMC2, a condensin subunit required for mechanical stability of mitotic chromosomes. Finally, we provide evidence that 53BP1 nuclear bodies shield chromosomal fragile sites sequestered in these compartments against erosion. Together, these data indicate that restoration of DNA or chromatin integrity at loci prone to replication problems requires mitotic transmission to the next cell generations.",
"title": "53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress"
},
{
"docid": "2947540",
"text": "Communication between organelles is crucial for eukaryotic cells to function as one coherent unit. An important means of communication is through membrane contact sites, where two organelles come into close proximity allowing the transport of lipids and small solutes between them. Contact sites are dynamic in size and can change in response to environmental or cellular stimuli; however, how this is regulated has been unclear. Here, we show that Saccharomyces cerevisiae Lam6 resides in several central contact sites: ERMES (ER/mitochondria encounter structure), vCLAMP (vacuole and mitochondria patch), and NVJ (nuclear vacuolar junction). We show that Lam6 is sufficient for expansion of contact sites under physiological conditions and necessary for coordination of contact site size. Given that Lam6 is part of a large protein family and is conserved in vertebrates, our work opens avenues for investigating the underlying principles of organelle communication.",
"title": "Lam6 Regulates the Extent of Contacts between Organelles"
},
{
"docid": "26283293",
"text": "Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.",
"title": "Structural and mechanistic insights into phospholipid transfer by Ups1–Mdm35 in mitochondria"
},
{
"docid": "32827351",
"text": "Aqueous solutions of lead salts (1, 2) and saturated solutions of lead hydroxide (1) have been used as stains to enhance the electron-scattering properties of components of biological materials examined in the electron microscope. Saturated solutions of lead hydroxide (1), while staining more intensely than either lead acetate or monobasic lead acetate (l , 2), form insoluble lead carbonate upon exposure to air. The avoidance of such precipitates which contaminate surfaces of sections during staining has been the stimulus for the development of elaborate procedures for exclusion of air or carbon dioxide (3, 4). Several modifications of Watson's lead hydroxide stain (1) have recently appeared (5-7). All utilize relatively high pH (approximately 12) and one contains small amounts of tartrate (6), a relatively weak complexing agent (8), in addition to lead. These modified lead stains are less liable to contaminate the surface of the section with precipitated stain products. The stain reported here differs from previous alkaline lead stains in that the chelating agent, citrate, is in sufficient excess to sequester all lead present. Lead citrate, soluble in high concentrations in basic solutions, is a chelate compound with an apparent association constant (log Ka) between ligand and lead ion of 6.5 (9). Tissue binding sites, presumably organophosphates, and other anionic species present in biological components following fixation, dehydration, and plastic embedding apparently have a greater affinity for this cation than lead citrate inasmuch as cellular and extracellular structures in the section sequester lead from the staining solution. Alkaline lead citrate solutions are less likely to contaminate sections, as no precipitates form when droplets of fresh staining solution are exposed to air for periods of up to 30 minutes. The resultant staining of the sections is of high intensity in sections of Aralditeor Epon-embedded material. Cytoplasmic membranes, ribosomes, glycogen, and nuclear material are stained (Figs. 1 to 3). STAIN SOLUTION: Lead citrate is prepared by",
"title": "THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY"
},
{
"docid": "797114",
"text": "A recent study revealed a mechanism of delaying aging in yeast by a natural compound which specifically impacts mitochondrial redox processes. In this mechanism, exogenously added lithocholic bile acid enters yeast cells, accumulates mainly in the inner mitochondrial membrane, and elicits an age-related remodeling of phospholipid synthesis and movement within both mitochondrial membranes. Such remodeling of mitochondrial phospholipid dynamics progresses with the chronological age of a yeast cell and ultimately causes significant changes in mitochondrial membrane lipidome. These changes in the composition of membrane phospholipids alter mitochondrial abundance and morphology, thereby triggering changes in the age-related chronology of such longevity-defining redox processes as mitochondrial respiration, the maintenance of mitochondrial membrane potential, the preservation of cellular homeostasis of mitochondrially produced reactive oxygen species, and the coupling of electron transport to ATP synthesis.",
"title": "A mitochondrially targeted compound delays aging in yeast through a mechanism linking mitochondrial membrane lipid metabolism to mitochondrial redox biology☆"
}
] |
51349
|
Paul Bettany was only Vision in Avengers: Age of Ultron.
|
[
{
"docid": "Paul_Bettany",
"text": "Paul Bettany ( born 27 May 1971 ) is an English actor . He is known for his voice role as J.A.R.V.I.S. in the Marvel Cinematic Universe , specifically the films Iron Man ( 2008 ) , Iron Man 2 ( 2010 ) , The Avengers ( 2012 ) , Iron Man 3 ( 2013 ) , and Avengers : Age of Ultron ( 2015 ) , in which he also portrayed the Vision , in the Marvel Cinematic Universe for which he garnered praise . He reprised his role as the Vision in Captain America : Civil War ( 2016 ) . He first came to the attention of mainstream audiences when he appeared in the British film Gangster No. 1 ( 2000 ) , and director Brian Helgeland 's film A Knight 's Tale ( 2001 ) . He has gone on to appear in a wide variety of films , including A Beautiful Mind ( 2001 ) , Master and Commander : The Far Side of the World ( 2003 ) , Dogville ( 2003 ) , Wimbledon ( 2004 ) , and the adaptation of the novel The Da Vinci Code ( 2006 ) . He has been nominated for various awards , including BAFTA Award for Best Actor in a Supporting Role and a Screen Actors Guild Award for Outstanding Performance by a Cast in a Motion Picture . Bettany is married to American actress Jennifer Connelly , with whom he has two children . His most commercially successful films have been The Avengers , which grossed over US$ 1.5 billion , its sequel Avengers : Age of Ultron , which grossed over $ 1.4 billion , Iron Man 3 , which grossed over US$ 1.2 billion , Captain America : Civil War , which grossed over US$ 1.1 billion , and The Da Vinci Code , which grossed US$ 758 million .",
"title": ""
}
] |
[
{
"docid": "Vision_(Marvel_Comics)",
"text": "Vision is the name of several fictional superheroes appearing in American comic books published by Marvel Comics . The first iteration was an alien created by Joe Simon and Jack Kirby who first appeared in Marvel Mystery Comics # 13 ( November 1940 ) . The second iteration is an android and a member of the Avengers who first appeared in The Avengers # 57 ( October 1968 ) by Roy Thomas , Stan Lee and John Buscema . The third Vision is a time traveler that fused with the second version 's operating system . The character is portrayed by Paul Bettany in the 2015 film Avengers : Age of Ultron and the 2016 film Captain America : Civil War .",
"title": ""
},
{
"docid": "Avengers:_Age_of_Ultron",
"text": "Avengers : Age of Ultron is a 2015 American superhero film based on the Marvel Comics superhero team the Avengers , produced by Marvel Studios and distributed by Walt Disney Studios Motion Pictures . It is the sequel to 2012 's The Avengers and the eleventh film in the Marvel Cinematic Universe ( MCU ) . The film was written and directed by Joss Whedon and features an ensemble cast that includes Robert Downey Jr. , Chris Hemsworth , Mark Ruffalo , Chris Evans , Scarlett Johansson , Jeremy Renner , Don Cheadle , Aaron Taylor-Johnson , Elizabeth Olsen , Paul Bettany , Cobie Smulders , Anthony Mackie , Hayley Atwell , Idris Elba , Stellan Skarsgård , James Spader , and Samuel L. Jackson . In Avengers : Age of Ultron , the Avengers fight Ultron , an artificial intelligence obsessed with causing human extinction . The sequel was announced in May 2012 , after the successful release of The Avengers . Whedon , the director of the first film , was brought back on board in August and a release date was set . By April 2013 , Whedon had completed a draft of the script , and casting began in June with the re-signing of Downey . Second unit filming began in February 2014 in South Africa with principal photography taking place between March and August 2014 . The film was primarily shot at Shepperton Studios in Surrey , England , with additional footage filmed in Italy , South Korea , Bangladesh , New York City , and various locations around England . While in post production , the film was converted to 3D and over 3,000 visual effects shots were added . Avengers : Age of Ultron premiered in Los Angeles on April 13 , 2015 , and was released on May 1 , 2015 , in North America , in 3D and IMAX 3D . The film received positive reviews from critics and grossed over $ 1.4 billion worldwide , making it the seventh-highest-grossing film in history and the fourth-highest-grossing film of 2015 . A sequel , Avengers : Infinity War , is scheduled to be released on May 4 , 2018 , and another untitled sequel is scheduled for May 3 , 2019 .",
"title": ""
},
{
"docid": "Avengers:_Infinity_War",
"text": "Avengers : Infinity War is an upcoming American superhero film based on the Marvel Comics superhero team the Avengers , produced by Marvel Studios and distributed by Walt Disney Studios Motion Pictures . It is intended to be the sequel to 2012 's Marvel 's The Avengers and 2015 's Avengers : Age of Ultron and the nineteenth film installment in the Marvel Cinematic Universe ( MCU ) . The film is directed by Anthony and Joe Russo , with a screenplay by Christopher Markus & Stephen McFeely , and features an ensemble cast that includes Robert Downey Jr. , Josh Brolin , Mark Ruffalo , Tom Hiddleston , Chris Evans , Chris Hemsworth , Jeremy Renner , Chris Pratt , Elizabeth Olsen , Sebastian Stan , Benedict Cumberbatch , Paul Bettany , Samuel L. Jackson , Cobie Smulders , Benedict Wong , Zoe Saldana , Karen Gillan , Vin Diesel , Dave Bautista , Pom Klementieff , Scarlett Johansson , Benicio del Toro , Tom Holland , and Anthony Mackie . In Avengers : Infinity War , the Avengers join forces with the Guardians of the Galaxy to confront Thanos , who is trying to amass the Infinity Stones . The film was announced in October 2014 as Avengers : Infinity War -- Part 1 . The Russo brothers came on board to direct in April 2015 and by May , Markus and McFeely signed on to write the script for the film . In July 2016 , Marvel shortened the titled to Avengers : Infinity War . Filming began in January 2017 , at Pinewood Atlanta Studios in Fayette County , Georgia , and is scheduled to last until June or July 2017 , shooting back-to-back with a direct sequel . Additional filming took place in Scotland and England . Avengers : Infinity War is scheduled to be released on May 4 , 2018 , in IMAX . An untitled sequel is scheduled to be released on May 3 , 2019 .",
"title": ""
},
{
"docid": "Avengers:_Age_of_Ultron_(soundtrack)",
"text": "Marvel 's Avengers : Age of Ultron Original Soundtrack is the film score for the Marvel Studios film , Avengers : Age of Ultron by Brian Tyler and Danny Elfman . Hollywood Records released the album digitally on April 28 , 2015 , and in physical formats on May 19 , 2015 .",
"title": ""
},
{
"docid": "Lego_Marvel's_Avengers",
"text": "Lego Marvel 's Avengers is a Lego-themed action-adventure video game developed by Traveller 's Tales and published by Warner Bros. . Interactive Entertainment , for the PlayStation 4 , PlayStation 3 , PlayStation Vita , Nintendo 3DS , Wii U , Xbox One , Xbox 360 , Macintosh and Microsoft Windows . It is the spiritual successor to Lego Marvel Super Heroes and the second installment of the Lego Marvel franchise . It follows the plots of both The Avengers and Avengers : Age of Ultron as well as Captain America : The First Avenger , Iron Man 3 , Thor : The Dark World , and Captain America : The Winter Soldier . The game features characters from the Marvel Cinematic Universe as well as characters from comic books . Characters include Iron Man , Captain America , Hulk , Black Widow , Hawkeye , Scarlet Witch , Quicksilver , Thor , Ultron , Loki , Winter Soldier , Falcon , Vision and War Machine and some lesser known characters such as Devil Dinosaur and Fin Fang Foom . It includes the characters of the Avengers team along with many others . The game was released on 26 January 2016 .",
"title": ""
},
{
"docid": "Ultron",
"text": "Ultron ( -LSB- ˈʌltrən -RSB- ) is a fictional supervillain appearing in American comic books published by Marvel Comics . He is most recognized as a nemesis of the Avengers , and has a quasi-familial relationship with his creator Hank Pym . He was the first Marvel Comics character to wield the fictitious metal alloy adamantium . Ultron has been voiced by Tom Kane and by Jim Meskimen in several media adaptations . The character is portrayed by James Spader in the 2015 film Avengers : Age of Ultron .",
"title": ""
},
{
"docid": "List_of_Marvel_Cinematic_Universe_film_actors",
"text": "The Marvel Cinematic Universe is a media franchise and shared fictional universe that is the setting of superhero films independently produced by Marvel Studios , based on characters that appear in Marvel Comics publications . Phase One of the franchise includes five films , featuring four different superhero properties , leading up to a crossover in the 2012 film Marvel 's The Avengers . The franchise 's Phase Two features three sequel films to properties that appeared in Phase One , as well as two new film properties , and the crossover Avengers : Age of Ultron , which released in 2015 . Phase Three will feature four sequel films to previous properties , and four new film properties , as well as the two-part crossover event Avengers : Infinity War and its untitled sequel . As the franchise is composed of films adapted from a variety of Marvel Comics properties , there are multiple lead actors : Robert Downey , Jr. stars as Tony Stark / Iron Man in the films Iron Man ( 2008 ) , Iron Man 2 ( 2010 ) , and Iron Man 3 ( 2013 ) ; Chris Hemsworth plays Thor in Thor ( 2011 ) , Thor : The Dark World ( 2013 ) , and Thor : Ragnarok ( 2017 ) ; and Chris Evans portrays Steve Rogers / Captain America in Captain America : The First Avenger ( 2011 ) , Captain America : The Winter Soldier ( 2014 ) , and again in Captain America : Civil War ( 2016 ) , where he is joined by Downey as Stark . All three actors star in The Avengers ( 2012 ) , and reprise their roles in Avengers : Age of Ultron ( 2015 ) , Avengers : Infinity War ( 2018 ) , and the untitled Avengers sequel ( 2019 ) . Edward Norton headlined The Incredible Hulk ( 2008 ) , playing Bruce Banner / Hulk , but did not reprise the role in the Avengers films , being replaced by Mark Ruffalo . Ruffalo also stars in Thor : Ragnarok . Chris Pratt portrays the lead character , Peter Quill / Star-Lord , in Guardians of the Galaxy ( 2014 ) , and returns for its sequel , Guardians of the Galaxy Vol . 2 ( 2017 ) , while Paul Rudd and Michael Douglas star as Scott Lang / Ant-Man and Hank Pym / Ant-Man , respectively , in Ant-Man ( 2015 ) ; Rudd also stars in Captain America : Civil War . Benedict Cumberbatch portrays Stephen Strange in Doctor Strange ( 2016 ) , while Tom Holland portrays Peter Parker / Spider-Man in Spider-Man : Homecoming ( 2017 ) and Chadwick Boseman portrays T'Challa / Black Panther in Black Panther ( 2018 ) , after both first appearing in Captain America : Civil War . Downey joins Holland in Spider-Man : Homecoming , while Cumberbatch joins Hemsworth in Thor : Ragnarok . Evangeline Lilly will rejoin Rudd and Douglas from Ant-Man as Hope van Dyne / Wasp in Ant-Man and the Wasp ( 2018 ) , and Brie Larson will portray Carol Danvers / Captain Marvel in Captain Marvel ( 2019 ) . Pratt , Cumberbatch and Holland also appear in Avengers : Infinity War and its untitled sequel , with Lilly also appearing in its sequel . Samuel L. Jackson had cameo and supporting appearances as Nick Fury in several of the early films in the franchise , before co-starring in The Avengers . Other cast members who recur across multiple films and series within the franchise include Hayley Atwell , Paul Bettany , Don Cheadle , Idris Elba , Jon Favreau , Tom Hiddleston , William Hurt , Scarlett Johansson , Anthony Mackie , Elizabeth Olsen , Gwyneth Paltrow , Jeremy Renner , Stellan Skarsgård , Cobie Smulders and Sebastian Stan . The list below is sorted by film and the character 's surname , as some characters have been portrayed by multiple actors . All characters that have made appearances in other MCU media , such as the short films , television series , and the digital series WHIH Newsfront and Marvel 's Agents of S.H.I.E.L.D. : Slingshot , are noted .",
"title": ""
},
{
"docid": "Paul_Norris_(visual_effects)",
"text": "Paul Norris is a British visual effects supervisor . Best known for his works in Harry Potter and the Prisoner of Azkaban ( 2004 ) , Harry Potter and the Goblet of Fire ( 2005 ) , Avengers : Age of Ultron ( 2015 ) , and Ex Machina ( 2015 ) . Norris won Best Visual Effects at the 88th Academy Awards for his work on the film Ex Machina , sharing with Sara Bennett , Andrew Whitehurst , and Mark Williams Ardington .",
"title": ""
},
{
"docid": "Baron_Strucker",
"text": "Baron Wolfgang von Strucker is a fictional supervillain appearing in American comic books published by Marvel Comics . Baron Strucker , a former Nazi officer , is one of the leaders of Hydra and an enemy of S.H.I.E.L.D. , the Avengers , and the interests of the United States of America and of the free world in general . He has been physically augmented to be nearly ageless . He has been seemingly killed in the past only to return to plague the world with schemes of world domination and genocide , time and time again . The character has been portrayed by Campbell Lane in the 1998 TV film Nick Fury : Agent of S.H.I.E.L.D. , and by Thomas Kretschmann in the 2014 film Captain America : The Winter Soldier and the 2015 film Avengers : Age of Ultron .",
"title": ""
},
{
"docid": "Avengers_Grimm",
"text": "Avengers Grimm is a 2015 American science fiction action adventure fantasy film written , co-edited , and directed by Jeremy M. Inman . The film , produced by B-movie film company The Asylum , stars Casper Van Dien , Lou Ferrigno , Kimo Leopoldo , Lauren Parkinson , Milynn Sarley , Marah Fairclough , Rileah Vanderbilt , and Elizabeth Peterson . The film is a mockbuster of the Marvel Studios superhero film Avengers : Age of Ultron and the ABC TV series Once Upon a Time .",
"title": ""
},
{
"docid": "Edwin_Jarvis",
"text": "Edwin Jarvis is a supporting character in the Marvel Comics titles Iron Man , The Avengers and Spider-Man . He is the loyal household butler of the Stark family . Since the 1990s , the character has appeared heavily in media adaptations of Iron Man and Avengers stories , and is commonly reimagined as J.A.R.V.I.S. , an artificial intelligence that assists the superhero Iron Man . In the Marvel Cinematic Universe , J.A.R.V.I.S. is voiced by Paul Bettany in the live-action Iron Man films while Edwin Jarvis is portrayed by James D'Arcy in the ABC television series Agent Carter . In 2012 , Edwin Jarvis was ranked 25th in IGN 's list of `` The Top 50 Avengers '' .",
"title": ""
},
{
"docid": "Maria_Hill",
"text": "Commander Maria Hill ( -LSB- pronmərˈaɪ.ər -RSB- , ) is a fictional character appearing in American comic books published by Marvel Comics . As the former director of the planetary defense/intelligence service S.H.I.E.L.D. , she appears in various storylines which often feature the Avengers or members of that group . She was featured in the late 2000s `` Civil War '' and `` Secret Invasion '' miniseries , and the monthly Iron Man series , in which she was a prominent supporting character during the `` Dark Reign '' and `` Stark Disassembled '' storylines . Maria Hill is portrayed by Cobie Smulders in the films The Avengers , Captain America : The Winter Soldier , Avengers : Age of Ultron and Avengers : Infinity War .",
"title": ""
},
{
"docid": "Avengers_A.I.",
"text": "Avengers A.I. was an ongoing comic book series published by Marvel Comics that was released in July 2013 , as part of the company 's Marvel NOW ! initiative . The series takes place after the events of Age of Ultron , where the world has been colonized by A.I.s `` who may or may not have positive feelings about the way humanity has been treating them for the past 100 years . '' The series ended in April , 2014 .",
"title": ""
},
{
"docid": "Hawkeye_(comics)",
"text": "Hawkeye ( Clint Barton ) is a fictional superhero appearing in American comic books published by Marvel Comics . Created by writer Stan Lee and artist Don Heck , the character first appeared as a villain in Tales of Suspense # 57 ( Sept. 1964 ) and later joined the Avengers in The Avengers # 16 ( May 1965 ) . He has been a prominent member of the team ever since . He was also ranked at # 44 on IGN 's Top 100 Comic Book Heroes list . Hawkeye is portrayed by Jeremy Renner in the Marvel Cinematic Universe , a shared fictional universe that is the setting of films produced by Marvel Studios . Renner first made an uncredited cameo appearance in Thor ( 2011 ) and later played a larger role in The Avengers ( 2012 ) , Avengers : Age of Ultron ( 2015 ) and Captain America : Civil War ( 2016 ) .",
"title": ""
},
{
"docid": "Alexandra_Byrne",
"text": "Alexandra Byrne ( born c. 1962 ) is an English costume designer . Much of her career has focused on creating costumes for historical period dramas . These films include Persuasion ( 1995 ) , Hamlet ( 1996 ) , Elizabeth ( 1998 ) , Captain Corelli 's Mandolin ( 2001 ) , Finding Neverland ( 2004 ) , The Phantom of the Opera ( 2004 ) , and Elizabeth : The Golden Age ( 2007 ) . Byrne 's costume design work has earned her four Academy Award nominations , and she won the award for Elizabeth : The Golden Age . Since 2011 , Byrne has also designed the costumes for many films in the Marvel Cinematic Universe , including Thor ( 2011 ) , The Avengers ( 2012 ) , Guardians of the Galaxy ( 2014 ) , and Avengers : Age of Ultron ( 2015 ) . Her latest film , Doctor Strange , was released in 2016 .",
"title": ""
},
{
"docid": "Erik_Selvig",
"text": "Erik Selvig is a character portrayed by Stellan Skarsgård in the films of the Marvel Cinematic Universe ( MCU ) . An astrophysicist who becomes involved with the alien Thor and the government organization S.H.I.E.L.D. , he first appeared in the 2011 film Thor . Skarsgård went on to reprise the role in The Avengers ( 2012 ) , Thor : The Dark World ( 2013 ) , and Avengers : Age of Ultron ( 2015 ) . To tie into these appearances , the character is seen in several MCU tie-in comics . The character also appears in other media , including non-MCU comics published by Marvel Comics .",
"title": ""
},
{
"docid": "Thanos",
"text": "Thanos ( -LSB- ˈθænɒs -RSB- , -LSB- ˈθænoʊs -RSB- ) is a fictional supervillain appearing in American comic books published by Marvel Comics . The character is usually depicted as a Titanian mutant -- Eternal superhuman . The character first appeared in Iron Man # 55 ( February 1973 ) and was created by writer Mike Friedrich and writer-artist Jim Starlin . Debuting in the Bronze Age of Comic Books , the character has been featured in more than four decades of Marvel continuity and a self-titled series . Thanos appears in the Marvel Cinematic Universe 's various films , including The Avengers ( 2012 ) , portrayed by Damion Poitier , and Guardians of the Galaxy ( 2014 ) , Avengers : Age of Ultron ( 2015 ) , Avengers : Infinity War ( 2018 ) and its untitled sequel ( 2019 ) , portrayed by Josh Brolin . The character has appeared in other Marvel-endorsed products , including animated television series , arcade , and video games .",
"title": ""
},
{
"docid": "Heimdall_(comics)",
"text": "Heimdall is a fictional character appearing in American comic books published by Marvel Comics . He is based on the god Heimdallr of Norse mythology . Heimdall is played by Idris Elba in the live-action films Thor , Thor : The Dark World and Avengers : Age of Ultron .",
"title": ""
},
{
"docid": "Mullae_Station",
"text": "Mullae Station is an underground station on Seoul Subway Line 2 . There is a 24-hour Home plus immediately outside Exit 4 . It also serves various apartment complexes and factories . Close to Exit 7 is the street where Avengers : Age of Ultron was filmed .",
"title": ""
},
{
"docid": "Vincent_Cirelli",
"text": "Vincent Cirelli is an American special effects supervisor . Known for his works at Luma Pictures as a visual effects supervisor in acclaimed films such as Pirates of the Caribbean : At World 's End ( 2007 ) , No Country for Old Men ( 2007 ) , The Midnight Meat Train ( 2008 ) , X-Men Origins : Wolverine ( 2008 ) , Harry Potter and the Half-Blood Prince ( 2009 ) , The Book of Eli ( 2010 ) , Battle : Los Angeles ( 2011 ) , Captain America : The First Avenger ( 2012 ) , Prometheus ( 2012 ) , The Avengers ( 2012 ) , Saving Mr. Banks ( 2013 ) , Guardians of the Galaxy ( 2014 ) , Avengers : Age of Ultron ( 2015 ) , In the Heart of the Sea ( 2015 ) , Deadpool ( 2015 ) and Doctor Strange ( 2016 ) , for which he received an Academy Award for Best Visual Effects nomination at the 89th Academy Awards .",
"title": ""
},
{
"docid": "Untitled_Avengers_film",
"text": "The untitled Avengers film is an upcoming American superhero film based on the Marvel Comics superhero team the Avengers , produced by Marvel Studios and distributed by Walt Disney Studios Motion Pictures . It is intended to be the direct sequel to 2018 's Avengers : Infinity War , as well as the sequel to 2012 's Marvel 's The Avengers and 2015 's Avengers : Age of Ultron and the twenty-second film installment in the Marvel Cinematic Universe ( MCU ) . The film is directed by Anthony and Joe Russo , with a screenplay by Christopher Markus & Stephen McFeely , and features an ensemble cast that includes Robert Downey , Jr. , Josh Brolin , Mark Ruffalo , Tom Hiddleston , Chris Evans , Chris Hemsworth , Jeremy Renner , Chris Pratt , Elizabeth Olsen , Benedict Cumberbatch , Samuel L. Jackson , Evangeline Lilly , Karen Gillan , Anthony Mackie , Tom Holland , and Zoe Saldana . The film was announced in October 2014 as Avengers : Infinity War -- Part 2 . The Russo brothers came on board to direct in April 2015 and by May , Markus and McFeely signed on to script the film . In July 2016 , Marvel removed the film 's title , referring to it simply as Untitled Avengers film . Filming is scheduled to begin in August 2017 , shooting back-to-back with Avengers : Infinity War after the completion of that film . The untitled Avengers film is scheduled to be released on May 3 , 2019 , in IMAX .",
"title": ""
},
{
"docid": "Bettany",
"text": "Bettany may refer to : Colin Bettany ( born 1932 ) , English professional footballer Fred Bettany ( 1860 -- 1924 ) , English footballer John Bettany ( born 1937 ) , English former professional footballer Paul Bettany ( born 1971 ) , English actor Thane Bettany , British actor and former dancer",
"title": ""
},
{
"docid": "Vuyo_Dabula",
"text": "Vuyo Dabula ( born 11 September 1976 ) is a South African actor most famous for acting as Kumkani Phakade brother-in law of Tau Mogale ( Rapulana Seiphemo ) in the soap '' Generations . Vuyo also appeared in Avengers : Age of ultron ( 2015 ) and is set to play a lead role in the upcoming movie Five fingers .",
"title": ""
},
{
"docid": "List_of_Avengers_Assemble_episodes",
"text": "Avengers Assemble is an animated television series based on the comic book super hero team known as the Avengers . It premiered on Disney XD on May 26 , 2013 . On June 1 , 2015 , the series was renewed for a third season titled Avengers : Ultron Revolution . It premiered on Disney XD on March 13 , 2016 . It has been renewed for a fourth season entitled Avengers : Secret Wars .",
"title": ""
},
{
"docid": "Thor_(Marvel_Comics)",
"text": "Thor Odinson is a fictional superhero appearing in American comic books published by Marvel Comics . The character , based on the Norse mythological deity of the same name , is the Asgardian god of thunder and possesses the enchanted hammer Mjolnir , which grants him the ability of flight and weather manipulation amongst his other superhuman attributes . Debuting in the Silver Age of Comic Books , the character first appeared in Journey into Mystery # 83 ( Aug. 1962 ) and was created by editor-plotter Stan Lee , scripter Larry Lieber , and penciller-plotter Jack Kirby . He has starred in several ongoing series and limited series , and is a founding member of the superhero team the Avengers , appearing in each volume of that series . The character has also appeared in associated Marvel merchandise including animated television series , clothing , toys , trading cards , video games , and movies . The character was first portrayed in live action by Eric Allan Kramer in the 1988 television movie The Incredible Hulk Returns . Chris Hemsworth portrays Thor in the Marvel Cinematic Universe films Thor , The Avengers , Thor : The Dark World and Avengers : Age of Ultron and will reprise his role in Thor : Ragnarok , Avengers : Infinity War , and its untitled sequel . Thor placed 14th on IGN 's list of `` Top 100 Comic Book Heroes of All Time '' in 2011 , and first in their list of `` The Top 50 Avengers '' in 2012 .",
"title": ""
},
{
"docid": "Jim_Van_Allen",
"text": "Jim Van Allen is a visual effects artist , and an Annie Awards winner . He won a 2016 Annie Award for Outstanding Achievement , Animated Effects in a Live Action Production for his work on Avengers : Age of Ultron . Van Allen won the award along with Michael Balog , Florent Andorra and Georg Kaltenbrunner .",
"title": ""
},
{
"docid": "Ben_Davis_(cinematographer)",
"text": "Benjamin V. `` Ben '' Davis , BSC ( born 1961 ) is an English cinematographer best known for his work with producer-director Matthew Vaughn . His major works include Kick-Ass ( 2010 ) , Hannibal Rising ( 2007 ) and the Marvel films Guardians of the Galaxy ( 2014 ) , Avengers : Age of Ultron ( 2015 ) and Doctor Strange ( 2016 ) .",
"title": ""
},
{
"docid": "Iron_Man_in_other_media",
"text": "The Marvel Comics character Iron Man has appeared in various other media since the character 's debut in Tales of Suspense # 39 ( March 1963 ) . Iron Man has been the focus of three animated series and a direct-to-DVD animated feature . Three live-action Iron Man feature films starring Robert Downey , Jr. in the title role have been released since 2008 with Downey also appearing as the character in The Incredible Hulk in 2008 , Marvel 's The Avengers in 2012 , Avengers : Age of Ultron in 2015 , and the Captain America : Civil War in 2016 as well as upcoming Spider-Man : Homecoming in 2017 .",
"title": ""
},
{
"docid": "Klaw_(Marvel_Comics)",
"text": "Klaw ( Ulysses Klaue ) is a fictional character , a supervillain appearing in American comic books published by Marvel Comics . He is depicted as a human physicist who has been transformed into solid sound , and who wears a sonic emitter on his right wrist as a prosthetic device . He has often been shown in conflict with the Fantastic Four and the Avengers and is an enemy of the Black Panther and Ka-Zar . The character is featured in other Marvel-endorsed products such as arcade and video games , animated television series , and merchandise such as trading cards . Andy Serkis portrays the character in the film Avengers : Age of Ultron and will reprise the role in the 2018 film Black Panther .",
"title": ""
},
{
"docid": "Stellan_Skarsgård",
"text": "Stellan John Skarsgård ( -LSB- ˈstɛlːan ˈskɑːʂɡoːɖ -RSB- ; born 13 June 1951 ) is a Swedish actor . He is known for his roles as Jan Nyman in Breaking the Waves ( 1996 ) , Prof. Gerald Lambeau in Good Will Hunting ( 1997 ) , Bootstrap Bill Turner in Pirates of the Caribbean : Dead Man 's Chest ( 2006 ) and Pirates of the Caribbean : At World 's End ( 2007 ) , Bill Anderson in Mamma Mia ! ( 2008 ) , Martin Vanger in The Girl With the Dragon Tattoo ( 2011 ) , Captain Tupolev in The Hunt for Red October ( 1990 ) , and Dr. Erik Selvig in the Marvel Cinematic Universe films Thor ( 2011 ) , The Avengers ( 2012 ) , Thor : The Dark World ( 2013 ) , and Avengers : Age of Ultron ( 2015 ) .",
"title": ""
}
] |
6964
|
Implications of a Canadian company IPO having a dual TSX/NYSE stock listing?
|
[
{
"docid": "256035",
"text": "Investors who are themselves Canadian and already hold Canadian dollars (CAD) would be more likely to purchase the TSX-listed shares that are quoted in CAD, thus avoiding the currency exchange fees that would be required to buy USD-quoted shares listed on the NYSE. Assuming Shopify is only offering a single class of shares to the public in the IPO (and Shopify's form F-1 only mentions Class A subordinate voting shares as being offered) then the shares that will trade on the TSX and NYSE will be the same class, i.e. identical. Consequently, the primary difference will be the currency in which they are quoted and trade. This adds another dimension to possible arbitrage, where not only the bare price could deviate between exchanges, but also due to currency fluctuation. An additional implication for a company to maintain such a dual listing is that they'll need to adhere to the requirements of both the TSX and NYSE. While this may have a hard cost in terms of additional filing requirements etc., in theory they will benefit from the additional liquidity provided by having the multiple listings. Canadians, in particular, are more likely to invest in a Canadian company when it has a TSX listing quoted in CAD. Also, for a company listed on both the TSX and NYSE, I would expect the TSX listing would be more likely to yield inclusion in a significant market index—say, one based on market capitalization, and thus benefit the company by having its shares purchased by index ETFs and index mutual funds that track the index. I'll also remark that this dual U.S./Canadian exchange listing is not uncommon when it comes to Canadian companies that have significant business outside of Canada.",
"title": ""
}
] |
[
{
"docid": "498356",
"text": "\"First, your question contains a couple of false premises: Options in the U.S. do not trade on the NYSE, which is a stock exchange. You must have been looking at a listing from an options exchange. There are a handful of options exchanges in the U.S., and while two of these have \"\"NYSE\"\" in the name, referring to \"\"NYSE\"\" by itself still refers to the stock exchange. Companies typically don't decide themselves whether options will trade for their stock. The exchange and other market participants (market makers) decide whether to create a market for them. The Toronto Stock Exchange (TSX) is also a stock exchange. It doesn't list any options. If you want to see Canadian-listed options on equities, you're looking in the wrong place. Next, yes, RY does have listed options in Canada. Here are some. Did you know about the Montreal Exchange (MX)? The MX is part of the TMX Group, which owns both the Toronto Stock Exchange (TSX) and the Montreal Exchange. You'll find lots of Canadian equity and index options trading at the MX. If you have an options trading account with a decent Canadian broker, you should have access to trade options at the MX. Finally, even considering the existence of the MX, you'll still find that a lot of Canadian companies don't have any options listed. Simply: smaller and/or less liquid stocks don't have enough demand for options, so the options exchange & market makers don't offer any. It isn't cost-effective for them to create a market where there will be very few participants.\"",
"title": ""
},
{
"docid": "581591",
"text": "\"One occastion where \"\"will not be quoted ex\"\" is used is when a corporate action is occurring such as a spin-off. In such a case, the rights to, and the spin-off itself may be quoted separately on the home country exchange. However, if the company is based abroad, it may not be worth the expense for them to have an additional securities listing on the local (US) exchange. For example: In November 2016, Yamana Gold (TSX: YRI, NYSE: AUY) announced it will have an initial public offering of a spin-off (Brio Gold, to be listed on TSX as BRIO). Existing shareholders received a right to one share of the spin-off for every 16 shares they held of YRI (or AUY). These rights were separately traded in advance of the IPO of the spin-off on TSX under \"\"YRI.RT\"\", but the prospectus they stated that the rights \"\"will not be quoted ex\"\" on NYSE, i.e. there was no separate listing on NYSE for these rights. The wording seems counter-intuitive, but I suspect that is the attorneys who were preparing the prospectus used those specific words as they may have a very specific meaning (e.g. from a statute or previous case).\"",
"title": ""
},
{
"docid": "390779",
"text": "\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \"\"Get Rich on Penny Stock\"\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\"",
"title": ""
},
{
"docid": "276983",
"text": "You haven't looked very far if you didn't find index tracking exchange-traded funds (ETFs) on the Toronto Stock Exchange. There are at least a half dozen major exchange-traded fund families that I'm aware of, including Canadian-listed offerings from some of the larger ETF providers from the U.S. The Toronto Stock Exchange (TSX) maintains a list of ETF providers that have products listed on the TSX.",
"title": ""
},
{
"docid": "510163",
"text": "\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \"\"IPO Date\"\" is wrong on this one. However, there are several companies that appear to do an \"\"IPO\"\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \"\"IPO\"\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \"\"IPO\"\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \"\"IPO\"\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \"\"Initial\"\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\"",
"title": ""
},
{
"docid": "3463",
"text": "You seem to think that stock exchanges are much more than they actually are. But it's right there in the name: stock exchange. It's a place where people exchange (i.e. trade) stocks, no more and no less. All it does is enable the trading (and thereby price finding). Supposedly they went into mysterious bankruptcy then what will happen to the listed companies Absolutely nothing. They may have to use a different exchange if they're planning an IPO or stock buyback, that's all. and to the shareholder's stock who invested in companies that were listed in these markets ? Absolutley nothing. It still belongs to them. Trades that were in progress at the moment the exchange went down might be problematic, but usually the shutdown would happen in a manner that takes care of it, and ultimately the trade either went through or it didn't (and you still have the money). It might take some time to establish this. Let's suppose I am an investor and I bought stocks from a listed company in NYSE and NYSE went into bankruptcy, even though NYSE is a unique business, meaning it doesn't have to do anything with that firm which I invested in. How would I know the stock price of that firm Look at a different stock exchange. There are dozens even within the USA, hundreds internationally. and will I lose my purchased stocks ? Of course not, they will still be listed as yours at your broker. In general, what will happen after that ? People will use different stock exchanges, and some of them migth get overloaded from the additional volume. Expect some inconveniences but no huge problems.",
"title": ""
},
{
"docid": "533075",
"text": "Assuming the data you're referring to is this line: the difference might be related to the different exchanges on which the stock trades. FINRA could be listing the reported volume from one exchange, while the NASDAQ data might be listing the volume on all exchanges. This is an important distinction because AAV is a Canadian company that is listed on the Toronto Stock Exchange and the NYSE. The Q at the end of the line stands for NASDAQ, according to FINRA's codebook for those data. My guess is that the FINRA data is only reporting the volume for the NASDAQ exchange and not the total volume for all exchanges (Toronto, NASDAQ, NYSE, etc.) while the data straight from NASDAQ, oddly enough, is reporting the total volume. However, FINRA could also face reporting discrepancies, since it's a regulatory body and therefore might not have the most up-to-date volume data that the various exchanges can access. I don't know if it's related or not, but looking at the NASDAQ historical data, it looks like the volume on March 6, the day you're asking about, was much lower than the volume in most of the days immediately before or after it. For all I know, something might have happened that day concerning that particular stock or the market as a whole. I don't remember anything in particular, but you never know.",
"title": ""
},
{
"docid": "147792",
"text": "Twitter is planning to go public on NYSE. You'll be able to start trading once the stock is listed for trading, which would be the day of the IPO. Note that since you're trading on the secondary market, you won't be able to buy at the IPO prices, whatever the time is. You're buying from someone who bought at IPO price.",
"title": ""
},
{
"docid": "390529",
"text": "\"In the US, a private company with less than 500 owners can dictate who can or can't become a shareholder (this is true in general, but I'm sure there are loopholes). Prior to Google's IPO I could not buy shares in Google at any price. The reason Google was \"\"forced\"\" to go public is the 500 shareholder rule. At a high level, with 500 shareholders the company is forced to do some extra financial accounting and they no longer can control who owns a share of the company, allowing me to purchase shares of google at that point. At that point, it typically becomes in the companies best interest to go public. See this article about Google approaching the 500 shareholder limit in 2003. Further, Sorkin is not quite correct that \"\"securities laws mandate that the company go public\"\" if by \"\"go public\"\" we mean list on a stock exchange, available for general purchase. Securities laws mandate what has to be reported in financial reporting and when you have to report it. Securities laws also can dictate restrictions on ownership of stock and if a company can impose their own restrictions. A group of investors cannot force a company onto a stock exchange. If shares of Facebook are already for sale to anyone, then having >500 shareholders will force Facebook to file more paperwork with the SEC, it won't force Facebook onto the NYSE or NASDAQ. When that point is reached, it may be in Facebook's best interest to have an IPO, but they will not be required by law to do so. Update: CNN article discusses likely Facebook IPO in 2012. When companies have more than 500 shareholders, they're required to make significant financial disclosures -- though they can choose to remain private and keep their stock from trading publicly. However, most companies facing mandatory disclosures opt to go public. The Securities and Exchange Commission gives businesses lots of time to prepare for that milestone. Companies have until 120 days after the end of the fiscal year in which they cross the 500-shareholder line to begin making their disclosures. If Facebook tips the scale this year, that gives it until April 2012 to start filing financial reports.\"",
"title": ""
},
{
"docid": "112461",
"text": "Say a stock is listed in Nasdaq, and the same company has a stock listed in Tsx. Does the Nasdaq price affect the Tsx price as trading commences? Not directly. Basically, an exchange is a market, and the price is defined only by supply and demand in that market. However, any substantial price differential for a commodity traded in multiple market creates an arbitrage opportunity, and there are many traders whose job it is exactly to find and use such opportunities. Their activity in turn has the effect of reducing the price differentials to the point where transaction costs make them unprofitable. With high-frequency traders around, the time for a price differential to disappear is nowadays measured in milliseconds. If a trader buys from one exchange, will it affect the price of the other? Only through the mechanism mentioned above. Are there any benefits to being listed in two exchanges? It increases the liquidity of a stock.",
"title": ""
},
{
"docid": "474279",
"text": "Listing on NYSE has more associated overhead costs than listing on NASDAQ. In the case of young technology companies, this makes NASDAQ a more attractive option. Perhaps the most important factor is that NYSE requires that a company has an independent compensation committee and an independent nominating committee while NASDAQ requires only that executive compensation and nominating decisions are made by a majority of independent directors. No self-respecting, would-be-instant-billionare tech entreprenuer is going to want some independent committee lording it over their pay packet. Additionally, listing on NYSE requires a company have stated guidance for corporate governance while NASDAQ imposes no such requirement. Similarly, NYSE requires a company have an internal audit team while NASDAQ imposes no such requirement. Fees on NYSE are also a bit higher than NASDAQ, but the difference is not significant. A good rundown of the pros/cons: http://www.investopedia.com/ask/answers/062215/what-are-advantages-and-disadvantages-listing-nasdaq-versus-other-stock-exchanges.asp",
"title": ""
},
{
"docid": "127578",
"text": "Technically, of course. Almost any company can go bankrupt. One small note: a company goes bankrupt, not its stock. Its stock may become worthless in bankruptcy, but a stock disappearing or being delisted doesn't necessarily mean the company went bankrupt. Bankruptcy has implications for a company's debt as well, so it applies to more than just its stock. I don't know of any historical instances where this has happened, but presumably, the warning signs of bankruptcy would be evident enough that a few things could happen. Another company, e.g. another exchange, holding firm, etc. could buy out the exchange that's facing financial difficulty, and the companies traded on it would transfer to the new company that's formed. If another exchange bought out the struggling exchange, the shares of the latter could transfer to the former. This is an attractive option because exchanges possess a great deal of infrastructure already in place. Depending on the country, this could face regulatory scrutiny however. Other firms or governments could bail out the exchange if no one presented a buyout offer. The likelihood of this occurring depends on several factors, e.g. political will, the government(s) in question, etc. For a smaller exchange, the exchange could close all open positions at a set price. This is exactly what happened with the Hong Kong Mercantile Exchange (HKMex) that MSalters mentioned. When the exchange collapsed in May 2013, it closed all open positions for their price on the Thursday before the shutdown date. I don't know if a stock exchange would simply close all open positions at a set price, since equity technically exists in perpetuity regardless of the shutdown of an exchange, while many derivatives have an expiration date. Furthermore, this might not be a feasible option for a large exchange. For example, the Chicago Mercantile Exchange lists thousands of products and manages hundreds of millions of transactions, so closing all open positions could be a significant undertaking. If none of the above options were available, I presume companies listed on the exchange would actively move to other, more financially stable exchanges. These companies wouldn't simply go bankrupt. Contracts can always be listed on other exchanges as well. Considering the high level of mergers and acquisitions, both unsuccessful and successful, in the market for exchanges in recent years, I would assume that option 1 would be the most likely (see the NYSE Euronext/Deutsche Börse merger talks and the NYSE Euronext/ICE merger that's currently in progress), but for smaller exchanges, there is the recent historical precedent of the HKMex that speaks to #3. Also, the above answer really only applies to publicly traded stock exchanges, and not all stock exchanges are publicly-held entities. For example, the Shanghai Stock Exchange is a quasi-governmental organization, so I presume option 2 would apply because it already receives government backing. Its bankruptcy would mean something occurred for the government to withdraw its backing or that it became public, and a discussion of those events occurring in the future is pure speculation.",
"title": ""
},
{
"docid": "339268",
"text": "\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \"\"T\"\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \"\"ANET\"\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \"\"P\"\" to the end for \"\"preferreds\"\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\"",
"title": ""
},
{
"docid": "272008",
"text": "\"Yes when I place an order with my broker they send it out to the exchange. - For individual investors, what are some cons and pros of trading on the exchanges directly versus indirectly via brokers? I may be mistaken(I highly doubt it), but from my understanding you cannot trade directly through an exchange as a retail investor. BATS allows membership but it is only for Your firm must be a registered broker-dealer, registered with a Self Regulatory Organization (SRO) and connected with a clearing firm. No apple (aapl) is listed on the NASDAQ so trades go through the NASDAQ for aapl. Caterpillar Inc (CAT) is listed on the NYSE so trades go through the NYSE. The exchange you trade on is dependent on the security, if it is listed on the NYSE then you trade on the NYSE. As a regular investor you will be going through a broker. When looking to purchase a security it is more important to know about the company and less important to know what exchange it is listed on. Since there are rules a company must comply with for it to be listed on certain exchanges, it does make a difference but that is more the case when speaking about a stock listed Over the Counter(OTC) or NYSE. It is not important when asking NYSE or NASDAQ? Selecting a broker is something that's dependent on your needs. You should ask your self, \"\"whats important to me?\"\", \"\"Do I want apps(IE: iPhone, android)?\"\" \"\"Do I need fancy trading tools?\"\". Generally all the brokers you listed will most likely do the trick for you. Some review sites: Brokerage Review Online Broker Review 2012 Barron's 2012 Online Broker Review\"",
"title": ""
},
{
"docid": "450099",
"text": "\"VIV.PA - is Vivendi listed on a stock exchange in Paris VIVEF - is Vivendi listed on the OTC Other Exchange. VIVHY - is Listed on the OTC:Pink Sheets. A company can be listed on multiple exchanges, they are known as a dual-listed company. It's a corporate structure in which two corporations function as a single operating business through a legal equalization agreement, but retain separate legal identities and stock exchange listings. Pretty much all DLCs are cross-border, and have tax advantages for the corporations and their stockholders. When a DLC is created, in essence two companies are created and have two separate bodies of shareholders, but they agree to share all the risks and rewards of the ownership of all their operating businesses in a fixed proportion, laid out in a contract called an \"\"equalization agreement\"\". The shares of a DLC parents have claim to the exact same underlying cash flows. So in theory the stock prices of these companies should move exactly the same. However in practice there can be differences between these prices. More info on OTC exchanges can be found here - keep in mind this info is from the company that runs these listings. Over the counter stocks are held to a FAR lesser regulation standard. I would recommend doing further interdependent research before pursuing any action.\"",
"title": ""
},
{
"docid": "272162",
"text": "\"Shariah compliant investments attempt to achieve your \"\"ethical investing\"\" ideals. Many countries around the world have a long list of shariah compliant investments and lots of journalists will go great lengths to reveal when a company is not really shariah compliant. Standard & Poors (S&P), an American financial services company, hosts a Shariah compliant index too, but on the Toronto Stock Exchange in Canada due to the Islamaphobia rampant in the United States. But of course, international companies are indifferent to any single country's social problems, and in your new pastime as an international speculator you will get the same luxury too and exemption from the political spectrum. S&P/TSX 60 information can be found here: http://web.tmxmoney.com/tmx_indices.php?section=tsx&index=%5ETXSI Business sectors prohibited from the Shariah index include: Gambling, Pornography, Tobacco, amongst others. In the United States, the concept has been renamed \"\"B-Corporation\"\" (a play on the federal term C-Corporation and S-Corporation), and has garnered enough of a movement that several states have created these as entities people can actually register them with the state, but these are not recognized as \"\"B-Corporations\"\" to the federal government. Shariah compliant investments will be easier to find worldwide, due to the popularity of the associated religion.\"",
"title": ""
},
{
"docid": "450184",
"text": "\"Depends. The short answer is yes; HSBC, for instance, based in New York, is listed on both the LSE and NYSE. Toyota's listed on the TSE and NYSE. There are many ways to do this; both of the above examples are the result of a corporation owning a subsidiary in a foreign country by the same name (a holding company), which sells its own stock on the local market. The home corporation owns the majority holdings of the subsidiary, and issues its own stock on its \"\"home country's\"\" exchange. It is also possible for the same company to list shares of the same \"\"pool\"\" of stock on two different exchanges (the foreign exchange usually lists the stock in the corporation's home currency and the share prices are near-identical), or for a company to sell different portions of itself on different exchanges. However, these are much rarer; for tax liability and other cost purposes it's usually easier to keep American monies in America and Japanese monies in Japan by setting up two \"\"copies\"\" of yourself with one owning the other, and move money around between companies as necessary. Shares of one issue of one company's stock, on one exchange, are the same price regardless of where in the world you place a buy order from. However, that doesn't necessarily mean you'll pay the same actual value of currency for the stock. First off, you buy the stock in the listed currency, which means buying dollars (or Yen or Euros or GBP) with both a fluctuating exchange rate between currencies and a broker's fee (one of those cost savings that make it a good idea to charter subsidiaries; could you imagine millions a day in car sales moving from American dealers to Toyota of Japan, converted from USD to Yen, with a FOREX commission to be paid?). Second, you'll pay the stock broker a commission, and he may charge different rates for different exchanges that are cheaper or more costly for him to do business in (he might need a trader on the floor at each exchange or contract with a foreign broker for a cut of the commission).\"",
"title": ""
},
{
"docid": "1577",
"text": "If I buy VUSA from one exchange, can I sell it in a different exchange, assuming my brokerage account lets me trade in both exchanges? Or is it somehow tied to the exchange I bought it from? This doesn't happen for all securities and between all stock exchanges. So that is dependent on broker and country. I checked for VUSA with Selftrade. They categorically refused allowing me to trade in VUSA in different exchanges. I can only buy and sell in same currency only, albeit sell(buy) in the same exchange where I buy(sell) from. Should be the same behaviour for all brokers for us mere mortals, if you are a bank or a millionaire than that might be a different question. The VUSA you quote is quoted in GBP in LSE and in EUR in AEX, and the ETF has been created by an Irish entity and has an Irish ISIN. As Chris mentioned below, happens between US and Canadian exchanges, but not sure it happens across all exchanges. You cannot deal in inter-listed stocks in LSE and NYSE. Since it's the same asset, its value should not vary across exchanges once you compensate for exchange rates, right? Yes, else it opens up itself for arbitrage (profit without any risk) which everybody wants. So even if any such instance occurs, either people will exploit it to make the arbitrage profit zero (security reflects the equilibrium price) or the profit from such transaction is so less, compared with the effort involved, that people will tend to ignore it. Anyways arbitrage profit is very difficult to garner nowadays, considering the super computers at work in the market who exploit these discrepancies, the moment they see them and bring the security right to the zero arbitrage profit point. If there's no currency risk because of #2, what other factors should I consider when choosing an exchange to trade in? Liquidity? Something else? Time difference, by the time you wake up to trade in Japan, the Japanese markets would have closed. Tax implications across multiple continents. Law of the land, providing protection to investors. Finding a broker dealing in markets you want to explore or dealing with multiple brokers. Regulatory headaches.",
"title": ""
},
{
"docid": "438121",
"text": "\"During GM's Chapter 11 reorganization in 2009, a new company was formed, with new stock. The old General Motors Corporation was renamed to \"\"Motors Liquidation Company,\"\" and the new company was named \"\"General Motors Company.\"\" The new company purchased some of the assets from the old company, and the old company was left to sell off the remaining assets and settle the debts. None of the stock transferred from the old company to the new one; if you were a GM stockholder of the old company and didn't sell, it is now worthless. When the new company formed, the stock was not traded publicly. The company was primarily owned by the United States and Canadian governments; together, they owned 72.5%. In 2010, GM had an IPO, and the US government sold most of their stake. By the end of 2013, the US government sold the remaining stake; the government no longer has any ownership in GM. When we talk about voting rights for stockholders, we are mainly talking about voting for the members of the board of directors. And yes, the government did indeed have a hand in selecting the board of the new company. The Treasury Department selected 10 members of the board, and the Canadian government selected 1 member. There were 19 board members total. (Source) Unlike some companies, there are not \"\"voting\"\" and \"\"non-voting\"\" classes of GM stock. All the shares sold by the US government are voting shares. Additional Sources:\"",
"title": ""
},
{
"docid": "386278",
"text": "how do they turn shares into cash that they can then use to grow their business? Once a Company issues an IPO or Follow-On Public Offer, the company gets the Money. Going over the list of question tagged IPO would help you with basics. Specifically the below questions; How does a company get money by going public in an IPO? Why would a company care about the price of its own shares in the stock market? Why would a stock opening price differ from the offering price? From what I've read so far, it seems that pre-IPO an investment bank essentially buys the companies public shares, and that bank then sells them on the open market. Is the investment bank buying 100% of the newly issued public shares? And then depositing the cash equivalent into the companies bank account? Additionally, as the stock price rises and falls over the lifetime of the company how does that actually impact the companies bank balance? Quite a bit on above is incorrect. Please read the answers to the question tagged IPO. Once an IPO is over, the company does not gain anything directly from the change in shareprice. There is indirect gain / loss.",
"title": ""
},
{
"docid": "87535",
"text": "I don't quite understand the NYSE argument that the credit system helps NASDAQ undercut NYSE on pricing and force brokers to trade on NASDAQ. I thought if you were trading a stock listed on NASDAQ, you traded through them and if you were trading a stock listed on NYSE, you'd trade over there. The choice of exchange coming down to the stocks you want to trade more than anything. Are the exchanges also acting as endpoints on trades for securities listed on the other exchange?",
"title": ""
},
{
"docid": "468381",
"text": "I have not looked in details but apparently the company has (at least) a dual listing in Hong Kong (its main listing, ticker 700) and in the US (ticker TCTZF). It also has an ADR (TCEHY), the underlying of which is the HK line. The two US listings essentially trade at the same price and will provide very similar returns but a major difference is that TCTZF pays dividends in HKD whereas TCEHY pays its dividends in USD. The latter may be more convenient depending on the account you use to trade the stock. The ADR line is also more liquid.",
"title": ""
},
{
"docid": "430974",
"text": "The quotes on JSE are for 100 share lots. The quotes on NYSE are for single shares. That still leaves some price difference, but much less than you calculated. (EDIT: Equivalently, the price is quoted in 1/100th of a Rand. The Reuter's listing makes this explicit since the price is listed as ZAc rather than ZAR. http://www.reuters.com/finance/stocks/overview?symbol=HARJ.J) As noted in the other answer currently up, NYSE is quoting American Depositary Receipts (ADRs) for this company, which is not directly its stock. The ADR in this case, if you check the prospectus, is currently 1 share of the ADR = 1 share of the stock on its home market. A US institution (in this case it looks like BNY Mellon) is holding shares of stock to back each ADR. Arbitrage is possible and does happen. It's not perfect though, because there are a variety of other cost and risk factors that need to be considered. There's a good review here: Report by JP Morgan Some summary points:",
"title": ""
},
{
"docid": "512062",
"text": "If the first one is literally a company name, then 'company name' is fine. However, companies can issue shares more than once, and those shares might be traded separately, so you could have 'Google ordinary', 'Google preference', 'Google ordinary issue B'. Seeing the name spelled out in full like this isn't as common as just the company name, but I'd normally see it referred to as 'display name'. The second one is 'symbol', 'ticker', 'ID', and others. Globally, there are many incompatible ways of referring to a stock, depending on where it's listed (companies can have dual listings, and different exchanges have different conventions), and who's referring to it (Bloomberg and Reuters have different sets of IDs, with no predictable mapping between them). So there's no one shorthand name, and the word you use depends on the context. However, 'symbol' or 'ticker' is normally fine.",
"title": ""
},
{
"docid": "435963",
"text": "A stock market is just that, a market place where buyers and sellers come together to buy and sell shares in companies listed on that stock market. There is no global stock price, the price relates to the last price a stock was traded at on a particular stock market. However, a company can be listed on more than one stock exchange. For example, some Australian companies are listed both on the Australian Stock Exchange (ASX) and the NYSE, and they usually trade at different prices on the different exchanges. Also, there is no formula to determine a stock price. In your example where C wants to buy at 110 and B wants to sell at 120, there will be no sale until one or both of them decides to change their bid or offer to match the opposite, or until new buyers and/or sellers come into the market closing the gap between the buy and sell prices and creating more liquidity. It is all to do with supply and demand and peoples' emotions.",
"title": ""
},
{
"docid": "99472",
"text": "\"Check your broker's IPO list. Adding a new stock to a stock exchange is called \"\"Initial Public Offering\"\" (IPO), and most brokers have a list of upcoming IPO's in which their clients can participate.\"",
"title": ""
},
{
"docid": "213507",
"text": "You can find the NYSE holiday dates listed on the exchange's own site (already linked in answer above), which should obviously be consulted as the most reliable source; they are also published in an article that I have written here: NYSE Holidays 2016, which provides additional information about traditions and events that can be expected to lead to unscheduled closures, and closed dates for holidays that are day-of-month rather than date specific (e.g. President's Day and Memorial Day). NYSE Holidays are not quite identical to those for the Chicago Mercantile Exchange, though most US stock exchange dates are the same. Also, note that both the Merc (via the Globex platform) and NYSE Arca have different normal cash sessions and trading hours to the New York Stock Exchange.",
"title": ""
},
{
"docid": "432727",
"text": "\"Shares sold to private investors are sold using private contracts and do not adhere to the same level of strict regulations as publicly traded shares. You may have different classes of shares in the company with different strings attached to them, depending on the deals made with the investors at the time. Since public cannot negotiate, the IPO prospectus is in fact the investment contract between the company and the public, and the requirements to what the company can put there are much stricter than private sales. Bob may not be able to sell his \"\"special\"\" stocks on the public exchange, as the IPO specifies which class of stock is being listed for trading, and Bob's is not the same class. He can sell it on the OTC market, which is less regulated, and then the buyer has to do his due diligence. Yes, OTC-sold stocks may have strings attached to them (for example a buy back option at a preset time and price).\"",
"title": ""
},
{
"docid": "546313",
"text": "\"Training8m Corporate Technologies Pty Ltd, Australia Australia ABN 48133544297 UK Company Number: 7538482 Maiden Pre-IPO offer from Training8m Corporate Technologies Pty Ltd, Australia!! Unique opportunity for investors!!! Move to a most profitable and defensive investment!!! We offer Preferential Allotment / Private Placement of Debt / Equity. Most Profitable offer from The Global Leader!! www.training8m.com Subscription Offer Open: First ever pre-IPO offer from Training8m Australia Group!! Unique opportunity for investors!!! Move to a most profitable and defensive investment!!! Preferential Allotment / Private Placement of Debt / Equity to multiple business investors pre IPO from $ 50k to $ 25 Mn for start up venture set up and Capital market Listing on Frankfurt Stock Exchange. We offer Preferential Allotment / Private Placement of Equity to multiple business investors Pre- IPO from $ 50K to $ 25 Mn. Higher investment welcome for this International public issue. Equivalent Debt / Equity / Options / Preference Shares can be discussed. Minority Equity participation can be discussed. We at Training8m Australia are Going Public Soon on Frankfurt Stock Exchange. Status: Approved funding by major Global Private Equity Fund. We are pleased to write that our major funding, raising funds from the equity market listing on Frankfurt Stock Exchange, is approved by major and most reputed Private Equity Group. This is one of the largest upcoming IPO, highly profitable with high ROI. Subscription: Open to Institutional and Retail Investors Pre IPO offer in Debt / Equity / Preference Shares / Options Serious investors only please. We would like to conclude this current deal immediately. We at Training8m, Australia are willing to discuss on the Debt / Equity / Options / preference shares and will be liberal for this transaction, which will be issued to you directly from our fund managers. This is definitely a really profitable and high return investment. Payback period: 1 - 2 years (expected turnover at least $ 2 Bn in 3 years) Start up Stage of business. This investment has very attractive returns. Unique opportunity to associate prior to the IPO on Global Stock Exchanges Location: Head Quartered in Gold Coast, Australia with Global Operating Offices. Set up including Property Investment, Recruitment and Appointment of permanent personnel, Fees for Listing on major Global Stock Exchange, other expenses as needed for the business. Business Models: Training8m Corporate Technologies Pty Ltd, Australia Corporate Training, Marketing, Premium Recruitment Portal, Premium and Moderated Recruitment Social Networking, Training and Development for all industry Verticals, Global Business Solutions. Advanced Lighting Designers Pty Ltd, Australia We offer International Lighting Technologies, Design, Specifications, Software Solutions and High End Information Technology Services to Global Industry sectors. Please do note that we are officially registered in Australia and UK for our Global Business ventures. With appropriate funding for takeovers, mergers and Acquisitions, we will be listing the companies Training8m Corporate Technologies Pty Ltd, and Advanced Lighting Designers Pty Ltd, on major global stock exchanges. The punch line of Advanced Lighting Designers Pty Ltd is “Go Green with Force Green\"\" in which we will be focussing on Green Energy Worldwide. Please feel free to ask details privately. Offer for limited time and closes on receipt of funds. E- Mails: [email protected], [email protected] Shrikant G. Shete Chairman and Managing Director Training8m, Australia LinkedIn: http://au.linkedin.com/in/shrikantshete +61-400769125 ................................Australia Mobiles +61-434415521 ................................Australia Mobiles\"",
"title": ""
},
{
"docid": "193312",
"text": "NYSE and Nasdaq are secondary markets where stocks are bought or sold. The process of creating new stocks via IPO or private placements etc are called Private Market.",
"title": ""
}
] |
2225
|
Pros, cons, and taxation of Per Diem compensation?
|
[
{
"docid": "550804",
"text": "Beware if injured on the job they will not add per diem to your wages meaning you make less and your wc benefits will be less !!",
"title": ""
},
{
"docid": "375748",
"text": "Hence new employer pays a part of the salary as per diem compensation along with regular salary and says that per-diem compensation is non-taxable. Per-diem is not taxable. But that is not what you're describing. It appears that either you or the prospective employer, misunderstood what per-diem is. As per US law is it legally allowed non taxable per diem compensation to employees? Yes. What are the pros and cons of having per diem compensation? Per-diem is not compensation. It is not part of your salary. It is not part of your employment contract. If I have to report my salary to any one like banks, insurance companies, do I need to include Per diem compensation or not? No, because it is not compensation. Back to the first item: Per-diem is paid to you during business trips when you're away from your (tax) home. It is not part of your compensation, and is only allowed for business trips. Contract work on site for any prolonged period of time (1 year or more, as a definitive rule, but can be less) is not a business trip. For that period of time your tax home becomes that location, so you're not away. You're home. You should discuss it with a licensed tax adviser (EA/CPA licensed in your State), but it seems to me that either you misunderstood something, or your prospective employer is trying to evade taxes (both yours and his) by disguising part of your compensation as per-diem. It is very likely that when you get caught, the employer will just issue you 1099 on the amounts and leave you hanging.",
"title": ""
}
] |
[
{
"docid": "76618",
"text": "\"Some of the 45,000 might be taxable. The question is how was the stipend determined. Was it based on the days away? The mile driven? The cities you worked in? The IRS has guidelines regarding what is taxable in IRS Pub 15 Per diem or other fixed allowance. You may reimburse your employees by travel days, miles, or some other fixed allowance under the applicable revenue procedure. In these cases, your employee is considered to have accounted to you if your reimbursement doesn't exceed rates established by the Federal Government. The 2015 standard mileage rate for auto expenses was 57.5 cents per mile. The rate for 2016 is 54 cents per mile. The government per diem rates for meals and lodging in the continental United States can be found by visiting the U.S. General Services Administration website at www.GSA.gov and entering \"\"per diem rates\"\" in the search box. Other than the amount of these expenses, your employees' business expenses must be substantiated (for example, the business purpose of the travel or the number of business miles driven). For information on substantiation methods, see Pub. 463. If the per diem or allowance paid exceeds the amounts substantiated, you must report the excess amount as wages. This excess amount is subject to income tax with-holding and payment of social security, Medicare, and FUTA taxes. Show the amount equal to the substantiated amount (for example, the nontaxable portion) in box 12 of Form W-2 using code “L\"\"\"",
"title": ""
},
{
"docid": "134118",
"text": "Per-diem is not taxable, if all the conditions are met. Conditions include: You can find this and more in this IRS FAQ document re the per-diem.",
"title": ""
},
{
"docid": "155843",
"text": "\"Loan officer here. Yes. You pay the per diem. I'd recommend not paying it off for like 6 months. You can pay it down to basically nothing and then hold it for six months and pay it off. Better for credit. If it's a simple interest rate, most car loans are, multiply the current principal balance by the interest rate and divide it by 365. That's the per diem or daily interest. For example, \"\"10,000 dollar auto loan at 3%. 10000*0.03= 300. 300/365= 0.82. So each day the balance is 10k the loan cost 82 cents. So in a month, your first payment is 100 dollars, 24.65 goes to interest 75.35 goes to principal. Then the new principal is 9924.65. So the next month, another 30 days with the new per diem of 0.815, the 100 payment is 75.50 in principal 24.50 in interest and so on.\"",
"title": ""
},
{
"docid": "457667",
"text": "I've been budgeting with MS Money since 2004 and was pretty disappointed to hear it's being discontinued. Budgeting is actually a stress-relieving hobby for me, and I can be a bit of a control-freak when it comes to finances, so I decided to start early looking for a replacement rather than waiting until MS Money can no longer download transactions. Here are the pros and cons of the ones I've tried (updated 10/2010): You Need A Budget Pro (YNAB) - Based on the old envelopes system, YNAB has you allot money from each paycheck to a specific budget category (envelope). It encourages you to live on last money's income, and if you have trouble with overspending, that can be a great plan. Personally, I'm a big believer in the envelope concept, so that's the biggest pro I found. Also, it's a downloaded software, so once I've bought it (for about $50) it's mine, without forced upgrades as far as I've seen. The big con for me was that it does not automatically download transactions. I would have to sign on to each institution's website and manually download to the program. Also, coming from Money, I'm used to having features that YNAB doesn't offer, like the ability to store information about my accounts. Overall, it's forward-thinking and a good budgeting system, but will take some extra time to download transactions and isn't really a comprehensive management tool for all my financial needs. You can try it out with their free trial. Mint - This is a free online program. The free part was a major pro. It also looks pretty, if that's important to you. Updating is automatic, once you've got it all set up, so that's a pro. Mint's budgeting tools are so-so. Basically, you choose a category and tell it your limit. It yells at you (by text or email) when you cross the line, but doesn't seem to offer any other incentive to stay on budget. When I first looked at Mint, it did not connect with my credit union, but it currently connects to all my banks and all but one of my student loan institutions. Another recent improvement is that Mint now allows you to manually add transactions, including pending checks and cash transactions. The cons for me are that it does not give me a good end-of-the-month report, doesn't allow me to enter details of my paychecks, and doesn't give me any cash-flow forecasting. Overall, Mint is a good casual, retrospective, free online tool, but doesn't allow for much planning ahead. Mvelopes - Here's another online option, but this one is subscription-based. Again, we find the old envelopes system, which I think is smart, so that's a pro for me. It's online, so it downloads transactions automatically, but also allows you to manually add transactions, so another pro. The big con on this one is the cost. Depending on how you far ahead you choose to pay (quarterly, yearly or biannually), you're paying $7.60 to $12 per month. They do offer a free trial for 14 days (plus another 14 days offered when you try to cancel). Another con is that they don't provide meaningful reports. Overall, a good concept, but not worth the cost for me. Quicken - I hadn't tried Quicken earlier because they don't offer a free trial, but after the last few fell short, I landed with Quicken 2009. Pro for Quicken, as an MS Money user is that it is remarkably similar in format and options. The registers and reports are nearly identical. One frustration I'd had with Money was that it was ridiculously slow at start-up, and after a year or so of entering data, Quicken is dragging. Con for Quicken, again as an MS Money user, is that it's budgeting is not as detailed as I would like. Also, it does not download transactions smoothly now that my banks all ask security questions as part of sign-in. I have to sign in to my bank's website and manually download. Quicken 2011 is out now, but I haven't tried it yet. Hopefully they've solved the problem of security questions. Quicken 2011 promises an improved cash-flow forecast, which sounds promising, and was a feature of MS Money that I have very much missed. Haven't decided yet if it's worth the $50 to upgrade to 2011.",
"title": ""
},
{
"docid": "474279",
"text": "Listing on NYSE has more associated overhead costs than listing on NASDAQ. In the case of young technology companies, this makes NASDAQ a more attractive option. Perhaps the most important factor is that NYSE requires that a company has an independent compensation committee and an independent nominating committee while NASDAQ requires only that executive compensation and nominating decisions are made by a majority of independent directors. No self-respecting, would-be-instant-billionare tech entreprenuer is going to want some independent committee lording it over their pay packet. Additionally, listing on NYSE requires a company have stated guidance for corporate governance while NASDAQ imposes no such requirement. Similarly, NYSE requires a company have an internal audit team while NASDAQ imposes no such requirement. Fees on NYSE are also a bit higher than NASDAQ, but the difference is not significant. A good rundown of the pros/cons: http://www.investopedia.com/ask/answers/062215/what-are-advantages-and-disadvantages-listing-nasdaq-versus-other-stock-exchanges.asp",
"title": ""
},
{
"docid": "268802",
"text": "Without commenting on your view of the TV market: Let's have a look at the main ways to get negative exposure: 1.Short the stocks Pros: Relatively Easy Cons: Interest rate, costs of shorting, linear bet 2.Options a. Write Calls b. Buy puts Pros: Convexity, leveraged, relatively cheap Cons: Zero Sum bet that expires with time, theta 3.Short Stock, Buy Puts, Write Calls Short X Units of each stock, Write calls on them , use call premiums to finance puts. Pros: 3x the power!, high kickout Cons: Unlimited pain",
"title": ""
},
{
"docid": "258439",
"text": "My experience (two purchases, Ontario, Canada) is that the property taxes are paid by whomever is the owner on the date the tax bill comes due. The bill might be due before the owners even decide to sell. However: A part of the closing process is a Statement of Adjustments, in which various costs that span the tenure of two owners are split on a per-diem basis. In your case, there would have been a charge against you of 2/365 of the tax bill on this statement at the time of closing (if you hadn't paid any 2014 taxes) The statement also includes things like flat-rate water bills, monthly cable bills, security system monitoring... All paid by one owner or the other, but split fairly on a per diem basis at the time of closing...",
"title": ""
},
{
"docid": "471686",
"text": "As I understand it (please correct me if i'm wrong, i've looked at this before and i've been a sole trader briefly but I've never formed a LTD company) there are pros and cons to forming a limited company. Pros Cons",
"title": ""
},
{
"docid": "315847",
"text": "Here are the pros and cons and an analytical framework for making a decision. Pros of walking away: Cons: Here's the framework: compare the value of first and second sections for you [1] http://www.nytimes.com/2009/07/30/business/30serviceside.html?_r=0 [2] http://www.mortgagecalculator.org/",
"title": ""
},
{
"docid": "564648",
"text": "Your NRI friend can use normal Banks or specialized remittance services. There are questions on this website that give pro's and con's. From Indian tax point of you, you have received a gift from friend and as such it falls under Gift Tax act. Any amount upto Rs 50,000 is tax free. Anything above it is taxable as per tax bracket.",
"title": ""
},
{
"docid": "211196",
"text": "Currently, the answer is no, you cannot get out of filing a tax return. As noted in the comments, if you want to pay more to get out of the drudgery of working on your return, you can pay an accountant to do it for you. You are not alone in thinking that the current income tax system in the U.S. is overly complicated. What you are essentially describing is a flat tax, a system where there would be a simple tax rate that is paid with no deductions, loopholes, etc., and minimal reporting requirements. Besides flat tax proposals, others have proposed eliminating the income tax altogether and switching to a national sales tax, such as the FairTax proposal. Each of these proposals has pros and cons over the current system, and if you have questions about them, feel free to ask a new question. But what they have in common is that they would drastically simplify the system of taxation in this country. If that sounds good to you, you can learn more about these proposals and support organizations and candidates that advocate these reforms.",
"title": ""
},
{
"docid": "557186",
"text": "\"I've been in a very similar situation to yours in the past. Since the company is reimbursing you at a flat rate (I assume you don't need to provide documentation/receipts in order to be paid the per diem), it's not directly connected to the $90 in expenses that you mention. Unless they were taking taxes out that would need to be reimbursed, the separate category for Assets:Reimbursable:Gotham City serves no real purpose, other than to categorize the expenses. Since there is no direct relationship between your expenses and the reimbursement, I would list them as completely separate transactions: Later, if you needed to locate all of the associated expenses with the Gotham trip, gnucash lets you search on memo text for \"\"Gotham\"\" and will display all of the related transactions. This is a lot cleaner than having to determine what piece of the per diem goes to which expenses, or having to create a new Asset account every time you go on a trip.\"",
"title": ""
},
{
"docid": "107898",
"text": "\"a link to this article grabbed my Interest as I was browsing the site for something totally unrelated to finance. Your question is not silly - I'm not a financial expert, but I've been in your situation several times with Carmax Auto Finance (CAF) in particular. A lot of people probably thought you don't understand how financing works - but your Car Loan set up is EXACTLY how CAF Financing works, which I've used several times. Just some background info to anyone else reading this - unlike most other Simple Interest Car Financing, with CAF, they calculate per-diem based on your principal balance, and recalculate it every time you make a payment, regardless of when your actual due date was. But here's what makes CAF financing particularly fair - when you do make a payment, your per-diem since your last payment accrued X dollars, and that's your interest portion that is subtracted first from your payment (and obviously per-diem goes down faster the more you pay in a payment), and then EVerything else, including Any extra payments you make - goes to Principal. You do not have to specify that the extra payment(S) are principal only. If your payment amount per month is $500 and you give them 11 payments of $500 - the first $500 will have a small portion go to interest accrued since the last payment - depending on the per-diem that was recalculated, and then EVERYTHING ELSE goes to principal and STILL PUSHES YOUR NEXT DUE DATE (I prefer to break up extra payments as precisely the amount due per month, so that my intention is clear - pay the extra as a payment for the next month, and the one after that, etc, and keep pushing my next due date). That last point of pushing your next due date is the key - not all car financing companies do that. A lot of them will let you pay to principal yes, but you're still due next month. With CAF, you can have your cake, and eat it too. I worked for them in College - I know their financing system in and out, and I've always financed with them for that very reason. So, back to the question - should you keep the loan alive, albeit for a small amount. My unprofessional answer is yes! Car loans are very powerful in your credit report because they are installment accounts (same as Mortgages, and other accounts that you pay down to 0 and the loan is closed). Credit cards, are revolving accounts, and don't offer as much bang for your money - unless you are savvy in manipulating your card balances - take it up one month, take it down to 0 the next month, etc. I play those games a lot - but I always find mortgage and auto loans make the best impact. I do exactly what you do myself - I pay off the car down to about $500 (I actually make several small payments each equal to the agreed upon Monthly payment because their system automatically treats that as a payment for the next month due, and the one after that, etc - on top of paying it all to principal as I mentioned). DO NOT leave a dollar, as another reader mentioned - they have a \"\"good will\"\" threshold, I can't remember how much - probably $50, for which they will consider the account paid off, and close it out. So, if your concern is throwing away free money but you still want the account alive, your \"\"sweet spot\"\" where you can be sure the loan is not closed, is probably around $100. BUT....something else important to consider if you decide to go with that strategy of keeping the account alive (which I recommend). In my case, CAF will adjust down your next payment due, if it's less than the principal left. SO, let's say your regular payment is $400 and you only leave a $100, your next payment due is $100 (and it will go up a few cents each month because of the small per-diem), and that is exactly what CAF will report to the credit bureaus as your monthly obligation - which sucks because now your awesome car payment history looks like you've only been paying $100 every month - so, leave something close to one month's payment (yes, the interest accrued will be higher - but I'm not a penny-pincher when the reward is worth it - if you left $400 for 1.5 years at 10% APR - that equates to about $50 interest for that entire time - well worth it in my books. Sorry for rambling a lot, I suck myself into these debates all the time :)\"",
"title": ""
},
{
"docid": "123835",
"text": "\"Canada would most likely not convert any time in the near future. The challenge for Canada converting to the US Dollar or the fictional \"\"Amero\"\" mentioned by JohnFX is that : Some of the benefits would be: The challenge right now for any government would be to sell the pros over the cons and from that viewpoint the cons would appear to have more negative impact to voters. Considering that Canada currently has a minority government with no expected change to that status for some time the risk would be very high. For more details see Pros and Cons of Canadian Monetary Union and to see the Mexican impact see North American Currency Union It is interesting to note that currency union was first proposed in 1999 when the Canadian Dollar fluctuated between $0.64 to $0.69 US. The Canadian Dollar is closer to par with the US Dollar currently (in fact it rose to $1.10 US in Nov. 2007). Look-up historical rates at the Bank of Canada\"",
"title": ""
},
{
"docid": "174784",
"text": "CrimsonX did a great job highlighting the primary pros and cons of HSAs, so I won't go into detail there. However, I did want to point out another pro - HSAs are (or can be) easy to manage. You said: Is this a better way to approach health care costs instead of itemizing health care expenses on yearly federal taxes? I'm not sure which company you are looking at establishing your HSA with, but with mine I have a debit card that I use when paying for medical care and then at the end of the year I get a 1099-SA that provides the amount of money spent on qualified purchases that calendar year. Yes, there are a few extra boxes I need to fill in for my 1040 come tax time, but I don't need to itemize my healthcare costs over the year. It really is pretty simple and straightforward. Also, one con that is worth noting is that you become much more sensitive to healthcare costs due to the high deductible healthcare plan an HSA requires. For example, in all the years we've had an HSA we've not yet met our deductible, which means we pay out of pocket for any non-routine doctor visits. (The health insurer pays 100% of routine visits, like my wife's annual, well-baby check ups for the little one, and so on.) So, when you're feeling really sick and think a doctor's visit would be warranted, you have to make a decision: After being faced with this decision a time or two you will start to envy those who have just a $20 copay! Of course, that's just an emotional con. Each year I run the numbers on how much we spent per year on out of pocket plus premiums and compare it to what it would cost in premiums for an HMO-type plan, and the HSA plan always comes ahead. (In part because we are a pretty healthy family and I work for myself so do not get to enjoy group discount rates.) But I thought it worth mentioning because there are certainly times when I know I need to see a doctor or specialist and I cringe because I know I am going to be slapped with a big bill in the not too distant future!",
"title": ""
},
{
"docid": "246547",
"text": "As far as the spam mail goes, I own a rental (in Connecticut) and live in Massachusetts, I get very little mail related to this property. I view this as a non-compelling reason. Your other reasons pick up quick in value. The protection from the rest of your assets is helpful, and the one con for most is the inability to get a loan with such a structure, but in your case, a cash purchase is mentioned. I don't know what the fees are to start an LLC, but overall, I believe the pros outweigh the cons. Yes, your Pro 4 looks good, an ongoing business with a track record will help the next purchase.",
"title": ""
},
{
"docid": "66453",
"text": "\"The pros and cons of investing in a closed end fund both stem from the fact that the price per share is likely to differ from the net asset value (NAV) of the underlying assets. That could work to your advantage if the fund is selling for LESS than NAV, or at a discount. Then you get the \"\"benefit of the bargain\"\" and hope to sell the shares in the future for \"\"par\"\" or even a premium (MORE than NAV). On the other hand, if you buy such a fund at a premium, you stand to have a RELATIVE loss if the value of the fund goes back to par (or a discount) compared to NAV. That's because a closed end fund has a FIXED number of shares, with the assets continually being reinvested. In essence, you are \"\"buying out\"\" an existing shareholder of the fund at a price determined by supply and demand. This differs from an OPEN end fund, in which your contribution creates NEW shares (all other things being equal). Then the fund, has to invest YOUR money (and charges you a fee for the service) on exactly a pro rata basis with other investors in the fund, meaning that you will enter and exit such a fund at \"\"par.\"\" In either case, your return depends mainly on the performance of the underlying assets. But there are premium/discount issues for investing in a closed end fund.\"",
"title": ""
},
{
"docid": "256362",
"text": "The good debt/bad debt paradigm only applies if you are considering this as a pure investment situation and not factoring in: A house is something you live in and a car is something you use for transportation. These are not substitutes for each other! While you can live in your car in a pinch, you can't take your house to the shops. Looking at the car, I will simplify it to 3 options: You can now make a list of pros and cons for each one and decide the value you place on each of them. E.g. public transport will add 5h travel time per week @ $X per hour (how much you value your leisure time), an expensive car will make me feel good and I value that at $Y. For each option, put all the benefits together - this is the value of that option to you. Then put all of the costs together - this is what the option costs you. Then make a decision on which is the best value for you. Once you have decided which option is best for you then you can consider how you will fund it.",
"title": ""
},
{
"docid": "202140",
"text": "Is it worth saving HSA funds until retirement? Yes Are there pros and cons from a tax perspective? Mostly pros. This has all of the benefits of an IRA, but if you use it for medical expenses then you get to use the money tax free on the other side. Retirement seems to be the time you are most likely to need money for medical expenses. So why wouldn't you want to start saving tax free to cover those expenses? The cons are similar to other tax advantaged retirement accounts. If you withdraw before retirement time for non-medical purposes, you will pay penalties, but if you withdraw at retirement time, you will pay the same taxes you would pay on an IRA. I should note that I put my money where my mouth is and I max out my contribution to my HSA every year.",
"title": ""
},
{
"docid": "374518",
"text": "\"Unfortunately I don't think any of the online personal finance applications will do what you're asking. Most (if not all) online person finance software uses a combination of partnerships with the banks themselves and \"\"screen scraping\"\" to import your data. This simplifies things for the user but is typically limited to whenever the service was activated. Online personal finance software is still relatively young and doesn't offer the depth available in a desktop application (yet). If you are unwilling to part with historical data you spent years accumulating you are better off with a desktop application. Online Personal Finance Software Pros Cons Desktop Personal Finance Software Pros Cons In my humble opinion the personal finance software industry really needs a hybrid approach. A desktop application that is synchronized with a website. Offering the stability and tools of a desktop application with the availability of a web application.\"",
"title": ""
},
{
"docid": "479542",
"text": "A per diem payment is a cost of doing business for the company, not for you. They can claim it (probably); you can't (definitely).",
"title": ""
},
{
"docid": "77972",
"text": "Tax concerns aside, there are managerial pros and cons for internal billing. For cost control purposes it's common to break individual business activities into divisions/sections which have a P&L or are cost centers. At that point, if you know (for example) that your quality control inspections cost on average 1% of your product cost then one might bill internally for use of this cost center. One argument for doing this is it makes those who are billed more cautious about using internal resources as there's a direct cost allocation. It also benchmarks that resource against outsourcing- for example it may be significantly cheaper to use an external resource. There can therefore be a 'healthy tension' between the cost center and user which in theory results in pressure for the cost center to improve efficiency. In practice I've found there are some significant cons. First issue is with cost allocation. The cost center in an attempt to make their service appear more efficient will battle to get minimal overhead costs allocated to them, creating friction between departments. Second and I think a major issue is a blanket cost for use of a service invariably winds up with a lot of exceptions. In the previous example there may be some very large programs where a 1% inspection fee winds up with a huge sum of money, one that the product team may argue unfairly reduces their net income and therefore compensation. Then there's the administrative cost of what essentially is passing money from the left hand to the right even if just on paper. Third issue is with some activities you might not want to provide a disincentive for people to use the service- for example charging a product team for quality assurance may result in skipped QA processes for the benefit of cost savings. What I've found works better is creation of cost centers with management of those centers. This is common in companies that have a matrix organizational structure. Using the same example again, QA costs are broken out and completely separated from other areas and QA management is benchmarked independently.",
"title": ""
},
{
"docid": "56027",
"text": "As with everything else, it's a question of trade-offs. Pros For Buying In Bulk Cons For Buying In Bulk Inventory cost. You need to purchase more shelving/cupboards to stock the goods. This is a real cost. The psychological effect of having more means you are more likely to use more, thus costing you more. Deflation of the cost of the item should occur over time in a well-functioning market economy. A $10 item today might be $9.50 in one year in real terms. There is a real opportunity cost associated with overbuying. Granted, an extra $100 in your bank account won't be earning too much if you have to spend it one month later, but it does mean you have less financial independence for that month. Risk of spoilage. There is a nonzero risk that your goods could be ruined by flood/fire/toddler/klutz damage. You need to decide which of these pros and cons are more important to you. Financially, you should only buy what you need between shopping trips. In reality the convenience of holding goods in storage for when you need them may outweigh the costs.",
"title": ""
},
{
"docid": "216356",
"text": "The loan is private, so the business is more of a red-herring. The fact that you're closing it and lost a lot of money explains the loan, but is rather irrelevant otherwise as the loan is personal. Do consider potential tax benefits on writing off a loss, talk to a local tax adviser on that. Pros: Cons: I'm sure there are more considerations, of course, and I'm not familiar with the Canadian social safety nets to understand how much of a damage con #1 would be.",
"title": ""
},
{
"docid": "349684",
"text": "this is not necessarily true. sometimes it makes sense for a public company to go private. usually a private equity firm will buy up the shares. the private equity firm would usually be financed by a bank and the cash flow from the company will help pay off the financing. there are pros and cons to both private and public companies. a pro for a private company is the reduced regulation and there is no need to follow sarbanes-oxley act.",
"title": ""
},
{
"docid": "192910",
"text": "This very informative link gives a clear and comprehensive comparison (pros and cons) of various popular brokers: https://www.nerdwallet.com/blog/investing/best-online-brokers-for-stock-trading/ (Best Online Brokers for Stock Trading 2016) There are indeed some significant cons for the super-low commission fee. Just for a quick example, the Interactive Broker requires a minimum of 10k account balance, as well as the frequent trading activity even on monthly basis (or the minimum $10 commission would be charged).",
"title": ""
},
{
"docid": "301609",
"text": "KMyMoney Pros: Cons:",
"title": ""
},
{
"docid": "324273",
"text": "Excel Pros: Cons:",
"title": ""
},
{
"docid": "171253",
"text": "Intuit Quicken. Pros: Cons:",
"title": ""
},
{
"docid": "488037",
"text": "Money Manager Ex PROS: CONS",
"title": ""
}
] |
2679
|
Can one be non-resident alien in the US without being a resident anywhere else?
|
[
{
"docid": "29817",
"text": "\"You may be considered a resident for tax purposes. To meet the substantial presence test, you must have been physically present in the United States on at least: 31 days during the current year, and 183 days during the 3 year period that includes the current year and the 2 years immediately before. To satisfy the 183 days requirement, count: All of the days you were present in the current year, and One-third of the days you were present in the first year before the current year, and One-sixth of the days you were present in the second year before the current year. If you are exempt, I'd check that ending your residence in Germany doesn't violate terms of the visa, in which case you'd lose your exempt status. If you are certain that you can maintain your exempt status, then the income would definitively not be taxed by the US as it is not effectively connected income: You are considered to be engaged in a trade or business in the United States if you are temporarily present in the United States as a nonimmigrant on an \"\"F,\"\" \"\"J,\"\" \"\"M,\"\" or \"\"Q\"\" visa. The taxable part of any U.S. source scholarship or fellowship grant received by a nonimmigrant in \"\"F,\"\" \"\"J,\"\" \"\"M,\"\" or \"\"Q\"\" status is treated as effectively connected with a trade or business in the United States. and your scholarship is sourced from outside the US: Generally, the source of scholarships, fellowship grants, grants, prizes, and awards is the residence of the payer regardless of who actually disburses the funds. I would look into this from a German perspective. If they have a rule similiar to the US for scholarships, then you will still be counted as a resident there.\"",
"title": ""
},
{
"docid": "230566",
"text": "If you aren't a US National (citizen or Green Card holder or some other exception I know not of), you're an alien, no matter where else you may or may not be a citizen. If you don't meet the residency tests, you're nonresident. Simple as that.",
"title": ""
},
{
"docid": "394059",
"text": "\"You'll need to read carefully the German laws on tax residency, in many European (and other) tax laws the loss of residency due to absence is conditioned on acquiring residency elsewhere. But in general, it is possible to use treaties and statuses so that you end up not being resident anywhere, but it doesn't mean that the income is no longer taxed. Generally every country taxes income sourced to it unless an exclusion applies, so if you can no longer apply the treaty due to not being a resident - you'll need to look for general exclusions in the tax law. I don't know how Germany taxes scholarships under the general rules, you'll have to check it. It is possible that they're not taxed. Many people try to raise the argument of \"\"I'm not a resident\"\" to avoid income taxes altogether on earnings on their work - this would not work. But with a special kind of income like scholarship, which may be exempt under the law, it may. Keep in mind, that the treaty has \"\"who is or was immediately before visiting a Contracting State a resident of the other Contracting State\"\" language in some relevant cases, so you may still apply it in the US even if no longer resident in Germany.\"",
"title": ""
}
] |
[
{
"docid": "116181",
"text": "\"If you are a permanent resident (and it wasn't taken away or abandoned), then you are a resident alien for U.S. tax purposes. (One of the two tests for being a resident alien is the \"\"green card test\"\".) Being a resident alien means all your worldwide income is subject to U.S. taxes, regardless of where you live or work. That doesn't necessarily mean you need to actually pay taxes on your income again if you've already paid it -- you may be able to use the Foreign Tax Credit to reduce your taxes by the amount already paid to a foreign government -- but you need to report it on U.S. tax forms just like income from the U.S., and you can then apply any tax credits that you may qualify for. As a resident alien, you file taxes using Form 1040. You are required to file taxes if your income for a particular year is above a certain threshold. This threshold is described in the first few pages of the 1040 instructions for each year. For 2013, for Single filing status under 65, it is $10000. The only way you can legally not file is if your income the whole year was below this amount. You should go back and file taxes if you were required to but failed to. Having filed taxes when required is very important if you want to naturalize later on. It is also one component of demonstrating you're maintaining residency in the U.S., which you're required to do as a permanent resident being outside the U.S. for a long time, or else you'll lose your permanent residency. (Even filing taxes might not be enough, as your description of your presence in the U.S. shows you only go there for brief periods each year, not really living there. You're lucky you haven't lost your green card already; any time you go there you run a great risk of them noticing and taking it away.)\"",
"title": ""
},
{
"docid": "347186",
"text": "Tax liability in US: You would need to determine if you are a resident alien or non resident alien. Resident alien are taxed normally as per US citizens. For the annual remuneration you have quoted it would be in the range of 25%. Refer http://www.moneychimp.com/features/tax_brackets.htm To determine if you are resident alien or non resident alien, you need to be present for certain period in US. There is also an exemption even if you meet this you can still be treated as non resident alien if your tax home is outside US [India in this case] Refer to the link for details to determine your category, the durations are for number of days in financial year, hence it matters when you are in US and the exact durations. http://www.irs.gov/taxtopics/tc851.html Also note that if you are assessed as resident alien, even the income from India will be taxed in US unless you declare there is no income in India. Tax liability in India: The tax liability in India would be depending on your NRI status. This again is tied to the financial year and the number of days you are in country. While the year you are going out of India you need to be away for atleast 183 days for you be considred are NRI. So if you are treated as Indian resident, you would have to pay tax in India on entire income. In the worst case, depending on the period you travel and the dates you travel, you could get classified as citizen in US as well as India and have to pay tax at both places. India and US do not have a dual tax avoidance treaty for individuals. Its there for certain category like small business and certain professions like teacher, research etc.",
"title": ""
},
{
"docid": "506755",
"text": "\"1040 or 1040NR depends on whether you are a resident alien or nonresident alien -- 1040/1040A/1040EZ for resident aliens, and 1040NR/1040NR-EZ for nonresident aliens. Determining whether you are a resident is somewhat complex, and there is not enough information in your question to determine it. Publication 519 is the guide for taxes for aliens. (It hasn't been updated for 2014 yet, so mentally shift all the years in the publication up by one year when you read it.) Since you don't have a green card, whether you are a resident is determined by the Substantial Presence Test. The test says that if (the number of days you were in the U.S. in 2014) + 1/3 of (the number of days you were in the U.S. in 2013) + 1/6 of (the number of days you were in the U.S. in 2012) >= 183 days (half a year), then you are a resident alien for 2014. However, there are exceptions to the test. Days that you are an \"\"exempt individual\"\" are not counted toward the Substantial Presence Test. And \"\"exempt individuals\"\" include international students, trainees, teachers, etc. However, there are exceptions to the exceptions. Students are not \"\"exempt individuals\"\" for a year if they have been exempt individuals for any part of 5 previous calendar years. (Different exceptions apply for teachers and trainees.) So whether you are an \"\"exempt individual\"\" for one year inductively depends on whether you have been an \"\"exempt individual\"\" in previous years. Long story short, if before you came to the U.S. as an F-1 student, you haven't been in the U.S. on F-1 or J-1 status, then you will be a nonresident alien for the first 5 calendar years (calendar year = year with a number, not 365 days) that you've been on F-1. We will assume this is the case below. So if you started your F-1 in 2009 (any time during that year) or before, then you would have already been an exempt individual for 5 calendar years (e.g. if you came in 2009, then 2009, 2010, 2011, 2012, 2013 are your 5 years), so you would not be an exempt individual for any part of 2014. Since you were present in the U.S. for most of 2014, you meet the Substantial Presence Test for 2014, and you are a resident alien for all of 2014. If, on the other hand, you started your F-1 in 2010 (any time during that year) or after, then you would still be an exempt individual for the part of 2014 that you were on F-1 status (i.e. prior to October 2014. OPT is F-1.). Days in 2014 in H1b status (3 months) are not enough for you to satisfy the Substantial Presence Test for 2014, so you would be a nonresident alien for all of 2014. If you fall into the latter case (nonresident alien), there are some alternative choices you have. If you were in the U.S. for most of those last 3 months, then you are eligible to choose to use the \"\"First-Year Choice\"\". I will not go into the steps to use this choice, but the result is that it makes you dual-status for 2014 -- nonresident until October, and resident since October. If you are single, then making this choice pretty much gives you no benefit. However, if you are married, then making this choice allows you to subsequently make another choice to become a resident for all of 2014. Being resident gives you some benefits, like being able to file as Married Filing Jointly (nonresidents can only file separately), being able to use the Standard Deduction, being able to use many other deductions and credits, etc. Though, depending on what country you're from, it may affect your treaty benefits, so check that before you consider it.\"",
"title": ""
},
{
"docid": "192083",
"text": "It's not just the US based mailing address for registration or US based credit-card or bank account: even if you had all these, like I do, you will find that these online filing companies do not have the infrastructure to handle non-resident taxes. The reason why the popular online filing companies do not handle non-resident taxes is because: Non-residents require a different set of forms to fill out - usually postfixed NR - like the 1040-NR. These forms have different rules and templates that do not follow the usual resident forms. This would require non-trivial programming done by these vendors All the NR forms have detailed instructions and separate set of non-resident guides that has enough information for a smart person to figure out what needs to be done. For example, check out Publication 519 (2011), U.S. Tax Guide for Aliens. As a result, by reading these most non-residents (or their accountants) seem to figure out how the taxes need to be filed. For the remaining others, the numbers perhaps are not significant enough to justify the non-trivial programming that need to be done by these vendors to incorporate the non-resident forms. This was my understanding when I did research into tax filing software. However, if you or anyone else do end up finding tax filing software that does allow non-resident forms, I wil be extremely happy to learn about them. To answer your question: you need to do it yourself or get it done by someone who knows non-resident taxes. Some people on this forum, including me for gratis, would be glad to check your work once you are done with it as long as you relieve us of any liability.",
"title": ""
},
{
"docid": "158136",
"text": "\"The current tax regime? Not sure if you are being serious or facetious, but: [US Citizens and Resident Aliens Abroad - Filing Requirements](https://www.irs.gov/individuals/international-taxpayers/us-citizens-and-resident-aliens-abroad-filing-requirements) >If you are a U.S. citizen or resident alien living or traveling outside the United States, **you generally are required to file income tax returns, estate tax returns, and gift tax returns and pay estimated tax in the same way as those residing in the United States.** In contrast, corporations don't pay taxes on profits earned abroad until repatriation [here](http://money.cnn.com/2014/08/14/news/economy/corporate-taxes-inversion/index.html), [here](https://www.nytimes.com/2017/03/09/business/economy/corporate-tax-report.html), [here](https://www.bloomberg.com/graphics/2016-apple-profits/). So guess what they NEVER do? This is why literally every large US multi-national corporate \"\"person\"\" pays next to nothing in taxes. It is quite obvious that this is a violation of the spirit if not the letter of tax law. That simple fix would wipe out massive amounts of government debt and force multi-national corporations and their shareholders to become engaged stake holders in the efficiency of government. But if, unlike W-2 paid human counterparts, you can dodge all taxation, \"\"Who cares if the government is using funds efficiently?\"\" That is incentive to actually game the system to force the government into wasteful spending because the subsequent fallout of increased taxation and/or failure of the state can be dodged without consequence.\"",
"title": ""
},
{
"docid": "367562",
"text": "I can only answer about the U.S. For question 2, I believe the answer is no. If you are a non-resident alien for tax purposes, then only income connected to the U.S. is reported as income on the tax return. Unless there were any non-deductible contributions to your pre-tax IRAs, when you convert to Roth IRA, the entire amount of the conversion is added to your income. So the tax consequence is the same as if you had that much additional U.S. income. If you are a non-resident alien with no other income in the U.S., then the income you have to report on your U.S. tax return will basically consist of the conversion. Non-resident aliens do not have a standard deduction. However, all people have a personal exemption. If we take 2013 as an example, the exemption is $3900 per person. We will assume that you will file as single or married filing separately (non-resident aliens cannot file as married filing jointly). The first $3900 of income is covered by the exemption, and is not counted in taxable income. For single and MFS, the next $8925 of income is taxed at 10%, then next $27325 of income is taxed at 15%, and so on. So if you convert less than the personal exemption amount every year ($3900 in 2013), then in theory you do not pay any taxes. If you convert a little bit more, then some of the conversion will be taxed at 10%, etc.",
"title": ""
},
{
"docid": "214690",
"text": "Gifts from your parents are not treated as income for tax purposes. You should not include that in your subsidy calculation. If you are here on a student-visa and have been in the US for less than 5 years, then you are considered a non-resident alien, and you are not required to buy a qualified plan through the insurance marketplace. You might be able to get a cheaper student plan through your school, but the subsidy might be enough that it's still worth it when calculated correctly. If you are a resident-alien or you are a citizen of the US, then you are required to get coverage, though you can choose not to purchase coverage and pay the tax for not having creditable coverage. That tax cannot be collected by the IRS unless you have already had federal tax withheld. They can only confiscate your tax return money to recoup that money. I don't have enough information to recommend one way or the other what you should do, but I would bet that if you recalculated your subsidy without including your parents income it would cover the majority of the cost. You should also consider applying for Medicaid if you meet the eligibility requirements in your state.",
"title": ""
},
{
"docid": "111531",
"text": "\"From what you've described, your spouse is a non-resident alien for US tax purposes. You have two choices: Use the Nonresident Spouse Treated As Resident election and file as Married Filing Jointly. Since your spouse doesn't have, and doesn't currently qualify for, an SSN, he/she will need to apply for an ITIN together with the tax filing. Note that by becoming a resident alien, your spouse's worldwide income the whole year would be subject to US taxes, and would need to be reported on your joint tax filing, though he/she will be able to use the Foreign Earned Income Exclusion to exclude $100k of her foreign earned income, since he/she will have been out of the US for 330 days in a 12-month period. Or, file as Married Filing Separately. You write \"\"NRA\"\" for your spouse's SSN on your tax return. As a nonresident alien, if your spouse doesn't have any US income, he/she doesn't have to file a US tax return, and doesn't need to apply for an ITIN. Which one is better is up to you to figure out.\"",
"title": ""
},
{
"docid": "43508",
"text": "\"The examples you provide in the question are completely irrelevant. It doesn't matter where the brokerage is or where is the company you own stocks in. For a fairly standard case of an non-resident alien international student living full time in the US - your capital gains are US sourced. Let me quote the following text a couple of paragraphs down the line you quoted on the same page: Gain or loss from the sale or exchange of personal property generally has its source in the United States if the alien has a tax home in the United States. The key factor in determining if an individual is a U.S. resident for purposes of the sourcing of capital gains is whether the alien's \"\"tax home\"\" has shifted to the United States. If an alien does not have a tax home in the United States, then the alien’s U.S. source capital gains would be treated as foreign-source and thus nontaxable. In general, under the \"\"tax home\"\" rules, a person who is away (or who intends to be away) from his tax home for longer than 1 year has shifted tax homes to his new location upon his arrival in that new location. See Chapter 1 of Publication 463, Travel, Entertainment, Gift, and Car Expenses I'll assume you've read this and just want an explanation on what it means. What it means is that if you move to the US for a significant period of time (expected length of 1 year or more), your tax home is assumed to have shifted to the US and the capital gains are sourced to the US from the start of your move. For example: you are a foreign diplomat, and your 4-year assignment started in May. Year-end - you're not US tax resident (diplomats exempt), but you've stayed in the US for more than 183 days, and since your assignment is longer than 1 year - your tax home is now in the US. You'll pay the 30% flat tax. Another example: You're a foreign airline pilot, coming to the US every other day flying the airline aircraft. You end up staying in the US 184 days, but your tax home hasn't shifted, nor you're a US tax resident - you don't pay the flat tax. Keep in mind, that tax treaties may alter the situation since in many cases they also cover the capital gains situation for non-residents.\"",
"title": ""
},
{
"docid": "239030",
"text": "\"Congrats on the upcoming wedding! Here is the official answer to this question, from the IRS. They note that you can choose to treat your spouse as a US resident for tax purposes and file jointly if you want to, by attaching a certain declaration to your tax return. Though I'm not a tax expert, if your partner has significant income it seems like this might increase your taxes due. You can also apply for an SSN (used for tax filings, joint or separate return) at a social security office or US consulate, by form SS-5, or file form W-7 with the IRS to get a Taxpayer Identification Number which is just as useful for this purpose. Without that, you can write \"\"Non Resident Alien\"\" (or \"\"NRA\"\") in the box for your partner's SSN, and mail in a paper return like that. See IRS Publication 17 page 22 (discussions on TurboTax here, here, etc.).\"",
"title": ""
},
{
"docid": "570639",
"text": "\"Transferring the money or keeping it in US does has no effect on taxes. Your residency status has. Assuming you are Resident Alien in US for tax purpose and have paid the taxes to IRS and you are \"\"Non-Resident\"\" Indian for tax purposes in India as you are more than 182 outside India. How would it effect my Tax in US and India If you are \"\"Non-Resident\"\" in India for tax purposes, there is no tax liability of this in India. I have transferred an amount of approx 15-20k$ to Indian Account (not NRE) By RBI regulation, if you are \"\"Non-Resident\"\" then you should get your savings account converted to \"\"NRO\"\". You may not may not choose to open an NRE account. To keep the paper work clear it helps that you open an NRE account in India. Any investment needed ? Where do i need to declare if any ? These are not relevant. Note any income generated in India, i.e. interest in Savings account / FDs / Rent etc; taxes need to be paid in India and declared in US and taxes paid in US as well. There is some relief under DTAA. There are quite a few question on this site that will help you clarify what needs to be done.\"",
"title": ""
},
{
"docid": "334379",
"text": "Plenty of retired people do stay in the US for longer than 60 days and don't pay taxes. In this IRS document 60 days stay appears to be the test for having a 'substantial presence' in the US, which is part of the test for determining residency. However the following is also written: Even if you meet the substantial presence test, you can be treated as a nonresident alien if you are present in the United States for fewer than 183 days during the current calendar year, you maintain a tax home in a foreign country during the year, and you have a closer connection to that country than to the United States. In other words, if your property in the US is not your main one, you pay tax in another country, and you stay there less than half the year, you should be treated as a non-resident (I am not a lawyer and this is not advice). This IRS webpage describes the tax situation of nonresident aliens. As I understand it, if you are not engaged in any kind of business in the US and have no income from US sources then you do not have to file a tax return. You should also look into the subject of double tax agreements. If your home country has one, and you pay taxes there, you probably won't need to pay extra tax to the US. But again, don't take my word for it.",
"title": ""
},
{
"docid": "575899",
"text": "Found a great article (with bibliography) that covers taxation on investment activity by non resident aliens - even covers the special 15% tax on dividends for Canadian residents. It's (dividend tax rate) generally 30% for other NRAs (your 2nd question). And it confirmed my suspicion that there are no capital gains taxes for NRAs. (1st Q) Source: http://invest-faq.com/articles/tax-non-us-nat.html",
"title": ""
},
{
"docid": "475115",
"text": "Per the IRS instructions on filing as Head of Household as a Citizen Living Abroad, if you choose to file only your own taxes, and you qualify for Head of Household without them, the IRS does not consider you married: If you are a U.S. citizen married to a nonresident alien you may qualify to use the head of household tax rates. You are considered unmarried for head of household purposes if your spouse was a nonresident alien at any time during the year and you do not choose to treat your nonresident spouse as a resident alien. However, your spouse is not a qualifying person for head of household purposes. You must have another qualifying person and meet the other tests to be eligible to file as a head of household. As such, you could file as Married Filing Separately (if you have no children) or Head of Household (if you have one or more children, a parent, etc. for whom you paid more than half of their upkeep - see the document for more information). You also may choose to file as Married Filing Jointly, if it benefits you to do so (it may, if she earns much less than you). See the IRS document Nonresident Spouse Treated As Resident for more information. If you choose to treat her as a resident, then you must declare her worldwide income. In some circumstances this will be beneficial for you, if you earn substantially more than her and it lowers your tax rate overall to do so. Married Filing Separately severely limits your ability to take some deductions and credits, so it's well worth seeing which is better.",
"title": ""
},
{
"docid": "493160",
"text": "\"That's a tricky question and you should consult a tax professional that specializes on taxation of non-resident aliens and foreign expats. You should also consider the provisions of the tax treaty, if your country has one with the US. I would suggest you not to seek a \"\"free advice\"\" on internet forums, as the costs of making a mistake may be hefty. Generally, sales of stocks is not considered trade or business effectively connected to the US if that's your only activity. However, being this ESPP stock may make it connected to providing personal services, which makes it effectively connected. I'm assuming that since you're filing 1040NR, taxes were withheld by the broker, which means the broker considered this effectively connected income.\"",
"title": ""
},
{
"docid": "84528",
"text": "\"Tax US corporate \"\"persons (citizens)\"\" under the same regime as US human persons/citizens, i.e., file/pay taxes on all income earned annually with deductions for foreign taxes paid. Problem solved for both shareholders and governments. [US Citizens and Resident Aliens Abroad - Filing Requirements](https://www.irs.gov/individuals/international-taxpayers/us-citizens-and-resident-aliens-abroad-filing-requirements) >If you are a U.S. citizen or resident alien living or traveling outside the United States, **you generally are required to file income tax returns, estate tax returns, and gift tax returns and pay estimated tax in the same way as those residing in the United States.** Thing is, we know solving this isn't the point. It is to misdirect and talk about everything, but the actual issues, i.e., the discrepancy between tax regimes applied to persons and the massive inequality it creates in tax responsibility. Because that would lead to the simple solutions that the populace need/crave. My guess is most US human persons would LOVE to pay taxes only on what was left AFTER they covered their expenses.\"",
"title": ""
},
{
"docid": "256395",
"text": "With a question like this you should talk to a tax professional who knows about international tax and knows about both the UK and the country you will be working in. They will give you up to date advice on what can be an extremely complex question. However to get you started I'll tell you what I was told when I did this nearly twenty years ago. It's all about whether you are resident in the UK for tax purposes or not. If you are, you will pay UK tax. If not, you wont (assuming you are being paid outside the UK - check with your professional exactly what is involved). In those days you could be counted as 'non resident' if you spent a complete period of twelve months outside the UK. You can make occasional visits to the UK without invalidating that. Again, check exactly how much you are allowed to return while still being not resident. Usually you will have to pay tax in the country where you are resident, but check the rules there. With some skilful timing you may be able to be considered non-resident in bouth countries, at least for some of the time. Again, your tax professional will know. The bank account question - again get a professional. I don't think it's a problem, but you may have to establish that you are being paid in the foreign country. In general you are going to need an account in the country where you work, so if its a problem get paid there and transfer any money you need in the UK.",
"title": ""
},
{
"docid": "308048",
"text": "It is absolutely legal. While studying on a F-1 you would typically be considered a non-resident alien for tax purposes. You can trade stocks, just like any other foreigner having an account with a US- or non-US based brokerage firm. Make sure to account for profit made on dividends/capital gain when doing your US taxes. A software package provided by your university for doing taxes might not be adequate for this.",
"title": ""
},
{
"docid": "397449",
"text": "You can keep your Mutual Funds. You have to communicate your new status to fund house. The SIP can continue. Please note you have to convert the savings account to NRO account. Most banks would keep the account number same, else you have to revise SIP debit to new NRO account. From a tax point of view, it would be similar to resident status. Right now short term gains are taxed. There are quite a few other things you may need to do. Although dated, this is a good article. PS: Once you become resident alien in US for tax purposes, you are liable for taxes on global income.",
"title": ""
},
{
"docid": "46791",
"text": "\"ECI is relevant to non-resident aliens who are engaged in trade or business in the US. For that, you have to be present in the US, to begin with, or to own a business or property in the US. So the people to whom it is relevant are non-resident aliens in the US or business/property owners, not foreign contractors. From the IRS: The following categories of income are usually considered to be connected with a trade or business in the United States. You are considered to be engaged in a trade or business in the United States if you are temporarily present in the United States as a nonimmigrant on an \"\"F,\"\" \"\"J,\"\" \"\"M,\"\" or \"\"Q\"\" visa. The taxable part of any U.S. source scholarship or fellowship grant received by a nonimmigrant in \"\"F,\"\" \"\"J,\"\" \"\"M,\"\" or \"\"Q\"\" status is treated as effectively connected with a trade or business in the United States. If you are a member of a partnership that at any time during the tax year is engaged in a trade or business in the United States, you are considered to be engaged in a trade or business in the United States. You usually are engaged in a U.S. trade or business when you perform personal services in the United States. If you own and operate a business in the United States selling services, products, or merchandise, you are, with certain exceptions, engaged in a trade or business in the United States. For example, profit from the sale in the United States of inventory property purchased either in this country or in a foreign country is effectively connected trade or business income. Gains and losses from the sale or exchange of U.S. real property interests (whether or not they are capital assets) are taxed as if you are engaged in a trade or business in the United States. You must treat the gain or loss as effectively connected with that trade or business. Income from the rental of real property may be treated as ECI if the taxpayer elects to do so.\"",
"title": ""
},
{
"docid": "507107",
"text": "A non-resident alien is only allowed for deductions connected to producing a US-sourced income (See IRC Sec. 873). Thus you can only deduct things that qualify as business expenses, and State taxes on your wages. In addition you can deduct a bunch of stuff explicitly allowed (like tax preparation, charitable contributions, casualty losses, etc) but sales tax is not in that list.",
"title": ""
},
{
"docid": "288993",
"text": "To build a US credit record, you need a Social Security Number (SSN), which is now not available for most non-residents. An alternative is an ITIN number, which is now available to non-residents only if they have US income giving a reason to file a US tax return (do you really want to get into all that...). Assuming you did have a reason to get a ITIN (one reason would be if you sold some ebooks via Amazon US, and need a withholding refund under the tax treaty), then recent reports on Flyertalk give mixed results on whether it's possible to get a credit card with an ITIN, and whether that would build a credit record. It does sound possible in some cases. A credit record in any other country would not help. You would certainly need a US address, and banks are increasingly asking for a physical address, rather than just a mailbox. Regardless, building this history would be of limited benefit to you if you later became a US resident, at that point you would be eligible for a new SSN (different from the ITIN) and have to largely start again. If getting a card is the aim, rather than the credit record, you may find some banks that will offer a secured card (or a debit card), to non-residents, especially in areas with lots of Canadian visitors (border, Florida, Arizona). You'd find it a lot easier with a US address though, and you'd need to shop around a lot of banks in person until you find one with the right rules. Most will simply avoid anyone without an SSN.",
"title": ""
},
{
"docid": "454563",
"text": "If you are tax-resident in the US, then you must report income from sources within and without the United States. Your foreign income generally must be reported to the IRS. You will generally be eligible for a credit for foreign income taxes paid, via Form 1116. The question of the stock transfer is more complicated, but revolves around the beneficial owner. If the stocks are yours but held by your brother, it is possible that you are the beneficial owner and you will have to report any income. There is no tax for bringing the money into the US. As a US tax resident, you are already subject to income tax on the gain from the sale in India. However, if the investment is held by a separate entity in India, which is not a US domestic entity or tax resident, then there is a separate analysis. Paying a dividend to you of the sale proceeds (or part of the proceeds) would be taxable. Your sale of the entity containing the investments would be taxable. There are look-through provisions if the entity is insufficiently foreign (de facto US, such as a Subpart-F CFC). There are ways to structure that transaction that are not taxable, such as making it a bona fide loan (which is enforceable and you must pay back on reasonable terms). But if you are holding property directly, not through a foreign separate entity, then the sale triggers US tax; the transfer into the US is not meaningful for your taxes, except for reporting foreign accounts. Please review Publication 519 for general information on taxation of resident aliens.",
"title": ""
},
{
"docid": "589123",
"text": "\"As you said, in the US LLC is (usually, unless you elect otherwise) not a separate tax entity. As such, the question \"\"Does a US LLC owned by a non-resident alien have to pay US taxes\"\" has no meaning. A US LLC, regardless of who owns it, doesn't pay US income taxes. States are different. Some States do tax LLCs (for example, California), so if you intend to operate in such a State - you need to verify that the extra tax the LLC would pay on top of your personal tax is worth it for you. As I mentioned in the comment, you need to check your decision making very carefully. LLC you create in the US may or may not be recognized as a separate legal/tax entity in your home country. So while you neither gain nor lose anything in the US (since the LLC is transparent tax wise), you may get hit by extra taxes at home if they see the LLC as a non-transparent corporate entity. Also, keep in mind that the liability protection by the LLC usually doesn't cover your own misdeeds. So if you sell products of your own work, the LLC may end up being completely worthless and will only add complexity to your business. I suggest you check all these with a reputable attorney. Not one whose business is to set up LLCs, these are going to tell you anything you want to hear as long as you hire them to do their thing. Talk to one who will not benefit from your decision either way and can provide an unbiased advice.\"",
"title": ""
},
{
"docid": "417455",
"text": "Many European countires allow you to an account for non-residents. You have to appear in the bank personally to open it, some of them even to get your own tax number for non-residents from the local government. I'm not sure if you get a Visa (Electron) chip card immediatelly or you have to wait for like 3 months before being issued one. I've heard that getting a tax number for non-residents and opening a bank account is easily done in one day in Brezice, Republic of Slovenia. They seem to have agile local bureaucracy and banks, since many pople from neighbouring (non-EU) countries (used to) come there to open an EU bank account. Funds can be transfered via Internet banking - US banks have that, do they? SWIFT and IBAN codes are used for international money transfer. But it takes some time (days!) for it to arrive to destination. Tansfers below $20000 per month or per transaction are considered normal, but for amouts above that the destination bank might ask you to explain the purpose, to prove it is not illegal. Some of them accept the explanaiton in writing (they forward it to the regulator that tracks such large transfers), some of them ask you to appear there in person for an interview and to sign a statement. Can't believe US banks are still issuing paing magnet stripe cards like it's still 1980s. I'd expect Europe to be 10 years behind USA in technology, but this seems to be a weird reverse. I've beed using Internet banking with one-time passwd tokens and TAN lists for almost 10 years, and chip cards exclusivley for over 5y. Can't remeber the last time I've seen mag stripe card only. American Express (event the regular green one) got the chip at least 5 years ago. And it is accepted regularly in Europe. Alegedly it's more popular in Europe (although Mastercard is a definite #1, with Visa close to that) that in USA.",
"title": ""
},
{
"docid": "558618",
"text": "What taxes will I have to pay to India? Income earned outside of India when your status is Non-Resident Indian, there is no tax applicable. You can repatriate the funds back to India within 7 years without any tax event. Someone else may put an answer about US taxes.",
"title": ""
},
{
"docid": "392313",
"text": "non-resident aliens to the US do not pay capital gains on US products. You pay tax in your home country if you have done a taxable event in your country. http://www.investopedia.com/ask/answers/06/nonusresidenttax.asp#axzz1mQDut9Ru but if you hold dividends, you are subject to US dividend tax. The UK-US treaty should touch on that though.",
"title": ""
},
{
"docid": "64103",
"text": "\"I took @littleadv 's recommendation that online apps only ask for citizenship due to post-9/11 legislation. I applied to 2 banks in person (one big, one small), and at the dealership. None of my in-person applications ever touched on the issue of citizenship. I even applied in person at the same bank that insta-rejected me online, and told them up front, \"\"I applied online but you rejected me because I'm not a permanent resident.\"\" The banker nodded, said \"\"that shouldn't matter here\"\", and continued processing my application. I did find it very hard to get a loan. I have a credit score in the \"\"excellent\"\" range, but have only 1 open credit card (for 5 years). Apparently, most lenders want to see more open credit before writing an auto loan. The big bank said outright \"\"We want to see 3-5 credit cards open\"\". However, the dealership did find a bank willing to extend me a loan. So: The most reliable way for a non-permanent resident alien to get an auto loan in the US is to avoid online applications. Also, if possible, establish a wide credit history before you try.\"",
"title": ""
},
{
"docid": "197576",
"text": "First of all depending on the type of IRA you may not have to pay taxes on withdrawals in the US at all. If you are withdrawing your principle from a Roth IRA then you don't owe taxes. Only when you withdraw the gains do you pay taxes on it. You have two options for withdrawals: Lump Sum Withdrawal: If you take a lump sum withdrawal you will owe taxes to the US (30% for non-resident aliens of the US), and according to DTAA; Article 23, you will file your taxes with India declaring your IRA or 401(k) withdrawal proceeds and claim credit on the taxes you paid to the US. Monthly Pension Withdrawal: You can also receive monthly pension payments and you will only be taxed in the country in which you are a resident of. This is according to DTAA, Article 20. You would then have to submit necessary documentation to your payer in the US so that they do not withhold any taxes in the US. Just as a side note it might be just better to keep the money where it is and let it grow or roll it over to a Roth IRA if you are currently in a lower tax bracket for maximum savings of your principle. Here is a link with more detailed information of what I provided you: http://articles.economictimes.indiatimes.com/2012-01-25/news/30663129_1_taxable-income-nri-401k-plan",
"title": ""
},
{
"docid": "397920",
"text": "I heard that a C-Corp being a one person shop (no other employees but the owner) can pay for the full amount 100% of personal rent if the residence is being used as a home office. Sure. Especially if you don't mind being audited. Technically, it doesn't matter how the money gets where it goes as long as the income tax filings accurately describe the tax situation. But the IRS hates it when you make personal expenses from a business account, even if you've paid the required personal income tax (because their computers simply aren't smart enough to keep up with that level of chaos). Also, on a non-tax level, commingling of business and personal funds can reduce the effectiveness of your company's liability protection and you could more easily become personally liable if the company goes bankrupt. From what I understand the 30% would be the expense, and the 70% profit distribution. I recommend you just pay yourself and pay the rent from your personal account and claim the allowed deductions properly like everyone else. Why & when it would make sense to do this? Are there any tax benefits? Never, because, no. You would still have to pay personal income tax on your 70% share of the rent (the 30% you may be able to get deductions for but the rules are quite complicated and you should never just estimate). The only way to get money out of a corporation without paying personal income tax is by having a qualified dividend. That's quite complicated - your accounting has to be clear that the money being issued as a qualified dividend came from an economic profit, not from a paper profit resulting from the fact that you worked hard without paying yourself market value.",
"title": ""
}
] |
179457
|
Collision Course was released by Warner Bros. and Machine Shop.
|
[
{
"docid": "Collision_Course_(album)",
"text": "Collision Course is a collaborative EP from American rapper Jay-Z and nu metal band Linkin Park , released on November 30 , 2004 by Roc-A-Fella , Machine Shop , Warner Bros. and Def Jam records . Before the album , Jay-Z had released collaborations with The Roots and R. Kelly , and Linkin Park had collaborated with various artists on their remix album Reanimation . The album was inspired by The Grey Album by Danger Mouse , which was a mash-up album between Jay-Z and The Beatles . MTV had originally planned on mashing up only one or two songs , but the project was eventually expanded to a six song EP . The album was mostly produced by Mike Shinoda and Jay-Z , and was recorded between July 16 and July 19 . Upon release , Collision Course reached # 1 on the Billboard 200 . As of June 2014 , it has sold 2 million copies in the United States alone . The album spawned one single , Numb/Encore which eventually won Best Rap/Sung Collaboration at the 2006 Grammy Awards .",
"title": ""
}
] |
[
{
"docid": "Instrumental_Album:_The_Rising_Tied",
"text": "Instrumental Album : The Rising Tied is the debut instrumental studio album of hip hop ensemble Fort Minor , the side project by Linkin Park rapper Mike Shinoda . The album was released on January 1 , 2005 through Warner Bros. . Records and Shinoda 's label Machine Shop Recordings . The album was released almost a year before the release of his debut studio album , The Rising Tied . It failed to charts for several occasions . Shinoda handled production for the album . Jay-Z , who worked with Linkin Park on their collaborative EP Collision Course in 2004 , served as an executive producer for the album . Shinoda collaborated with Styles of Beyond 's DJ Cheapshot , Eric Bobo of Cypress Hill and Linkin Park turntablist Joe Hahn for this album .",
"title": ""
},
{
"docid": "The_Rising_Tied",
"text": "The Rising Tied is the debut studio album of hip hop ensemble Fort Minor , the side project by Linkin Park rapper Mike Shinoda . The album was released on November 22 , 2005 through Warner Bros. . Records and Shinoda 's label Machine Shop Recordings . Instrumental Album : The Rising Tied is the first and only instrumental studio debut album of Fort Minor , which contains no lyrics and guest appearances , with music written and composed by Shinoda . It was released on January 1 , 2005 worldwide through Warner Bros. and Machine Shop , but failed to charts for several occasions . Shinoda handled production for the album . Jay Z , who worked with Linkin Park on their collaborative EP Collision Course , served as an executive producer for the album . Shinoda collaborated with many longtime friends ( such as hip hop group Styles of Beyond , Jonah Matranga , Holly Brook and Linkin Park turntablist Joe Hahn ) , as well as many notable and underground hip-hop and R&B artists ( such as Common , John Legend , Black Thought , Lupe Fiasco , Kenna , Eric Bobo , Sixx John and Celph Titled ) for the album . It spawned four singles : `` Petrified '' , `` Remember the Name '' , `` Believe Me '' and `` Where 'd You Go '' , the latter of which was responsible for propelling Fort Minor to mainstream success . The Rising Tied was met with positive reviews from music critics , who praised Shinoda for straying from mainstream hip hop stereotypes , as well as acclaim from internet and independent music publications . The Rising Tied was a moderate commercial success , peaking at number fifty-one on the Billboard 200 .",
"title": ""
},
{
"docid": "Numb/Encore",
"text": "`` Numb/Encore '' is a song by American rapper Jay Z and rock band Linkin Park from their album Collision Course ( 2004 ) . It was released as a single on December 13 , 2004 , by Warner Bros. , Machine Shop , Def Jam , and Roc-A-Fella Records . The song is a mash-up combining lyrics from Linkin Park 's 2003 single `` Numb '' and `` Encore '' by Jay Z. The only single released from the album , the track went on to reach number 20 on the Billboard Hot 100 . Billboard also placed the single at number 93 on their Billboard Year-End Hot 100 singles of 2005 chart . Outside the United States , the single peaked at number 14 in the United Kingdom , number five in France and the Netherlands and spent three weeks at number one in Ireland . A trailer for Titanfall 2 featured Numb/Encore .",
"title": ""
},
{
"docid": "The_Making_of_Minutes_to_Midnight",
"text": "The Making of Minutes to Midnight is the sixth DVD by Linkin Park , released on May 14 , 2007 through Warner Bros. . Records and Machine Shop Records . The release documented the band while recording their third studio album , Minutes to Midnight . It was included in the limited edition of the album . It also features the band recording some demos like `` QWERTY '' , `` No Roads Left '' and `` Across the Line '' , which were later released in the LP Underground extended plays and in the EP , Songs from the Underground .",
"title": ""
},
{
"docid": "White_Noise_(Linkin_Park_song)",
"text": "White Noise is a song by American rock band Linkin Park , which was released on October 17 , 2014 through Warner Bros. . Records and Machine Shop Records . The song was released in the promotion of a 2014 American drama film based on a novel written by Eric Bogosian named as Mall . The song is one of the four unreleased demos by the band included in the original motion picture soundtrack to the same name of the film .",
"title": ""
},
{
"docid": "8-Bit_Rebellion!_(soundtrack)",
"text": "8-Bit Rebellion ! is the soundtrack album for the online video game of the same name , consisting of songs recorded by American rock band Linkin Park . It was released on April 26 , 2010 via Warner Bros. and Machine Shop and produced by Mike Shinoda . This is the fourth soundtrack released by the band . The previous soundtrack Transformers : Revenge of the Fallen -- The Score , released in June 12 , 2009 in the UK and June 23 , 2009 in the United States , was a collaborated film score album with music composer Steve Jablonsky for the 2009 Transformers sequel Transformers : Revenge of the Fallen .",
"title": ""
},
{
"docid": "Recharged_(album)",
"text": "Recharged is the second remix album of recordings by American rock band Linkin Park . The album was released on October 29 , 2013 , through Warner Bros. . Records and Machine Shop Recordings . It is entirely produced by Rick Rubin and Mike Shinoda . The album includes remixes of ten of the songs from the band 's fifth studio album Living Things , as well as a new song , `` A Light That Never Comes '' ( and a remix of it ) with Steve Aoki , which is the album 's first single , released on September 16 . Recharged received mixed reviews from critics .",
"title": ""
},
{
"docid": "The_Meeting_of_a_Thousand_Suns",
"text": "The Meeting of A Thousand Suns ( also known as The Making of A Thousand Suns ) is the eighth DVD by Linkin Park , released on September 08 , 2010 through Warner Bros. . Records and Machine Shop Records . The release documented the band while recording their fourth studio album , A Thousand Suns . It was included in the limited edition of the album . It also features the band recording some demos like `` Dingleberry '' , `` Meadowlands '' , `` Pac-Manny '' and `` Violent Lullaby '' . All of these demos are still left unreleased . But all the demos are modified and released as singles and tracks `` When They Come for Me '' , `` Waiting for the End '' , `` Blackout '' and `` The Catalyst '' respectively for the album .",
"title": ""
},
{
"docid": "Until_It's_Gone_(Linkin_Park_song)",
"text": "`` Until It 's Gone '' is a song written by American rock band Linkin Park . The song was originally recorded by the band for their sixth studio album , The Hunting Party , where it appears as the seventh track on the album . Produced by Mike Shinoda and Brad Delson , the track also appears on the single of the same name , which was released by Warner Bros. . Records and Machine Shop on May 6 , 2014 . The single is the second to be released in promotion of The Hunting Party . The single is also included in the music for the action-adventure video game Transformers : Rise of the Dark Spark , which was released on June 24 , 2014 .",
"title": ""
},
{
"docid": "Inside_Living_Things",
"text": "Inside Living Things is a documentary short film by Linkin Park , released on June 19 , 2012 through Warner Bros. . Records and Machine Shop Records . The video was released a week before the band 's fifth studio album , Living Things . The release documented the band while recording their fifth studio album , Living Things . Unlike the other making of album video albums , this album was not included as a special edition DVD , but instead of that it was released as a video on the YouTube channel of the band . The video includes various footages from various videos from the `` LPTV '' . The album was also previewed on Tumblr . The cover art of the album was the same which was used for the vinyl version of the album .",
"title": ""
},
{
"docid": "Show_(The_Jesus_Lizard_album)",
"text": "Show is a live album by the Chicago noise rock band The Jesus Lizard . It was recorded at CBGB 's in New York City . It was a joint release by Collision Arts and Warner Bros. subsidiary label Giant Records .",
"title": ""
},
{
"docid": "Mall_(soundtrack)",
"text": "Mall : Music from the Motion Picture is the original motion picture soundtrack for the 2014 American drama film Mall , consisting of songs written , recorded and performed by American rock band Linkin Park with Alec Puro , drummer of American rock band Deadsy . It was released through Warner Bros. and Machine Shop on December 12 , 2014 . The soundtrack was produced by Mike Shinoda and Brad Delson , along with Rob Cavallo and Bill Boyd , who are both serving as executive producers . This is the sixth soundtrack soon to be released by the band . The previous soundtrack , Transformers : Dark of the Moon -- The Album , was released on June 14 , 2011 for the 2011 American live-action film , Transformers : Dark of the Moon . The soundtrack is now available in the Australian iTunes store , and the New Zealand iTunes store .",
"title": ""
},
{
"docid": "List_of_Festival_Mushroom_Records_artists",
"text": "An asterisk denotes an artist/company who no longer records for the label . A caret denotes an artist who has recorded for both Festival Mushroom Records ( FMR ) and Warner Bros. . Records Inc. ( WB ) . Current Artists : The Veronicas + ( Sire/FMR/Warner Bros. . ) Mika + ( FMR/Warner Bros. . ) Paris Hilton + ( Heiress/FMR/Warner Bros. . ) Jesse McCartney ( Hollywood/FMR/Warner Bros. . ) Nelly Furtado * ( DreamWorks/FMR/Warner Bros. . ) Kylie Minogue Enya + ( FMR/Warner Bros. . ) Eskimo Joe Thirsty Merc Former Artists : The Flying Emus Madonna + ( FMR/Warner Bros. . ) Skyhooks The Dingoes Jimmy Barnes * The Whitlams * Split Enz Jason Donovan Scandal ` us The Saints Delta Goodrem ( on self tiled album - 2007 ) Paul Norton Wendy Stapleton The Badloves Chain Matt Taylor Frente Toni Pearen Gwen Stefani ( on 2006 's Wind It Up release ) Kate Alexa Jo Beth Taylor Johnny O'Keefe Col Joye & The Joy Boys Normie Rowe The Bee Gees Johnny Young Jimmy Little George Machine Gun Fellatio Motor Ace Amiel Hilary Duff ( Hollywood/FMR/Warner Bros. . ) Neighbours * Home and Away * Home and Away -- Holiday Coast Garbage Yothu Yindi Weddings Parties Anything Wilson Diesel Vika and Linda Madder Lake Chantoozies Models Swoop Christie Allen Uncanny X-Men Dannii Minogue * The Mavis 's Deborah Conway Mark Seymour Chris Bailey Renée Geyer The Sports Mick Molloy Sunnyboys Ol' 55 Paul Kelly Hunters & Collectors Billy Thorpe & The Aztecs Peter Allen Sherbet Olivia Newton-John ABC TV ( joint with Festival Video which later changed its name to Roadshow Entertainment in 1994 ) Kath & Kim ( includes cast ) ( Warner Bros. / FMR ) Choirboys Ian Moss Kate Ceberano * Peter Andre S2S Tom Jones 28 Days Baha Men Moby Gwyneth Paltrow ( Hollywood/FMR/Warner Bros. . ) J Wess Project Scribe Daniel Powter + ( FMR/Warner Bros. . ) The Androids Deni Hines Leonardo 's Bride The Angels Television DVDs : Wheel of Fortune ( Australian game show ) ( 1981 -- present ) Thomas & Friends ( 1984 -- present ) Kath & Kim ( 2002 -- 2004 , 2007 -- present ) Emma & Ali 's Catch Phrase ( 2007 -- present ) The Support Unit 2005 ( 2005 ) Leigh & Brad 's Story ( 2005 ) Home and Away -- Holiday Coast ( 1990 -- present )",
"title": ""
},
{
"docid": "Download_to_Donate_for_Haiti",
"text": "Download to Donate for Haiti is a compilation album by various artists . It was released on January 19 , 2010 through Machine Shop and Warner Bros. . Records . The album was produced by Mike Shinoda and co-produced by Enrique Iglesias . American rock band Linkin Park started a project called Music for Relief in 2005 , which has done relief work for the Indian Ocean Tsunami in 2004 , the 2010 Haiti earthquake , the 2011 Tōhoku earthquake and tsunami and Hurricane Sandy in 2012 . Linkin Park released a single for the album titled as `` Not Alone '' , which was recorded for their third studio album Minutes to Midnight , as the first and introductory track on this album . The single was released almost after two years of the release of the album , due to the release of their fourth album A Thousand Suns . This album is one of the albums released via Download to Donate . In 2011 , a sequel to the album , titled Download to Donate for Haiti V2 .0 , was released .",
"title": ""
},
{
"docid": "Warner_Bros._World_Abu_Dhabi",
"text": "Warner Bros. . World Abu Dhabi is a planned indoor amusement park in Abu Dhabi , United Arab Emirates owned and developed by Miral Asset Management , LLC at an expected cost of $ 1 billion . The park will feature characters from Warner Bros 's franchises , such as Looney Tunes , DC Comics , Hanna-Barbera and others licensed by Miral . The park will be located on Yas Island near Ferrari World and Yas Waterpark and would be the Warner Bros. 's third theme park . A companion Warner Bros. hotel is also being built at the center of Yas Island . The park contain 1.65 million square feet covering more than 15 hectares with 29 rides , restaurants , interactive attractions , shops and shows .",
"title": ""
},
{
"docid": "One_More_Light",
"text": "One More Light is the seventh studio album by American rock band Linkin Park . It was released on May 19 , 2017 through Warner Bros. . Records and Machine Shop , following the 2014 album The Hunting Party . The album 's first single , `` Heavy '' was released on March 16 , 2017 . It is their first album with a title track . In deciding on the title track , they felt that the song `` One More Light '' was the heart of the album . The album features guest vocal appearances from Pusha T , Stormzy , and Kiiara , and production and songwriting collaborations with Julia Michaels , Justin Tranter , Ross Golan , Andrew Goldstein , blackbear , and Eg White . Acoustic performances of the lead single by Chester Bennington and Mike Shinoda helped promote One More Light . A few of them included performances with Kiiara , Waxx , and Sofia Karlberg .",
"title": ""
},
{
"docid": "Warner_Home_Video",
"text": "Warner Home Video is the home video distribution arm of Warner Bros. , a subsidiary of Time Warner . Founded in 1978 as WCI Home Video ( standing for Warner Communications , Inc. ) , the company primarily releases titles from the film and television library of Warner Bros. . Entertainment , as well as programs from other Time Warner companies . Warner Home Video is a business unit of Warner Bros. . Home Entertainment , along with Warner Bros. . Digital and Warner Bros. . Interactive Entertainment .",
"title": ""
},
{
"docid": "The_Hunting_Party_(album)",
"text": "The Hunting Party is the sixth studio album by American rock band Linkin Park . The album , produced by band members Mike Shinoda and Brad Delson , was released by Warner Bros. . Records and Machine Shop on June 13 , 2014 . It is the first album since Meteora ( 2003 ) not to be produced with Rick Rubin , after producing the band 's previous three studio albums . The title The Hunting Party is a contextual metaphor : Linkin Park is the party that is hunting to bring back the energy and soul of rock . The Hunting Party is a departure from the electronic rock sound of the band 's previous two studio albums . The album , described by Shinoda as simply `` a rock record '' , serves a statement by the band against contemporary mainstream and active rock bands , accused by him as `` trying to be other bands and playing it safe '' . Packaged by an artwork by Brandon Parvini based on an original drawing by James Jean , the album took under a year to record and produce , with material being improvisationally written by the band . The album also features guest appearances from Page Hamilton of Helmet , Daron Malakian of System of a Down , Tom Morello of Rage Against the Machine , and Rakim , marking the first time Linkin Park has collaborated with other artists on a studio album . The album was promoted by the band and Warner Bros , with multiple promotional teasers and interviews produced and published in the lead-up to the album 's release and listening parties of the album being held worldwide on multiple dates . The band embarked on the Carnivores Tour , a double-headline tour with Thirty Seconds to Mars , as well as The Hunting Party Tour , in support of the album . Five singles from The Hunting Party have been released ; `` Guilty All the Same '' in March 2014 , `` Until It 's Gone '' in May 2014 , and `` Wastelands '' , `` Rebellion '' and `` Final Masquerade '' in June 2014 . The album received generally positive reviews from critics , who praised its return to the heavier rock sound of their older albums . It debuted at number three on Billboard 200 , and has placed at number four on Revolver 's list of `` The 20 Best Albums of 2014 '' .",
"title": ""
},
{
"docid": "Little_Machines",
"text": "Little Machines is the third studio album by Canadian electropop singer-songwriter Lights , released on September 23 , 2014 through Warner Bros. . Records . It was preceded in July 2014 by the release of its lead single `` Up We Go '' , which debuted on the Canadian Hot 100 at 84 . In October 2014 , Little Machines debuted on the Canadian Albums Chart at No. 5 , and on the US Billboard 200 at No. 34 . The album sold 8,500 copies in its first week in Canada . On March 15 , 2015 , ` Little Machines ' won the ` Pop Album of the Year ' award at the 2015 JUNO Awards . The album title comes from a lyric in the song `` Running with the Boys '' .",
"title": ""
},
{
"docid": "Download_to_Donate:_Tsunami_Relief",
"text": "Download to Donate : Tsunami Relief ( sometimes known as Download to Donate for Japan ) is a compilation of songs by Music for Relief from different artists in which the proceeds went to Save the Children that helped the victims of the 2011 Tōhoku earthquake and tsunami . The third Download to Donate compilation album , it was launched on March 22 , 2011 through Warner Bros. . Records and Machine Shop Records . The songs were no longer available for download as of June 7 , 2011 .",
"title": ""
},
{
"docid": "Dusty_Drake_(album)",
"text": "Dusty Drake is the self-titled debut album of American country music artist Dusty Drake . Released in 2003 ( see 2003 in country music ) , it is also his only studio album to be released . The tracks `` And Then '' , `` One Last Time '' , and `` Smaller Pieces '' were all released as singles , peaking at # 57 , # 26 , and # 50 , respectively , on the Billboard Hot Country Songs charts that year . The album itself reached # 30 on the Top Country Albums charts , and # 22 on Top Heatseekers . `` The Hard Way '' was covered by John Waite on his 2006 album Downtown : Journey of a Heart . After the release of this album , Drake issued a fourth single for Warner Bros. , entitled `` I Am the Working Man '' . This single failed to reach Top 40 , however , and Drake was dropped from Warner Bros. in 2004 . Although he recorded a second album for Big Machine Records in 2007 , it was never released ( although its lead-off single `` Say Yes '' charted in the Top 40 ) . `` One Last Time '' is a memorial to the passengers on the planes of 9/11 .",
"title": ""
},
{
"docid": "Collision_course_(disambiguation)",
"text": "Collision course refers to one opposing object or philosophy moving towards another expecting to collide . Collision Course may also refer to : Collision Course ( album ) , a 2004 album by Jay-Z & Linkin Park Collision Course ( 2004 film ) , a film released by Jay-Z & Linkin Park about the album Collision Course ( Paradox album ) , a 2000 album by German band Paradox Collision Course ( 1989 film ) , a 1989 action comedy film starring actors Jay Leno and Pat Morita The Crocodile Hunter : Collision Course , a 2002 Australian comedy-adventure film starring Steve Irwin Collision Course , a novel by Nigel Hinton Collision Course ( Silverberg novel ) , a 1958 novel by Robert Silverberg Collision Course ( Bayley novel ) , a novel by Barrington J. Bayley `` Collision Course '' ( Space : 1999 ) , an episode from the first series of Space : 1999 Collision Course ( Star Trek : Academy ) , a novel by William Shatner and Judith and Garfield Reeves-Stevens",
"title": ""
},
{
"docid": "Warner_Bros._Animation",
"text": "Warner Bros. . Animation ( currently known alternatively as Warner Animation Group for theatrically released films ) is the animation division of Warner Bros. , a subsidiary of Time Warner . The studio is closely associated with the Looney Tunes and Merrie Melodies characters , among others . The studio is the successor to Warner Bros. . Cartoons ( formerly Leon Schlesinger Productions ) , the studio which produced Looney Tunes and Merrie Melodies cartoon shorts from 1933 to 1963 , and from 1967 to 1969 . Warner reestablished its own animation division in 1980 to produce Looney Tunes -- related works . Since 1990 , Warner Bros. . Animation has primarily focused upon the production of television and feature animation of other properties , notably including those related to Time Warner 's DC Comics publications .",
"title": ""
},
{
"docid": "Fort_Minor:_We_Major",
"text": "Fort Minor : We Major , often known as We Major , is an official mixtape by American rapper Mike Shinoda 's side-project Fort Minor , hosted by DJ Green Lantern ( who also served as a mixer , producer and mixtape presenter ) . The mixtape was made as a warm-up/prequel to promote their first album The Rising Tied , and was first released on the internet as a free download . It was released on October 30 , 2005 , through the Warner Bros. and Machine Shop record labels . A hard-copy compact disc was also released to members of the Fort Minor Street Team , and some participants of contests at that time . A limited edition of the mixtape was released in 2006 with a different cover art . The mixtape 's title is based on a rap song of the same name by Kanye West featuring Nas and Really Doe from West 's second studio album , Late Registration . It may also be in reference to the lyric `` You minor , we major '' from `` Shook Ones Pt . 2 '' by Mobb Deep . Executive production for the limited edition of the mixtape was handled by Jay-Z , credited as Shawn Carter on the cover .",
"title": ""
},
{
"docid": "Another_Time_(Earth,_Wind_&_Fire_album)",
"text": "Another Time is a compilation album by Earth , Wind & Fire released on September 7 , 1974 on Warner Bros. . Records . Released as a double album Another Time featured songs from the band 's Warner Bros. studio albums Earth , Wind & Fire and The Need of Love which were both also released on Warner Bros. . Records . It also includes the song `` Handwriting on the Wall '' which was n't released before or since .",
"title": ""
},
{
"docid": "The_Sky_Kings",
"text": "The Sky Kings was an American country music supergroup formed in 1991 as Four Wheel Drive . The band consisted of John Cowan , Bill Lloyd , Patrick Simmons and Rusty Young . They were signed to a recording deal with RCA Nashville and completed an album which for the label was never released . Warner Bros. . Records signed the group in 1993 . Threatened with lawsuits from bands who had copyrighted the name Four Wheel Drive , they secured the rights to the name The Sky Kings . After opening for The Doobie Brothers on their 1993 tour , Simmons left The Sky Kings to rejoin The Doobie Brothers . Now a trio , The Sky Kings released three singles on Warner Bros. : `` Picture Perfect , '' `` Fooled Around and Fell in Love '' and `` That Just About Says It All . '' `` Picture Perfect '' was the only single to chart , peaking at No. 52 on the Billboard Hot Country Singles & Tracks chart . An eponymous album was scheduled to be released in 1997 , but eventually shelved . Rhino Handmade released From Out of the Blue , an album which collected the entire unreleased 1997 Warner Bros. album , non-album Warner Bros. singles , and recordings and demos made for a second unreleased Warner Bros. album , in 2000 .",
"title": ""
},
{
"docid": "Warner_Bros._Cartoons",
"text": "Warner Bros. . Cartoons , Inc. was the in-house division of Warner Bros. . Pictures during the Golden Age of American animation . One of the most successful animation studios in American media history , Warner Bros. . Cartoons was primarily responsible for the Looney Tunes and Merrie Melodies theatrical cartoon short subjects . The characters featured in these cartoons , including Bugs Bunny , Daffy Duck , Porky Pig , Speedy Gonzales , Sylvester and Tweety , Wile E. Coyote and the Road Runner , are among the most famous and recognizable characters in the world . Many of the creative staff members at the studio , including directors and animators such as Chuck Jones , Friz Freleng , Robert McKimson , Tex Avery , Robert Clampett and Frank Tashlin , are considered major figures in the art and history of traditional animation . The Warner animation division was founded in 1933 as Leon Schlesinger Productions , an independent company which produced the popular Looney Tunes and Merrie Melodies animated short subjects for release by Warner Bros. . Pictures . In 1944 , Schlesinger sold the studio to Warner Bros. , who continued to operate it as Warner Bros. . Cartoons , Inc. until 1963 . Looney Tunes and Merrie Melodies were briefly subcontracted to Freleng 's DePatie-Freleng Enterprises studio from 1964 until 1967 . The Warner Bros. . Cartoons studio briefly re-opened in 1967 before shutting its doors for good two years later . A successor company , Warner Bros. . Animation , was established in 1980 . That company continues to produce Looney Tunes-related works , in addition to television shows and feature films centering on other properties . The classic Warner Bros. animation studio is sometimes referred to as `` Termite Terrace '' , a name given to the temporary headquarters Tex Avery and his animators were assigned to during Avery 's first year as a Looney Tunes director .",
"title": ""
},
{
"docid": "Ain't_but_the_One_Way",
"text": "Ai n't But the One Way is the tenth and final album by Sly and the Family Stone , released by Warner Bros. . Records in 1982 . The album began its existence as a collaborative project between Sly Stone and George Clinton , a sequel to Stone 's appearance on the 1981 Funkadelic album The Electric Spanking of War Babies . While working on Ai n't But the One Way , Clinton and Funkadelic quarreled with and eventually left Warner Bros. . Records , and Sly Stone went into self-seclusion and could not be found . Producer Stewart Levine was assigned to take control of the project , and do what he could to complete an album . Upon its 1982 release , Ai n't But The One Way underperformed and marked the end of Sly Stone 's career with Warner Bros. . Records . Both of Sly Stone 's Warner Bros. albums , Ai n't But The One Way and Back on the Right Track , along with five unissued recordings , were combined by Rhino Records into a compilation called Who In The Funk Do You Think You Are : The Warner Bros. . Recordings in 2001 .",
"title": ""
},
{
"docid": "Neil_Fanning",
"text": "Neil Fanning ( born 12 April 1967 ) is an Australian voice actor , stuntman and actor . He is most known for voicing Scooby-Doo in both of the theatrical live-action international blockbusters , Scooby-Doo and Scooby-Doo 2 : Monsters Unleashed . Neil 's entertainment career has spanned over 25 years and over 50 movie , television and commercial roles . Among his stunt credits are Daybreakers , The Crocodile Hunter : Collision Course , and Ghost Ship . TV appearances include Sea Patrol and the 1998 TV movie Chameleon . Neil has also performed as an actor and stuntman on shows including Nim 's Island , Peter Pan , and Jackie Chan 's First Strike . As an opening day entertainer in 1991 , Neil performed for 14 years in the Police Academy Stunt Show at Warner Bros. . Movie World on the Gold Coast in Queensland , Australia and was their Employee of the Year in 1997 . Neil was the Manager of the Police Academy Stunt Show for many years and represented Movie World internationally performing shows in Asia . Neil was nominated as Australia 's International Performer Of The Year at the 1998 International Theme Parks Awards in the USA . Neil was also a Stunt Driving Instructor for locally based company The Stunt Driving Experience and represented Warner Bros. . Movie World performing as a High Speed Precision Stunt Driver for multiple shows from 1998 to 2001 as a feature of the on-track entertainment for the Gold Coast Indy 300 event in the early 2000s . Neil also wrote and created The Brodie And Dad Show , a comedy Podcast of skits and stories with multiple voices and characters performed with his son Brodie that reached Number 3 on iTunes in 2010 . Neil is currently a Precision Drift Stunt Driver for Showtime Entertainment in the Hollywood Stunt Driver 2 Show - Inner City Rush , at Warner Bros. . Movie World and is actively involved in the film and television industry . Combining all his experience , Neil also continues to work and perform constantly in the Corporate Entertainment sector writing , producing and performing in live shows for major companies and local and state government departments .",
"title": ""
},
{
"docid": "Free_Willy_(TV_series)",
"text": "Free Willy is an American/Canadian animated television series , inspired by the 1993 film of the same name . This television series was produced by Warner Bros. . Television , Regency Enterprises and the Canadian company Nelvana for Warner Bros. . Studios . The show , which aired for one season ( 1994 ) on American Broadcasting Company ( ABC ) , continues the adventures of the orca Willy and Jesse , the boy who freed him from captivity as shown in the film . In retrospect , the series also anticipates multiple plot elements of the film sequel , Free Willy 2 : The Adventure Home , released the following summer . The overarching conflict is reminiscent of Moby-Dick : a powerful oil baron , known to the main characters only as a cyborg called `` The Machine '' until the final episodes , loses his arm and part of his face to Willy while committing an environmental atrocity and wants revenge upon `` that rotten whale ... and his boy '' .",
"title": ""
}
] |
PLAIN-655
|
barley
|
[
{
"docid": "MED-2021",
"text": "AIM: To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms. METHODS: We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years. RESULTS: One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died. CONCLUSION: In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.",
"title": "Celiac disease: Management of persistent symptoms in patients on a gluten-free diet"
},
{
"docid": "MED-5154",
"text": "OBJECTIVE: To measure whole-grain intake in college students and determine the association with body mass index (BMI). DESIGN: Cross-sectional convenience sample of college students enrolled in an introductory nutrition course. SETTING: Large state university. PARTICIPANTS: 159 college students, mean age: 19.9. MAIN OUTCOME MEASURES: Intake of whole grains, refined grains, calories, and fiber from food records; BMI determined from height and weight measurements. ANALYSIS: Analysis of variance with linear contrasts; participants grouped by BMI category (P<.05). RESULTS: Average intake of cereal grains was 5.4 servings per day, of which whole-grain intake accounted for an average of 0.7 servings per day. Whole-grain intake was significantly higher in normal weight students than in overweight and obese students (based on BMI). CONCLUSIONS AND IMPLICATIONS: The low intake of whole grains in this population of college students indicates the need for interventions aiming to increase whole-grain intake to the recommended minimum of 3 servings per day. College students who are concerned about their body weight may be motivated to increase their intake of whole-grain foods; however, their intake of whole grains is likely to be influenced by the availability of these food items in campus dining halls and other locations around the college campus.",
"title": "Whole-grain intake is associated with body mass index in college students."
},
{
"docid": "MED-2024",
"text": "Celiac disease (CD) is a gluten-dependent immune-mediated disease with a prevalence in the general population estimated between 0.3% and 1.2%. Large-scale epidemiological studies have shown that only 10-20% of cases of CD are identified on the basis of clinical findings and that laboratory tests are crucial to identify subjects with subtle or atypical symptoms. The correct choice and clinical use of these diagnostic tools may enable accurate diagnosis and early recognition of silent CD cases. In this review, we have considered some relevant aspects related to the laboratory diagnosis of CD and, more extensively, of gluten intolerance, such as the best combination of tests for early and accurate diagnosis, the diagnostic role of new tests for detecting antibodies against neoepitopes produced by the transglutaminase-gliadin complex, the forms of non-celiac gluten intolerance (gluten sensitivity), and the use and significance of measuring cytokines in CD.",
"title": "Cutting-edge issues in celiac disease and in gluten intolerance."
},
{
"docid": "MED-2029",
"text": "A large national investigation into the extent of gluten cross-contamination of naturally gluten-free ingredients (flours and starches) sold in Canada was performed. Samples (n = 640) were purchased from eight Canadian cities and via the internet during the period 2010-2012 and analysed for gluten contamination. The results showed that 61 of the 640 (9.5%) samples were contaminated above the Codex-recommended maximum level for gluten-free products (20 mg kg⁻¹) with a range of 5-7995 mg kg⁻¹. For the ingredients that were labelled gluten-free the contamination range (5-141 mg kg⁻¹) and number of samples were lower (3 of 268). This picture was consistent over time, with approximately the same percentage of samples above 20 mg kg⁻¹ in both the initial set and the subsequent lot. Looking at the total mean (composite) contamination for specific ingredients the largest and most consistent contaminations come from higher fibre ingredients such as soy (902 mg kg⁻¹), millet (272 mg kg⁻¹) and buckwheat (153 mg kg⁻¹). Of the naturally gluten-free flours and starches tested that do not contain a gluten-free label, the higher fibre ingredients would constitute the greatest probability of being contaminated with gluten above 20 mg kg⁻¹.",
"title": "Gluten contamination of naturally gluten-free flours and starches used by Canadians with celiac disease."
},
{
"docid": "MED-2034",
"text": "Recent studies support the existence of a new condition, nonceliac gluten sensitivity, which manifests as intestinal or extraintestinal symptoms that improve or disappear after gluten withdrawal in individuals with normal small-bowel mucosa and negative results on serum antitransglutaminase and antiendomysial antibody testing. Although the clinical value of this concept is under debate, the prevalence of nonceliac gluten sensitivity in the general population is supposed to be many times higher than that of celiac disease. The lack of an unambiguous definition of nonceliac gluten sensitivity, a major pitfall, is primarily related to the heterogeneous cause of this condition, whose symptoms are presumed to be caused by different mechanisms. If nonceliac gluten sensitivity is an etiologically heterogeneous syndrome, then management options should vary according to the predominant or concomitant underlying pathogenic pathways.",
"title": "Nonceliac gluten sensitivity: sense or sensibility?"
},
{
"docid": "MED-2022",
"text": "Epidemiological studies find that whole-grain intake is protective against cancer, CVD, diabetes, and obesity. Despite recommendations to consume three servings of whole grains daily, usual intake in Western countries is only about one serving/d. Whole grains are rich in nutrients and phytochemicals with known health benefits. Whole grains have high concentrations of dietary fibre, resistant starch, and oligosaccharides. Whole grains are rich in antioxidants including trace minerals and phenolic compounds and these compounds have been linked to disease prevention. Other protective compounds in whole grains include phytate, phyto-oestrogens such as lignan, plant stanols and sterols, and vitamins and minerals. Published whole-grain feeding studies report improvements in biomarkers with whole-grain consumption, such as weight loss, blood-lipid improvement, and antioxidant protection. Although it is difficult to separate the protective properties of whole grains from dietary fibre and other components, the disease protection seen from whole grains in prospective epidemiological studies far exceeds the protection from isolated nutrients and phytochemicals in whole grains.",
"title": "Whole grains and human health."
},
{
"docid": "MED-2030",
"text": "Background Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86.",
"title": "An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity"
},
{
"docid": "MED-2020",
"text": "OBJECTIVE: Wheat fiber appears to protect from cardiovascular disease despite its lack of consistent effect on serum lipids. We therefore wished to determine whether reported inconsistencies in the effect of wheat bran resulted from differences in particle size or its high gluten content. METHODS: Two studies were conducted. In one-month metabolic diets, 24 hyperlipidemic subjects consumed breads providing an additional 19 g/d dietary fiber as medium or ultra-fine wheat bran and extra protein (10% of energy as wheat gluten). In two-week ad libitum diets, 24 predominantly normolipidemic subjects consumed breakfast cereals providing an additional 19 g/d of dietary fiber as coarse or a mixture of ultra-fine and coarse wheat bran with no change in gluten intake. Both studies followed a randomized crossover design with control periods when subjects ate low-fiber breads and cereals respectively with no added gluten. Fasting blood lipids were measured on day zero and at the end of each phase. RESULTS: Wheat bran had no effect on total, LDL or HDL cholesterol irrespective of particle size or level of gluten in the diet. However, consumption of increased gluten in the metabolic study was associated with a 13+/-4% reduction in serum triglycerides (p = 0.005) which was not seen in the normal-gluten ad libitum study. CONCLUSIONS: The protective effect of wheat fiber in cardiovascular disease cannot be explained by an effect of wheat bran in reducing serum cholesterol although in hyperlipidemic subjects displacement of carbohydrate by gluten on the high-fiber phases was associated with lower serum triglycerides.",
"title": "Effect of wheat bran on serum lipids: influence of particle size and wheat protein."
},
{
"docid": "MED-4099",
"text": "OBJECTIVE: A meta-analysis was performed on epidemiologic studies to assess the relation between β-glucan consumption from oats and from barley on blood cholesterol level, triglyceride/triacylglycerol (TGL/TAG) level, and blood glucose level (BGL) in humans. In addition, the effect of β-glucan on total cholesterol (TC) and BGL was translated into an empirical dose-response model. METHODS: Thirty research articles that evaluated the effect of different exposure levels of β-glucan on blood cholesterol and BGL were analyzed, yielding 126 clinical studies. RESULTS: There was a significant inverse relation in TC (-0.60 mmol/L, 95% confidence interval [CI] -0.85 to -0.34), low-density lipoprotein (-0.66 mmol/L, 95% CI -0.96 to -0.36), and TGL/TAG (-0.04 mmol/L, 95% CI -0.15 to 0.07) after consumption of β-glucan. In contrast, an increase in high-density lipoprotein cholesterol was noted (0.03 mmol/L, 95% CI -0.06 to 0.13) with the random-effect model. The analysis showed a significant change in BGL (-2.58 mmol/L, 95% CI -3.22 to -1.84) with high heterogeneity between (I(2) = 97%) and across (τ(2) = 5.88) the studies. The fixed-effect model showed a significant change in TC, low-density lipoprotein, and BGL, whereas it showed no significant changes in high-density lipoprotein and TGL/TAG. The dose-response model showed that a 3-g/d dose of oat or barley β-glucan was sufficient to decrease TC. CONCLUSION: Consumption of 3 g/d of oat or barley β-glucan is sufficient to decrease blood cholesterol, whereas the effect on BGL is still inconclusive, with high heterogeneity, and requires further clinical research studies with longer intervention periods. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Meta-analysis of the effect of β-glucan intake on blood cholesterol and glucose levels."
},
{
"docid": "MED-2033",
"text": "BACKGROUND: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this \"new\" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS: We reviewed the international literature through PubMed and Medline, using the search terms \"wheat (hyper)sensitivity,\" \"wheat allergy,\" \"wheat intolerance,\" \"gluten (hyper)sensitivity,\" and \"gluten intolerance,\" and we discuss current knowledge about NCGS. RESULTS: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.",
"title": "Non-celiac gluten sensitivity: literature review."
},
{
"docid": "MED-2028",
"text": "The ingestion of dietary gluten sometimes may trigger allergic, autoimmune or nonallergic and nonautoimmune response. The typical gluten‑related allergic disorder is the wheat allergy (WA). Celiac disease (CD) is a well‑known gluten‑related autoimmune condition. The clinical expression of a gluten‑related nonallergic and nonautoimmune response is nonceliac gluten sensitivity (NCGS), an emerging condition whose framework is yet unclear and whose diagnosis is suggested only by demonstration of gluten‑dependency in patient' symptoms after exclusion of WA and CD. This review discusses the current tools to identify patients suffering from WA, CD, and NCGS, as well as the most recent insights in the differential diagnosis among these gluten‑related gastrointestinal disorders .",
"title": "Reactivity to dietary gluten: new insights into differential diagnosis among gluten‑related gastrointestinal disorders."
},
{
"docid": "MED-4686",
"text": "There is ample reason to believe that diets rich in phytochemicals provide protection from vascular diseases and many cancers; direct antioxidant activity as well as modulation of enzyme expression or hormone activity contribute to this effect. Phytochemicals derived from diverse foods presumably can interact additively and (possibly) synergistically; thus, the total dietary load of phytochemicals may have important implications for health. As a means of very roughly quantifying this load, a \"phytochemical index\" (PI) is proposed, defined as the percent of dietary calories derived from foods rich in phytochemicals. Calories derived from fruits, vegetables (excluding potatoes), legumes, whole grains, nuts, seeds, fruit/vegetable juices, soy products, wine, beer, and cider - and foods compounded therefrom - would be counted in this index. Partial credit could be given for antioxidant-rich extra virgin olive oil. Other added oils, refined sugars, refined grains, potato products, hard liquors, and animal products - regrettably, the chief sources of calories in typical Western diets - would be excluded. Although the PI would provide only a very rough approximation of the quantity or quality of phytochemical nutrition, it nonetheless could aid epidemiologists in exploring the health consequences of diets high in phytochemical-rich plant foods, and could also help clinical nutritionists in their efforts to improve the phytochemical nutrition of their clients.",
"title": "Proposal for a dietary \"phytochemical index\"."
},
{
"docid": "MED-2018",
"text": "A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.",
"title": "Spectrum of gluten-related disorders: consensus on new nomenclature and classification"
},
{
"docid": "MED-2026",
"text": "OBJECTIVES: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample. METHODS: This study included 7,798 persons aged 6 years or older who participated in the National Health and Nutrition Examination Survey 2009-2010. Serum samples from all participants were tested for immunoglobulin A (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for IgA endomysial antibodies. Information about prior diagnosis of CD and use of a gluten-free diet (GFD) was obtained by direct interview. CD was defined as having either double-positive serology (serologically diagnosed CD) or a reported diagnosis of CD by a doctor or other health-care professional and being on a GFD (reported clinical diagnosis of CD). RESULTS: CD was found in 35 participants, 29 of whom were unaware of their diagnosis. Median age was 45 years (interquartile range, 23-66 years); 20 were women and 29 were non-Hispanic white. The prevalence of CD in the United States was 0.71% (95% confidence interval (CI), 0.58-0.86%), with 1.01% (95% CI, 0.78-1.31%) among non-Hispanic whites. In all, 55 participants reported following a GFD, which corresponded to a prevalence of 0.63% (95% CI, 0.36-1.07%). CONCLUSIONS: The prevalence of CD in the United States was 0.71% (1 in 141), similar to that found in several European countries. However, most cases were undiagnosed. CD was rare among minority groups but affected 1% of non-Hispanic whites. Most persons who were following a GFD did not have a diagnosis of CD.",
"title": "The prevalence of celiac disease in the United States."
},
{
"docid": "MED-2019",
"text": "Nine healthy volunteers were divided into a test group (n = 5) and a control group (n = 4). The test group consumed 3 grams per d of wheat gluten hydrolysate for 6 d, and their NK cell activity and hematological parameters were measured: The same assessments were performed in the control group, which did not receive wheat gluten hydrolysate. In the test group, NK cell activity increased significantly (P = 0.018) after wheat gluten hydrolysate intake. No adverse effects were observed in either group.",
"title": "Effect of wheat gluten hydrolysate on the immune system in healthy human subjects."
},
{
"docid": "MED-2027",
"text": "Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet (GFD), is largely a self-reported diagnosis and would appear to be very common. The aims of this study were to characterize patients who believe they have NCGS. Materials and Methods: Advertising was directed toward adults who believed they had NCGS and were willing to participate in a clinical trial. Respondents were asked to complete a questionnaire about symptoms, diet, and celiac investigation. Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years, and 130 were women. Seventy-two percent did not meet the description of NCGS due to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite gluten restriction (24%), and not following a GFD (27%), alone or in combination. The GFD was self-initiated in 44% of respondents; in other respondents it was prescribed by alternative health professionals (21%), dietitians (19%), and general practitioners (16%). No celiac investigations had been performed in 15% of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or inadequate gluten intake at the time of endoscopy. Inadequate celiac investigation was common if the GFD was initiated by self (69%), alternative health professionals (70%), general practitioners (46%), or dietitians (43%). In 40 respondents who fulfilled the criteria for NCGS, their knowledge of and adherence to the GFD were excellent, and 65% identified other food intolerances. Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria for its diagnosis. Initiation of a GFD without adequate exclusion of celiac disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite gluten avoidance. © 2014 American Society for Parenteral and Enteral Nutrition.",
"title": "Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity."
}
] |
[
{
"docid": "MED-3639",
"text": "Several foods have been shown to contain natural components (especially polyphenols) which display anti-adhesive properties against Streptococcus mutans, the aetiological agent responsible for dental crown caries, as well as inhibition of glucosyltransferases, which are the S. mutans enzymes involved in the synthesis of an adherent, water-insoluble glucan from sucrose. Other studies have demonstrated an in vitro action on oral plaque biofilm formation and desorption. This study evaluated whether the activity displayed in vitro by food compounds could affect the microbiological composition of saliva and dental plaque of subjects with a diet rich in these foods, comparing the results with those obtained from subjects with a different diet. The foods considered were: coffee, barley coffee, tea and wine. A total of 93 subjects were recruited into the study. Six samples of both plaque and saliva were collected from each subject at roughly one-monthly intervals. Total bacteria, total streptococci, S. mutans and lactobacilli counts were determined by culture in both saliva and dental plaque. The highest bacterial titres were recorded for the control population, while each drinking habit subgroup showed counts roughly one log lower than the controls. These differences in bacterial counts proved statistically significant (P<0.05). As far as dental plaque was concerned, while total counts did not significantly vary per mg of plaque in the subjects belonging to the different drinking habit subgroups, a significant decrease (P<0.05) was observed in those subjects drinking coffee, tea, barley coffee and wine when mutans streptococci and lactobacilli were evaluated. In several cases a more than one log decrease was observed. Plaque indices were also determined, and a significant (P<0.05) reduction in values was recorded in the subjects belonging the specific drinking habit subgroups compared to the control group. This study indicates that there is a correlation between consumption of specific foods and oral health in terms of reduced plaque deposition and lower counts of odontopathogens.",
"title": "Differences in microbiological composition of saliva and dental plaque in subjects with different drinking habits."
},
{
"docid": "MED-4446",
"text": "Twenty-four plant lignans were analyzed by high-performance liquid chromatography-tandem mass spectrometry in bran extracts of 16 cereal species, in four nut species, and in two oilseed species (sesame seeds and linseeds). Eighteen of these were lignans previously unidentified in these species, and of these, 16 were identified in the analyzed samples. Four different extraction methods were applied as follows: alkaline extraction, mild acid extraction, a combination of alkaline and mild acid extraction, or accelerated solvent extraction. The extraction method was of great importance for the lignan yield. 7-Hydroxymatairesinol, which has not previously been detected in cereals because of destructive extraction methods, was the dominant lignan in wheat, triticale, oat, barley, millet, corn bran, and amaranth whole grain. Syringaresinol was the other dominant cereal lignan. Wheat and rye bran had the highest lignan content of all cereals; however, linseeds and sesame seeds were by far the most lignan-rich of the studied species.",
"title": "Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts."
},
{
"docid": "MED-2013",
"text": "As the gluten-free diet (GFD) gains in popularity with the general public, health practitioners are beginning to question its real health benefits. For those patients with celiac disease (CD), the GFD is considered medical nutrition therapy, as well as the only proven treatment that results in improvements in symptomatology and small bowel histology. Those with wheat allergy also benefit from the GFD, although these patients often do not need to restrict rye, barley, and oats from their diet. Gluten sensitivity is a controversial subject, where patients who have neither CD nor wheat allergy have varying degrees of symptomatic improvement on the GFD. Conditions in this category include dermatitis herpetiformis (DH), irritable bowel syndrome (IBS), and neurologic diseases such as gluten-sensitive ataxia and autism. It is important for patients and healthcare practitioners to understand the differences between these conditions, even though they may all respond to a GFD. Patients with CD can experience comorbid nutrition deficiencies and are at higher risk for the development of cancers and other autoimmune conditions. Those with wheat allergy and gluten sensitivity are thought not to be at higher risk for these complications. Defining the symptoms and biochemical markers for gluten-sensitive conditions is an important area for future investigations, and high-quality, large-scale randomized trials are needed to prove the true benefits of the GFD in this evolving field.",
"title": "Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad."
},
{
"docid": "MED-1874",
"text": "It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.",
"title": "The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century."
},
{
"docid": "MED-2432",
"text": "It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions.",
"title": "The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century."
},
{
"docid": "MED-4511",
"text": "BACKGROUND: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. METHODS: Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. RESULTS: 49 subjects were tested. Most subjects (10th to 90th percentile) had followed this diet 23-49 months. 6 subjects had serum B12 concentrations <147 pmol/l (200 pg/ml). 37 subjects (76%) had serum B12 concentrations <221 pmol/l (300 pg/ml). 23 subjects (47%) had abnormal urinary MMA concentrations above or equal to 4.0 microg/mg creatinine. Sublingual cyanocobalamin and nutritional yeast, but not probiotic supplements, significantly reduced group mean MMA concentrations (tablet p < 0.01; yeast p < 0.05, probiotic > 0.20). CONCLUSIONS: The urinary MMA assay is effective for identifying early metabolic cobalamin deficiency. People following the Hallelujah diet and other raw-food vegetarian diets should regularly monitor their urinary MMA levels, consume a sublingual cobalamin supplement, or consume cobalamin in their food.",
"title": "Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements."
},
{
"docid": "MED-1619",
"text": "BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.",
"title": "No evidence of insulin resistance in normal weight vegetarians. A case control study."
},
{
"docid": "MED-2041",
"text": "in English, German Die Zöliakie ist weltweit eine der häufigsten Erkrankungen, die aus einer Kombination von Umwelt-(Gluten) und genetischen (humanes Leukozyten-Antigen (HLA) und Nicht-HLA-Gene) Faktoren resultiert. Abhängig von der geographischen Lage, wird die Prävalenz der Zöliakie auf etwa 0,5-1% der Bevölkerung geschätzt. Die einzige Behandlung, die derzeit bei Zöliakie verfügbar ist, besteht in einer glutenfreien Diät (GFD), die glutenhaltige Getreide wie Weizen, Roggen und Gerste sowie andere Lebensmittel mit natürlichem oder zugesetztem Gluten ausschließt. Die Complianceraten und die Akzeptanz durch die Patienten sind jedoch oft schlecht. Weiterhin kann die Diät selbst bei Patienten, die diese vollständig einhalten, möglicherweise nicht zu einer klinischen oder histologischen Verbesserung führen. Daher ist es nicht verwunderlich, dass Studien zeigen, dass Zöliakie-Patienten sehr an nichtdiätetischen Alternativen interessiert sind. Die folgende Übersicht konzentriert sich auf aktuelle pathophysiologische Konzepte der Zöliakie, bei denen jene Signalwege herausgestellt werden, die als mögliche neue, nichtdiätetische therapeutische Ansatzpunkte in der Behandlung der Zöliakie dienen könnten. Coeliac disease (CD) is one of the most common diseases worldwide, resulting from a combination of environmental (gluten) and genetic (human leucocyte antigen (HLA) and non-HLA genes) factors. Depending on the geographical location, the prevalence of CD has been estimated to approximate 0.5-1%. The only treatment currently available for CD is a gluten-free diet (GFD) excluding gluten-containing cereals such as wheat, rye, and barley, and other foodstuffs with natural or added gluten. However, adherence rates and patient acceptance are often poor. Moreover, even in fully adherent patients, the diet may fail to induce clinical or histological improvement. Hence, it is unsurprising that studies show CD patients to be highly interested in non-dietary alternatives. The following review focuses on current pathophysiological concepts of CD, spotlighting those pathways which may serve as new possible, non-dietary therapeutic targets in the treatment of CD.",
"title": "Coeliac Disease - New Pathophysiological Findings and Their Implications for Therapy."
},
{
"docid": "MED-3538",
"text": "OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). CONCLUSIONS: Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation, it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults. Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign. Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses, but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions. This suggests that sleep debt is perhaps best understood as resulting in additional wakefulness that has a neurobiological \"cost\" which accumulates over time.",
"title": "The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restricti..."
},
{
"docid": "MED-4281",
"text": "Over the past 20 years, growing interest in the biochemistry, nutrition, and pharmacology of L-arginine has led to extensive studies to explore its nutritional and therapeutic roles in treating and preventing human metabolic disorders. Emerging evidence shows that dietary L-arginine supplementation reduces adiposity in genetically obese rats, diet-induced obese rats, finishing pigs, and obese human subjects with Type-2 diabetes mellitus. The mechanisms responsible for the beneficial effects of L-arginine are likely complex, but ultimately involve altering the balance of energy intake and expenditure in favor of fat loss or reduced growth of white adipose tissue. Recent studies indicate that L-arginine supplementation stimulates mitochondrial biogenesis and brown adipose tissue development possibly through the enhanced synthesis of cell-signaling molecules (e.g., nitric oxide, carbon monoxide, polyamines, cGMP, and cAMP) as well as the increased expression of genes that promote whole-body oxidation of energy substrates (e.g., glucose and fatty acids) Thus, L-arginine holds great promise as a safe and cost-effective nutrient to reduce adiposity, increase muscle mass, and improve the metabolic profile in animals and humans.",
"title": "Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health."
},
{
"docid": "MED-1261",
"text": "Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, ‘catalytic’ doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of ‘catalytic’ doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring ‘catalytic’ fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD − 0·40, 95 % CI − 0·72, − 0·08) and fasting glucose (MD − 0·25, 95 % CI − 0·44, − 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that ‘catalytic’ fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using ‘catalytic’ fructose to confirm these results.",
"title": "‘Catalytic’ doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials"
},
{
"docid": "MED-4673",
"text": "OBJECTIVE: The present study aimed to evaluate the knowledge and practices of public-sector primary-care health professionals and final-year students regarding the role of nutrition, physical activity and smoking cessation (lifestyle modification) in the management of chronic diseases of lifestyle within the public health-care sector. DESIGN: A comparative cross-sectional descriptive quantitative study was conducted in thirty primary health-care facilities and four tertiary institutions offering medical and/or nursing programmes in Cape Town in the Western Cape Metropole. Stratified random sampling, based on geographical location, was used to select the health facilities while convenience sampling was used to select students at the tertiary institutions. A validated self-administered knowledge test was used to obtain data from the health professionals. RESULTS: Differential lifestyle modification knowledge exists among both health professionals and students, with less than 10 % achieving the desired scores of 80 % or higher. The majority of health professionals seem to be promoting the theoretical concepts of lifestyle modification but experience difficulty in providing practical advice to patients. Of the health professionals evaluated, doctors appeared to have the best knowledge of lifestyle modification. Lack of time, lack of patient adherence and language barriers were given as the main barriers to providing lifestyle counselling. CONCLUSIONS: The undergraduate curricula of medical and nursing students should include sufficient training on lifestyle modification, particularly practical advice on diet, physical activity and smoking cessation. Health professionals working at primary health-care facilities should be updated by providing lifestyle modification education as part of continuing medical education.",
"title": "They think they know but do they? Misalignment of perceptions of lifestyle modification knowledge among health professionals."
},
{
"docid": "MED-2124",
"text": "Acne appears to represent a visible indicator disease of over-activated mTORC1 signalling, an unfavour-able metabolic deviation on the road to serious common Western diseases of civilisation associated with increased body mass index and insulin resistance. Exaggerated mTORC1 signalling by Western diet explains the association of acne with increased body mass index, insulin resistance, and early onset of menarche. Both, a high glycaemic load and increased consumption of milk and milk products, staples of Western diet, aggravate mammalian target of rapamycin complex 1 signalling. This review of the literature summarises present evidence for an association between acne, increased body mass index, insulin resistance and Western diet. By dietary intervention with a Palaeolithic-type diet, the dermatologist has the chance to attenuate patients' increased mTORC1 signalling by reducing glycaemic load and milk consumption, which may not only improve acne but may delay the march to more serious mTORC1-driven diseases of civilisation.",
"title": "Acne: risk indicator for increased body mass index and insulin resistance."
},
{
"docid": "MED-4658",
"text": "Skin functions and structure are significantly influenced by nutrients. Antioxidants protect the supportive layer of the skin against any damaging irradiation effects and the action of free radicals. A lack of suitable methods means that the pharmacokinetic properties of systemically applied carotenoids transferred into the skin remain poorly understood. In this study, a natural kale extract or placebo oil were given orally to 22 healthy volunteers for 4 weeks. Carotenoid bioaccessibility was evaluated using non-invasive resonance Raman spectroscopy on the palm and forehead skin. For the analysis of the blood serum, the standard HPLC method was used. The blood and skin levels of the carotenoids increased significantly during the study but compared to the blood serum values, increases in skin were delayed and depended on the dermal area as well as on the carotenoid. Lycopene, measured as being low in the extract, increases more in the skin compared to the blood indicating that the natural mixture of the extract stabilizes the antioxidative network in the skin. After supplementation had ended, the carotenoids decreased much faster in the blood than in the skin. The delayed decrease in the skin may indicate a peripheral buffer function of the skin for carotenoids. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Bioavailability of natural carotenoids in human skin compared to blood."
},
{
"docid": "MED-1460",
"text": "Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms.",
"title": "Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function"
},
{
"docid": "MED-5006",
"text": "We projected future prevalence and BMI distribution based on national survey data (National Health and Nutrition Examination Study) collected between 1970s and 2004. Future obesity-related health-care costs for adults were estimated using projected prevalence, Census population projections, and published national estimates of per capita excess health-care costs of obesity/overweight. The objective was to illustrate potential burden of obesity prevalence and health-care costs of obesity and overweight in the United States that would occur if current trends continue. Overweight and obesity prevalence have increased steadily among all US population groups, but with notable differences between groups in annual increase rates. The increase (percentage points) in obesity and overweight in adults was faster than in children (0.77 vs. 0.46-0.49), and in women than in men (0.91 vs. 0.65). If these trends continue, by 2030, 86.3% adults will be overweight or obese; and 51.1%, obese. Black women (96.9%) and Mexican-American men (91.1%) would be the most affected. By 2048, all American adults would become overweight or obese, while black women will reach that state by 2034. In children, the prevalence of overweight (BMI >/= 95th percentile, 30%) will nearly double by 2030. Total health-care costs attributable to obesity/overweight would double every decade to 860.7-956.9 billion US dollars by 2030, accounting for 16-18% of total US health-care costs. We continue to move away from the Healthy People 2010 objectives. Timely, dramatic, and effective development and implementation of corrective programs/policies are needed to avoid the otherwise inevitable health and societal consequences implied by our projections .",
"title": "Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic."
},
{
"docid": "MED-4858",
"text": "BACKGROUND/OBJECTIVE: beta-Carotene is often used as a marker for the amount of fruit and vegetables consumed, but little is known about plasma beta-carotene concentrations in subjects whose habitual (long-term) diets are characterized by different amounts of foods of plant origin. We compared dietary beta-carotene intake and plasma concentrations in women on habitual diets differing in the consumed amounts of foods of plant origin. METHODS: A comparison of dietary beta-carotene intakes and plasma beta-carotene concentrations in women adhering to an average Western diet (n = 172), wholesome nutrition (following preventive recommendations) (n = 238) or a raw food diet (n = 104). RESULTS: Dietary beta-carotene intake was 5.5, 9.3, 14.7 mg/day for women adhering to an average Western diet, wholesome nutrition and raw food diet, respectively (p < 0.001). Corresponding multivariate adjusted plasma beta-carotene concentrations were 1.07, 1.65, and 1.16 micromol/l, respectively (p < 0.001). Comparable dietary beta-carotene intake resulted in lower multivariate adjusted plasma beta-carotene in women adhering to a raw food diet and average Western diet compared to those on wholesome nutrition (p < 0.001 for all intake groups up to 20 mg/day). The amount of fruit and vegetable intake did not predict plasma beta-carotene levels in women consuming a raw food diet. CONCLUSIONS: Plasma beta-carotene concentrations differed among the diet groups, with highest plasma levels in women adhering to wholesome nutrition. Plasma beta-carotene concentrations may not reflect beta-carotene intake and the amount of fruit and vegetables consumed. 2009 S. Karger AG, Basel.",
"title": "Plasma beta-carotene is not a suitable biomarker of fruit and vegetable intake in german subjects with a long-term high consumption of fruits and v..."
},
{
"docid": "MED-2445",
"text": "Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.",
"title": "Dietary polyphenols in the prevention and treatment of allergic diseases."
},
{
"docid": "MED-3991",
"text": "Few foods contain ergocalciferol or cholecalciferol. Treatment of mushrooms with UV light increases ergocalciferol content and could provide a dietary source of vitamin D. We evaluated the impact of consuming UV-treated white button mushrooms (Agaricus bisporus) on the vitamin D status of healthy adults. Thirty-eight volunteers were randomized to 4 treatments consumed with a standard meal for 6 wk: the control (C) group received untreated mushrooms providing 0.85 μg/d ergocalciferol (n = 10); groups M1 and M2 received UV-treated mushrooms providing 8.8 (n = 10) and 17.1 μg/d (n = 9), respectively; and the supplement (S) group received purified ergocalciferol plus untreated mushrooms, providing a total of 28.2 μg/d (n = 9). Serum total 25-hydroxyvitamin D [25(OH)D] and 25-hydroxyergocalciferol [25(OH)D2] were 83 ± 38 and 2.4 ± 2.0 nmol/L, respectively, at baseline (mean ± SD). At wk 6, 25(OH)D2 had increased and was higher in all treatment groups than in the C group, whereas 25-hydroxycholecalciferol [25(OH)D3] had decreased and was lower in the M2 and S groups than in the C group. Increases in 25(OH)D2 for groups C, M1, M2, and S were 1.2 ± 5.2, 13.8 ± 7.3, 12.7 ± 3.7, and 32.8 ± 3.3 nmol/L and decreases in 25(OH)D3 were -3.9 ± 16.3, -10.4 ± 6.4, -20.6 ± 14.6, and -29.5 ± 15.9 nmol/L, respectively. Concentrations did not change in group C. In summary, ergocalciferol was absorbed and metabolized to 25(OH)D2 but did not affect vitamin D status, because 25(OH)D3 decreased proportionally.",
"title": "Ergocalciferol from mushrooms or supplements consumed with a standard meal increases 25-hydroxyergocalciferol but decreases 25-hydroxycholecalcifer..."
},
{
"docid": "MED-4968",
"text": "Vibrios are ubiquitous in the aquatic environment and are commonly present in or on shellfish and other seafood. A small subset of strains/species are able to cause human disease, including the cholera toxin-producing strains of Vibrio cholerae that are responsible for epidemic/pandemic cholera; thermostable direct hemolysin-producing strains of Vibrio parahaemolyticus; and Vibrio vulnificus, which can cause fulminant sepsis. Cholera outbreaks can be initiated by transmission of \"epidemic\" V. cholerae strains from their environmental reservoir to humans through seafood or other environmentally related food or water sources. \"Nonepidemic\" strains of V. cholerae and strains of other Vibrio species, including V. parahaemolyticus and V. vulnificus, are generally acquired by eating seafood (particularly raw oysters/oysters on the half shell). Although the primary clinical manifestation of infection with these strains is gastroenteritis, they can also cause wound infections and (particularly for V. vulnificus) septicemia in persons who have liver disease or are immunocompromised.",
"title": "Cholera and other types of vibriosis: a story of human pandemics and oysters on the half shell."
},
{
"docid": "MED-332",
"text": "This review explores the potential adverse impact of the increasing phosphorus content in the American diet on renal, cardiovascular, and bone health of the general population. Increasingly, studies show that phosphorus intakes in excess of the nutrient needs of a healthy population may significantly disrupt the hormonal regulation of phosphate, calcium, and vitamin D, which contributes to disordered mineral metabolism, vascular calcification, impaired kidney function, and bone loss. Moreover, large epidemiologic studies suggest that mild elevations of serum phosphate within the normal range are associated with cardiovascular disease (CVD) risk in healthy populations without evidence of kidney disease. However, few studies linked high dietary phosphorus intake to mild changes in serum phosphate because of the nature of the study design and inaccuracies in the nutrient composition databases. Although phosphorus is an essential nutrient, in excess it could be linked to tissue damage by a variety of mechanisms involved in the endocrine regulation of extracellular phosphate, specifically the secretion and action of fibroblast growth factor 23 and parathyroid hormone. Disordered regulation of these hormones by high dietary phosphorus may be key factors contributing to renal failure, CVD, and osteoporosis. Although systematically underestimated in national surveys, phosphorus intake seemingly continues to increase as a result of the growing consumption of highly processed foods, especially restaurant meals, fast foods, and convenience foods. The increased cumulative use of ingredients containing phosphorus in food processing merits further study given what is now being shown about the potential toxicity of phosphorus intake when it exceeds nutrient needs.",
"title": "Public health impact of dietary phosphorus excess on bone and cardiovascular health in the general population."
},
{
"docid": "MED-2159",
"text": "AIMS: Coffee consumption has been recently linked with decreased blood gamma-glutamyltransferase (GGT) activities and protection from alcoholic liver disease. To explore the relationship and dose response, we assessed the impacts of coffee and alcohol intake on serum GGT activity in apparently healthy men and women with varying levels of coffee and alcohol consumption. METHODS: Data on coffee, alcohol consumption and serum GGT activities were collected from 18,899 individuals (8807 men and 10,092 women), mean age 48 years, range 25-74 years, who participated in a large national cross-sectional health survey. Body mass index, smoking index and age were used as covariates in all analyses. RESULTS: Among the study population, 89.8% reported varying levels of coffee consumption; 6.9% were abstainers from alcohol, 86.1% moderate drinkers, 3.7% heavy drinkers and 3.3% former drinkers. In men, the elevation of GGT induced by heavy drinking (>280 g/week) was found to be significantly reduced by coffee consumption exceeding 4 cups per day. A similar trend was also observed among women, which however, did not reach statistical significance. CONCLUSION: Coffee modulates the effect of ethanol on serum GGT activities in a dose- and gender-dependent manner. These observations should be implicated in studies on the possible hepatoprotective effects of coffee in alcohol consumers.",
"title": "Dose- and gender-dependent interactions between coffee consumption and serum GGT activity in alcohol consumers."
},
{
"docid": "MED-3457",
"text": "Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.",
"title": "Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise."
},
{
"docid": "MED-2700",
"text": "Blood components, especially hemoglobin, are powerful promoters of lipid oxidation and may decrease the shelf life of meat products. Therefore, this study examined different slaughter techniques to determine their effects on pH (24 h), color (L*a*b* values at 24 h), lipid oxidation, residual hemoglobin concentration (24 h), and sensory evaluation (d 1 and 4 postmortem; PM) in broiler breast fillets. The treatments included 1) CO(2) slaughter and not bled, 2) no stunning and bled, 3) electrical stunning (ES) and bled, 4) CO(2) stunning and bled, and 5) ES and decapitation. The birds were conventionally processed, and analyses were performed at 24 h PM except residual hemoglobin for which the samples were frozen (-80 degrees C) until analyses ( < 2 mo). There were no significant differences in pH or b* values at 24 h PM among any of the treatments. L* values were significantly higher, indicating lighter fillets in the ES and decapitated birds compared with the darker fillets from the CO(2) stunned and bled birds. The CO(2) slaughter and not bled birds had significantly higher a* values, indicating more red color, when compared with the ES and bled and decapitated birds. There were no significant differences in the residual hemoglobin contents in the broiler breast muscle when comparing all of the treatments except CO(2) slaughter and not bled, which was significantly (around 15%) greater. Overall TBA-reactive substances (TBARS; raw, cooked at 24 h, and cooked at 72 h PM) indicated that ES and bled birds had the lowest TBARS when compared with the remaining treatments. Consumer panels detected increased aroma (chicken meaty and warmed-over aromas) and flavor (chicken meaty and warmed-over flavors) in not bled samples at 24 h PM. By 72 h PM, however, there were no significant differences in aroma or flavor. Therefore, different slaughter and bleeding method may affect color and sensory properties of the broiler breast fillets, and the ES and decapitation method had the most favorable results for sensory quality.",
"title": "The effect of blood removal on oxidation and shelf life of broiler breast meat."
},
{
"docid": "MED-830",
"text": "Water-soluble polysaccharides were separated from maca (Lepidium meyenii) aqueous extract (MAE). The crude polysaccharides were deproteinized by Sevag method. During the preparation process of maca polysaccharides, amylase and glucoamylase effectively removed starch in maca polysaccharides. Four Lepidium meyenii polysaccharides (LMPs) were obtained by changing the concentration of ethanol in the process of polysaccharide precipitation. All of the LMPs were composed of rhamnose, arabinose, glucose and galactose. Antioxidant activity tests revealed that LMP-60 showed good capability of scavenging hydroxyl free radical and superoxide radical at 2.0mg/mL, the scavenging rate was 52.9% and 85.8%, respectively. Therefore, the results showed that maca polysaccharides had a high antioxidant activity and could be explored as the source of bioactive compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.",
"title": "Extraction, purification and antioxidant activities of the polysaccharides from maca (Lepidium meyenii)."
},
{
"docid": "MED-4789",
"text": "Objectives To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. Design Six-month, randomized, controlled, clinical trial. Setting Veterans Affairs Puget Sound Health Care System clinical research unit. Participants Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age,70 years). Intervention Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. Main Outcome Measures Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42. Results Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance. Conclusions This study provides support, using rigorous controlled methodology, for a potent nonpharma-cologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.",
"title": "Effects of Aerobic Exercise on Mild Cognitive Impairment"
},
{
"docid": "MED-1243",
"text": "Frequently, patients identified as high risk for postoperative nausea and vomiting (PONV) are treated prophylactically with intravenous (IV) ondansetron and postoperatively with IV promethazine. The purpose of this study was to determine if using an aromatic therapy of 70% isopropyl alcohol (IPA) would be more effective than promethazine in resolution of breakthrough PONV symptoms in groups of high-risk patients administered prophylactic ondansetron. All subjects enrolled were identified as high risk for PONV, administered general anesthesia and a prophylactic antiemetic of 4 mg of IV ondansetron, and randomized to receive IPA or promethazine for treatment of breakthrough PONV Demographics, verbal numeric rating scale (VNRS) scores for nausea, time to 50% reduction in VNRS scores, and overall antiemetic and incidence of PONV were measured. The data for 85 subjects were included in analysis; no differences in demographic variables or baseline measurements were noted between groups. The IPA group reported a faster time to 50% reduction in VNRS scores and decreased overall antiemetic requirements. A similar incidence in PONV was noted between groups. Based on these findings, we recommend that inhalation of 70% IPA is an option for treatment of PONV in high-risk patients who have received prophylactic ondansetron.",
"title": "Comparison of inhalation of isopropyl alcohol vs promethazine in the treatment of postoperative nausea and vomiting (PONV) in patients identified a..."
},
{
"docid": "MED-3923",
"text": "OBJECTIVE: Inadvertent exposure to the ubiquitous weed, Urtica dioica, called \"stinging nettles\" produces an immediate stinging and burning sensation on the skin. This investigation evaluates the structural effect that stinging nettle spicules may have on the clinical manifestation of these symptoms. This hypothesis was investigated by exposing murine skin to stinging nettles and then evaluating the skin using electron microscopy. It was hypothesized that the mechanism of action of stinging nettles is both biochemical and mechanical, which may have clinical significance regarding treatment for acute exposure. METHODS: Fresh post-mortem dermis samples from the carcasses of genetically modified hairless mice were brushed under the stem and leaf of a stinging nettle plant, mimicking the clinical method of exposure a patient might experience. Another set of mouse skin samples was obtained but not exposed to the nettles. Both sets of skin samples were imaged with scanning electron microscopy. RESULTS: The skin samples that were not exposed to nettle leaves were uniform, with occasional striated hairs on the skin surface and no nettle spicules. The skin samples exposed to nettle leaves showed many smooth nettle spicules piercing the skin surface. A few spicules retained their bases, which appear empty of any liquid contents. CONCLUSIONS: The mechanism of action of stinging nettles dermatitis appears to be both biochemical and mechanical. Impalement of spicules into the skin likely accounts for the mechanical irritation in addition to the known adverse chemical effects of stinging nettles. Further investigation of treatment modalities is warranted. Copyright © 2011 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.",
"title": "Mechanism of action of stinging nettles."
},
{
"docid": "MED-1292",
"text": "There has been enormous interest in the biologic activity of mushrooms and innumerable claims have been made that mushrooms have beneficial effects on immune function with subsequent implications for inhibition of tumor growth. The majority of these observations are anecdotal and often lack standardization. However, there remains considerable data on both in vitro and in vivo effects that reflect on the potential of mushroom compounds to influence human immunity. A number of these effects are beneficial but, unfortunately, many responses are still characterized based on phenomenology and there is more speculation than substance. With respect to tumor biology, although many neoplastic lesions are immunogenic, tumor antigens frequently are self antigens and induce tolerance and many patients with cancer exhibit suppressed immune responses, including defective antigen presentation. Therefore, if and when mushroom extracts are effective, they more likely function as a result of improved antigen presentation by dendritic cells than by a direct cytopathic effect. In this review we attempt to place these data in perspective, with a particular focus on dendritic cell populations and the ability of mushroom extracts to modulate immunity. There is, at present, no scientific basis for the use of either mushrooms or mushroom extracts in the treatment of human patients but there is significant potential for rigorous research to understand the potential of mushrooms in human disease and thence to focus on appropriate clinical trials to demonstrate effectiveness and/ or potential toxicity.",
"title": "The immunobiology of mushrooms."
},
{
"docid": "MED-4755",
"text": "OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.",
"title": "Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence."
}
] |
PLAIN-2833
|
Diet Soda and Preterm Birth
|
[
{
"docid": "MED-5058",
"text": "Various mechanisms by which sucrose could influence behavior are reviewed. Firstly there is food intolerance. There are dozens of foods to which an adverse reaction has been demonstrated, although a reaction to sucrose is less frequent than many other foods. A second possible mechanism is hypoglycemia. There is evidence that a tendency to develop low blood glucose levels, but higher than those that can be described clinically as hypoglycemic, is associated with irritability and violence. However, sucrose is not the predominant cause of swings in blood glucose levels. Thirdly, the role of sucrose intake on micro-nutrient status has been considered as studies have found that micro-nutrient supplementation decreased anti-social behavior. Micro-nutrient intake is more closely associated with the total energy rather than sucrose intake; typically the amount of sucrose in the diet does not lead to micro-nutrient deficiency. In fact meta-analysis of well designed studies that have examined the impact of sucrose on the behavior of children produced no evidence that it has an adverse influence.",
"title": "Sucrose and behavioral problems."
},
{
"docid": "MED-4602",
"text": "The strategy of \"manufacturing uncertainty\" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called \"product defense\" or \"litigation support.\" As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.",
"title": "Manufactured uncertainty: protecting public health in the age of contested science and product defense."
},
{
"docid": "MED-4127",
"text": "We report for the first time an unusual musculoskeletal adverse effect of aspartame in two patients. A 50-year-old woman had been suffering from widespread pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia. During a vacation in a foreign country, she did not suffer from painful symptoms since she had forgotten to take her aspartame. All of the symptoms reappeared in the days following her return when she reintroduced aspartame into her daily diet. Thus, aspartame was definitively excluded from her diet, resulting in a complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for a 3-year history of bilateral forearm, wrist, and hand and cervical pain with various unsuccessful treatments. A detailed questioning allowed to find out that he had been taking aspartame for three years. The removal of aspartame was followed by a complete regression of pain, without recurrence. We believe that these patients' chronic pain was due to the ingestion of aspartame, a potent flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio of considering the diagnosis of aspartame-induced chronic pain is obvious: the potential benefit is to cure a disabling chronic disease, to spare numerous laboratory and imaging investigations, and to avoid potentially harmful therapies; the potential risk is to temporarily change the patient's diet. Thus, practitioners should ask patients suffering from fibromyalgia about their intake of aspartame. In some cases, this simple question might lead to the resolution of a disabling chronic disease.",
"title": "Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain."
}
] |
[
{
"docid": "MED-1951",
"text": "Late preterm (LP) birth (34 0/7 - 36 6/7 weeks' gestation) accounts for nearly three-fourths of all preterm births, making this population a sizeable public health concern. The immature fetal development associated with LP delivery increases the risk of mortality and short-term medical complications. Which combination of maternal, fetal, or neonatal risk factors may be most critical has only recently begun to be addressed, and whether LP birth's disruptive impact on brain development will exert adverse effects on neuropsychological functioning in childhood and adolescence has been understudied. Early data have shown a graded response, with LP children often functioning better than very preterm children but worse than term children, and with subtle intellectual and neuropsychological deficits in LP children compared with healthy children born at term gestational age. Further characterization of the neuropsychological profile is required and would be best accomplished through prospective longitudinal studies. Moreover, since moderate and LP births result in disparate medical and psychological outcomes, the common methodology of combining these participants into a single research cohort to assess risk and outcome should be reconsidered. The rapidly growing LP outcomes literature reinforces a critical principle: fetal development occurs along a dynamic maturational continuum from conception to birth, with each successive gestational day likely to improve overall outcome.",
"title": "Late preterm birth: a review of medical and neuropsychological childhood outcomes."
},
{
"docid": "MED-4772",
"text": "(1) Iron-deficiency anaemia during pregnancy increases the risk of low birth weight and preterm birth; (2) In a randomised double-blind placebo-controlled trial, iron supplementation in pregnant women with haemoglobin levels of at least 13.2 g/100 ml at the beginning of the 2nd trimester was associated with low birth weight and maternal hypertension; (3) In a trial in women with haemoglobin levels of at least 11.5 g/100 ml who took supplemental iron, haemoglobin levels above 14.5 g/100 ml at 28 weeks of gestation were associated with an 8-fold increase in the risk of preterm birth and a 6-fold increase in the risk of low birth weight; (4) An epidemiological study showed a link between high maternal haemoglobin levels and low birth weight; (5) In practice, iron supplements should not be taken by pregnant women whose haemoglobin levels exceed 11 g/100 ml during the 1st and 3rd trimesters and 10.5 g/100 ml during the 2nd trimester.",
"title": "Non-anaemic pregnant women should not take iron supplements."
},
{
"docid": "MED-1952",
"text": "There is growing interest in the long-term mental health sequelae of extremely preterm birth. In this paper we review literature relating to mental health outcomes across the lifespan. Studies conducted in the preschool years, school age and adolescence, and adulthood show continuity in outcomes and point to an increased risk for inattention, socio-communicative problems and emotional difficulties in individuals born extremely preterm. Both behavioural and neuroimaging studies also provide evidence of a neurodevelopmental origin for mental health disorders in this population. Here we summarise contemporary evidence and highlight key methodological considerations for carrying out and interpreting studies in this field. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Growing up after extremely preterm birth: lifespan mental health outcomes."
},
{
"docid": "MED-1949",
"text": "The first infants to experience modern pre- and neonatal care are now in their thirties, an age at which the incidence of cardiometabolic disease is low. However, data from cohorts born preterm prior to the introduction of modern care suggest an increased risk of type 2 diabetes. For young adult cohorts of former very small or very preterm infants, there is accumulating evidence of increased risk factors for later cardiovascular disease, including higher blood pressure, lower lean body mass, impaired glucose regulation, and perhaps a more atherogenic lipid profile. Regarding lifestyle, adults born very small or very preterm undertake less non-conditioning physical activity and may have a lower intake of fruit and milk products. Any intervention reducing risk factors, in particular blood pressure and low physical activity, would have a substantial potential to reduce the lifetime disease burden in small preterm infants. There are now enough data to warrant an expert evaluation of the level of evidence for cardiometabolic disease in individuals born very small or very preterm, which has possible public health implications. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Is very preterm birth a risk factor for adult cardiometabolic disease?"
},
{
"docid": "MED-1954",
"text": "The behaviour problems of children born preterm at school age are well known, but there have been few studies on the behaviour problems of preterm-born infants during infancy and at preschool age. Fourteen cohort studies published in PubMed and PsycINFO between 2000 and 2012 were reviewed with a focus on the type, occurrence, comorbidity, stability, prediction, perinatal, social, and relational risk factors for behaviour problems of preterm-born children in infancy (0-2y) and at preschool age (3-5y). The relational risk factor was considered in an additional four papers. Very-preterm, very-low-birthweight, and moderately-preterm children, in both age groups, show more behaviour problems than term-born comparison children even after perinatal and social risk factors and cognitive performance have been controlled for. Poor social/interactive skills, poor behavioural and emotional self-regulation, emotional difficulties, and reduced attention are the most common behaviour problems. Behaviour problems in infancy are predictive of later behaviour problems and they should be included in follow-up programmes. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.",
"title": "Preterm birth and behaviour problems in infants and preschool-age children: a review of the recent literature."
},
{
"docid": "MED-3691",
"text": "Background Previous reviews (2005 to 2009) on preterm infants given probiotics or prebiotics with breast milk or mixed feeds focused on prevention of Necrotizing Enterocolitis, sepsis and diarrhea. This review assessed if probiotics, prebiotics led to improved growth and clinical outcomes in formula fed preterm infants. Methods Cochrane methodology was followed using randomized controlled trials (RCTs) which compared preterm formula containing probiotic(s) or prebiotic(s) to conventional preterm formula in preterm infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Heterogeneity was assessed by visual inspection of forest plots and a chi2 test. An I2 test assessed inconsistencies across studies. I2> 50% represented substantial heterogeneity. Results Four probiotics studies (N=212), 4 prebiotics studies (N=126) were included. Probiotics: There were no significant differences in weight gain (MD 1.96, 95% CI: -2.64 to 6.56, 2 studies, n=34) or in maximal enteral feed (MD 35.20, 95% CI: -7.61 to 78.02, 2 studies, n=34), number of stools per day increased significantly in probiotic group (MD 1.60, 95% CI: 1.20 to 2.00, 1 study, n=20). Prebiotics: Galacto-oligosaccharide / Fructo-oligosaccharide (GOS/FOS) yielded no significant difference in weight gain (MD 0.04, 95% CI: -2.65 to 2.73, 2 studies, n=50), GOS/FOS yielded no significant differences in length gain (MD 0.01, 95% CI: -0.03 to 0.04, 2 studies, n=50). There were no significant differences in head growth (MD −0.01, 95% CI: -0.02 to 0.00, 2 studies, n=76) or age at full enteral feed (MD −0.79, 95% CI: -2.20 to 0.61, 2 studies, n=86). Stool frequency increased significantly in prebiotic group (MD 0.80, 95% CI: 0.48 to 1.1, 2 studies, n=86). GOS/FOS and FOS yielded higher bifidobacteria counts in prebiotics group (MD 2.10, 95% CI: 0.96 to 3.24, n=27) and (MD 0.48, 95% CI: 0.28 to 0.68, n=56). Conclusions There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants.",
"title": "Probiotics, prebiotics infant formula use in preterm or low birth weight infants: a systematic review"
},
{
"docid": "MED-1108",
"text": "Background: Despite safety reports of the artificial sweetener aspartame, health-related concerns remain. Objective: We prospectively evaluated whether the consumption of aspartame- and sugar-containing soda is associated with risk of hematopoetic cancers. Design: We repeatedly assessed diet in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). Over 22 y, we identified 1324 non-Hodgkin lymphomas (NHLs), 285 multiple myelomas, and 339 leukemias. We calculated incidence RRs and 95% CIs by using Cox proportional hazards models. Results: When the 2 cohorts were combined, there was no significant association between soda intake and risks of NHL and multiple myeloma. However, in men, ≥1 daily serving of diet soda increased risks of NHL (RR: 1.31; 95% CI: 1.01, 1.72) and multiple myeloma (RR: 2.02; 95% CI: 1.20, 3.40) in comparison with men who did not consume diet soda. We observed no increased risks of NHL and multiple myeloma in women. We also observed an unexpected elevated risk of NHL (RR: 1.66; 95% CI: 1.10, 2.51) with a higher consumption of regular, sugar-sweetened soda in men but not in women. In contrast, when sexes were analyzed separately with limited power, neither regular nor diet soda increased risk of leukemia but were associated with increased leukemia risk when data for men and women were combined (RR for consumption of ≥1 serving of diet soda/d when the 2 cohorts were pooled: 1.42; 95% CI: 1.00, 2.02). Conclusion: Although our findings preserve the possibility of a detrimental effect of a constituent of diet soda, such as aspartame, on select cancers, the inconsistent sex effects and occurrence of an apparent cancer risk in individuals who consume regular soda do not permit the ruling out of chance as an explanation.",
"title": "Consumption of artificial sweetener– and sugar-containing soda and risk of lymphoma and leukemia in men and women"
},
{
"docid": "MED-1586",
"text": "Women with a multiple pregnancy face greater risks for themselves and their infants than women pregnant with one child. Pre-pregnancy care should focus on avoiding multiple pregnancy. Early prenatal care centres on determining chorionicity and screening for fetal anomalies, with later care focusing on the presentation, prediction and management of preterm birth, and intrauterine growth restriction. The optimal timing and mode of birth are the focus of current multicentre, randomised, controlled trials. However, the data from such trials on care for women with a multiple pregnancy are limited. Many areas of care require better-quality information, including when using assisted reproductive techniques, the optimal number of embryos to be transferred, care after the diagnosis of chorionicity, and the benefits of specialised multiple pregnancy clinics. Better-quality information is required to inform clinical practice for women with complications of multiple pregnancy, including monoamniotic twin pregnancy, treatment of twin-to-twin transfusion syndrome, and care following single intrauterine fetal death.",
"title": "Evidence-based care of women with a multiple pregnancy."
},
{
"docid": "MED-1955",
"text": "Objective To examine whether an association exists between maternal dietary patterns and risk of preterm delivery. Design Prospective cohort study. Setting Norway, between 2002 and 2008. Participants 66 000 pregnant women (singletons, answered food frequency questionnaire, no missing information about parity or previously preterm delivery, pregnancy duration between 22+0 and 41+6 gestational weeks, no diabetes, first enrolment pregnancy). Main outcome measure Hazard ratio for preterm delivery according to level of adherence to three distinct dietary patterns interpreted as “prudent” (for example, vegetables, fruits, oils, water as beverage, whole grain cereals, fibre rich bread), “Western” (salty and sweet snacks, white bread, desserts, processed meat products), and “traditional” (potatoes, fish). Results After adjustment for covariates, high scores on the “prudent” pattern were associated with significantly reduced risk of preterm delivery hazard ratio for the highest versus the lowest third (0.88, 95% confidence interval 0.80 to 0.97). The prudent pattern was also associated with a significantly lower risk of late and spontaneous preterm delivery. No independent association with preterm delivery was found for the “Western” pattern. The “traditional” pattern was associated with reduced risk of preterm delivery for the highest versus the lowest third (hazard ratio 0.91, 0.83 to 0.99). Conclusion This study showed that women adhering to a “prudent” or a “traditional” dietary pattern during pregnancy were at lower risk of preterm delivery compared with other women. Although these findings cannot establish causality, they support dietary advice to pregnant women to eat a balanced diet including vegetables, fruit, whole grains, and fish and to drink water. Our results indicate that increasing the intake of foods associated with a prudent dietary pattern is more important than totally excluding processed food, fast food, junk food, and snacks.",
"title": "Maternal dietary patterns and preterm delivery: results from large prospective cohort study"
},
{
"docid": "MED-3091",
"text": "Phosphate toxicity is an important determinant of mortality in patients with chronic kidney disease (CKD), particularly those undergoing hemodialysis treatments. CKD patients are advised to take a low phosphate-containing diet, and are additionally prescribed with phosphate-lowering drugs. Since these patients usually seek guidance from their physicians and nurses for their dietary options, we conducted a survey to determine the levels of awareness regarding the high phosphate content in commercially processed food and drinks among medical and nursing students at the Hirosaki University School of Medicine in Japan. For this survey, 190 medical and nursing students (average age 21.7±3 years) were randomly selected, and provided with a list of questions aimed at evaluating their awareness of food and drinks containing artificially added phosphate ingredients. While 98.9% of these students were aware of the presence of sugar in commercially available soda drinks, only 6.9% were aware of the presence of phosphate (phosphoric acid). Similarly, only 11.6% of these students were aware of the presence of phosphate in commercially processed food, such as hamburgers and pizza. Moreover, around two thirds of the surveyed students (67.7%) were unaware of the harmful effects of unrestricted consumption of phosphate-containing food and drinks. About 28% of the surveyed students consume such “fast food” once a week, while 40% drink at least 1∼5 cans of soda drinks/week. After realizing the potential long-term risks of consuming excessive phosphate-containing food and drinks, 40.5% of the survey participants considered reducing their phosphate intake by minimizing the consumption of commercially processed “fast food” items and soda drinks. Moreover, another 48.4% of students showed interest in obtaining more information on the negative health effects of consuming excessive amounts of phosphate. This survey emphasizes the need for educational initiative to raise awareness of the health risks posed by excessive consumption of phosphate additives.",
"title": "Lack of Awareness among Future Medical Professionals about the Risk of Consuming Hidden Phosphate-Containing Processed Food and Drinks"
},
{
"docid": "MED-925",
"text": "We present a case of a six-week-old infant who developed life-threatening complications after unintentional sodium bicarbonate intoxication. Baking soda was being used by the mother as a home remedy to \"help the baby burp.\" A review of the literature regarding the use (or misuse) of baking soda follows. Our patient, along with the other noted case reports, emphasizes the need for warnings on baking soda products whose labels recommend its use as an antacid. Poisonings must be high in the differential diagnosis of any patient, regardless of age, who presents with altered mental status or status epilepticus.",
"title": "Baking soda: a potentially fatal home remedy."
},
{
"docid": "MED-4038",
"text": "We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes. The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS). The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period. In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.",
"title": "IMPACT OF BARBECUED MEAT CONSUMED IN PREGNANCY ON BIRTH OUTCOMES ACCOUNTING FOR PERSONAL PRENATAL EXPOSURE TO AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS. BIRTH COHORT STUDY IN POLAND"
},
{
"docid": "MED-924",
"text": "Oral ingestion of baking soda (sodium bicarbonate) has been used for decades as a home remedy for acid indigestion. Excessive bicarbonate ingestion places patients at risk for a variety of metabolic derangements including metabolic alkalosis, hypokalemia, hypernatremia, and even hypoxia. The clinical presentation is highly variable but can include seizures, dysrhythmias, and cardiopulmonary arrest. We present two cases of severe metabolic alkalosis in patients with unsuspected antacid overdose. The presentation and pathophysiology of antacid-related metabolic alkalosis is reviewed.",
"title": "Severe metabolic alkalosis due to baking soda ingestion: case reports of two patients with unsuspected antacid overdose."
},
{
"docid": "MED-2421",
"text": "Background: Acrylamide is a common dietary exposure that crosses the human placenta. It is classified as a probable human carcinogen, and developmental toxicity has been observed in rodents. Objectives: We examined the associations between prenatal exposure to acrylamide and birth outcomes in a prospective European mother–child study. Methods: Hemoglobin (Hb) adducts of acrylamide and its metabolite glycidamide were measured in cord blood (reflecting cumulated exposure in the last months of pregnancy) from 1,101 singleton pregnant women recruited in Denmark, England, Greece, Norway, and Spain during 2006–2010. Maternal diet was estimated through food-frequency questionnaires. Results: Both acrylamide and glycidamide Hb adducts were associated with a statistically significant reduction in birth weight and head circumference. The estimated difference in birth weight for infants in the highest versus lowest quartile of acrylamide Hb adduct levels after adjusting for gestational age and country was –132 g (95% CI: –207, –56); the corresponding difference for head circumference was –0.33 cm (95% CI: –0.61, –0.06). Findings were similar in infants of nonsmokers, were consistent across countries, and remained after adjustment for factors associated with reduced birth weight. Maternal consumption of foods rich in acrylamide, such as fried potatoes, was associated with cord blood acrylamide adduct levels and with reduced birth weight. Conclusions: Dietary exposure to acrylamide was associated with reduced birth weight and head circumference. Consumption of specific foods during pregnancy was associated with higher acrylamide exposure in utero. If confirmed, these findings suggest that dietary intake of acrylamide should be reduced among pregnant women.",
"title": "Birth Weight, Head Circumference, and Prenatal Exposure to Acrylamide from Maternal Diet: The European Prospective Mother–Child Study (NewGeneris)"
},
{
"docid": "MED-1950",
"text": "Several studies have found associations between microbial infections during pregnancy and preterm delivery (PTD). We investigated the influence of food with antimicrobial and prebiotic components on the risk of spontaneous PTD. A literature search identified microbes associated with spontaneous PTD. Subsequently, 2 main food types (alliums and dried fruits) were identified to contain antimicrobial components that affect the microbes associated with spontaneous PTD; they also contained dietary fibers recognized as prebiotics. We investigated intake in 18,888 women in the Norwegian Mother and Child Cohort (MoBa), of whom 950 (5%) underwent spontaneous PTD (<37 gestational weeks). Alliums (garlic, onion, leek, and spring onion) [OR: 0.82 (95% CI: 0.72, 0.94), P = 0.005] and dried fruits (raisins, apricots, prunes, figs, and dates) [OR: 0.82 (95% CI: 0.72, 0.94); P = 0.005] were associated with a decreased risk of spontaneous PTD. Intake of alliums was related to a more pronounced risk reduction in early spontaneous PTD (gestational weeks 28–31) [OR: 0.39 (95% CI: 0.19, 0.80)]. The strongest association in this group was with garlic [OR: 0.47 (95% CI: 0.25–0.89)], followed by cooked onions. Intake of dried fruits showed an association with preterm prelabor rupture of membranes (PPROM) [OR: 0.74 (95% CI: 0.65, 0.95)]; the strongest association in this group was with raisins [OR: 0.71 (95% CI: 0.56, 0.92)]. The strongest association with PPROM in the allium group was with garlic [OR: 0.74 (95% CI: 0.56, 0.97)]. In conclusion, intake of food with antimicrobial and prebiotic compounds may be of importance to reduce the risk of spontaneous PTD. In particular, garlic was associated with overall lower risk of spontaneous PTD. Dried fruits, especially raisins, were associated with reduced risk of PPROM.",
"title": "Intakes of Garlic and Dried Fruits Are Associated with Lower Risk of Spontaneous Preterm Delivery"
},
{
"docid": "MED-4391",
"text": "Cancer is a leading cause of death worldwide. There are a lot of cancer causing agents which are divided as physical carcinogens, chemical carcinogens and biological carcinogens. But most of the carcinogens or causes of cancer are related to our lifestyle like diet, habit, occupation, radiation and some infection, etc. Chemoprevention is highly necessary to prevent cancer related preterm death. For this besides avoiding the causes of cancer we should concentrate ourselves on our diet. Because, numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents and recently attention has been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals. In this study, we tried to describe lifestyle related causes of cancer and the molecular basis of cancer prevention through the phytochemicals.",
"title": "Lifestyle related causes of cancer and chemoprevention through phytonutrients."
},
{
"docid": "MED-1729",
"text": "We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed.",
"title": "Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA."
},
{
"docid": "MED-4878",
"text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.",
"title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)"
},
{
"docid": "MED-926",
"text": "A case of severe metabolic alkalosis (MA) resulting from ingestion of baking soda (sodium bicarbonate) is presented. On admission to the emergency department, the patient was alert and stable with an initial examination that was remarkable only for carpopedal spasm. Shortly thereafter, the patient had a sudden, unexpected cardiopulmonary arrest. Following resuscitation, without administration of sodium bicarbonate, the arterial blood gas revealed a pH of 7.73, pO2 of 51 mm Hg, and pCO2 of 52 mm Hg. After admission to the intensive care unit, the patient's MA was corrected using IV 0.25 N hydrochloric acid. The patient remained comatose as a result of severe anoxic encephalopathy and died two weeks after admission. We believe this is the first reported case of severe MA resulting in sudden cardiopulmonary arrest in a previously ambulatory patient.",
"title": "Severe metabolic alkalosis in the emergency department."
},
{
"docid": "MED-3469",
"text": "The purpose of this study was to compare the effects of unsweetened fruit juice and regular, decaffeinated soda on postprandial serum glucose levels in individuals with non-insulin-dependent diabetes mellitus (NIDDM) when these liquids are ingested separately as part of mixed meals. Eighteen individuals with NIDDM consumed three test breakfasts calculated using the diabetic exchange meal-planning system. Foods were identical in each of the breakfasts except for foods in the fruit exchange. Carbohydrate-equivalent amounts of fresh orange slices, unsweetened orange juice, and regular, decaffeinated Coke were consumed in breakfasts 1, 2, and 3, respectively. Serum glucose samples were drawn at fasting and 1, 2, and 3 hours postprandially. No difference was found in the postprandial serum glucose response when Coke versus orange juice was consumed in the breakfast. These findings question the appropriateness of using unsweetened fruit juices in routine meal planning for individuals with NIDDM.",
"title": "Postprandial glycemic response to orange juice and nondiet cola: is there a difference?"
},
{
"docid": "MED-1587",
"text": "OBJECTIVE: To evaluate the possible biochemical effect of diet and heredity on the rates of monozygotic and dizygotic twinning. STUDY DESIGN: In that insulin-like growth factor (IGF) has been found to be elevated in cows selected for their demonstrated increased twinning rate, the effect of agents that influence the level of IGF in women was examined. This was correlated with their prior history of singleton versus twin birthing. In particular, the effect of diets consisting of or excluding animal products that have elevated IGF content (e.g., milk) was considered. RESULTS: Vegan women, who exclude dairy products from their diets, have a twinning rate which is one-fifth that of vegetarians and omnivores. CONCLUSION: The results reported here support the proposed IGF model of dizygotic twinning. Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation.",
"title": "Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate."
},
{
"docid": "MED-1276",
"text": "Previous evidence for spatial clustering of amyotrophic lateral sclerosis is inconclusive. Studies that have identified apparent clusters have often been based on a small number of cases, which means the results may have occurred by chance processes. Also, most studies have used the geographic location at the time of death as the basis for cluster detection, rather than exploring clusters at other points in the life cycle. In this study, the authors examine 1,000 cases of amyotrophic lateral sclerosis distributed throughout Finland who died between June 1985 and December 1995. Using a spatial-scan statistic, the authors examine whether there are significant clusters of the disease at both time of birth and time of death. Two significant, neighboring clusters were identified in southeast and south-central Finland at the time of death. A single significant cluster was identified in southeast Finland at the time of birth, closely matching one of the clusters identified at the time of death. These results are based on a large sample of cases, and they provide convincing evidence of spatial clustering of this condition. The results demonstrate also that, if the cluster analysis is conducted at different stages of the cases' life cycle, different conclusions about where potential risk factors may exist might result.",
"title": "Spatial clustering of amyotrophic lateral sclerosis in Finland at place of birth and place of death."
},
{
"docid": "MED-1585",
"text": "As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Effects of twin gestation on maternal morbidity."
},
{
"docid": "MED-1190",
"text": "The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.",
"title": "High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae."
},
{
"docid": "MED-2082",
"text": "BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S..."
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-5168",
"text": "OBJECTIVE: To investigate the possible role of the maternal diet, particularly vegetarianism and consumption of phytoestrogens, in the origin of hypospadias, which is reported to be increasing in prevalence. SUBJECTS AND METHODS: Detailed information was obtained prospectively from mothers, including previous obstetric history, lifestyle and dietary practices, using structured self-completed questionnaires during pregnancy. Previously recognized associations with environmental and parental factors were examined, focusing particularly on the hypothesized hormonal link. Multivariate logistic regression was used to identify independent associations. RESULTS: Of 7928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, 51 hypospadias cases were identified. There were no significant differences in the proportion of hypospadias cases among mothers who smoked, consumed alcohol or for any aspect of their previous reproductive history (including the number of previous pregnancies, number of miscarriages, use of the contraceptive pill, time to conception and age at menarche). Significant differences were detected for some aspects of the maternal diet, i.e. vegetarianism and iron supplementation in the first half of pregnancy. Mothers who were vegetarian in pregnancy had an adjusted odds ratio (OR) of 4.99 (95% confidence interval, CI, 2.10-11.88) of giving birth to a boy with hypospadias, compared with omnivores who did not supplement their diet with iron. Omnivores who supplemented their diet with iron had an adjusted OR of 2.07 (95% CI, 1.00-4.32). The only other statistically significant association for hypospadias was with influenza in the first 3 months of pregnancy (adjusted OR 3.19, 95% CI 1.50-6.78). CONCLUSION: As vegetarians have a greater exposure to phytoestrogens than do omnivores, these results support the possibility that phytoestrogens have a deleterious effect on the developing male reproductive system.",
"title": "A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood."
},
{
"docid": "MED-3702",
"text": "BACKGROUND: Increased prevalence of allergic diseases in western societies has been described as an epidemic. The precise turning point for the epidemic and the antigens responsible for it remain obscure. OBJECTIVE: To evaluate how the prevalence of atopic disease has changed in terms of detectable sensitization to aeroallergens and dietary allergens in a cross-sectional comparison of subjects from birth cohorts more than 60 years apart. METHODS: We studied four groups of 100 subjects each (at ages 7, 27, 47 and 67 years), representing those born in 1990, 1963-66, 1943-46 and in 1923-26, respectively. Serum total and specific IgE concentrations against aeroallergens and dietary allergens were determined. A questionnaire elicited information on symptoms, allergic diseases and medication. RESULTS: The proportion of subjects with detectable IgE antibodies against aeroallergens increased consistently from the oldest to the youngest birth cohorts; chi2 trend=56.809, P<0.0001. Similar progression was not seen in sensitization to dietary allergens. The proportion of those with diagnosed asthma differed significantly (chi2=13.45, P=0.004) across the birth cohorts. The lowest prevalence of asthma and sensitization to dietary allergens was detected in those born in 1943-46, i.e. during or immediately after World War II. CONCLUSION: Prevalence of sensitization to airborne allergens, unlike that to dietary allergens, has increased over a long period of time. Our results support the concept of the immune function being programmed by external factors early in life. They also call for caution when interpretations of the pace and possible causes of the allergy epidemic are made on the basis of short-term studies.",
"title": "The allergy epidemic extends beyond the past few decades."
},
{
"docid": "MED-1832",
"text": "The need for a dietary supply of docosahexaenoic acid (DHA) and arachidonic aid (AA) in term infants was evaluated in a double-masked randomized clinical trial of the effects of supplementation of term infant formula with DHA (0.35% of total fatty acids) or with DHA (0.36%) and AA (0.72%) on visual acuity development. One hundred and eight healthy term infants were enrolled in the study; 79 were exclusively formula-fed from birth (randomized group) and 29 were exclusively breast-fed (gold standard group). Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition, growth, sweep visual evoked potential (VEP) acuity, and forced choice preferential looking acuity. Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell (RBC) lipid composition. Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6, 17, and 52 wk of age but not at 26 wk of age, when acuity development reaches a plateau. The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants, whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants. Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol. Infants in all diet groups had similar rates of growth and tolerated all diets well. Thus, early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant.",
"title": "Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants."
},
{
"docid": "MED-995",
"text": "This study was designed to determine the body burden of polybrominated diphenyl ethers (PBDEs) among first-time mothers in the Greater Boston, Massachusetts area and to explore key routes of exposure. We collected breast milk samples from 46 first-time mothers, 2-8 weeks after birth. We also sampled house dust from the homes of a subset of participants by vacuuming commonly used areas. Data on personal characteristics, diet, home furniture, and electrical devices were gathered from each participant using a questionnaire. Breast milk and dust samples were analyzed for PBDEs using gas chromatography/ mass spectrometry. PBDE concentrations were log-normally distributed in breast milk and dust. We found statistically significant, positive associations between PBDE concentrations in breast milk and house dust (r = 0.76, p = 0.003, not including BDE-209), as well as with reported dietary habits, particularly the consumption of dairy products (r = 0.41, p = 0.005) and meat (r = 0.37, p = 0.01). Due to low detection rates, it was not possible to draw conclusions about the association between BDE-209 in milk and dust. Our results support the hypothesis that the indoor environment and diet both play prominent roles in adult human exposure to PBDEs.",
"title": "Human exposure to PBDEs: associations of PBDE body burdens with food consumption and house dust concentrations."
}
] |
PLAIN-1549
|
Lyon Diet Heart Study
|
[
{
"docid": "MED-1397",
"text": "Human beings evolved on a diet that was balanced in the omega-6 and omega-3 polyunsaturated fatty acids (PUFA), and was high in antioxidants. Edible wild plants provide alpha-linolenic acid (ALA) and higher amounts of vitamin E and vitamin C than cultivated plants. In addition to the antioxidant vitamins, edible wild plants are rich in phenols and other compounds that increase their antioxidant capacity. It is therefore important to systematically analyze the total antioxidant capacity of wild plants and promote their commercialization in both developed and developing countries. The diets of Western countries have contained increasingly larger amounts of linoleic acid (LA), which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of low density lipoprotein (LDL) cholesterol and increases platelet response to aggregation. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of arachidonic acid (AA) metabolism. In clinical studies, ALA contributed to lowering of blood pressure, and a prospective epidemiological study showed that ALA is inversely related to the risk of coronary heart disease in men. Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to longer-chain omega-3 PUFAs. Relatively large reserves of LA in body fat. as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over omega-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.",
"title": "Omega-3 fatty acids and antioxidants in edible wild plants."
},
{
"docid": "MED-1489",
"text": "PURPOSE: Plant-based nutrition achieved coronary artery disease (CAD) arrest and reversal in a small study. However, there was skepticism that this approach could succeed in a larger group of patients. The purpose of our follow-up study was to define the degree of adherence and outcomes of 198 consecutive patient volunteers who received counseling to convert from a usual diet to plant-based nutrition. METHODS: We followed 198 consecutive patients counseled in plant-based nutrition. These patients with established cardiovascular disease (CVD) were interested in transitioning to plant-based nutrition as an adjunct to usual cardiovascular care. We considered participants adherent if they eliminated dairy, fish, and meat, and added oil. RESULTS: Of the 198 patients with CVD, 177 (89%) were adherent. Major cardiac events judged to be recurrent disease totaled one stroke in the adherent cardiovascular participants—a recurrent event rate of .6%, significantly less than reported by other studies of plant-based nutrition therapy. Thirteen of 21 (62%) nonadherent participants experienced adverse events. CONCLUSION: Most of the volunteer patients with CVD responded to intensive counseling, and those who sustained plant-based nutrition for a mean of 3.7 years experienced a low rate of subsequent cardiac events. This dietary approach to treatment deserves a wider test to see if adherence can be sustained in broader populations. Plant-based nutrition has the potential for a large effect on the CVD epidemic.",
"title": "A way to reverse CAD?"
},
{
"docid": "MED-1398",
"text": "The concept that the Mediterranean diet was associated with a lower incidence of cardiovascular disease (CVD) was first proposed in the 1950s. Since then, there have been randomized controlled trials and large epidemiological studies that reported associations with lower CVD: in 1994 and 1999, the reports of the intermediate and final analyses of the trial Lyon Diet Heart Study; in 2003, a major epidemiological study in Greece showing a strong inverse association between a Mediterranean score and the risk of cardiovascular complications; in 2011-2012, several reports showing that even non-Mediterranean populations can gain benefits from long-term adhesion to the Mediterranean diet; and in 2013, the PREDIMED trial showing a significant risk reduction in a low-risk population. Contrary to the pharmacological approach of cardiovascular prevention, the adoption of the Mediterranean diet has been associated with a significant reduction in new cancers and overall mortality. Thus, in terms of evidence-based medicine, the full adoption of a modern version of the Mediterranean diet pattern can be considered one of the most effective approaches for the prevention of fatal and nonfatal CVD complications.",
"title": "Mediterranean diet and cardiovascular disease: historical perspective and latest evidence."
},
{
"docid": "MED-1393",
"text": "OBJECTIVE: The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height, the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk. APPROACH AND RESULTS: In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA, bifurcation, and common) were sonographically assessed at baseline and after intervention for a mean of 2.4 years. We evaluated 164 subjects with complete data. In a multivariate model, mean ICA-IMT progressed in the control diet group (mean [95% confidence interval], 0.052 mm [-0.014 to 0.118 mm]), whereas it regressed in the MedDiet+nuts group (-0.084 mm [-0.158 to -0.010 mm]; P=0.024 versus control). Similar results were observed for maximum ICA-IMT (control, 0.188 mm [0.077 to 0.299 mm]; MedDiet+nuts, -0.030 mm [-0.153 to 0.093 mm]; P=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm]; MedDiet+nuts, -0.091 mm [-0.206 to 0.023 mm]; P=0.047). There were no changes in ICA-IMT or plaque after the MedDiet+extra virgin olive oil. CONCLUSIONS: Compared with a control diet, consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.",
"title": "Changes in ultrasound-assessed carotid intima-media thickness and plaque with a Mediterranean diet: a substudy of the PREDIMED trial."
},
{
"docid": "MED-1400",
"text": "BACKGROUND: The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes. OBJECTIVE: We aimed to update our previous meta-analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status. DESIGN: We conducted a comprehensive literature search through electronic databases up to June 2010. RESULTS: The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality. CONCLUSION: This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases.",
"title": "Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis."
},
{
"docid": "MED-1394",
"text": "BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).",
"title": "Primary prevention of cardiovascular disease with a Mediterranean diet."
},
{
"docid": "MED-1399",
"text": "BACKGROUND: The Lyon Diet Heart Study is a randomized secondary prevention trial aimed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infarction. An intermediate analysis showed a striking protective effect after 27 months of follow-up. This report presents results of an extended follow-up (with a mean of 46 months per patient) and deals with the relationships of dietary patterns and traditional risk factors with recurrence. METHODS AND RESULTS: Three composite outcomes (COs) combining either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events requiring hospital admission (CO 3) were studied. In the Mediterranean diet group, CO 1 was reduced (14 events versus 44 in the prudent Western-type diet group, P=0.0001), as were CO 2 (27 events versus 90, P=0.0001) and CO 3 (95 events versus 180, P=0. 0002). Adjusted risk ratios ranged from 0.28 to 0.53. Among the traditional risk factors, total cholesterol (1 mmol/L being associated with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count >9x10(9)/L), female sex (adjusted risk ratios, 0.27 to 0. 46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were each significantly and independently associated with recurrence. CONCLUSIONS: The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet. It should be associated with other (pharmacological?) means aimed at reducing modifiable risk factors. Further trials combining the 2 approaches are warranted.",
"title": "Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Di..."
},
{
"docid": "MED-1395",
"text": "In a prospective, randomised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infarct prudent diet. After a first myocardial infarction, patients were randomly assigned to the experimental (n = 302) or control group (n = 303). Patients were seen again 8 weeks after randomisation, and each year for 5 years. The experimental group consumed significantly less lipids, saturated fat, cholesterol, and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma. Serum lipids, blood pressure, and body mass index remained similar in the 2 groups. In the experimental group, plasma levels of albumin, vitamin E, and vitamin C were increased, and granulocyte count decreased. After a mean follow up of 27 months, there were 16 cardiac deaths in the control and 3 in the experimental group; 17 non-fatal myocardial infarction in the control and 5 in the experimental groups: a risk ratio for these two main endpoints combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for prognostic variables. Overall mortality was 20 in the control, 8 in the experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p = 0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death.",
"title": "Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease."
}
] |
[
{
"docid": "MED-5271",
"text": "OBJECTIVES: This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND: The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS: We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS: All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS: In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.",
"title": "The postprandial effect of components of the Mediterranean diet on endothelial function."
},
{
"docid": "MED-1363",
"text": "Dietary guidelines to promote good health are usually based on foods, nutrients, and dietary patterns predictive of chronic disease risk in epidemiologic studies. However, sound nutritional recommendations for cardiovascular prevention should be based on the results of large randomized clinical trials with \"hard\" end-points as the main outcome. Such evidence has been obtained for the Mediterranean diet from the PREDIMED (Prevención con Dieta Mediterránea) trial and the Lyon Heart Study. The traditional Mediterranean diet was that found in olive growing areas of Crete, Greece, and Southern Italy in the late 1950s. Their major characteristics include: a) a high consumption of cereals, legumes, nuts, vegetables, and fruits; b) a relatively high-fat consumption, mostly provided by olive oil; c) moderate to high fish consumption; d) poultry and dairy products consumed in moderate to small amounts; e) low consumption of red meats, and meat products; and f) moderate alcohol intake, usually in the form of red wine. However, these protective effects of the traditional Mediterranean diet may be even greater if we upgrade the health effects of this dietary pattern changing the common olive oil used for extra-virgin olive oil, increasing the consumption of nuts, fatty fish and whole grain cereals, reducing sodium intake, and maintaining a moderate consumption of wine with meals. © 2013 Elsevier B.V. All rights reserved.",
"title": "\"Towards an even healthier Mediterranean diet\"."
},
{
"docid": "MED-1366",
"text": "My concern about diet as a public health problem began in the early 1950s in Naples, where we observed very low incidences of coronary heart disease associated with what we later came to call the \"good Mediterranean diet.\" The heart of this diet is mainly vegetarian, and differs from American and northern European diets in that it is much lower in meat and dairy products and uses fruit for dessert. These observations led to our subsequent research in the Seven Countries Study, in which we demonstrated that saturated fat is the major dietary villain. Today, the healthy Mediterranean diet is changing and coronary heart disease is no longer confined to medical textbooks. Our challenge is to persuade children to tell their parents to eat as Mediterraneans do.",
"title": "Mediterranean diet and public health: personal reflections."
},
{
"docid": "MED-4255",
"text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.",
"title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition."
},
{
"docid": "MED-4613",
"text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.",
"title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition."
},
{
"docid": "MED-1257",
"text": "Meat protein is associated with an increase in risk of heart disease. Recent data have shown that meat protein appeared to be associated with weight gain over 6.5 years, with 1 kg of weight increase per 125 g of meat per day. In the Nurses' Health Study, diets low in red meat, containing nuts, low-fat dairy, poultry, or fish, were associated with a 13% to 30% lower risk of CHD compared with diets high in meat. Low-carbohydrate diets high in animal protein were associated with a 23% higher total mortality rate whereas low-carbohydrate diets high in vegetable protein were associated with a 20% lower total mortality rate. Recent soy interventions have been assessed by the American Heart Association and found to be associated with only small reductions in LDL cholesterol. Although dairy intake has been associated with a lower weight and lower insulin resistance and metabolic syndrome, the only long-term (6 months) dairy intervention performed so far has shown no effects on these parameters.",
"title": "Protein and coronary heart disease: the role of different protein sources."
},
{
"docid": "MED-4496",
"text": "BACKGROUND: Many constituents of fruits and vegetables may reduce the risk for coronary heart disease, but data on the relationship between fruit and vegetable consumption and risk for coronary heart disease are sparse. OBJECTIVE: To evaluate the association of fruit and vegetable consumption with risk for coronary heart disease. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study and the Health Professionals' Follow-Up Study. PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. MEASUREMENTS: The main outcome measure was incidence of nonfatal myocardial infarction or fatal coronary heart disease (1127 cases in women and 1063 cases in men). Diet was assessed by using food-frequency questionnaires. RESULTS: After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a relative risk for coronary heart disease of 0.80 (95% CI, 0.69 to 0.93) compared with those in the lowest quintile of intake. Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend). Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake. CONCLUSIONS: Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C-rich fruits and vegetables, appears to have a protective effect against coronary heart disease.",
"title": "The effect of fruit and vegetable intake on risk for coronary heart disease."
},
{
"docid": "MED-1254",
"text": "OBJECTIVE: To investigate the effect of replacing lean meat with a soy product, tofu, on coronary heart disease risk factors including serum lipoproteins, lipoprotein (a), factor VII, fibrinogen and in vitro susceptibility of LDL to oxidation. DESIGN: A randomized cross over dietary intervention study. SETTING: Free-living individuals studied at Deakin University. SUBJECTS: Forty-five free-living healthy males aged 35 to 62 years completed the dietary intervention. Three subjects were non-compliant and excluded prior to analysis. INTERVENTIONS: A diet containing 150 grams of lean meat per day was compared to a diet containing 290 grams of tofu per day in an isocaloric and isoprotein substitution. Each dietary period was one month duration. RESULTS: Analysis of the seven-day diet record showed that diets were similar in energy, protein, carbohydrate, total fat, saturated and unsaturated fat, polyunsaturated to saturated fat ratio, alcohol and fiber. Total cholesterol and triglycerides were significantly lower, and in vitro LDL oxidation lag phase was significantly longer on the tofu diet compared to the meat diet. The hemostatic factors, factor VII and fibrinogen, and lipoprotein(a) were not significantly affected by the tofu diet. CONCLUSIONS: The increase in LDL oxidation lag phase would be expected to be associated with a decrease in coronary heart disease risk.",
"title": "Effect of meat replacement by tofu on CHD risk factors including copper induced LDL oxidation."
},
{
"docid": "MED-2528",
"text": "OBJECTIVE: To describe changes in negative emotions among participants of a cholesterol-lowering study. DESIGN: Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. SETTING: Community-dwelling families of the Family Heart Study, Portland, Oregon. PARTICIPANTS: One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). MEASUREMENTS: Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). RESULTS: Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat \"American diet.\" CONCLUSIONS: Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels.",
"title": "Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study."
},
{
"docid": "MED-1410",
"text": "In 15 cohorts of the Seven Countries Study, comprising 11,579 men aged 40-59 years and \"healthy\" at entry, 2,288 died in 15 years. Death rates differed among cohorts. Differences in mean age, blood pressure, serum cholesterol, and smoking habits \"explained\" 46% of variance in death rate from all causes, 80% from coronary heart disease, 35% from cancer, and 45% from stroke. Death rate differences were unrelated to cohort differences in mean relative body weight, fatness, and physical activity. The cohorts differed in average diets. Death rates were related positively to average percentage of dietary energy from saturated fatty acids, negatively to dietary energy percentage from monounsaturated fatty acids, and were unrelated to dietary energy percentage from polyunsaturated fatty acids, proteins, carbohydrates, and alcohol. All death rates were negatively related to the ratio of monounsaturated to saturated fatty acids. Inclusion of that ratio with age, blood pressure, serum cholesterol, and smoking habits as independent variables accounted for 85% of variance in rates of deaths from all causes, 96% coronary heart disease, 55% cancer, and 66% stroke. Oleic acid accounted for almost all differences in monounsaturates among cohorts. All-cause and coronary heart disease death rates were low in cohorts with olive oil as the main fat. Causal relationships are not claimed but consideration of characteristics of populations as well as of individuals within populations is urged in evaluating risks.",
"title": "The diet and 15-year death rate in the seven countries study."
},
{
"docid": "MED-1381",
"text": "Perhaps one of the most unexpected and novel findings in nutritional epidemiology in the past 5 y has been that nut consumption seems to protect against ischemic heart disease (IHD). Frequency and quantity of nut consumption have been documented to be higher in vegetarian than in nonvegetarian populations. Nuts also constitute an important part of other plant-based diets, such as Mediterranean and Asian diets. In a large, prospective epidemiologic study of Seventh-day Adventists in California, we found that frequency of nut consumption had a substantial and highly significant inverse association with risk of myocardial infarction and death from IHD. The Iowa Women's Health Study also documented an association between nut consumption and decreased risk of IHD. The protective effect of nuts on IHD has been found in men and women and in the elderly. Importantly, nuts have similar associations in both vegetarians and nonvegetarians. The protective effect of nut consumption on IHD is not offset by increased mortality from other causes. Moreover, frequency of nut consumption has been found to be inversely related to all-cause mortality in several population groups such as whites, blacks, and the elderly. Thus, nut consumption may not only offer protection against IHD, but also increase longevity.",
"title": "Nut consumption, vegetarian diets, ischemic heart disease risk, and all-cause mortality: evidence from epidemiologic studies."
},
{
"docid": "MED-4833",
"text": "Effective diets reduce blood lipids and oxidative damage, both of which have been linked to the complications of diabetes and coronary heart disease. Our objective was to assess the effect of adding strawberries, as a source of antioxidants, to improve the antioxidant effect of a cholesterol-lowering diet (dietary portfolio). To this end, 28 hyperlipidemic subjects who had followed the dietary portfolio consisting of soy, viscous fiber, plant sterol, and nuts for a mean of 2.5 years were randomized to receive supplements of strawberries (454 g/d, 112 kcal) or additional oat bran bread (65 g/d, 112 kcal, approximately 2 g beta-glucan) (control) in a randomized 1-month crossover study with a 2-week washout. Strawberry supplementation resulted in a greater reduction in oxidative damage to low-density lipoprotein (LDL) measured as thiobarbituric acid-reactive substances in the LDL fraction (P = .014). At the end of the strawberry period, reductions in LDL cholesterol and in the ratio of total to high-density lipoprotein cholesterol were maintained close to 1-year values at -13.4% +/- 2.1% and -15.2% +/- 1.7%, respectively (P < .001), and were similar to the post-oat bran bread values. Strawberries also improved the palatability of the diet. We conclude that strawberry supplementation reduced oxidative damage to LDL while maintaining reductions in blood lipids and enhancing diet palatability. Added fruit may improve the overall utility of diets designed to lower coronary heart disease risk.",
"title": "The effect of strawberries in a cholesterol-lowering dietary portfolio."
},
{
"docid": "MED-3197",
"text": "Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.",
"title": "Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins"
},
{
"docid": "MED-5027",
"text": "BACKGROUND: Ischemic heart disease (IHD) is a leading cause of death in India. Dietary changes could reduce risk, but few studies have addressed the association between diet and IHD risk in India. OBJECTIVE: The goal was to address the association between diet and IHD risk among Indians in New Delhi (northern India) and Bangalore (southern India). DESIGN: We collected data from 350 cases of acute myocardial infarction and 700 controls matched on the basis of age, sex, and hospital as part of a hospital-based case-control study in 8 hospitals. Long-term dietary intake was assessed by using food-frequency questionnaires developed for New Delhi and Bangalore. We used conditional logistic regression to control for the matching factors and other predictors of risk. RESULTS: We observed a significant and dose-dependent inverse association between vegetable intake and IHD risk. The inverse association was stronger for green leafy vegetables; in multivariate analysis, persons consuming a median of 3.5 servings/wk had a 67% lower relative risk (RR: 0.33; 95% CI: 0.17, 0.64; P for trend = 0.0001) than did those consuming 0.5 servings/wk. Controlling for other dietary covariates did not alter the association. Cereal intake was also associated with a lower risk. Use of mustard oil, which is rich in alpha-linolenic acid, was associated with a lower risk than was use of sunflower oil [for use in cooking: RR: 0.49 (95% CI: 0.24, 0.99); for use in frying, RR: 0.29 (95% CI: 0.13, 0.64)]. CONCLUSION: Diets rich in vegetables and use of mustard oil could contribute to the lower risk of IHD among Indians.",
"title": "Diet and risk of ischemic heart disease in India."
},
{
"docid": "MED-1529",
"text": "BACKGROUND: Few previous prospective studies have examined differences in incident ischemic heart disease (IHD) risk between vegetarians and nonvegetarians. OBJECTIVE: The objective was to examine the association of a vegetarian diet with risk of incident (nonfatal and fatal) IHD. DESIGN: A total of 44,561 men and women living in England and Scotland who were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% consumed a vegetarian diet at baseline, were part of the analysis. Incident cases of IHD were identified through linkage with hospital records and death certificates. Serum lipids and blood pressure measurements were available for 1519 non cases, who were matched to IHD cases by sex and age. IHD risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. RESULTS: After an average follow-up of 11.6 y, there were 1235 IHD cases (1066 hospital admissions and 169 deaths). Compared with nonvegetarians, vegetarians had a lower mean BMI [in kg/m(2); -1.2 (95% CI: -1.3, -1.1)], non-HDL-cholesterol concentration [-0.45 (95% CI: -0.60, -0.30) mmol/L], and systolic blood pressure [-3.3 (95% CI: -5.9, -0.7) mm Hg]. Vegetarians had a 32% lower risk (HR: 0.68; 95% CI: 0.58, 0.81) of IHD than did nonvegetarians, which was only slightly attenuated after adjustment for BMI and did not differ materially by sex, age, BMI, smoking, or the presence of IHD risk factors. CONCLUSION: Consuming a vegetarian diet was associated with lower IHD risk, a finding that is probably mediated by differences in non-HDL cholesterol, and systolic blood pressure.",
"title": "Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study."
},
{
"docid": "MED-1190",
"text": "The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.",
"title": "High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae."
},
{
"docid": "MED-2381",
"text": "The inverse association of nut consumption and risk markers of coronary heart disease (lipids) has sparked the interest of the scientific and lay community. The objective of this study was to conduct a systematic review to investigate the effects of nuts on the lipid profile. Medline and Web of Science databases were searched from the start of the database to August 2004 and supplemented by cross-checking reference lists of relevant publications. Human intervention trials with the objective of investigating independent effects of nuts on lipid concentrations were included. From the literature search, 415 publications were screened and 23 studies were included. These papers received a rating based upon the methodology as it appeared in the publication. No formal statistical analysis was performed due to the large differences in study designs of the dietary intervention trials. The results of 3 almond (50-100 g/d), 2 peanut (35-68 g/d), 1 pecan nut (72 g/d), and 4 walnut (40-84 g/d) studies showed decreases in total cholesterol between 2 and 16% and LDL cholesterol between 2 and 19% compared with subjects consuming control diets. Consumption of macadamia nuts (50-100 g/d) produced less convincing results. In conclusion, consumption of approximately 50-100 g (approximately 1.5-3.5 servings) of nuts > or = 5 times/wk as part of a heart-healthy diet with total fat content (high in mono- and/or polyunsaturated fatty acids) of approximately 35% of energy may significantly decrease total cholesterol and LDL cholesterol in normo- and hyperlipidemic individuals.",
"title": "A systematic review of the effects of nuts on blood lipid profiles in humans."
},
{
"docid": "MED-4632",
"text": "Vegetarians have an apparent diminished risk for the development of ischemic coronary heart disease. This may be secondary to dietary effects of plasma lipids and lipoproteins, but platelets, which may also play a role, have also been observed to have aberrant functions in vegetarians. We measured plasma lipid and lipoprotein levels, platelet function, platelet fatty acid levels, and platelet active prostaglandins in ten strict vegetarians (vegans), 15 lactovegetarians, and 25 age- and sex-matched omnivorous controls. The most striking observations were a highly significant rise in platelet linoleic acid concentration and a decline in platelet arachidonic acid concentration in both vegetarian subgroups as compared with omnivorous controls. Serum thromboxane and prostacyclin levels as well as results of platelet aggregation studies did not differ among the groups tested. Cholesterol levels were significantly lower in both vegetarian groups as compared with controls, but plasma high- and low-density lipoprotein levels were lower only in the vegan subgroup as compared with omnivores. If diet produces these changes in platelet fatty acid and plasma lipid levels it may contribute to the decreased risk of coronary heart disease and possibly atherosclerosis in vegetarians.",
"title": "The effect of vegetarian diets on plasma lipid and platelet levels."
},
{
"docid": "MED-2590",
"text": "Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high-protein diets demonstrated statistically greater levels of disease.",
"title": "Reversing heart disease in the new millennium--the Fleming unified theory."
},
{
"docid": "MED-4905",
"text": "Black rice and its pigment fraction have shown anti-atherogenic activities in several animal models, but whether their beneficial effects will recur in humans remains unknown. The aim of the present study is to investigate the influence of black rice pigment fraction (BRF) supplementation on selected cardiovascular risk factors in patients with coronary heart disease (CHD). Sixty patients with CHD aged 45-75 years were recruited from the Second Affiliated Hospital of Sun Yat-Sen University in Guangzhou, China and randomly divided into two groups. In the test group, the diet was supplemented with 10 grams of BRF derived from black rice for 6 months; While in the placebo group, the diet was supplemented with 10 grams of white rice pigment fraction (WRF) derived from white rice. At baseline, plasma antioxidant status and the levels of inflammatory biomarkers and other measured variables were similar between two groups. After 6 months' intervention, compared to WRF supplementation, BRF supplementation greatly enhanced plasma total antioxidant capacity (TAC) (p=0.003), significantly reduce plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) (p=0.03), soluble CD40 ligand (sCD40L) (p=0.002) and high sensitive C-reactive protein (hs-CRP) (p=0.002) in the test group. No significant changes were observed in plasma total superoxide dismutase (T-SOD) activity, lipids level and carotid artery intima-media thickness (IMT) between two groups. These results may suggest that BRF could exert cardioprotective effects on patients with CHD by improving plasma antioxidant status and inhibiting inflammatory factors.",
"title": "Supplementation of black rice pigment fraction improves antioxidant and anti-inflammatory status in patients with coronary heart disease."
},
{
"docid": "MED-4249",
"text": "BACKGROUND AND AIMS: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. METHODS AND RESULTS: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance. CONCLUSION: The results confirm the cholesterol lowering properties of nut-enriched diets. They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content, which clearly deserves further study. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers."
},
{
"docid": "MED-4515",
"text": "BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.",
"title": "The effect of a plant-based low-carbohydrate (\"Eco-Atkins\") diet on body weight and blood lipid concentrations in hyperlipidemic subjects."
},
{
"docid": "MED-1540",
"text": "A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.",
"title": "Vegetarian diets: what do we know of their effects on common chronic diseases?"
},
{
"docid": "MED-1679",
"text": "BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.",
"title": "Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an..."
},
{
"docid": "MED-1331",
"text": "Many changes in diet and in physical activity are occurring simultaneously in the developing world. These diet shifts include large increases in energy density, in the proportion of the population consuming a high fat diet and in animal product intake. Animal source foods (ASF) play a major role in these diet shifts. This article documents the large shifts in the composition of diets and obesity across the developing world and notes that these changes are accelerating. Using China as a case study, evidence of the speeding up of this process is presented in descriptive and more rigorous dynamic longitudinal analysis. The implications of these changes for dietary and obesity patterns and cardiovascular disease are great. Indeed, developing countries are at a point where the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector. Current agriculture development policy in many developing countries focuses on livestock promotion and does not consider the potential adverse health consequences of this strategy. Although linkages between ASF intake and obesity cannot be established as clearly as they are for high ASF intakes, heart disease and cancer, the potential adverse health effects linked with an increased ASF intake should no longer be ignored.",
"title": "Dynamics of the nutrition transition toward the animal foods sector in China and its implications: a worried perspective."
},
{
"docid": "MED-1548",
"text": "This document details the procedures and recommendations of the Goals and Metrics Committee of the Strategic Planning Task Force of the American Heart Association, which developed the 2020 Impact Goals for the organization. The committee was charged with defining a new concept, cardiovascular health, and determining the metrics needed to monitor it over time. Ideal cardiovascular health, a concept well supported in the literature, is defined by the presence of both ideal health behaviors (nonsmoking, body mass index <25 kg/m(2), physical activity at goal levels, and pursuit of a diet consistent with current guideline recommendations) and ideal health factors (untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, and fasting blood glucose <100 mg/dL). Appropriate levels for children are also provided. With the use of levels that span the entire range of the same metrics, cardiovascular health status for the whole population is defined as poor, intermediate, or ideal. These metrics will be monitored to determine the changing prevalence of cardiovascular health status and define achievement of the Impact Goal. In addition, the committee recommends goals for further reductions in cardiovascular disease and stroke mortality. Thus, the committee recommends the following Impact Goals: \"By 2020, to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%.\" These goals will require new strategic directions for the American Heart Association in its research, clinical, public health, and advocacy programs for cardiovascular health promotion and disease prevention in the next decade and beyond.",
"title": "Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Go..."
},
{
"docid": "MED-1708",
"text": "High intakes of dietary sugars in the setting of a worldwide pandemic of obesity and cardiovascular disease have heightened concerns about the adverse effects of excessive consumption of sugars. In 2001 to 2004, the usual intake of added sugars for Americans was 22.2 teaspoons per day (355 calories per day). Between 1970 and 2005, average annual availability of sugars/added sugars increased by 19%, which added 76 calories to Americans' average daily energy intake. Soft drinks and other sugar-sweetened beverages are the primary source of added sugars in Americans' diets. Excessive consumption of sugars has been linked with several metabolic abnormalities and adverse health conditions, as well as shortfalls of essential nutrients. Although trial data are limited, evidence from observational studies indicates that a higher intake of soft drinks is associated with greater energy intake, higher body weight, and lower intake of essential nutrients. National survey data also indicate that excessive consumption of added sugars is contributing to overconsumption of discretionary calories by Americans. On the basis of the 2005 US Dietary Guidelines, intake of added sugars greatly exceeds discretionary calorie allowances, regardless of energy needs. In view of these considerations, the American Heart Association recommends reductions in the intake of added sugars. A prudent upper limit of intake is half of the discretionary calorie allowance, which for most American women is no more than 100 calories per day and for most American men is no more than 150 calories per day from added sugars.",
"title": "Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association."
},
{
"docid": "MED-1380",
"text": "Objective To investigate the relative importance of the individual components of the Mediterranean diet in generating the inverse association of increased adherence to this diet and overall mortality. Design Prospective cohort study. Setting Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC). Participants 23 349 men and women, not previously diagnosed with cancer, coronary heart disease, or diabetes, with documented survival status until June 2008 and complete information on nutritional variables and important covariates at enrolment. Main outcome measure All cause mortality. Results After a mean follow-up of 8.5 years, 652 deaths from any cause had occurred among 12 694 participants with Mediterranean diet scores 0-4 and 423 among 10 655 participants with scores of 5 or more. Controlling for potential confounders, higher adherence to a Mediterranean diet was associated with a statistically significant reduction in total mortality (adjusted mortality ratio per two unit increase in score 0.864, 95% confidence interval 0.802 to 0.932). The contributions of the individual components of the Mediterranean diet to this association were moderate ethanol consumption 23.5%, low consumption of meat and meat products 16.6%, high vegetable consumption 16.2%, high fruit and nut consumption 11.2%, high monounsaturated to saturated lipid ratio 10.6%, and high legume consumption 9.7%. The contributions of high cereal consumption and low dairy consumption were minimal, whereas high fish and seafood consumption was associated with a non-significant increase in mortality ratio. Conclusion The dominant components of the Mediterranean diet score as a predictor of lower mortality are moderate consumption of ethanol, low consumption of meat and meat products, and high consumption of vegetables, fruits and nuts, olive oil, and legumes. Minimal contributions were found for cereals and dairy products, possibly because they are heterogeneous categories of foods with differential health effects, and for fish and seafood, the intake of which is low in this population.",
"title": "Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study"
},
{
"docid": "MED-4243",
"text": "CONTEXT: The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. OBJECTIVES: To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. DESIGN: Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. PATIENTS: Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. SETTING: Two tertiary care university medical centers. INTERVENTION: Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. MAIN OUTCOME MEASURES: Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. RESULTS: Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). CONCLUSIONS: More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.",
"title": "Intensive lifestyle changes for reversal of coronary heart disease."
},
{
"docid": "MED-4437",
"text": "Offals are widely consumed in different cuisines, but information on the occurrence of dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in these foods is sparse. In the first structured investigation of its kind, this study reports levels of these contaminants in commonly consumed offals (n=173) such as lamb, ox, deer and pig's liver, kidneys, tongue and heart, and offal products such as pâté, haggis, tripe and black pudding. The results support literature observations on the preferential accumulation of contaminants in liver tissue, as the highest concentrations of PCDD/Fs were observed in liver, relative to the other organs (e.g. 8.4 ng WHO-TEQ kg(-1) lamb liver compared to 1.1 ng WHO-TEQ kg(-1) lamb kidney and 1.27 ng WHO-TEQ kg(-1) lamb heart). Offal products generally showed lower contaminant levels which may be a result of processing or dilution. For most samples, the main contribution to WHO-TEQ arose from PCDD/Fs rather than PCBs. Just under half of the lamb liver samples showed PCDD/F concentrations that exceeded the EU maximum limit of 6 ng kg(-1) fat weight (although deer liver which is not subject to the regulation, generally showed higher levels). Dietary exposure estimates indicate that the weekly consumption of up to two 100g portions of lamb, ox, calf or pig liver or one portion of deer liver would not breach the tolerable daily intake (TDI) level even when the rest of the diet was included. However, the consumption of more than one portion of deer liver per week may lead to the TDI being exceeded. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.",
"title": "Dioxins (PCDD/Fs) and PCBs in offal: occurrence and dietary exposure."
}
] |
8003
|
Why would a company have 2 listings on the same exchange?
|
[
{
"docid": "528516",
"text": "Some companies like Royal Dutch Shell have multiple share classes to suit the tax regimes in Holland and the UK the A shares have dutch withholding tax applied and the B shares dont. Also some split capital investment trusts have multiple share classes http://www.trustnet.com/Education/Split.aspx?ms=1",
"title": ""
},
{
"docid": "251713",
"text": "A company can issue different kinds of shares. For example, some kinds of shares may get preference in dividends or payment in event of (company) bankruptcy. Preferred shares are an example of this. A company might have several kinds of preferred shares and a 'common stock'. Here is a good explanation. See too the Wikipedia article about preferred stock. Toronto-Dominion Bank (TD) is an example of a company that has fourteen different preferred share issues, each with its own listing on the Toronto Stock Exchange (TSE) and symbol. TD has one kind of common stock, which is also listed on the TSE. However, TD common equity trades much more actively than the preferred shares. Remember that preferred stock is a different security type than common stock e.g. common has voting rights, preferred does not.",
"title": ""
}
] |
[
{
"docid": "450099",
"text": "\"VIV.PA - is Vivendi listed on a stock exchange in Paris VIVEF - is Vivendi listed on the OTC Other Exchange. VIVHY - is Listed on the OTC:Pink Sheets. A company can be listed on multiple exchanges, they are known as a dual-listed company. It's a corporate structure in which two corporations function as a single operating business through a legal equalization agreement, but retain separate legal identities and stock exchange listings. Pretty much all DLCs are cross-border, and have tax advantages for the corporations and their stockholders. When a DLC is created, in essence two companies are created and have two separate bodies of shareholders, but they agree to share all the risks and rewards of the ownership of all their operating businesses in a fixed proportion, laid out in a contract called an \"\"equalization agreement\"\". The shares of a DLC parents have claim to the exact same underlying cash flows. So in theory the stock prices of these companies should move exactly the same. However in practice there can be differences between these prices. More info on OTC exchanges can be found here - keep in mind this info is from the company that runs these listings. Over the counter stocks are held to a FAR lesser regulation standard. I would recommend doing further interdependent research before pursuing any action.\"",
"title": ""
},
{
"docid": "256035",
"text": "Investors who are themselves Canadian and already hold Canadian dollars (CAD) would be more likely to purchase the TSX-listed shares that are quoted in CAD, thus avoiding the currency exchange fees that would be required to buy USD-quoted shares listed on the NYSE. Assuming Shopify is only offering a single class of shares to the public in the IPO (and Shopify's form F-1 only mentions Class A subordinate voting shares as being offered) then the shares that will trade on the TSX and NYSE will be the same class, i.e. identical. Consequently, the primary difference will be the currency in which they are quoted and trade. This adds another dimension to possible arbitrage, where not only the bare price could deviate between exchanges, but also due to currency fluctuation. An additional implication for a company to maintain such a dual listing is that they'll need to adhere to the requirements of both the TSX and NYSE. While this may have a hard cost in terms of additional filing requirements etc., in theory they will benefit from the additional liquidity provided by having the multiple listings. Canadians, in particular, are more likely to invest in a Canadian company when it has a TSX listing quoted in CAD. Also, for a company listed on both the TSX and NYSE, I would expect the TSX listing would be more likely to yield inclusion in a significant market index—say, one based on market capitalization, and thus benefit the company by having its shares purchased by index ETFs and index mutual funds that track the index. I'll also remark that this dual U.S./Canadian exchange listing is not uncommon when it comes to Canadian companies that have significant business outside of Canada.",
"title": ""
},
{
"docid": "339268",
"text": "\"You cannot determine this solely by the ticker length. However, there are some conventions that may help steer you there. Nasdaq has 2-4 base letters BATS has 4 base letters NYSE equity securities have 1-4 base letters. NYSE Mkt (formerly Amex) have 1-4 base letters. NYSE Arca has 4 base letters OTC has 4 base letters. Security types other than equities may have additional letters added, and each exchange (and data vendors) have different conventions for how this is handled. So if you see \"\"T\"\" for a US-listed security it would be only be either NASDAQ, NYSE or NYSE Mkt. If you see \"\"ANET\"\" then you cannot tell which exchange it is listed on. (In this case, ANET Arista Networks is actually a NYSE stock). For some non-equity security types, such as hybrids, and debt instruments, some exchanges add \"\"P\"\" to the end for \"\"preferreds\"\" (Nasdaq and OTC) and NYSE/NYSE Mkt have a variety of methods (including not adding anything) to the ticker. Examples include NYSE:TFG, NYSEMkt:IPB, Nasdaaq: AGNCP, Nasdaq:OXLCN. It all becomes rather confusing given the changes in conventions over the years. Essentially, you require data that provides you with ticker, listing location and security type. The exchanges allocate security tickers in conjunction with the SEC so there are no overlaps. eg. The same ticker cannot represent two different securities. However, tickers can be re-used. For example, the ticker AB has been used by the following companies:\"",
"title": ""
},
{
"docid": "151132",
"text": "\"First, keep in mind that there are generally 2 ways to buy a corporation's shares: You can buy a share directly from the corporation. This does not happen often; it usually happens at the Initial Public Offering [the first time the company becomes \"\"public\"\" where anyone with access to the stock exchange can become a part-owner], plus maybe a few more times during the corporations existence. In this case, the corporation is offering new ownership in exchange for a price set the corporation (or a broker hired by the corporation). The price used for a public offering is the highest amount that the company believes it can get - this is a very complicated field, and involves many different methods of evaluating what the company should be worth. If the company sets the price too low, then they have missed out on possible value which would be earned by the previous, private shareholders (they would have gotten the same share % of a corporation which would now have more cash to spend, because of increased money paid by new shareholders). If the company sets the price too high, then the share subscription might only be partially filled, so there might not be enough cash to do what the company wanted. You can buy a share from another shareholder. This is more common - when you see the company's share price on the stock exchange, it is this type of transaction - buying out other current shareholders. The price here is simply set based on what current owners are willing to sell at. The \"\"Bid Price\"\" listed by an exchange is the current highest bid that a purchaser is offering for a single share. The \"\"Ask Price\"\" is the current lowest offer that a seller is offering to sell a single share they currently own. When the bid price = the ask price, a share transaction happens, and the most recent stock price changes.\"",
"title": ""
},
{
"docid": "127578",
"text": "Technically, of course. Almost any company can go bankrupt. One small note: a company goes bankrupt, not its stock. Its stock may become worthless in bankruptcy, but a stock disappearing or being delisted doesn't necessarily mean the company went bankrupt. Bankruptcy has implications for a company's debt as well, so it applies to more than just its stock. I don't know of any historical instances where this has happened, but presumably, the warning signs of bankruptcy would be evident enough that a few things could happen. Another company, e.g. another exchange, holding firm, etc. could buy out the exchange that's facing financial difficulty, and the companies traded on it would transfer to the new company that's formed. If another exchange bought out the struggling exchange, the shares of the latter could transfer to the former. This is an attractive option because exchanges possess a great deal of infrastructure already in place. Depending on the country, this could face regulatory scrutiny however. Other firms or governments could bail out the exchange if no one presented a buyout offer. The likelihood of this occurring depends on several factors, e.g. political will, the government(s) in question, etc. For a smaller exchange, the exchange could close all open positions at a set price. This is exactly what happened with the Hong Kong Mercantile Exchange (HKMex) that MSalters mentioned. When the exchange collapsed in May 2013, it closed all open positions for their price on the Thursday before the shutdown date. I don't know if a stock exchange would simply close all open positions at a set price, since equity technically exists in perpetuity regardless of the shutdown of an exchange, while many derivatives have an expiration date. Furthermore, this might not be a feasible option for a large exchange. For example, the Chicago Mercantile Exchange lists thousands of products and manages hundreds of millions of transactions, so closing all open positions could be a significant undertaking. If none of the above options were available, I presume companies listed on the exchange would actively move to other, more financially stable exchanges. These companies wouldn't simply go bankrupt. Contracts can always be listed on other exchanges as well. Considering the high level of mergers and acquisitions, both unsuccessful and successful, in the market for exchanges in recent years, I would assume that option 1 would be the most likely (see the NYSE Euronext/Deutsche Börse merger talks and the NYSE Euronext/ICE merger that's currently in progress), but for smaller exchanges, there is the recent historical precedent of the HKMex that speaks to #3. Also, the above answer really only applies to publicly traded stock exchanges, and not all stock exchanges are publicly-held entities. For example, the Shanghai Stock Exchange is a quasi-governmental organization, so I presume option 2 would apply because it already receives government backing. Its bankruptcy would mean something occurred for the government to withdraw its backing or that it became public, and a discussion of those events occurring in the future is pure speculation.",
"title": ""
},
{
"docid": "450184",
"text": "\"Depends. The short answer is yes; HSBC, for instance, based in New York, is listed on both the LSE and NYSE. Toyota's listed on the TSE and NYSE. There are many ways to do this; both of the above examples are the result of a corporation owning a subsidiary in a foreign country by the same name (a holding company), which sells its own stock on the local market. The home corporation owns the majority holdings of the subsidiary, and issues its own stock on its \"\"home country's\"\" exchange. It is also possible for the same company to list shares of the same \"\"pool\"\" of stock on two different exchanges (the foreign exchange usually lists the stock in the corporation's home currency and the share prices are near-identical), or for a company to sell different portions of itself on different exchanges. However, these are much rarer; for tax liability and other cost purposes it's usually easier to keep American monies in America and Japanese monies in Japan by setting up two \"\"copies\"\" of yourself with one owning the other, and move money around between companies as necessary. Shares of one issue of one company's stock, on one exchange, are the same price regardless of where in the world you place a buy order from. However, that doesn't necessarily mean you'll pay the same actual value of currency for the stock. First off, you buy the stock in the listed currency, which means buying dollars (or Yen or Euros or GBP) with both a fluctuating exchange rate between currencies and a broker's fee (one of those cost savings that make it a good idea to charter subsidiaries; could you imagine millions a day in car sales moving from American dealers to Toyota of Japan, converted from USD to Yen, with a FOREX commission to be paid?). Second, you'll pay the stock broker a commission, and he may charge different rates for different exchanges that are cheaper or more costly for him to do business in (he might need a trader on the floor at each exchange or contract with a foreign broker for a cut of the commission).\"",
"title": ""
},
{
"docid": "537222",
"text": "If a company's shares trade in multiple exchanges, the prices in every exchange are very near to each other, otherwise you could earn money by doing arbitrage deals (buying in one, selling in the other) - and people do that once it becomes worth it. Which stock exchange you use is more a convenience for the buyer/seller - many investment banks offer only something local/near, and you have to go to specific investment banks to use other exchanges. For example, in Germany, it is easy to deal in Frankfurt, but if you want to trade at the the NASDAQ, you have to run around and find a bank that offers it, and you probably have to pay extra for it. In the USA, most investment banks offer NASDAQ, but if you want to trade in Frankfurt, you will have run around for an international company that offers that. As a stock owner/buyer, you can sell/buy your shares on any stock exchange where the company is listed (again, assuming your investment broker supports it). So you can buy in Frankfurt and sell in Tokyo seconds later, as nothing needs to be physically moved. Companies that are listed in multiple stock exchangs are typically large, and offer this to make trading their shares easier for a larger part of the world. Considering your 'theoretical buy all shares' - the shares are not located in the exchanges, they are in the hands of the owners, and not all are for sale, for various reasons. The owners decide if and when they want them offered for sale, and they also decide which stock exchange they offer them on; so you would need to go to all exchanges to buy them all. However, if you raise your offer price in one exchange only slightly, someone will see the arbitrage and buy them in the other locations and offer them to you in your stock exchange; in other words, for a small fee the shares will come to you. But again, most shares are typically not for sale. It's the same as trying to buy all Chevy Tahoes - even if you had the money, most owners wouldn't know or care about you. You would have to go around and contact every single one and convince them to sell.",
"title": ""
},
{
"docid": "126719",
"text": "You pointed out that HFT does not create ipods are mine minerals. Neither does human trading. HFT is a proxy for human trading. Although the computer is executing trades automatically based on an algorithm, it is still using money from a human being's account so the trading is still being done with someone's money. Fast execution of trades is desirable in exchanges. Imagine two exchanges: One only executes trades once a month, the other executes trades once a week. Which exchange would be more desirable? The exchange that trades once a week. Why? Because if I'm holding a stock that I would like to sell, I want to sell it now - not a month from now. Same reason for buying. This concept works all the way down to seconds and fractions of seconds. The issue with HFT, however, is there are cases where the market goes against the HFT algorithm and the algorithm continues to execute trades driving prices up or down by large amounts in the matter of minutes or even seconds. The exchange frequently cancels these trades which only encourages more aggressive HFT trading since HFT traders can have their losses cancelled. This is a privilege that LFTs (low frequency traders) do not receive. This is a valid criticism of HFTs. A short list of such cancelled trades: 8/26/2010: Nasdaq cancels trades of CORE stock 10/4/2010: Nasdaq cancels trades of CENX stock 10/15/2010: NYSE cancels trades of PAY stock 10/18/2010: NYSE cancels $500 million worth of SPY trades 5/18/2011: NYSE cancels 15,900 trades of BEE.PR.C 6/21/2011: Nasdaq cancels CNTY trades 12/2/2011: London Metals Exchange cancel trades of copper",
"title": ""
},
{
"docid": "189819",
"text": "Interest rate swaps are used to transfer risk from one party to another. They can be used to transfer many types of risk but most common are interest rate risk and exchange rate risk There are a few key concepts that I have noticed most people have trouble with which Are below: 1) The Notional amount: this is the amount that the two legs (the floating and fixed) will be based on. If you think about each leg as a loan the notional amount would be the principal, however in a swap this amount never changes hands. Rather it is just an amount used to calculate what the dollar amount exchanged should be. 2) The floating and fixed legs are the interest rates that will be exchanged. The fixed leg will always pay out the same amount no matter the changes in the market while the floating rate will change periodically depending on market conditions. As a side note it is often agreed that only the difference in the two rates will be paid rather then sending the money back and forth. 3) And finally it is important to note that at the inception of the swap the notional value will always be 0. Many people miss this but when you think about it no company would want to sign a deal the from inception puts them in a loosing position. I hope that helped without a more specific question all I can do is list random facts about swaps and hope they are useful to you.",
"title": ""
},
{
"docid": "434212",
"text": "A stock exchange is a marketplace where people can bring their goods [shares] to be traded. There are certain rules. Stock Exchange does not own any shares of the companies that are trading in. The list of who owns with stock is with the registrar of each company. The electronic shares are held by a Financial Institution [Securities Depository]. So even if the exchange itself goes down, you still hold the same shares as you had before it went down. One would now have to find ways to trade these shares ... possibly via other stock exchange. This leaves the question of inflight transactions, which again would be recorded and available. Think of it similar to eBay. What happens when eBay goes bankrupt? Nothing much, all the seller still have their goods with them. All the buyers who had purchased good before have it when them ... so the question remains on inflight goods where the buyer has paid the seller and not yet received shipments ...",
"title": ""
},
{
"docid": "257404",
"text": "The process would look something like: 1. Register your investment company with the SEC 2. Get the ETF approved by the SEC 3. Get a custodian bank (likely requires min assets of a few million) 4. Get listed on an exchange like NYSEARCA by meeting requirements and have an IPO 1 and 2 probably require a lot of time and fees and would be wise to have a lawyer advising, 3 is obviously difficult due to asset requirements and 4 would probably involve an investment bank plus more fees",
"title": ""
},
{
"docid": "3463",
"text": "You seem to think that stock exchanges are much more than they actually are. But it's right there in the name: stock exchange. It's a place where people exchange (i.e. trade) stocks, no more and no less. All it does is enable the trading (and thereby price finding). Supposedly they went into mysterious bankruptcy then what will happen to the listed companies Absolutely nothing. They may have to use a different exchange if they're planning an IPO or stock buyback, that's all. and to the shareholder's stock who invested in companies that were listed in these markets ? Absolutley nothing. It still belongs to them. Trades that were in progress at the moment the exchange went down might be problematic, but usually the shutdown would happen in a manner that takes care of it, and ultimately the trade either went through or it didn't (and you still have the money). It might take some time to establish this. Let's suppose I am an investor and I bought stocks from a listed company in NYSE and NYSE went into bankruptcy, even though NYSE is a unique business, meaning it doesn't have to do anything with that firm which I invested in. How would I know the stock price of that firm Look at a different stock exchange. There are dozens even within the USA, hundreds internationally. and will I lose my purchased stocks ? Of course not, they will still be listed as yours at your broker. In general, what will happen after that ? People will use different stock exchanges, and some of them migth get overloaded from the additional volume. Expect some inconveniences but no huge problems.",
"title": ""
},
{
"docid": "94336",
"text": "\"listed simultaneously in New York, London, and maybe even some Asian markets - is this correct? If the exchanges are not connected, then in primary market the shares are listed. On other exchanges, the \"\"Depository Receipts\"\" are listed. i.e. the Company will keep say 100,000 shares with the primary stock exchange / depository. Based on this it would create new instruments \"\"Depository Receipts\"\". They can be 1:1 or whatever ratio. hypothetically, if I want to buy all of the company's stock Even if it is on one exchange, buying all stocks would trigger various regulatory aspects of Companies Act, or Stock Exchange rules. This is not simple or easy like clicking some buttons and buying everything. That is, let's say that in New York the company has listed 1000 shares, and in London only 10 shares, each worth 10 USD Market capitalization is sum of all outstanding shares into value.\"",
"title": ""
},
{
"docid": "255097",
"text": "Liquidity on dual listed equities is rarely the same on both exchanges. More liquidity means you would typically get a better price assuming you execute the trades using the same order types. It's recommended to trade where the liquidity is greater unless your trading method benefits somehow from it being lower. It's important to remember that some ADRs (some European companies listed in US) have ADR fees which vary. USD/EUR transaction fees are low when using a decent broker but you're obviously participating in the currency risk.",
"title": ""
},
{
"docid": "322168",
"text": "\"Nearly every country has its own exchange because so many countries have their own currency, and currency permeates every part of an exchange's business. Generally, an exchange will support transaction and settlement only in local currency. Securities (except those that explicitly enable FX trading) are denominated and will trade in a single currency-- you can only buy a share of IBM in U.S. dollars. Securities trading always seeks to be a clean, frictionless, scalable process, and adding cross-currency translation to the mix would just complicate things. So it's one exchange, one currency. In most countries, citizens and even businesses are largely restricted to having bank accounts in local currency. There are various political reasons for this, but there it is: it is difficult or impossible to open a domestic bank account in a foreign-denominated currency. A public company headquartered in a given country will be required to publish financial statements in local currency, will be more likely to do business with the local citizenry and businesses in that currency, and so will likely look for investors from that same pool-- which generally means listing in local currency, which means on an exchange in that country. There are exceptions, of course. Big multinationals do business all over the world, and many seek investors all over the world as well. Mechanisms have been created to permit this (American Depositary Receipts or ADRs, for example). But once again, cross-currency translation makes things more complicated, so ADRs and their like are only practical for very big international players. As to why there may be many exchanges in a single country, IMO Nick R has it right. Read \"\"Flash Boys\"\"; many market makers profit from trading between exchanges, and so have an interest in there being many of them. And in the U.S., regulators have expressed an interest in \"\"innovation\"\" in the exchange space, and so permit them. There is also an argument to be made against having a single \"\"Too Big To Fail\"\" exchange just like the argument for banks, but I wouldn't call that a \"\"reason\"\" for the current state of affairs.\"",
"title": ""
},
{
"docid": "246062",
"text": "The suffix represents the stock exchange the stock is traded on. N represents the New York Stock Exchange and O represents the Nasdaq. Sometimes a stock can be listed on more than one exchange so the suffix will give you an indication of which exchange the stock is on. For example the Australian company BHP Billiton Ltd is listed on multiple exchanges so is given a different suffix for the different exchanges (especially when the code is the same for each exchange). Below are a few examples of BHP:",
"title": ""
},
{
"docid": "260023",
"text": "Every company has Stocks. For the stocks to be traded via some stock exchange, the companies must follow the eligibility criteria and guidelines. Once done, these are then listed on the stock exchange and can be traded. The advantage [amongst others] of listing is liquidity and stocks can easily be bought and sold. Some small companies or closely held companies may not want to list on stock exchange and hence are not traded. This does not mean they can't be bought and sold, they can be outside of the market, however the deals are complex and every deal has to be worked out. During the course of time a stock that is traded on a stock exchange, would either fail to meet the criteria or voluntarily choose not to be traded and follow the delisting process [either by stock exchange or by company]. After this the stocks are no longer traded on the exchange.",
"title": ""
},
{
"docid": "1577",
"text": "If I buy VUSA from one exchange, can I sell it in a different exchange, assuming my brokerage account lets me trade in both exchanges? Or is it somehow tied to the exchange I bought it from? This doesn't happen for all securities and between all stock exchanges. So that is dependent on broker and country. I checked for VUSA with Selftrade. They categorically refused allowing me to trade in VUSA in different exchanges. I can only buy and sell in same currency only, albeit sell(buy) in the same exchange where I buy(sell) from. Should be the same behaviour for all brokers for us mere mortals, if you are a bank or a millionaire than that might be a different question. The VUSA you quote is quoted in GBP in LSE and in EUR in AEX, and the ETF has been created by an Irish entity and has an Irish ISIN. As Chris mentioned below, happens between US and Canadian exchanges, but not sure it happens across all exchanges. You cannot deal in inter-listed stocks in LSE and NYSE. Since it's the same asset, its value should not vary across exchanges once you compensate for exchange rates, right? Yes, else it opens up itself for arbitrage (profit without any risk) which everybody wants. So even if any such instance occurs, either people will exploit it to make the arbitrage profit zero (security reflects the equilibrium price) or the profit from such transaction is so less, compared with the effort involved, that people will tend to ignore it. Anyways arbitrage profit is very difficult to garner nowadays, considering the super computers at work in the market who exploit these discrepancies, the moment they see them and bring the security right to the zero arbitrage profit point. If there's no currency risk because of #2, what other factors should I consider when choosing an exchange to trade in? Liquidity? Something else? Time difference, by the time you wake up to trade in Japan, the Japanese markets would have closed. Tax implications across multiple continents. Law of the land, providing protection to investors. Finding a broker dealing in markets you want to explore or dealing with multiple brokers. Regulatory headaches.",
"title": ""
},
{
"docid": "505865",
"text": "Okay. They're faster than most other computers. They either have a dedicated fiber line or are physically closer. But anyways, they flood the NYSE with tons of orders to slow it down. So they see another broker's order in the line up and delete the bogus orders. They can then make the purchase faster than the other guy. The other guy now has to pay a higher strike price than he initially thought the bid would be. So let's say Apple's quote is 1.00 They send one order for apple One for IBM One for Yahoo One for NBC Comcast They see another guy wants Apple. So they cancel the orders for IBM, Yahoo and NBC Comcast and leave the Apple one to complete. The Apple one goes through and then they automatically resell it to the guy looking to buy Apple at a price of 1.0001 TLDR They flood a bunch of orders at a bunch of different prices/quantities. They cancel before it goes through unless they see someone else wants it. If that person wants it they don't cancel. edit: I don't even know if all or any of those stocks are listed on the NYSE. In today's world it doesn't make a difference anymore. However, replace NYSE with any exchange and the stock with any ticker symbol. edit 2: They could also manipulate cross listing. Listing the same stock on two different exchanges. Those prices are mostly uniform but of course higher volume on one could mean a higher price on one before they stabilize. So if you can move fast you can buy the stock at the lower price and sell it on the exchange with the higher price.",
"title": ""
},
{
"docid": "516078",
"text": "I work at BATS Chi-X Europe and wanted to provide some clarity/answers to these questions. BATS Chi-X Europe is a Recognised Investment Exchange, so it is indeed a stock exchange. Sometimes the term “equity market” could be used when explaining our business, but essentially we are a stock exchange. As some background, BATS Chi-X Europe was formed by the acquisition of Chi-X Europe by BATS Trading in November 2011. At the time of the acquisition, each company operated as a Multilateral Trading Facility (MTF) for the trading of pan-European equities via a single trading platform. The category of MTF was introduced by MIFID (markets in Financial Instrument Directive) in 2007, which introduced competition in equities trading and allowed European stocks, to be traded on any European platform. Until 2007, many European stocks had to be traded only their local exchanges due to so-called “Concentration Rules”. Following the acquisition, BATS Chi-X Europe became the largest MTF in Europe, offering trading in more than 2,000 securities (2,700 securities by September 2013) across 15 major European markets, on a single trading platform. In May 2013, BATS Chi-X Europe received Recognised Investment Exchange status from the UK Financial Conduct Authority, meaning that BATS Chi-X Europe has changed from an MTF status to full exchange status. In response to question 1: The equities traded on BATS Chi-X Europe are listed on stock exchanges such as the LSE but also listed on the other European Exchanges. The term “third party” equities is not particularly useful as all stock trading in Europe is generally a “second hand” business referred to as “secondary market” trading. At the time of listing a firm issues shares; trading in these shares after the listing exercise is generally what happens in equity markets and these shares can be bought and sold on stock exchanges across Europe. Secondary market trading describes all trading on all exchanges or MTFs that takes place after the listing. In response to question 2: BATS Chi-X Europe trades over 2,700 stocks on its own trading platform. When trading on BATS Chi-X Europe, orders are executed on their own platform and will not end up of the LSE order books or platform. The fact that a stock was first listed on the LSE, does not mean that all trading in this stock happens via the LSE. However settlement process ensures that stocks end up being logged in a single depository. This means that a stock bought on BATS Chi-X Europe can be offset against the same stock sold on the LSE. In response to question 3: As noted above, BATS Chi-X Europe received Recognised Investment Exchange (RIE) status from the UK Financial Conduct Authority in May 2013, meaning that BATS Chi-X Europe has changed from an MTF status to full stock exchange status. As an exchange / RIE, BATS Chi-X Europe is authorised to offer primary and secondary listings alongside its existing business. According to the Federations of European Securities Exchanges (FESE), BATS Chi-X Europe has been the largest equity exchange in Europe by value traded in every month so far in 2013. In August, 24.1% of European equities trading in the 15 markets covered were traded on BATS Chi-X Europe. In July and August, the average notional value traded on BATS Chi-X Europe was around €7.2 billion per day. Hope this information is helpful.",
"title": ""
},
{
"docid": "498356",
"text": "\"First, your question contains a couple of false premises: Options in the U.S. do not trade on the NYSE, which is a stock exchange. You must have been looking at a listing from an options exchange. There are a handful of options exchanges in the U.S., and while two of these have \"\"NYSE\"\" in the name, referring to \"\"NYSE\"\" by itself still refers to the stock exchange. Companies typically don't decide themselves whether options will trade for their stock. The exchange and other market participants (market makers) decide whether to create a market for them. The Toronto Stock Exchange (TSX) is also a stock exchange. It doesn't list any options. If you want to see Canadian-listed options on equities, you're looking in the wrong place. Next, yes, RY does have listed options in Canada. Here are some. Did you know about the Montreal Exchange (MX)? The MX is part of the TMX Group, which owns both the Toronto Stock Exchange (TSX) and the Montreal Exchange. You'll find lots of Canadian equity and index options trading at the MX. If you have an options trading account with a decent Canadian broker, you should have access to trade options at the MX. Finally, even considering the existence of the MX, you'll still find that a lot of Canadian companies don't have any options listed. Simply: smaller and/or less liquid stocks don't have enough demand for options, so the options exchange & market makers don't offer any. It isn't cost-effective for them to create a market where there will be very few participants.\"",
"title": ""
},
{
"docid": "306561",
"text": "\"The case you are looking at is rather special, because the Chinese government for the longest time did not allow foreigners to invest in Chinese stocks. The ADRs explained in @DStanley's answer are a way around that restriction; recently there are some limited official ways, In general, it is perfectly normal for a stock to appear on different exchanges, in different currencies, and it's all the \"\"real\"\" stock. Because remember: a stock exchange is really nothing more than a fancy place for people to buy and sell stocks. There is absolutely no reason why a specific stock should only be traded in one place. Companies that have decided to be publically tradeable generally want to be traded in as many exchanges as possible, because it makes the stock more liquid, which helps their shareholders. Individual exchanges have different requirements for a stock to be listed for trading there, some may even do it without the company's explicit approval.\"",
"title": ""
},
{
"docid": "407185",
"text": "\"Mutual funds don't pay taxes themselves, they distribute any dividends or capital gains to the shareholders. Thus, if you hold a mutual fund in a tax-advantaged account like a 401k or IRA then the distribution isn't a taxable event while in a regular taxable account you would have to pay taxes on the distributions. From Forbes: There can be foreign companies on US stock exchanges that would still work the same way. Unilever for example is an Anglo-Dutch multinational listed on the NYSE as \"\"UN.\"\"\"",
"title": ""
},
{
"docid": "112461",
"text": "Say a stock is listed in Nasdaq, and the same company has a stock listed in Tsx. Does the Nasdaq price affect the Tsx price as trading commences? Not directly. Basically, an exchange is a market, and the price is defined only by supply and demand in that market. However, any substantial price differential for a commodity traded in multiple market creates an arbitrage opportunity, and there are many traders whose job it is exactly to find and use such opportunities. Their activity in turn has the effect of reducing the price differentials to the point where transaction costs make them unprofitable. With high-frequency traders around, the time for a price differential to disappear is nowadays measured in milliseconds. If a trader buys from one exchange, will it affect the price of the other? Only through the mechanism mentioned above. Are there any benefits to being listed in two exchanges? It increases the liquidity of a stock.",
"title": ""
},
{
"docid": "85484",
"text": "\"In the US, stocks are listed on one exchange but can be traded on multiple venues. You need to confirm exactly what your data is showing: a) trades on the primary-listed exchange; or b) trades made at any venue. Also, the trade condition codes are important. Only certain trade condition codes contribute towards the day's open/high/low/close and some others only contribute towards the volume data. The Consolidated Tape Association is very clear on which trades should contribute towards each value - but some vendors have their own interpretation (or just simply an erroneous interpretation of the specifications). It may surprise you to find that the majority of trading volume for many stocks is not on their primary-listed exchange. For example, on 2 Mar 2015, NASDAQ:AAPL traded a total volume across all venues was 48096663 shares but trading on NASDAQ itself was 12050277 shares. Trades can be cancelled. Some data vendors do not modify their data to reflect these busted trades. Some data vendors also \"\"snapshot\"\" their feed at a particular point in time of the data. Some exchanges can provide data (mainly corrections) 4-5 hours after the closing bell. By snapshotting the data too early and throwing away any subsequent data is a typical cause of data discrepancies. Some data vendors also round prices/volumes - but stocks don't just trade to two decimal places. So you may well be comparing two different sets of trades (with their own specific inclusion rules) against the same stock. You need to confirm with your data sources exactly how they do things. Disclosure: Premium Data is an end-of-day daily data vendor.\"",
"title": ""
},
{
"docid": "391156",
"text": "\"I can see two possibilities. Either a deal is struck that someone (the company itself, or a large owner) buys out the remaining shares. This is the scenario @mbhunter is talking about, so I won't go too deeply into it, but it simply means that you get money in your bank account for the shares in question the same as if you were to sell them for that price (in turn possibly triggering tax effects, etc.). I imagine that this is by far the most common approach. The other possibility is that the stock is simply de-listed from a public stock exchange, and not re-listed elsewhere. In this case, you will still have the stock, and it will represent the same thing (a portion of the company), but you will lose out on most of the \"\"market\"\" part of \"\"stock market\"\". That is, the shares will still represent a monetary value, you will have the same right to a portion of the company's profits as you do now, etc., but you will not have the benefit of the market setting a price per share so current valuation will be harder. Should you wish to buy or sell stock, you will have to find someone yourself who is interested in striking a deal with you at a price point that you feel comfortable with.\"",
"title": ""
},
{
"docid": "289762",
"text": "\"I guess there are accepted channels for this sort of thing, but I don't really understand why. Couldn't anyone sell them to anyone else at any time in any kind of market? I mean, if I had a friend who was talking the the IPO up, couldn't I have just said, \"\"Hey Fred, I'll sell you a Facebook share in two weeks time for thirty five bucks\"\" and be done with it? Do exchanges provide legal services? Is there a law that says you have to go through them? And even if you *did* have to go through them, why wouldn't multiple exchanges list them instead of just one, and why wouldn't an exchange start listing them from the minute the gun fired (or before)?\"",
"title": ""
},
{
"docid": "227232",
"text": "Gold is traded on the London stock exchange (LSE) and the New York stock exchange (NYSE) under various separate asset tickers, mainly denominated in sterling and US dollars respectively. These stocks will reflect FX changes very quickly. If you sold LSE gold and foreign exchanged your sterling to dollars to buy NYSE gold you would almost certainly lose on the spreads upon selling, FX'ing and re-buying. In short, the same asset doesn't exist in multiple currencies. It may have the same International Securities Identification Number (ISIN), but it can trade with different Stock Exchange Daily Official List (SEDOL) identifiers, reflecting different currencies and/or exchanges, each carrying a different price at any one time.",
"title": ""
},
{
"docid": "351570",
"text": "number of shares is finite Yes it is I would assume that the repurchase numbers exceed the numbers of created shares Number of shares repurchased by company would never exceed in theory the total number of shares. It can become Zero, however its unlikely as it would run on its own and its not possible. In practise company generally repurchase a small percentage say 5% - 10% of the outstanding shares. The number of shares additional created is irrelevant. Its the total shares that is relevant. Edit: A company starts with say 100 shares, over the period it creates new shares [via various mechanisms, Rights issue, split, Additional shares, etc] say to the extent of 50. So now the company has total shares of 150. This lets say is held by 15 entities. The company can buy back say 15 shares in a year, and keep doing this, next year another 10 etc. However a company if it purchased all 150 of its own shares is unlikely as the Majority shareholders will not like this to happen and loose control. There are 2 different things, buying out of minority shareholders, typically different percentage of the shares are held by non-promoters and available for trade can range from 10% to 70% ... there are also listing norms. Quite a few stock-exchange need atleast 10% shares to be available for trade [held by non-promotors]. In case a company has a small number of shares held by non-promoters, it can buy back the shares and delist the company from the exchange.",
"title": ""
},
{
"docid": "474296",
"text": "\"Spend your first 50 euros on research materials. Warren Buffett got started as a boy by reading every book in the Library of Congress on investing and stock market analysis. You can research the company filings for Canadian companies at http://www.sedar.com, U.S companies at http://www.edgar.com, and European companies at https://www.gov.uk/government/organisations/companies-house. Find conflicting arguments and strategies and decide for yourself which ones are right. The Motley Fool http://www.fool.ca offers articles on good stocks to add to your portfolio and why, as well as why not. They provide a balanced judgement instead of just hype. They also sell advice through their newsletter. In Canada the Globe & Mail runs a daily column on screening stocks. Every day they present a different stock-picking strategy and the filters used to reach their end list. They then show how much that portfolio would have increased or decreased as well as talking about some of the good & bad points of the stocks in the list. It's interesting to see over time a very few stocks show up on multiple lists for different strategies. These ones in my opinion are the stocks to be investing in. While the Globe's stock picks focus on Canadian and US exchanges, you might find the strategies worthwhile. You can subscribe to the digital version at http://www.theglobeandmail.com Once you have your analytical tools ready, pick any bank or stock house that offers a free practice account. Use that account and their screening tools to try out your strategies and see if you can make money picking stocks. My personal stock-picking strategy is to look for companies with: - a long uninterrupted history of paying dividends, - that are regularly increased, - and do not exceed the net profit per share of the company - and whose share price has a long history of increasing These are called unicorn companies, because there are so very few of them. Another great read is, \"\"Do Stocks Outperform Treasury Bills?\"\" by Hendrik Bessembinder. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2900447 In this paper the author looks at the entire history of the U.S. stock universe and finds that less than 4% of stocks are responsible for 100% of the wealth creation in the U.S. stock market. He discusses his strategies for picking the winners, but it also suggests that if you don't want to do any research, you could pick pretty much any stock at random, short it, and wait. I avoid mutual funds because they are a winner only for the fellas selling them. A great description on why the mutual fund industry is skewed against the investor can be found in a book called \"\"The RRSP Secret\"\" by Greg Habstritt. \"\"Unshakeable\"\" by Tony Robbins also discusses why mutual funds are not the best way to invest in stocks. The investor puts up 100% of the money, takes 100% of the risk, and gets at best 30% of the return. Rich people don't invest like that.\"",
"title": ""
}
] |
PLAIN-1475
|
kombucha tea
|
[
{
"docid": "MED-4713",
"text": "INTRODUCTION: Kombucha \"mushroom'' tea is touted to have medicinal properties. Here, we present a case of hyperthermia, lactic acidosis, and acute renal failure within 15 hours of Kombucha tea ingestion. CASE PRESENTATION: A 22 year old male, newly diagnosed with HIV, became short of breath and febrile to 103.0F, within twelve hours of Kombucha tea ingestion. He subsequently became combative and confused, requiring sedation and intubation for airway control. Laboratories revealed a lactate of 12.9 mmol/L, and serum creatinine of 2.1 mg/dL. DISCUSSION: Kombucha tea is black tea fermented in a yeast-bacteria medium. Several case reports exist of serious, and sometimes fatal, hepatic dysfunction and lactic acidosis within close proximity to ingestion. CONCLUSION: While Kombucha tea is considered a healthy elixir, the limited evidence currently available raises considerable concern that it may pose serious health risks. Consumption of this tea should be discouraged, as it may be associated with life-threatening lactic acidosis.",
"title": "A case of Kombucha tea toxicity."
}
] |
[
{
"docid": "MED-4332",
"text": "There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce \"artificial\" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as \"scavenging\" the reactive intermediate(s).",
"title": "Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay."
},
{
"docid": "MED-1853",
"text": "PURPOSE: To measure the pH, titratable acidity, fluoride concentration and erosive potential of brewed teas. METHODS: Bag teas were purchased to represent black, green, citrus, fruity, and floral tea flavors from Tulsi, Bigelow, HyVee, Tazo, and Yogi brands and brewed (1 bag/240 ml) in boiling water for 3 minutes. The pH, titratable acidity, and fluoride concentrations were measured. Following these measurements, a representative tea from each flavor was selected for investigation of erosion potential. Six extracted human molars were randomly assigned to each tea. Teeth were painted with fingernail polish to expose a 1 x 4 mm window and then soaked in tea for a total of 25 hours with teas refreshed every 5 hours. Teeth were then sectioned using a microtome and photographed using a polarized light microscope. Lesion depths (i.e., eroded surfaces) were measured using Image Pro Plus software. Differences in physiochemical properties and lesion depths between beverages were investigated using one-way ANOVA with post-hoc Tukey's HSD test. Relationships among lesion depths and physiochemical properties were evaluated using the Pearson correlation test. RESULTS: pH, titratable acidity and fluoride concentrations differed between tea flavors (P < 0.05) and between brands (P < 0.05). Lesion depths produced by the citrus tea (83.1 +/- 10.3 microm) were greater than those produced by the fruity tea (56.5 +/- 6.1 microm); both teas produced greater depths than black (30.1 +/- 7.4 microm), floral (25.0 +/- 3.2 microm) or green (22.3 +/- 6.3 microm) teas (P < 0.05). pH (r = -0.96; P = 0.009) was inversely and titratable acidity (r = 0.97; P = 0.006) was positively associated with lesion depths.",
"title": "Erosive potentials of brewed teas."
},
{
"docid": "MED-4902",
"text": "AIMS: Experimental and clinical studies indicate that tea exerts protection against cardiovascular diseases. However, a question of much debate is whether addition of milk modifies the biological activities of tea. We studied the vascular effects of tea, with or without milk, in humans and elucidated the impact of individual milk proteins in cell culture experiments, with isolated rat aortic rings and by HPLC analysis. METHODS AND RESULTS: A total of 16 healthy female volunteers consumed either 500 mL of freshly brewed black tea, black tea with 10% skimmed milk, or boiled water as control. Flow-mediated dilation (FMD) was measured by high-resolution vascular ultrasound before and 2 h after consumption. Black tea significantly improved FMD in humans compared with water, whereas addition of milk completely blunted the effects of tea. To support these findings, similar experiments were performed in isolated rat aortic rings and endothelial cells. Tea induced vasorelaxation in rat aortic rings and increased the activity of endothelial nitric oxide synthase by phosphorylation of the enzyme in endothelial cells. All effects were completely inhibited by the addition of milk to tea. Of the various kinds of milk proteins, the caseins accounted for these inhibiting effects of milk, probably by formation of complexes with tea catechins. CONCLUSION: Milk counteracts the favourable health effects of tea on vascular function. This finding indicates the need for particular awareness in the interpretation and design of studies comprising nutritional flavonoids.",
"title": "Addition of milk prevents vascular protective effects of tea."
},
{
"docid": "MED-898",
"text": "BACKGROUND: The aims of this review are (1) to evaluate the literature on the likely impact of tea drinking on the iron status of different groups within the UK population and (2) to formulate targeted and evidence based advice on tea drinking in the context of iron nutrition in different groups of people. METHOD: A literature search identified 35 references specific to the effects of black tea on iron absorption and iron nutrition plus one recent review article. Each study was assessed in terms of methodogical quality and relevance to the tea drinking patterns of the UK population. RESULTS: There is clear evidence to show that tea drinking limits the absorption of nonhaem iron. However, there are few studies which have assessed the influence of tea drinking on indicators of iron status. There are no intervention studies and the conclusions reported in this review are based on 12 observational studies mostly from other countries. These studies have reported either significant negative correlations between tea drinking and blood indicators of iron status or more cases of anemia in tea drinkers compared with nontea drinkers. Many of the studies reviewed report additional relationships between iron status indices and other factors (both dietary and nondietary), highlighting the complexity of influences on iron absorption and iron status. CONCLUSION: From the available evidence there is no need to advise any restriction on tea drinking in healthy people with no risk of iron deficiency. In groups at risk of iron deficiency the advice should be to drink tea between meals and to wait at least 1 h after eating before drinking tea.",
"title": "Impact of tea drinking on iron status in the UK: a review."
},
{
"docid": "MED-5241",
"text": "The present meta-analysis shows no clear association between coffee consumption and the risk of hip fractures. There was a nonlinear association between tea consumption and the risk of hip fracture. Compared to no tea consumption, drinking 1-4 cups of tea daily was associated with a lower risk of hip fracture. INTRODUCTION: Prospective cohort and case-control studies have suggested that coffee and tea consumption may be associated with the risk of hip fracture; the results have, however, been inconsistent. We conducted a meta-analysis to assess the association between coffee and tea consumption and the risk of hip fracture. METHODS: We performed systematic searches using MEDLINE, EMBASE, and OVID until February 20, 2013, without limits of language or publication year. Relative risks (RRs) with 95% confidence intervals (CI) were derived using random-effects models throughout all analyses. We conducted categorical, dose-response, heterogeneity, publication bias, and subgroup analyses. RESULTS: Our study was based on 195,992 individuals with 9,958 cases of hip fractures from 14 studies, including six cohort and eight case-control studies. The pooled RRs of hip fractures for the highest vs. the lowest categories of coffee and tea consumption were 0.94 (95% CI 0.71-1.17) and 0.84 (95% CI 0.66-1.02), respectively. For the dose-response analysis, we found evidence of a nonlinear association between tea consumption and the risk of hip fracture (p(nonlinearity) < 0.01). Compared to no tea consumption, 1-4 cups of tea per day may reduce the risk of hip fracture by 28% (0.72; 95% CI 0.56-0.88 for 1-2 cups/day), 37% (0.63; 95% CI 0.32-0.94 for 2-3 cups/day), and 21% (0.79; 95% CI 0.62-0.96 for 3-4 cups/day). CONCLUSIONS: We found no significant association between coffee consumption and the risk of hip fracture. A nonlinear association emerged between tea consumption and the risk of hip fracture; individuals drinking 1-4 cups of tea per day exhibited a lower risk of hip fractures than those who drank no tea. The association between 5 daily cups of tea, or more, and hip fracture risk should be investigated.",
"title": "Coffee, tea, and the risk of hip fracture: a meta-analysis."
},
{
"docid": "MED-4330",
"text": "Scope Observational studies have evaluated the relationship between green tea intake and cancers of the ovary and endometrium, but we are not aware of the published studies on green tea intake and risk of human papillomavirus (HPV)-related cancers of the cervix, vagina, or vulva. Methods and results A critical review of the published literature on tea intake and risk of ovarian and endometrial cancers was conducted. In meta-analyses, we report inverse associations for green tea intake and risk of ovarian cancer (odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.54, 0.80), and for green tea and risk of endometrial cancer (OR = 0.78, 95% CI: 0.62, 0.98). There was no association for black tea and ovarian cancer risk (OR = 0.94, 95% CI: 0.87, 1.02) and a positive association with endometrial cancer risk (OR = 1.20, 95% CI: 1.05, 1.38). We summarized the experimental evidence supporting the antiviral and immunomodulatory activities of green tea catechins, and results from randomized clinical trials that demonstrated green tea catechin efficacy on treatment of cervical lesions and external genital warts. Conclusion Observational data support a protective role of green tea on risk of ovarian and endometrial cancers. Observational data are needed to evaluate whether green tea reduces risk of human papillomavirus-related cancers.",
"title": "Green and black tea in relation to gynecologic cancers"
},
{
"docid": "MED-4776",
"text": "Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential efficacy of green or black tea for the prevention of obesity, the underlying mechanisms remain unclear. The results of human intervention studies are mixed and the role of caffeine has not been clearly established. Finally, there is emerging evidence that high doses of tea polyphenols may have adverse side effects. Given that the results of scientific studies on dietary components, including tea polyphenols, are often translated into dietary supplements, understanding the potential toxicities of the tea polyphenols is critical to understanding their potential usefulness in preventing obesity. In this review, we will critically evaluate the evidence for the prevention of obesity by tea, discuss the relevance of proposed mechanisms in light of tea polyphenol bioavailability, and review the reports concerning the toxic effects of high doses of tea polyphenols and the implication that this has for the potential use of tea for the prevention of obesity. We hope that this review will expose areas for further study and encourage research on this important public health issue.",
"title": "Laboratory, Epidemiological, and Human Intervention Studies Show That Tea (Camellia sinensis) May Be Useful in the Prevention of Obesity"
},
{
"docid": "MED-1647",
"text": "BACKGROUND: Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA). Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. CONCLUSIONS: Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.",
"title": "Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease."
},
{
"docid": "MED-5156",
"text": "Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.",
"title": "Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas."
},
{
"docid": "MED-1645",
"text": "BACKGROUND: Tea consumption is associated with decreased cardiovascular risk. Flow-mediated dilatation (FMD) of the brachial artery is related to coronary endothelial function and it is an independent predictor of cardiovascular risk. Black tea has a beneficial effect on endothelial function; the effect, however, of green tea on brachial artery reactivity has not been defined yet. DESIGN AND METHODS: We studied 14 healthy individuals (age 30+/-3 years) with no cardiovascular risk factors except from smoking (50%) on three separate occasions on which they took: (a) 6 g of green tea, (b) 125 mg of caffeine (the amount contained in 6 g of tea), or (c) hot water. FMD of the brachial artery was measured before each intervention and 30, 90, and 120 min afterward. High-sensitivity C-reactive protein, interleukins 6 (Il-6) and 1b (Il-1b), total plasma antioxidative capacity, and total plasma oxidative status/stress were measured at baseline and at 120 min after each intervention. RESULTS: Resting and hyperemic brachial artery diameter did not change either with tea or with caffeine. FMD increased significantly with tea (by 3.69%, peak at 30 min, P<0.02), whereas it did not change significantly with caffeine (increase by 1.72%, peak at 30 min, P=NS). Neither tea nor caffeine had any effect on high-sensitivity C-reactive protein, Il-6, Il-1b, total plasma antioxidative capacity, or total plasma oxidative status/stress. CONCLUSION: Green tea consumption has an acute beneficial effect on endothelial function, assessed with FMD of the brachial artery, in healthy individuals. This may be involved in the beneficial effect of tea on cardiovascular risk.",
"title": "The acute effect of green tea consumption on endothelial function in healthy individuals."
},
{
"docid": "MED-5245",
"text": "BACKGROUND: Coffee and tea are believed to cause gastro-oesophageal reflux; however, the effects of these beverages and of their major component, caffeine, have not been quantified. The aim of this study was to evaluate gastro-oesophageal reflux induced by coffee and tea before and after a decaffeination process, and to compare it with water and water-containing caffeine. METHODS: Three-hour ambulatory pH-metry was performed on 16 healthy volunteers, who received 300 ml of (i) regular coffee, decaffeinated coffee or tap water (n = 16), (ii) normal tea, decaffeinated tea, tap water, or coffee adapted to normal tea in caffeine concentration (n = 6), and (iii) caffeine-free and caffeine-containing water (n = 8) together with a standardized breakfast. RESULTS: Regular coffee induced a significant (P < 0.05) gastro-oesophageal reflux compared with tap water and normal tea, which were not different from each other. Decaffeination of coffee significantly (P < 0.05) diminished gastro-oesophageal reflux, whereas decaffeination of tea or addition of caffeine to water had no effect. Coffee adapted to normal tea in caffeine concentration significantly (P < 0.05) increased gastro-oesophageal reflux. CONCLUSIONS: Coffee, in contrast to tea, increases gastro-oesophageal reflux, an effect that is less pronounced after decaffeination. Caffeine does not seem to be responsible for gastro-oesophageal reflux which must be attributed to other components of coffee.",
"title": "Effect of decaffeination of coffee or tea on gastro-oesophageal reflux."
},
{
"docid": "MED-1840",
"text": "OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.",
"title": "Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P."
},
{
"docid": "MED-5257",
"text": "BACKGROUND: The present analysis was conducted in response to inconsistent epidemiologic studies on the relation between consumption of tea and cardiovascular diseases. OBJECTIVE: We undertook a literature review of the consistency and strength of the associations between tea and cardiovascular diseases on the basis of published observational studies and meta-analyses addressing tea or tea flavonoids and cardiovascular disease risk. DESIGN: We performed a search in 3 databases for meta-analyses and compared them with studies they subsumed. We performed an additional search for subsequent studies to determine whether the conclusions were consistent. RESULTS: Many epidemiologic studies have been conducted and summarized in 5 meta-analyses on either tea consumption or flavonoid consumption and cardiovascular disease or the subset of stroke. Heterogeneity of effect was seen when the outcome included all cardiovascular diseases. In the case of stroke, a consistent, dose-response association with tea consumption on both incidence and mortality was noted with RRs of 0.80 (95% CI: 0.65, 0.98) for flavonoids and 0.79 (95% CI: 0.73, 0.85) for tea when high and low intakes were compared or the addition of 3 cups/d was estimated. CONCLUSION: Thus, the strength of this evidence supports the hypothesis that tea consumption might lower the risk of stroke.",
"title": "Tea consumption and cardiovascular disease risk."
},
{
"docid": "MED-1635",
"text": "Background Tea consumption is associated with a lower risk of cardiovascular disease including stroke. Direct effects of tea components on the vasculature, particularly the endothelium, may partly explain this association. Objective We performed a meta-analysis of controlled human intervention studies on the effect of tea on flow-mediated dilation (FMD) of the brachial artery, a measurement of endothelial function, which is suggested to be associated with cardiovascular risk. Methods Human intervention studies were identified by systematic search of the databases Medline, Embase, Chemical s and Biosis through March 2009 and by hand-searching related articles. Studies were selected based on predefined criteria: intervention with tea as the sole experimental variable, placebo-controlled design, and no missing data on FMD outcome or its variability. A random effects model was used to calculate the pooled overall effect on FMD due to the intake of tea. The impact of various subject and treatment characteristics was investigated in the presence of heterogeneity. Results In total, 9 studies from different research groups were included with 15 relevant study arms. The overall absolute increase in FMD of tea vs. placebo was 2.6% of the arterial diameter (95% CI: 1.8-3.3%; P-value <0.001) for a median daily dose of 500 mL of tea (2–3 cups). This is a relative increase of approximately 40% compared to the average FMD of 6.3% measured under placebo or baseline conditions. There was significant heterogeneity between studies (P-value <0.001) that might partly be explained by the cuff position either distal or proximal to the area of FMD measurement. No indication for publication bias was found. Conclusion Moderate consumption of tea substantially enhances endothelial-dependent vasodilation. This may provide a mechanistic explanation for the reduced risk of cardiovascular events and stroke observed among tea drinkers.",
"title": "Tea Consumption Enhances Endothelial-Dependent Vasodilation; a Meta-Analysis"
},
{
"docid": "MED-5046",
"text": "Epidemiological evidence suggests a role for tea catechins in reduction of chronic disease risk. However, stability of catechins under digestive conditions is poorly understood. The objective of this study was to characterize the effect of common food additives on digestive recovery of tea catechins. Green tea water extracts were formulated in beverages providing 4.5, 18, 23, and 3.5 mg per 100 mL epicatechin (EC), epigallocatechin (EGC), epigallocatechin-gallate (EGCG), and epicatechin-gallate (ECG), respectively. Common commercial beverage additives; citric acid (CA), BHT, EDTA, ascorbic acid (AA), milk (bovine, soy, and rice), and citrus juice (orange, grapefruit, lemon, and lime) were formulated into finished tea beverages at incremental dosages. Samples were then subjected to in vitro digestion simulating gastric and small intestinal conditions with pre- and post-digestion catechin profiles assessed by HPLC. Catechin stability in green tea was poor with <20% total catechins remaining post-digestion. EGC and EGCG were most sensitive with less, not double equals 10% recovery. Teas formulated with 50% bovine, soy, and rice milk increased total catechin recovery significantly to 52, 55, and 69% respectively. Including 30 mg AA in 250 mL of tea beverage significantly (p<0.05) increased catechin recovery of EGC, EGCG, EC, and ECG to 74, 54, 82, and 45% respectively. Juice preparation resulted in the highest recovery of any formulation for EGC (81-98%), EGCG (56-76%), EC (86-95%), and ECG (30-55%). These data provide evidence that tea consumption practices and formulation factors likely impact catechin digestive recovery and may result in diverse physiological profiles.",
"title": "Common tea formulations modulate in vitro digestive recovery of green tea catechins."
},
{
"docid": "MED-897",
"text": "The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.",
"title": "Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages."
},
{
"docid": "MED-1637",
"text": "Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.",
"title": "Black tea increases coronary flow velocity reserve in healthy male subjects."
},
{
"docid": "MED-1867",
"text": "OBJECTIVES: There is increasing evidence that intake of sour tea (Hibiscus sabdariffa) has hypoglycemic and hypolipidemic effects and may benefit patients suffering from metabolic disorders such as diabetes. The objective of the present study was to investigate the hypolipidemic effects of sour tea in patients with diabetes and compare them with those of black tea. DESIGN: In this sequential randomized controlled clinical trial, 60 patients with diabetes were recruited and randomly assigned into two groups: sour tea (ST) and black tea (BT). They were instructed to consume sour tea or black tea two times a day for 1 month. OUTCOME MEASURES: Fasting blood samples were taken at the beginning and at the end of the study for evaluation of lipids, lipoproteins, and apoproteins. RESULTS: Fifty-three (53) patients concluded the study. In the ST group, mean of high-density lipoprotein-cholesterol (HDLc) increased significantly (p = 0.002) at the end of the study, whereas changes in apolipoprotein-A1, and lipoprotein (a) were not significant. Also, a significant decrease in the mean of total cholesterol, low density lipoprotein-cholesterol, triglycerides, and Apo-B100 were seen in this group. In the BT group, only HDLc showed significant change (p = 0.002) at the end of the study and changes in the other measures were not statistically significant. CONCLUSIONS: The results of the present study showed that ST has a significant effect on blood lipid profile in patients with diabetes.",
"title": "Effects of sour tea (Hibiscus sabdariffa) on lipid profile and lipoproteins in patients with type II diabetes."
},
{
"docid": "MED-4365",
"text": "A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Adverse effects of concentrated green tea extracts."
},
{
"docid": "MED-5047",
"text": "Our objective was to examine whether habitual green tea consumption is associated with blood glucose levels and other biomarkers of glucose metabolism. We conducted a cross-sectional study of 35 male volunteers, 23–63 years old and residing in Shizuoka Prefecture in Japan. Biochemical data were measured and we conducted a questionnaire survey on health, lifestyle, and nutrition, as well as frequency of consumption and concentrations (1%, 2%, and 3%) of green tea. Men who consumed a 3% concentration of green tea showed lower mean values of fasting blood glucose and fructosamine than those who consumed a 1% concentration. Fasting blood glucose levels were found to be significantly associated with green tea concentration (β = −0.14, p = 0.03). However, green tea consumption frequency showed no significant differences in mean levels of blood glucose, fructosamine and hemoglobin A1c. In conclusion, our findings suggest that the consumption of green tea at a high concentration has the potential to reduce blood glucose levels.",
"title": "The Association between Concentrations of Green Tea and Blood Glucose Levels"
},
{
"docid": "MED-1847",
"text": "The in vitro speciation of aluminium (Al) in black tea infusion (pH 4.8) was assessed using 3000, 10,000 and 30,000 Da cut-off ultrafilters, and the effect of adding human gastric juice (pH 2.3) and then raising the pH to 6.5 were also studied. 78% Al in the tea infusion passed through the 3000-Da ultrafilter; this percentage increased to more than 90% with the addition of gastric juice at pH 2.3, but then reduced to approximately 5% when the incubate was adjusted to pH 6.5. The breakdown of tea-derived polyphenols to low molecular weight phenols in vivo was measured using high-resolution 1H nuclear magnetic resonance spectroscopic analysis of ileostomy effluent, but there was no evidence of low molecular weight breakdown products from the polyphenols of ingested tea in this effluent. These results suggest that only a small proportion of Al in tea is potentially available for absorption throughout the small bowel. It may be misleading to estimate systemic Al absorption from tea drinking simply from total urinary aluminium excretion as has been done previously.",
"title": "Gastro-intestinal availability of aluminium from tea."
},
{
"docid": "MED-4777",
"text": "The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer.",
"title": "Green tea: nature's defense against malignancies."
},
{
"docid": "MED-4779",
"text": "ABSTRACT BACKGROUND Tea consumption has been extensively studied in relation to various diseases, several epidemiologic studies have been performed to investigate the association of tea consumption with type 2 diabetes; however, the results of these studies were not entirely consistent. OBJECTIVE To conduct a meta-analysis of studies that assessed the association of tea consumption and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We performed a systematic literature search through November 2008 in PUBMED, MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. The search was limited to English-language studies. Studies were excluded if they were type 1 diabetes, animal studies. Nine cohort studies were identified by two authors, and summary relative risks (RRs) were calculated using a random-effects model. RESULTS We identified nine cohort studies, including 324,141 participants and 11,400 incident cases of type 2 diabetes with follow-up ranging from 5 to 18 years. The summary adjusted RR did not show that tea consumption was associated with a reduced type 2 diabetes risk (RR, 0.96; 95% confidence interval (CI), 0.92–1.01). Evidence from the results of our stratified analyses revealed that tea consumption ≥4 cups per day (RR, 0.8; 95% CI, 0.7–0.93) might play a role in the prevention of type 2 diabetes. However, no statistically significant association was observed for sex and the follow-up durations stratified between tea consumption and type 2 diabetes. CONCLUSIONS This meta-analysis indicates that tea consumption ≥4 cups per day may lower the risk of type 2 diabetes.",
"title": "Tea Consumption and Risk of Type 2 Diabetes: A Meta-Analysis of Cohort Studies"
},
{
"docid": "MED-5049",
"text": "OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.",
"title": "Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli..."
},
{
"docid": "MED-4864",
"text": "To elucidate the health benefit of herbal teas on the cytotoxicity induced by H(2)O(2) in V79-4 cells, herbal extracts and its flavonoids were tested using lactate dehydrogenase release and determining intracellular reactive oxygen species generation and antioxidant activity with superoxide radical scavenging assay. Significant decrease in cell viability was observed on V79-4 cells treated with H(2)O(2) (1 mM), while herbal extracts and its flavonoids including catechin and epigallocatechin gallate prevented the LDH release from H(2)O(2) cytotoxicity. Total catechin contents of green tea (65.6 mg/g of dry matter) were significantly higher than other herbal teas (35.8 to 1.2 mg/g of DM). The relative concentration of the 4 major tea catechins ranked EGCG > EGC > EC > C. Green tea exhibited the lowest IC(50) values (2 g fresh herb/100 mL) of superoxide radical scavenging activity among the tested herbal tea, which indicates powerful antioxidant activity in O(2)(*-) radicals scavenging, followed by black tea, dandelion, hawthorn, rose hip, chamomile.",
"title": "Comparative flavonoids contents of selected herbs and associations of their radical scavenging activity with antiproliferative actions in V79-4 cells."
},
{
"docid": "MED-5052",
"text": "OBJECTIVE: Habitual green tea consumption has long been associated with health benefits including chemoprevention and cardiovascular protection. This non-systematic literature review presents the clinical evidence to date. METHOD: A literature review of peer-reviewed articles on observational and interventional studies was conducted to include green tea, its extract or its purified polyphenol (-)-epigallocatechin-3-gallate (EGCG). Electronic databases searched included PubMed (1966-2009) and the Cochrane Library (Issue 4, 2008). RESULTS: Observational studies are inconclusive on the benefits of habitual consumption of green tea in the prevention of most cancers. However, there are trends towards prevention in breast and prostate cancers. Interventional studies have demonstrated reduction in relapses following surgical resection in colorectal adenomas and increased survival rates in epithelial ovarian cancer. Observational studies indicate that green tea may provide protection against hypertension and reduce the risk for stroke, and interventional studies are providing biochemical and physiological evidence. CONCLUSION: Although the overall clinical evidence is inconclusive, habitual green tea consumption may be providing some level of chemoprevention in prostate and breast cancer. Green tea may also attenuate the risk factors association with the development of atherosclerosis thus reducing the incidence of cardiovascular events and stoke.",
"title": "Can green tea do that? A literature review of the clinical evidence."
},
{
"docid": "MED-4331",
"text": "There is a belief that caffeinated drinks, such as tea, may adversely affect hydration. This was investigated in a randomised controlled trial. Healthy resting males (n 21) were recruited from the general population. Following 24 h of abstention from caffeine, alcohol and vigorous physical activity, including a 10 h overnight fast, all men underwent four separate test days in a counter-balanced order with a 5 d washout in between. The test beverages, provided at regular intervals, were 4 × 240 ml black (i.e. regular) tea and 6 × 240 ml black tea, providing 168 or 252 mg of caffeine. The controls were identical amounts of boiled water. The tea was prepared in a standardised way from tea bags and included 20 ml of semi-skimmed milk. All food taken during the 12 h intervention period was controlled, and subjects remained at rest. No other beverages were offered. Blood was sampled at 0, 1, 2, 4, 8 and 12 h, and a 24 h urine sample was collected. Outcome variables were whole blood cell count, Na, K, bicarbonate, total protein, urea, creatinine and osmolality for blood; and total volume, colour, Na, K, creatinine and osmolality for urine. Although data for all twenty-one participants were included in the analysis (mean age 36 years and mean BMI 25·8 kg/m(2)), nineteen men completed all conditions. Statistical analysis, using a factorial ANOVA approach within PROC MIXED, revealed no significant differences between tea and water for any of the mean blood or urine measurements. It was concluded that black tea, in the amounts studied, offered similar hydrating properties to water.",
"title": "Black tea is not significantly different from water in the maintenance of normal hydration in human subjects: results from a randomised controlled ..."
},
{
"docid": "MED-1845",
"text": "12 healthy volunteers on a controlled aluminium (Al) diet each consumed a tea infusion (500 ml/70 kg body weight), with either milk or lemon juice as additives, or mineral water, following a three-way crossover design. The concentrations of Al were determined in the diet, mineral water and tea infusions, and in plasma samples collected before and up to 24 hr after consumption of tea or water, using graphite-furnace atomic absorption spectrophotometry or inductively coupled plasma emission spectrometry. Consumption of up to 1.60 mg Al from tea with milk or lemon juice did not increase plasma Al levels compared with consumption of approximately 0.001 mg Al from mineral water. The results suggest that, in the short-term, drinking tea does not contribute significantly to the total body burden of Al.",
"title": "Plasma levels of aluminium after tea ingestion in healthy volunteers."
},
{
"docid": "MED-4775",
"text": "PURPOSE: To investigate the association between green tea consumption and mortality from all causes, cancer, and cardiovascular disease (CVD) among elderly people. METHODS: In a population-based, prospective cohort study, a total of 14,001 elderly residents (aged 65-84 years), randomly chosen from all 74 municipalities in Shizuoka, Japan, completed questionnaires that included items about frequency of green tea consumption. They were followed for up to 6 years, from December 1999 to March 2006. Consequently, 12,251 subjects were analyzed to estimate the hazard ratios (HRs) for all-cause mortality, cancer, and CVD. RESULTS: Among 64,002 person-years, 1,224 deaths were identified (follow-up rate, 71.6%). The multivariate HRs and 95% confidence intervals (CIs) for CVD mortality compared those who consumed seven or more cups per day with those who consumed less than one cup per day, were 0.24 (0.14-0.40), 0.30 (0.15-0.61), and 0.18 (0.08-0.40) for total participants, men, and women, respectively. Although green tea consumption was not inversely associated with cancer mortality, green tea consumption and colorectal cancer mortality were inversely associated with a moderate dose-response relationship. CONCLUSIONS: Green tea consumption is associated with reduced mortality from all causes and CVD. This study also suggests that green tea could have protective effects against colorectal cancer.",
"title": "Green tea consumption and mortality among Japanese elderly people: the prospective Shizuoka elderly cohort."
},
{
"docid": "MED-5253",
"text": "Background Fractures are important causes of healthy damage and economic loss nowadays. The conclusions of observational studies on tea consumption and fracture risk are still inconsistent. The objective of this meta-analysis is to determine the effect of tea drinking on the risk of fractures. Methods A comprehensive literature search was conducted in PubMed, Embase and reference lists of the relevant articles. Observational studies that reported an estimate of the association between tea drinking and incidence of fractures were included. A meta-analysis was conducted by the STATA software. Results A total of 9 studies involving 147,950 individuals that examined the association between tea consumption and risk of fractures were included in this meta-analysis. The odds risks (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. The pooled OR of 9 observational studies for the tea consumption on risk of fracture was 0.89 (95% CI, 0.78-1.04). In the subgroup analyses, no significant association was detected in neither cohort studies (n = 3; OR, 0.97; 95% CI, 0.89-1.06) nor case–control studies (n = 6; OR, 0.91; 95% CI, 0.70-1.19), respectively. No significant association was detected in the dose–response meta-analysis. Conclusions Tea consumption might not be associated with the risk of fractures. The following large-sample and well-designed studies are required to confirm the existing conclusions. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5309904231178427.",
"title": "Tea consumption didn’t modify the risk of fracture: a dose–response meta-analysis of observational studies"
}
] |
93466
|
Lewis Hamilton has multiple F1 titles.
|
[
{
"docid": "2014_Formula_One_season",
"text": "The 2014 Formula One season was the 68th season of FIA Formula One motor racing . It featured the 2014 Formula One World Championship , a motor racing championship for Formula One cars , recognised by the sport 's governing body , the Fédération Internationale de l'Automobile ( FIA ) , as the highest class of competition for open-wheel racing cars . The season started in Australia on 16 March and concluded in Abu Dhabi on 23 November . In the nineteen Grands Prix of the season , a total of eleven teams and twenty-four drivers competed for the World Drivers ' and World Constructors ' championships . It was the first Formula One season since to see an accident with ultimately fatal consequences as Jules Bianchi succumbed to the injuries he sustained during the 2014 Japanese Grand Prix . He died on 17 July 2015 after spending nine months in a coma following the accident . In 2014 , the championship saw the introduction of a revised engine formula , in which the 2.4 litre V8 engine configuration -- previously used between 2006 and 2013 -- was replaced with a new formula specifying a 1.6 litre turbocharged V6 engine that incorporated an energy recovery system into its build . The 2014 calendar featured substantial revisions from the 2013 season ; the Russian Grand Prix ( held the first time in a century ) was held at the Sochi Autodrom , and the Austrian Grand Prix was revived with the race held at the Red Bull Ring in Spielberg . The Indian Grand Prix was put on hiatus , whilst the Korean Grand Prix was removed from the schedule entirely . Sebastian Vettel started the season as defending World Drivers ' Champion having secured his fourth consecutive Drivers ' title the previous season at the 2013 Indian Grand Prix . His team , Infiniti Red Bull Racing , also started the season as defending World Constructors ' Champion having secured its fourth consecutive Constructors ' title last season at the same Grand Prix in which its lead driver secured his title . Mercedes driver Lewis Hamilton won his second World Drivers ' Championship with 384 points and 11 victories having previously won his first Drivers ' title in 2008 , ahead of his teammate , Nico Rosberg with 317 points and 5 victories . Rosberg also won the inaugural FIA Pole Trophy having amassed a total of 11 pole positions over the course of the season . Mercedes secured their first World Constructors ' Championship in Russia , and finished the season with 701 points , 296 points ahead of Red Bull Racing . The season also saw the first three wins of Daniel Ricciardo , who finished third in the championship for Red Bull Racing .",
"title": ""
},
{
"docid": "Lewis_Hamilton",
"text": "Lewis Carl Davidson Hamilton , MBE ( born 7 January 1985 ) is a British Formula One racing driver from England , currently racing for the Mercedes AMG Petronas team . A three-time Formula One World Champion , he is regarded by fellow and former drivers as one of the greatest Formula One drivers in the history of the sport . He won his first title with McLaren in 2008 before moving to Mercedes , where he won back-to-back titles in 2014 and 2015 . In December 1995 , at the age of ten , he approached McLaren team principal Ron Dennis at the Autosport Awards ceremony and told him , `` I want to race for you one day ... I want to race for McLaren . '' Less than three years later McLaren and Mercedes-Benz signed him to their Young Driver Support Programme . After winning the British Formula Renault , Formula Three Euroseries , and GP2 championships on his way up the racing career ladder , he drove for McLaren in 2007 , making his Formula One debut 12 years after his initial encounter with Dennis . Hamilton 's contract for the McLaren driver development program made him the youngest ever driver to secure a contract which later resulted in a Formula One drive . Coming from a mixed background , with a black father and white mother , Hamilton is the first black driver to race in Formula One . Hamilton commented on this , saying `` The way I see it , my colour is an advantage in that it 's something people talk about '' , `` Being the first black man does n't matter much to me personally , but for the sport itself it probably means quite a lot . '' In his first season in Formula One , Hamilton set numerous records while finishing second in the 2007 Formula One Championship , just one point behind Kimi Räikkönen . He won the World Championship the following season in dramatic fashion , becoming the then-youngest Formula One World Champion in history before Sebastian Vettel broke the record two years later . Following his second world title in 2014 , he was named BBC Sports Personality of the Year . In 2015 , he became the first British driver in history to win consecutive F1 titles , and the second British driver to win three titles after Jackie Stewart . He also became the first English driver to reach that milestone . He is the first driver in the history of F1 to have made the podium after starting 20th place or lower at least 3 times . He is the only driver in the history of the sport to have won at least one race in each season he has competed to date , with McLaren from 2007 until 2012 , and with Mercedes since 2013 . He has more race victories than any other British driver in the history of Formula One . His Grand Prix victories is the second highest of all-time having surpassed Alain Prost 's total of 51 at the 2016 Brazilian Grand Prix , behind only Michael Schumacher at 91 . Hamilton also holds the record for most wins in the season without winning the World Championship , after winning 10 times in the 2016 season where he finished runner-up to teammate Nico Rosberg .",
"title": ""
},
{
"docid": "2015_Formula_One_season",
"text": "The 2015 Formula One season was the 69th season of FIA Formula One motor racing . It featured the 2015 Formula One World Championship , a motor racing championship for Formula One cars , recognised by the sport 's governing body , the Fédération Internationale de l'Automobile ( FIA ) , as the highest class of competition for open-wheel racing cars . Twenty-two drivers representing ten teams contested nineteen Grands Prix , starting in Australia on 15 March and ending in Abu Dhabi on 29 November as they competed for the World Drivers ' and World Constructors ' championships . Lewis Hamilton was the defending Drivers ' Champion after securing his second title at the 2014 Abu Dhabi Grand Prix . His team , Mercedes , began the season as the defending Constructors ' Champion , having clinched its first championship title at the 2014 Russian Grand Prix . The calendar featured two significant changes from the 2014 season . The first was the return of the Mexican Grand Prix , held for the first time since . The other change was the cancellation of the German Grand Prix after a venue could not be agreed upon , leaving the nation without a World Championship event for the first time in fifty-five years . Hamilton secured his third Drivers ' Championship with three races left in the season . The runner-up was his teammate Nico Rosberg , 59 points behind , with Ferrari 's Sebastian Vettel third , another 44 points adrift . Mercedes clinched the 2015 Constructors ' title at the Russian Grand Prix , ahead of Ferrari and Williams , and ended the season with a record 703 points . Hamilton also won the FIA Pole Trophy with a total of 11 pole positions in the season and the DHL Fastest Lap Award . Ferrari won the inaugural DHL Fastest Pit Stop Award .",
"title": ""
}
] |
[
{
"docid": "F1_Race_Stars",
"text": "F1 Race Stars is a video game developed by Codemasters , released in November 2012 . It is a kart racing game loosely based on the 2012 Formula One season , with circuits redesigned to feature loops , jumps and short-cuts . It is a spin-off from the traditional Formula One video games , and is the first kart-racing game developed by Codemasters . The player is able to choose cartoonish versions of Formula One racing drivers , such as Sebastian Vettel , Lewis Hamilton , Kimi Räikkönen , Nico Rosberg , Mark Webber , Michael Schumacher and Fernando Alonso . It was announced on 13 July 2012 at the San Diego Comic-Con International . Codemasters have described the game as being designed to emphasise entertainment rather than simulation . On 6 December 2012 it was confirmed to be ported to Wii U under the title F1 Race Stars : Powered Up Edition , where it was released on 16 January 2014 .",
"title": ""
},
{
"docid": "Tooned",
"text": "Tooned is an animated cartoon by McLaren starring Jenson Button , Fernando Alonso and comedian Alexander Armstrong ; and formerly , Lewis Hamilton , Kevin Magnussen and Sergio Pérez . It was aired on Sky Sports F1 before the start of each Formula One race . The first season , which starred former McLaren driver Lewis Hamilton aired from the 2012 British Grand Prix onwards . The second season aired from the 2013 British Grand Prix onwards . All episodes can be watched on McLaren 's YouTube channel and the Sky Sports F1 website any time after the premiere . The episodes are a little more than 3 minutes long . On 16 May 2014 it was announced on McLaren 's YouTube channel that a season 3 was in progress . It was announced when Jenson Button was shown a picture of his 2014 team mate Kevin Magnussen 's character on Tooned and also added that ` the production of Season 3 was going well ' . It was announced by McLaren on 19 October 2016 that Tooned would be making a return , featuring Fernando Alonso and Stoffel Vandoorne ( and possibly Button ) .",
"title": ""
},
{
"docid": "Mercedes_F1_W07_Hybrid",
"text": "The Mercedes F1 W07 Hybrid was a highly successful Mercedes-Benz Formula One racing car designed and developed under the direction of Aldo Costa , Geoff Willis and Paddy Lowe , to compete in the 2016 Formula One season . The cars were driven by , and World Drivers ' Champion Lewis Hamilton , and Nico Rosberg , both of whom remained with the team for a fourth and a seventh season , respectively . In addition , it was the last Formula One car driven by Rosberg , following his announcement on his retirement from the sport after clinching his first World Drivers ' Championship title . The chassis was named `` F1 W07 Hybrid '' to represent the seventh Formula One car that Mercedes had constructed since , while the hybrid was marked to recognize the utilization of fully integrated hybrid power units . The car made its competitive debut at the 2016 Australian Grand Prix , the opening round of the 2016 season . After participating 20 rounds of grand prix racing , the car made its final competition appearance at the season finale race -- 2016 Abu Dhabi Grand Prix , before retirement . With a total of 19 wins , 20 pole positions , 33 podium finishes and a total of 765 constructors championship points in a single season , the F1 W07 Hybrid is statistically the most dominant Formula One car in the history of the sport .",
"title": ""
},
{
"docid": "Mercedes_F1_W04",
"text": "The Mercedes F1 W04 ( originally known as the Mercedes AMG W04 ) is a Formula One racing car designed and built by the Mercedes team for use in the 2013 season . It was driven by 2008 World Champion Lewis Hamilton , who joined the team after Michael Schumacher 's retirement , and Nico Rosberg , who remained with the team for a fourth season . This was the first Mercedes car to feature sponsorship from BlackBerry .",
"title": ""
},
{
"docid": "CRG_(kart_manufacturer)",
"text": "CRG is a kart chassis manufacturer of recent years , with world champions from 2001-2003 . Famous alumni include Alex Zanardi and F1 racer Vitantonio Liuzzi and F1 GP Winner Max Verstappen . They were founded in the late 1970s by three Italian racers ( Carlo Vanaria , Roberto Vanaria and Giancarlo Tinini ) , and were originally known as Kali Karts . In the beginning the company was a laughing stock , with Zanardi being told by his original team DAP that if he did n't stop complaining they would `` send him to Kali '' . By the mid 1980s Kali had recovered from its inauspicious beginnings and was winning World Championships with drivers like Mike Wilson . The name change to CRG took place gradually in the early 1990s and ushered in an era of more World Championships from Danilo Rossi and Alessandro Manetti . CRG has also a straight relation with Dino Chiesa ( Chiesa Corse ) . The Italian chassis mechanic ( known as the best in the world of karting ) assisted the multiple world champions , Alessandro Piccini and Giorgio Pantano ; as well as many other drivers through CRG . CRG started to build engines in the mid-1990s but they were never widely used outside of the factory teams . In 2001 they were replaced by the Maxter brand which produces 100 cc and 125 cc gearbox engines . They also make the Maxter engine range and the Maranello , Vanspeed , and Zanardi chassis ranges . They have also recently signed a deal to produce the new Lewis Hamilton kart .",
"title": ""
},
{
"docid": "McLaren_MP4-27",
"text": "The McLaren MP4-27 was a Formula One racing car designed by Vodafone McLaren Mercedes for the 2012 Formula One season . The car was driven by former World Champions Jenson Button and Lewis Hamilton . It was launched on 1 February at the McLaren team base in Woking , Surrey , ahead of the first winter test sessions at Jerez de la Frontera . This was the last McLaren car that Lewis Hamilton drove for the team , as he moved to the Mercedes AMG Petronas F1 Team in 2013 . , it is also the last car made by McLaren to achieve a race victory . The car achieved 7 wins , 8 poles and third place in the Constructors ' Championship in 2012 .",
"title": ""
},
{
"docid": "Mercedes_F1_W05_Hybrid",
"text": "The Mercedes F1 W05 Hybrid , originally known as the Mercedes F1 W05 , was a highly successful Mercedes-Benz Formula One racing car designed and developed under the direction of Aldo Costa , Geoff Willis and Paddy Lowe , to compete in the 2014 Formula One season . The cars were driven by World Drivers ' Champion Lewis Hamilton and Nico Rosberg , both of whom remained with the team for a second and fifth season , respectively . The F1 W05 was designed to use Mercedes 's new 1.6-litre V6 turbocharged engine , the PU106A Hybrid . The chassis was named `` F1 W05 Hybrid '' to represent the fifth Formula One car that Mercedes had constructed since , while the hybrid was marked to recognize the utilization of fully integrated hybrid power units . The car made its competitive debut at the 2014 Australian Grand Prix , the opening round of the 2014 season . After participating in 18 rounds of Grand Prix racing , the car made its final competition appearance at the season finale race -- the 2014 Abu Dhabi Grand Prix , before retirement .",
"title": ""
},
{
"docid": "Direxiv",
"text": "Direxiv was a company with motorsport links to the GP2 Series , a series which is closely linked to Formula One and future drivers in F1 are likely to have raced in GP2 . Direxiv had submitted an entry to run a Formula 1 team in 2008 onwards , although they faced tough competition from other companies as Carlin Motorsport , Eddie Jordan , Paul Stoddart and current GP2 team Racing Engineering . Direxiv lost out on the chance to gain entry to the 2008 season when the FIA chose to give the entries to the current 11 teams and David Richards ' Prodrive taking the final spot . The team was also involved in Super GT and Formula Nippon , and sponsor McLaren in F1 as well as former McLaren and former WilliamsF1 driver Alexander Wurz . Direxiv were linked with creating a `` McLaren B Team '' which , in could have given the then-GP2 racer Lewis Hamilton ( who has now been promoted to the McLaren team itself ) and possibly either Pedro de la Rosa or Gary Paffett a race drive in F1 . Former F1 driver Jean Alesi was also working with the Direxiv squad in their attempts . However , after the 2006 French GP , Dave Richards who had his entry to the 2008 F1 season accepted , announced that he was looking to bring his Prodrive team into F1 as the McLaren B Team . This brought an end to the dream of a Direxiv McLaren B Team , but due to a change in FIA rules , it seems that the Prodrive Mclaren B team will now not happen . Therefore , even if the Direxiv entry had been accepted , and Direxiv were to still exist , their F1 dream would not have materialised . In August 2006 , Direxiv announced that they will pull out of the Super GT due to the loss of their primary backer , Akiyama Holdings . The Suzuka 1000km was their last race in the series .",
"title": ""
},
{
"docid": "2008_Race_of_Champions",
"text": "The 2008 Race of Champions was the 21st running of the event , and took place on December 14 , 2008 at Wembley Stadium , London . Two special races were due to take place during the event , the first of which , with Olympic gold medallist Chris Hoy cycling against the reigning Formula One World Champion Lewis Hamilton , who was due to be driving a Mercedes road car . However , due to the slippery track at Wembley , Hoy could not take part on the bicycle . Hamilton did demonstrate his championship-winning Vodafone McLaren Mercedes Formula One car at the event , his first major British public appearance since winning the F1 title . There was also a celebrity race , with eight celebrities taking part in Fiat 500 Abarth Assetto Corses . These celebrities were Hoy , boxers Frank Bruno , David Haye , Amir Khan and Enzo Maccarinelli , chef James Martin , footballer Bacary Sagna and singer Shayne Ward .",
"title": ""
},
{
"docid": "Adrian_Sutil",
"text": "Adrian Sutil ( -LSB- ˈadɾjan zuˈtil -RSB- ; born 11 January 1983 ) is a German racing driver who most recently drove for Sauber in Formula One for the 2014 season . He was the reserve driver for the Williams team in . Sutil started karting at the age of 14 and moved into single seater racing in 2002 in the Swiss Formula Ford series where he won the title . He moved up into Formula Masters Austria and started 1 race before stepping into Formula BMW ADAC in 2003 . Sutil then raced in the Formula 3 Euroseries where he was the runner-up to Lewis Hamilton in 2005 . He went to Japan in 2006 to race in the All-Japan Formula Three Championship and also finished 3rd in the Macau Grand Prix . Having been involved in the Midland F1 test team , Sutil was promoted to a race seat for the new Spyker F1 team in 2007 . Sutil continued to race with the team under their new guise Force India in 2008 where he remained until 2011 . Having made his return to the sport in 2013 again with Force India , he competed in the 2014 season with Sauber .",
"title": ""
},
{
"docid": "McLaren_young_driver_programme",
"text": "The McLaren young driver programme , formerly known as McLaren Driver Development Programme and McLaren Mercedes Young Driver Support Programme , is a program created by McLaren . It has been designed to offer year-by-year guidance , assistance and endorsement to help promising young racers -- regardless of nationality -- to climb the motorsport ladder . The highlight of the programme is Lewis Hamilton , who is the part of the programme since his karting days and graduated to the F1 team and subsequently winning the driver championship in 2008 .",
"title": ""
},
{
"docid": "Mark_Hughes_(journalist)",
"text": "Mark P. Hughes is the Grand Prix editor for Motor Sport magazine , a position he has held since the start of 2014 . He is also an F1 correspondent for The Sunday Times and technical editor for the renowned motor racing annual , Autocourse . Hughes also provides analysis for British television coverage of Formula One , currently working in the role of technical analyst for Sky Sports following his previous role as commentary box producer for the BBC 's coverage , in case commentators David Coulthard and Martin Brundle miss anything on track . He worked in a similar role for ITV when they had the rights to F1 , assisting Brundle and James Allen . He has also written articles that have been published in The Daily Telegraph . When Hughes worked for Autosport his Formula One race reports were widely acclaimed for their combination of cockpit insight , technical understanding and vivid prose ; veteran motorsport author Eoin Young has described Hughes as `` a talent with an amazing ability '' , and has compared him to Ernest Hemingway . Hughes has had several F1-related books published . Speed Addicts ( published by Harper Collins ) was awarded ` Best Illustrated Book ' at the 2006 British Sports Book Awards . Mark Hughes is also the author of the 2008 book Lewis Hamilton , The Full Story . His co-authoured book with racing driver Tommy Byrne , Crashed And Byrned , won the 2008 William Hill Irish Sports Book of the Year . His brother is the racing driver Warren Hughes , and he is married .",
"title": ""
},
{
"docid": "Mercedes-AMG_Project_One",
"text": "The Mercedes-AMG Project One ( stylized as ONE ) is an upcoming production sports car that will be powered by Formula 1 technology . It will be launched at the 2017 Frankfurt Motor Show . As it does have a F1 powertrain , it will become the first to do so . Although looking like a F1-inspired sports car with a strong character , Mercedes-AMG boss , Tobias Moers , says the car 's main character is to be a sports car with full comfort on the road . The Project One 's is currently being evaluated by its performance , durability , and ability in Mercedes-Benz 's proving grounds and on racing circuits . Tobias Moers also says when `` the time is right '' , Mercedes-AMG Petronas F1 driver Lewis Hamilton will be testing the prototypes . In April 16 , 2017 , the Project One became sold out for the United States . The Project One will be competing alongside the Aston Martin Valkyrie , and unnamed sports cars by Audi and BMW .",
"title": ""
},
{
"docid": "Mercedes_AMG_F1_W08_EQ_Power+",
"text": "The Mercedes AMG F1 W08 EQ Power + is a Mercedes-Benz Formula One racing car designed and developed under the direction of Aldo Costa , Geoff Willis and James Allison , to compete during the 2017 Formula One season . The car is driven by , and World Drivers ' Champion Lewis Hamilton , who remained with the team for a fifth season , and Valtteri Bottas , who joined the team after World Champion Nico Rosberg 's retirement from the sport . The chassis was originally named the `` Mercedes F1 W08 '' to represent the eighth Formula One car that Mercedes had constructed since . The `` EQ Power + '' was added to increase exposure of Mercedes ' electric road car models , whilst AMG was included to reflect the relationship between Mercedes-AMG and Mercedes-Benz . The car made its competitive début at the , the opening round of the 2017 season .",
"title": ""
},
{
"docid": "Arden_International",
"text": "Arden International is a multiple formula racing team created and run by Christian Horner , Red Bull Racing 's F1 team principal . It currently runs teams in the GP2 Series , GP3 Series and the Formula Renault 3.5 series . It has been competing since 1997 and has raced in the Formula 3000 International Championship , the Italian Formula 3000 series , and the A1 GP series for Great Britain . Due to the Arden 's strong business connections and sponsorship , and because Horner is team principal at Red Bull Racing , the team often signs Red Bull Junior Team drivers as a way to pave forward future F1 drivers . Many drivers have been Red Bull Juniors , including Michael Ammermüller , Neel Jani , Adrian Zaugg , Filipe Albuquerque , Sébastien Buemi , Lewis Williamson , António Félix da Costa , Daniil Kvyat , Carlos Sainz , Jr. , Luis Leeds , Niko Kari and Dan Ticktum .",
"title": ""
},
{
"docid": "Mercedes_F1_W06_Hybrid",
"text": "The Mercedes F1 W06 Hybrid was a highly successful Mercedes-Benz Formula One racing car designed and developed under the direction of Aldo Costa , Geoff Willis and Paddy Lowe , to compete in the 2015 Formula One season . The cars were driven by and World Drivers ' Champion Lewis Hamilton and Nico Rosberg , both of whom remained with the team for a third and sixth season , respectively . The chassis was named `` F1 W06 Hybrid '' to represent the sixth Formula One car that Mercedes had constructed since , while the hybrid was marked to recognize the utilization of fully integrated hybrid power units . The car made its competitive debut at the 2015 Australian Grand Prix , the opening round of the 2015 season . After participating in 18 rounds of Grand Prix racing , the car made its final competition appearance at the season finale race -- the 2015 Abu Dhabi Grand Prix , before retirement . This was the last Mercedes car to feature sponsorship from BlackBerry .",
"title": ""
},
{
"docid": "GP2_Series",
"text": "The GP2 Series was a form of open wheel motor racing introduced in 2005 following the discontinuation of the long-term Formula One feeder series , Formula 3000 . The GP2 format was conceived by Bernie Ecclestone and Flavio Briatore , while Ecclestone also has the rights to the name GP1 . In 2010 , the GP3 Series class was launched , as a feeder class for the GP2 series . In 2017 , the series was rebranded as the FIA Formula 2 Championship . Designed to make racing affordable for the teams and to make it the perfect training ground for life in Formula One , GP2 has made it mandatory for all of the teams to use the same chassis , engine and tyre supplier so that true driver ability is reflected . All but three races had taken place as support races at Formula One race weekends to boost the series ' profile , to give drivers experience of the Grand Prix environment , and to take advantage of the infrastructure ( marshals , medical facilities etc. ) in place for a Formula One event . GP2 mainly races on European circuits , but has appearances on other international race tracks as well with their most recent races in the 2012 season at the Sepang International Circuit in Malaysia and the Marina Bay Street Circuit in Singapore . Many drivers have used GP2 as a stepping stone into Formula One . The 2005 Champion Nico Rosberg was hired by the Williams team for the 2006 F1 campaign , 2006 GP2 winner Lewis Hamilton made the transition to F1 the following year with McLaren and the 2007 Champion Timo Glock to Toyota for the 2008 F1 season . 2009 GP2 champion Nico Hülkenberg moved up to a Williams F1 race driver in the 2010 Formula 1 season . In addition , Heikki Kovalainen ( 2005 ) , Nelson Piquet Jr. ( 2006 ) and Lucas di Grassi ( 2007 ) -- all runners up -- became Renault test drivers the following year . All three earned F1 seats , but have since been replaced . Karun Chandhok , Bruno Senna and Vitaly Petrov were also granted an F1 seat in 2010 . For 2011 Pastor Maldonado was granted the hot seat at Williams . This meant that Nico Hülkenberg was deposed by Williams . Sergio Pérez was given the drive alongside Kamui Kobayashi , another former GP2 driver and GP2 Asia Series winner , at Sauber . Jérôme d'Ambrosio got his Virgin Racing drive for the 2011 season . However , some drivers have reached Formula One without competing in GP2 , for example Paul di Resta , Daniel Ricciardo , Jean-Éric Vergne , Valtteri Bottas , and Kevin Magnussen . During 2011 , it was announced that in 2012 the GP2 and GP2 Asia Series would combine to make a single , longer GP2 series .",
"title": ""
},
{
"docid": "Italian_American_Motor_Engineering",
"text": "Italian American Motor Engineering ( IAME ) is an Italian company founded in 1968 . It is the parent company of the `` Parilla '' , `` Komet '' and `` Sirio '' brand names and is the largest kart engines manufacturer . Its factory is located in the province of Bergamo , Italy , near the city of Milan . The company has won 25 Karting World Championships . The manufacturer won the European Formula A championship in 2000 with Lewis Hamilton , in 2001 with Carlo Van Dam and in 2004 with Nick De Bruijn . 2005 and 2006 Formula One World Champion , Fernando Alonso , won the karting Junior World Cup in 1996 with a Parilla engine made by IAME . In 2011 , F1 GP winner Max Verstappen won the WSK Euro Series in an Parilla-powered CRG .",
"title": ""
},
{
"docid": "J._Hamilton_Lewis",
"text": "James Hamilton Lewis ( May 18 , 1863 -- April 9 , 1939 ) was the first Senator to hold the title of Whip in the United States Senate . Lewis was born in Danville , Virginia , and also grew up in Augusta , Georgia . He was educated at the University of Virginia and studied law in Savannah , Georgia before he served in the Spanish -- American War .",
"title": ""
},
{
"docid": "Matt_Bishop",
"text": "Matt Bishop , who was born in London in 1962 , is Group Director of Media , Content and Communications for McLaren , which Formula One team he joined in January 2008 , having been an automotive journalist and editor since 1991 , specialising in Formula One since 1996 . He works closely with the current two McLaren drivers , 2005 and 2006 Formula One World Champion Fernando Alonso , and 2015 GP2 Series Champion Stoffel Vandoorne , as well as 2009 Formula One World Champion Jenson Button , who remains contracted to the McLaren team albeit now in an ambassadorial role . Bishop also works closely with McLaren Technology Group Executive Director Zak Brown , as well as the team 's Racing Director and Chief Operating Officer , Eric Boullier and Jonathan Neale . Bishop used to work closely with the 2008 Formula One World Champion Lewis Hamilton , before Hamilton left McLaren to join Mercedes-Benz at the end of the 2012 Formula One season . Previously , Bishop had been Editor in Chief of the Formula One magazine F1 Racing . He took on the editorship of F1 Racing in December 1996 and left it in December 2007 , by which time F1 Racing had become the world 's best-selling grand prix magazine , according to its own strap-line which appears on its front cover every month . Bishop introduced a series of celebrity columnists to F1 Racing , including Murray Walker , Damon Hill , Jenson Button and many more . in 2014 Bishop co-authored with the 1972 and 1974 Formula One World Champion Emerson Fittipaldi the autobiographical work 'Em mo : a Racer 's Soul ' , published by Haymarket Media Group . Bishop is known in Formula One circles as ` The Bish ' and is known for his larger-than-life wardrobe that includes a seemingly limitless number of very garish shirts . Bishop 's journalism was published in F1 Racing and Autosport.com , for which he used to write a famously trenchant fortnightly column entitled ` From the Pulpit ' . On 26 September 2007 it was announced that Bishop would leave Haymarket , publisher of F1 Racing and Autosport , to become Group Head of Communications and Public Relations for McLaren , effective January 2008 . Bishop 's father is the US-born concert pianist , Stephen Kovacevich . His mother is the late Bernardine Bishop , a noted British psychotherapist and novelist . Bishop attended the Cardinal Vaughan Memorial School in Holland Park , London .",
"title": ""
},
{
"docid": "Harmonic_mixer",
"text": "The harmonic mixer and subharmonic mixer are a type of frequency mixer , which is a circuit that changes one signal frequency to another . The ordinary mixer has two input signals and one output signal . If the two input signals are sinewaves at frequencies f1 and f2 , then the output signal consists of frequency components at the sum f1 + f2 and difference f1 − f2 frequencies . In contrast , the harmonic and subharmonic mixers form sum and difference frequencies at a harmonic multiple of one of the inputs . The output signal then contains frequencies such as f1 + kf2 and f1 − kf2 where k is an integer .",
"title": ""
},
{
"docid": "2013_Japanese_Grand_Prix",
"text": "The 2013 Japanese Grand Prix ( formally known as the 2013 Formula 1 Japanese Grand Prix ) was a Formula One motor race that was held on 13 October 2013 at the Suzuka Circuit in Suzuka , Japan . The race was the fifteenth round of the 2013 season , and marked the 40th running of the Japanese Grand Prix . The race , contested over 53 laps , was won by Sebastian Vettel , driving a Red Bull after starting from second on the grid . Mark Webber , who started on pole position , settled for second after being forced to switch to a three stop strategy , which in the end was not successful . Romain Grosjean took his second podium in succession in third position for Lotus F1 . This was Red Bull 's 14th one-two finish in Formula One . The result meant that the title was not sealed at Suzuka but Vettel could seal it with 5th place at the next race in India . Meanwhile , Fernando Alonso stretched his lead to 30 points over Kimi Räikkönen but was still 90 behind Vettel 's total . Räikkönen in turn also increased his lead over Lewis Hamilton to 16 points after the Briton retired from puncture damage after colliding with Vettel on lap one . The result also meant that only Alonso can deprive Vettel of becoming world champion as Hamilton and Räikkönen fell out of contention .",
"title": ""
},
{
"docid": "Kreator_TV",
"text": "Kreator TV is a specialized sports network from Croatia . It broadcasts their program in all major IPTV & cable operators in Croatia ( Max TV , B.Net , Iskon TV , Opti TV , Amis TV , VIP TV ) and in Bosnia and Herzegovina ( Home TV ) . Kreator TV 's studios and broadcast facilities are located in Jastrebarsko . Kreator TV first started in 2011 . under the name Kreator F1 and Kreator F1 HD for broadcasting only Formula 1 in biggest Croatian provider Max TV - part of Croatian Telecom as Kreator 's owner acquired exclusive Formula 1 media rights for Croatia . Name Kreator TV was used from the second half of 2013 after Formula 1 co-operation . Kreator TV has a history with premium sports rights and they owned and broadcast-ed such rights as Formula 1 , MotoGP , MX GP , FIA WTCC , FIA ERC and others . Among the others Kreator TV produced the season 2015 of the Second Croatian Football league . Channel is specialized for the Motorsports and journalists from the Kreator TV made some exclusive interviews with the top sportsman like Lewis Hamilton , Nico Rosberg ( one of the last interviews before retirement ) , Valentino Rossi , Ken Block and others .",
"title": ""
},
{
"docid": "Lewis_Hamilton_(disambiguation)",
"text": "Lewis Hamilton ( born 1985 ) is a British Formula One racing driver . Lewis Hamilton may also refer to : Lewis Hamilton ( footballer ) ( born 1984 ) , English footballer Lewis Hamilton ( Cars ) , fictional character SS Lewis Hamilton , cargo ship Lewis Hamilton : Secret Life , alternate reality game",
"title": ""
},
{
"docid": "Philippe_Chiappe",
"text": "Philippe Chiappe ( born 21 November 1963 ) is a French driver in the Formula 1 Powerboat World Championship , currently competing for the CTIC F1 Shenzen China Team . A three-time champion , he won his first title in 2014 , becoming the first Frenchman to do so , and then retained the championship in the following two seasons in 2015 and 2016 . Chiappe is one of the longest-serving current drivers in the field , having made his debut in 2001 and entered his first full season in 2003 . He started his 100th race at the Grand Prix of Sharjah in 2015 . Chiappe has spent all bar three of his seasons in F1 with Philippe Dessertenne 's team which has undergone several name changes over the years and most recently has been heavily supported by Chinese sponsors . As one of only four drivers to win back-to-back championships , Chiappe has done so in a French-based team , driving a French Moore boat . His success has improved the sport 's exposure in his own country and after his first title , France re-appeared on the series ' calendar with a race of its own after an eight-year hiatus . Away from Formula 1 , Chiappe has also had success in endurance powerboat racing , having won multiple classes at the 24 Hours of Rouen event . He began his career in the French S850 class where he competed from 1998 to 2000 and afterwards moved to the French Vitesse S3000 class for 2001 . Chiappe stayed for 2002 before making the step-up to F1 full-time in 2003 , but returned to the S3000 class in 2006 and won the championship .",
"title": ""
},
{
"docid": "Heikki_Kovalainen",
"text": "Heikki Johannes Kovalainen ( -LSB- ˈheikki ˈkoʋɑlɑinen -RSB- ; born 19 October 1981 ) is a Finnish racing driver . He raced in Formula 1 between 2007 and 2013 for the Renault , McLaren , Team Lotus and Lotus F1 teams . He was supported by the Renault Driver Development programme early in his racing career , during which he won the World Series by Nissan championship and finished runner-up in the GP2 series . Renault signed him on as a full-time Formula One test driver for , and then promoted him to a race seat for . He gained his first podium by finishing second in the Japanese Grand Prix that year . He moved to McLaren for the season , where he partnered Lewis Hamilton . His second season saw him achieve his first pole position at Silverstone and his first victory at Hungaroring , becoming the 100th driver to win a Formula One Grand Prix . He remained with the team for the season . In , he moved to the newly created Team Lotus where he also remained for and , with the team renamed Caterham F1 for 2012 . 2012 was his last full season in Formula One . Kovalainen competed in the last two races of the season for Lotus F1 as a short-notice stand-in for regular driver Kimi Räikkönen . In 2015 , Kovalainen moved to Japan to compete in Super GT in the GT500 class .",
"title": ""
},
{
"docid": "Formula_One_drivers_from_the_United_Kingdom",
"text": "There have been 160 Formula One drivers from the United Kingdom , three of whom raced in the 2016 season . The country has produced ten World Champions . Of those , Jackie Stewart and Lewis Hamilton have won the most , with three titles each . Hamilton is still active in the sport : he has won the most races and amassed the most points of any British driver ( along with sharing the same number of World Championships as Jackie Stewart ) .",
"title": ""
},
{
"docid": "2012_Bahrain_Grand_Prix",
"text": "The 2012 Bahrain Grand Prix ( formally known as the 2012 Formula 1 Gulf Air Bahrain Grand Prix ) was a Formula One motor race held on 22 April 2012 at the Bahrain International Circuit in Sakhir , Bahrain . It was the first time Formula One returned to Bahrain after the 2011 race was cancelled due to ongoing anti-government protests . The race , the eighth running of the Bahrain Grand Prix , was contested over 57 laps and was the fourth round of the 2012 Formula One season . Sebastian Vettel started the race from pole position , leading into the first corner and for the majority of the race en route to victory . He was not without pressure though , as the Lotus of Kimi Räikkönen climbed the field , having started in eleventh place , and challenged for the lead before finishing second . Räikkönen 's teammate Romain Grosjean took the first podium finish of his career by finishing third , after having a strong start and quickly moving into second place by overtaking Lewis Hamilton and Mark Webber . Räikkönen passed Grosjean for second place roughly halfway through the race , being on a better tyre strategy . Hamilton started on the front row , but pitstop errors and degrading tyres left him eighth ; his McLaren teammate , Jenson Button , retired with two laps remaining . As a consequence of the race , Sebastian Vettel took the lead in the Drivers ' Championship from Lewis Hamilton . He became the fourth driver to top the standings from four races , and also the fourth race winner . Hamilton remained second , four points behind Vettel , whilst Webber jumped in front of Button to move into third with his fourth consecutive fourth place . Webber was just one point behind Hamilton , and Button was only five points behind him ; Nico Rosberg was fifth . The Constructors ' Championship was now led by Red Bull , who also took the lead from McLaren ( who were now nine points behind them ) . Lotus F1 moved up from sixth to third in the standings after their first podium . Ferrari fell to fourth whilst Mercedes remained fifth . The decision to hold the race despite ongoing protests and violence has been described as `` controversial '' by Al Jazeera English , CNN , AFP and Sky News . The Independent named it `` one of the most controversial in the history of the sport '' .",
"title": ""
},
{
"docid": "2016_Formula_One_season",
"text": "The 2016 Formula One season was the 70th season of the Fédération Internationale de l'Automobile ( FIA ) 's Formula One motor racing . It featured the 67th Formula One World Championship , a motor racing championship for Formula One cars which is recognised by the sport 's governing body , the FIA , as the highest class of competition for open-wheel racing cars . Teams and drivers took part in twenty-one Grands Prix -- making for the longest season in the sport 's history -- starting in Australia on 20 March and finishing in Abu Dhabi on 27 November as they competed for the World Drivers ' and World Constructors ' championships . The 2016 season saw the grid expand to twenty-two cars with the addition of the Haas F1 Team entry . Renault returned to the sport as a constructor after a four-year absence following their takeover of Lotus prior to the start of the season . The calendar has similarly expanded , with the return of the German Grand Prix . The European Grand Prix was also revived , with the event visiting a new circuit in Azerbaijan 's capital city , Baku . Nico Rosberg won his only World Drivers ' Championship title in the final race of the season . With nine wins and seven other podiums , Rosberg beat teammate and defending World Champion Lewis Hamilton by five points . In doing so , Rosberg followed the success of his father in and became the second son of a champion to become champion himself , a feat previously achieved by Graham and Damon Hill . This would later prove to be Rosberg 's last season , as he announced his retirement from the sport shortly after winning the title . In the World Constructors ' Championship , Mercedes successfully defended their title for the second consecutive year , beating Red Bull Racing by two hundred and ninety-seven points . Ferrari finished third overall , a further seventy points behind .",
"title": ""
},
{
"docid": "2007_MTV_Europe_Music_Awards",
"text": "The 14th annual MTV European Music Awards were held at the Olympiahalle in Munich , Germany on November 1 , 2007 . The show received a total of 78 million votes , the most in MTV Europe Music Awards history . Foo Fighters opened the show , with frontman Dave Grohl hosting the VIP ` Glamour Pit ' area , interviewing celebrities live on air . Other performances on the night included Amy Winehouse with `` Back to Black '' , Tokio Hotel , will.i.am and Babyshambles . Presenters on the night included Joss Stone , model Lily Cole , R.E.M. 's Michael Stipe and F1 driver Lewis Hamilton .",
"title": ""
}
] |
3066
|
Home owners association for houses, pro/cons
|
[
{
"docid": "421833",
"text": "\"I agree with the basic purpose of an HOA. Unlike the poster above Jay, I do believe that people painting their houses purple will definitely affect the value of my house or property. I for one would not want to live next to someone who has a wild purple house, even though it is his right to do so. In saying that I know that there are very few people who would want to buy my house were it situated next to the \"\"purple house\"\". So in the sense of limiting known eyesores I agree with the purpose of HOA's. That being said, I do not agree with the fact that HOA's are not regulated and that its rules are formed by community members who may be very strict on what or what isn't allowed. If it were simple rules like not painting the house disturbing colors (we all know what they are) or not having junk cars or loud music after a certain time (except on holidays or special calendar days like New Years etc.\"",
"title": ""
},
{
"docid": "130350",
"text": "I think it depends a lot on your idea of how you should relate to your neighbors. Personally, I think that I should be allowed to do just about whatever I want with my property, and I grant my neighbor the same right. If my neighbor wants to paint his house purple with orange stripes and fill his front lawn with pink flamingos, I think that's his right. If I don't like it, I don't have to look at his house. (I would draw the line at things that I cannot avoid by simply looking the other way, like running jet engines in his back yard at 2 in the morning, as I could not avoid the noise. Or dumping toxic waste on the street, as it will cause health problems. Etc.) Others think it IS their business what their neighbor does with his property and want to be able to control it. They want someone who has the authority to force everyone in the neighborhood to paint their house in colors deemed acceptable, to meet certain requirements for yard work. And that's what Home Owners Associations are for: to require that everyone in the neighborhood maintain their property according to a standard set by the HOA, which should theoretically represent the wishes of the majority. Of course the price you pay for giving you the right to tell your neighbor what kind of fence he is allowed to have is that now your neighbors can tell you what kind of fence you can have. Advocates of HOAs often say that they are necessary to protect property values. Personally I think this is something of a circular argument: I must have the right to prevent my neighbor from doing something that, in my opinion, makes his house ugly, not because I necessarily have no choice but to stare out my window at his house all day and be repulsed by it, but because someday I may want to sell my house to someone who will have no choice but to stare out the window at his house all day and be repulsed by it and so will not want to buy my house. Of course if we all just minded our own business, this wouldn't be an issue. Okay, this was pretty much an anti-HOA post, but I did TRY to state the other side of it.",
"title": ""
},
{
"docid": "152563",
"text": "Some examples where an HOA is a positive thing: 1) Amenities: Maybe it is professionally maintained landscaping at the front of the subdivision, or a playground, or community pool. An HOA provides a convenient way to have things like that and share the costs among all the people who benefit. 2) Legal Advocacy: I live in a neighborhood (rural) without an HOA. My neighbor decided to start an auto-repair shop on his property which was CLEARLY a violation of the covenants. There isn't really a Government body you can report them to that will swoop in and make them stop a neighbor from destroying your property values even if they signed an agreement when they bought it to the contrary. You need to hire a lawyer and sue them and that costs money and time. Also, in many cases if you wait too long they can get an exception grandfathered in because no one raised an issue about it. An HOA exists to watch for this kind of thing and nip it in the bud rather than making homeowners have to hassle with the time/expense. 3) Independence: Assuming no HOA, and assuming you are okay with suing your neighbor over violating a covenant. That makes for a very uncomfortable situation between you and that neighbor. Having a neutral 3rd party take action on your behalf anonymously can greatly help that situation. It's not all about making people ditch their basketball goals, or garden gnomes. They also protect you from other obnoxious stuff like junky mobile homes in high-end neighborhoods, the guy who blocks half the street permanently with his RV/Boat parked on the curb, three foot tall grass that is an eyesore and a fire hazard, a taco stand opening in your neighbors garage, etc.",
"title": ""
},
{
"docid": "27433",
"text": "At its best, a HOA provides the same benefits as a condo association -- shared investment in the shared neighborhood resources/environment. At its worst, a HOA has the same problems as a condo association, potentially creating unreasonable constraints on what you can or can't do with your own property because your decisions might affect the value of someone else's property or demanding shared investment in something you don't consider worthwhile. Basically, if an HOA is active in your neighborhood, (A) make sure you know its history and biases before you buy, and (B) make sure you're active in it, or you may be unpleasantly surprised by its decisions.",
"title": ""
},
{
"docid": "148233",
"text": "\"As I understand it the basic premiss of a HOA is to ease communication between neighbors and help work towards common community goals. As I understand it the reality is that the HOA works to keep the community homogenous so there are no \"\"sore thumb\"\" neighbors. As to why look for one or avoid one. If you would want a uniform image out of your neighbors and don't mind towing the party line, then they are for you. If you don't care about what your neighbors do with their property (within civic ordinance) and would like freedom to do things different from your neighbors (paint your house blue, hang a clothes line, increase the size of your flower beds), then they are to be avoided.\"",
"title": ""
}
] |
[
{
"docid": "598807",
"text": "Pros: Cons: Before the housing bubble the conventional wisdom was to buy as much home as you could afford, thereby borrowing as much you can afford. Because variable rates lead to lower mortgages, they were preferred by many as you could buy more house. This of course lead to many people losing their home and many thousands of dollars. A bubble is not necessary to trigger a chain of events that can lead to loss of a home. If an interest only borrower is late on a payment, this often triggers a rate increase. Couple that with some other things that can happen negatively, and you are up $hit's creek. IMO it is not wise.",
"title": ""
},
{
"docid": "262546",
"text": "\"Outside of broadly hedging interest rate risk as I mentioned in my other answer, there may be a way that you could do what you are asking more directly: You may be able to commit to purchasing a house/condo in a pre-construction phase, where your bank may be willing to lock in a mortgage for you at today's rates. The mortgage wouldn't actually be required until you take ownership from the builder, but the rates would be set in advance. Some caveats for this approach: (1) You would need to know the house/condo you want to move into in advance, and you would be committing to that move today. (2) The bank may not be willing to commit to rates that far in advance. (3) Construction would likely take far less than 5 years, unless you are buying a condo (which is the reason I mention condos specifically). (4) You are also committing to the price you are paying for your property. This hedges you somewhat against price fluctuation in your future area, but because you currently own property, you are already somewhat hedged against property price fluctuation, meaning this is taking on additional risk. The 'savings' associated with this plan as they relate to your original question (which are really just hedging against interest rate fluctuations) are far outweighed by the external pros and cons associated with buying property in advance like this. By that I mean - if it was something else you were already considering, this might be a (small) tick in the \"\"Pro\"\" column, but otherwise is far too committal / complex to be considered for interest rate hedging on its own.\"",
"title": ""
},
{
"docid": "429106",
"text": "Our company does a lot of research on the self-directed IRA industry. We also provide financial advice in this area. In short, we have seen a lot in this industry. You mentioned custodian fees. This can be a sore spot for many investors. However, not all custodians are expensive, you should do your research before choosing the best one. Here is a list of custodians to help with your research Here are some of the more common pros and cons that we see. Pros: 1) You can invest in virtually anything that is considered an investment. This is great if your expertise is in an area that cannot be easily invested in with traditional securities, such as horses, private company stock, tax liens and more. 2) Control- you have greater control over your investments. If you invest in GE, it is likely that you will not have much say in the running of their business. However, if you invest in a rental property, you will have a lot of control over how the investment should operate. 3) Invest in what you know. Peter lynch was fond of saying this phrase. Not everyone wants to invest in the stock market. Many people won't touch it because they are not familiar with it. Self-directed IRAs allow you to invest in assets like real estate that you know well. Cons: 1) many alternative investments are illiquid. This can present a problem if you need to access your capital for withdrawals. 2) Prohibited transactions- This is a new area for many investors who are unfamiliar with how self-directed IRAs work 3) Higher fees- in many cases, the fees associated with self-directed IRA custodians and administrators can be higher. 4) questionable investment sponsors tend to target self-directed IRA owners for fraudulent investments. The SEC put out a good PDF about the risks of fraud with self-directed IRAs. Self Directed IRAs are not the right solution for everyone, but they can help certain investors focus on the areas they know well.",
"title": ""
},
{
"docid": "512827",
"text": "As with most strategies there are pros and cons associated with this approach: Advantages of using LEAPS: Disadvantages of using LEAPS: Read more about it in great detail on my blog: http://www.thebluecollarinvestor.com/leaps-and-covered-call-writing-2/",
"title": ""
},
{
"docid": "56027",
"text": "As with everything else, it's a question of trade-offs. Pros For Buying In Bulk Cons For Buying In Bulk Inventory cost. You need to purchase more shelving/cupboards to stock the goods. This is a real cost. The psychological effect of having more means you are more likely to use more, thus costing you more. Deflation of the cost of the item should occur over time in a well-functioning market economy. A $10 item today might be $9.50 in one year in real terms. There is a real opportunity cost associated with overbuying. Granted, an extra $100 in your bank account won't be earning too much if you have to spend it one month later, but it does mean you have less financial independence for that month. Risk of spoilage. There is a nonzero risk that your goods could be ruined by flood/fire/toddler/klutz damage. You need to decide which of these pros and cons are more important to you. Financially, you should only buy what you need between shopping trips. In reality the convenience of holding goods in storage for when you need them may outweigh the costs.",
"title": ""
},
{
"docid": "473008",
"text": "Go to glassdoor.com & do some research. “Corrupt Middle Management Not Noticed By Christian Owners ” Current Employee - Senior Underwriter in Cincinnati, OH Pros Don't have to do much to get paid. Slackers are rewarded. Cons Middle and top management below the owners and their direct reports are corrupt. They violate the rules they make everyone else follow and look to pad their own pockets off of the profits earned by those below them. Notice that ONLY the Interns think this is a great company. Over the past 5 years, with the change in human resources management the company consistently lets go of top knowledge and top performers...who are over the age of 45. Advice to Management Clean house, starting with top human resources leadership. Those at the top of human resources are incompetent. That's why you pay so much for consultants and nothing changes. Read the reviews - the benefits are not even comparable to what other companies offer. So much money is spent for consultants to do Total Rewards work. Top human resources leadership doesn't respect anyone, including the rest of the C-Suite and the owners themselves. Other executives are called names and their lack of political savvy is commented on in front of staff level employees regularly. They describe themselves as the puppet masters; guess who the puppets are? The owners are too good of a family, have done too much good for Cincinnati and have too good of a company to let these corrupt human resources leaders tarnish their good name and strong business. Doesn't Recommend Neutral Outlook Tl;dr: Looks like interns get paid 15/hour, & it'll be a good intro on how to deal with corrupt, conservative management.",
"title": ""
},
{
"docid": "293083",
"text": "Your calculations are good as far as they go, but there are lots of other factors and pros and cons to each decision. Yes, you should certainly compare the monthly rent to what your mortgage payments would be, as you have done. Yes, you should consider how long you might live there. If you do move out, how difficult will it be to sell the house, given market conditions in your area? If you try to rent it, how difficult is it to find a tenant, and what rent could you expect to receive? Speaking of moving out and renting the place: Who will manage the property and do maintenance? Would you still be close enough to do this yourself? Would you be willing and able to spend the time? Or would you have to hire someone? Also, what if the tenant does not pay the rent? How difficult is it to evict someone in your area? Speaking from personal experience, I own a rental property in Ohio, and the law says you can evict someone with 3 days notice. But in practice they don't just leave, so then you have to take them to court. It takes months to get a court date and months longer before the police actually show up to order them out of the house. And you have to pay the lawyer and court fees. In that time they're living in your property rent free. In my case one tenant also totally trashed the place and stole everything that wasn't nailed down -- I had to spend $13,000 on repairs to a house worth a fraction of what you're talking about. Being a landlord is NOT just a matter of sitting back and collecting rent checks: there's a fair amount of work and a lot of risk. What do you have to pay the realtor, and what other closing costs would you have to pay? Where I live, realtors typically charge 6 to 7%. You may also have to pay for an appraisal, title search, and bunch of other little fees. Mortgage interest is deductible on your federal income taxes. Rent is not. If you own and something needs to be repaired, you have to pay for it. If you rent, the landlord has to pay for it. If you own, you can do pretty much what you like with the property -- subject to zoning ordinances and building codes and maybe homeowners association rules, but you should have a pretty good amount of leeway. If you want to install ceiling fans or remodel the kitchen or add a deck, it's up to you. If you're renting, it's up to the landlord to decide what you can do to the property. And if he agrees to let you do some upgrade, when you're done, it belongs to him. With a condo, you are not usually responsible for exterior maintenance, like mowing the lawn and trimming the bushes and washing the outer walls. With a house, you are. You might pay someone to do this, which adds to the cost, or you might do it yourself, which takes time. Insurance on a condo or aparment is much less than insurance on a house. In my area, anyway. You should investigate those costs. If you buy, eventually you own the place and don't have to pay a mortgage any more. If you rent, you continue to pay forever. (Even if you don't live in the same house forever, as long as you don't take a terrible loss when you sell you should then have some money left over to apply to the next house, so you are still building equity.) Some of these pros and cons are easily quantifiable. Others are probabilities, like how likely is it that your water heater will fail?, and how long is it likely to take to find a buyer if you want to sell? And others are pretty subjective.",
"title": ""
},
{
"docid": "134764",
"text": "\"Given the current low interest rates - let's assume 4% - this might be a viable option for a lot of people. Let's also assume that your actual interest rate after figuring in tax considerations ends up at around 3%. I think I am being pretty fair with the numbers. Now every dollar that you save each month based on the savings and invest with a higher net return of greater than 3% will in fact be \"\"free money\"\". You are basically betting on your ability to invest over the 3%. Even if using a conservative historical rate of return on the market you should net far better than 3%. This money would be significant after 10 years. Let's say you earn an average of 8% on your money over the 10 years. Well you would have an extra $77K by doing interest only if you were paying on average of $500 a month towards interest on a conventional loan. That is a pretty average house in the US. Who doesn't want $77K (more than you would have compared to just principal). So after 10 years you have the same amount in principal plus $77k given that you take all of the saved money and invest it at the constraints above. I would suggest that people take interest only if they are willing to diligently put away the money as they had a conventional loan. Another scenario would be a wealthier home owner (that may be able to pay off house at any time) to reap the tax breaks and cheap money to invest. Pros: Cons: Sidenote: If people ask how viable is this. Well I have done this for 8 years. I have earned an extra 110K. I have smaller than $500 I put away each month since my house is about 30% owned but have earned almost 14% on average over the last 8 years. My money gets put into an e-trade account automatically each month from there I funnel it into different funds (diversified by sector and region). I literally spend a few minutes a month on this and I truly act like the money isn't there. What is also nice is that the bank will account for about half of this as being a liquid asset when I have to renegotiate another loan.\"",
"title": ""
},
{
"docid": "268802",
"text": "Without commenting on your view of the TV market: Let's have a look at the main ways to get negative exposure: 1.Short the stocks Pros: Relatively Easy Cons: Interest rate, costs of shorting, linear bet 2.Options a. Write Calls b. Buy puts Pros: Convexity, leveraged, relatively cheap Cons: Zero Sum bet that expires with time, theta 3.Short Stock, Buy Puts, Write Calls Short X Units of each stock, Write calls on them , use call premiums to finance puts. Pros: 3x the power!, high kickout Cons: Unlimited pain",
"title": ""
},
{
"docid": "204485",
"text": "\"But look at the bright side. The Home Owners Association is telling your neighbor (for the low low fee of $200 every 4 months) to put his garbage can into his garage after every garbage pickup. Your house is worth a fortune, even if nobody is willing to buy the 12 houses for sale on your block (never mind the fact that they have been for sale for the past 2 years or the fact that nobody is willing to \"\"rent\"\" a place in butt fuck Egypt for $1500 a month).\"",
"title": ""
},
{
"docid": "422468",
"text": "\"In some cases perhaps, but in others not. Several homes near me were sold over and over again during the bubble years (at incrementally higher and higher sale prices) -- the last owners in nearly all cases defaulted and the banks (after dragging their feet for a couple of years) finally foreclosed and sold the homes off cheap. In all but one of the \"\"distressed sale\"\" cases, the people buying the houses now ARE in fact moving into them as their primary home (the exception being a current resident who bought the adjacent home with the intentions of fixing it up & renting it out, I believe at least initially to a family member); but in ALL cases (in no small part due to the fact that they were able to purchase the properties cheap) these new owners are investing substantial money into fixing them up (new roof & gutters, new windows & doors, paint and/or siding, often all new carpeting, some landscaping, etc). Also, from the perspective of our homeowners association, all of these new people think our annual HOA fees are a \"\"bargain\"\", whereas the previous bubble-era \"\"homeowners\"\" (if, having invested almost nothing, they could truly be called that) did nothing but whine and complain (well, and once they began defaulting on their mortgages, they also defaulted on their HOA fees). So it's a win-win for our neighborhood. We're getting good, solid residents who are planning on taking care of their properties... the exact opposite of what you are claiming. (The \"\"house-flippers\"\" you decry were the ones buying with \"\"no money down\"\" during the bubble era -- and they nearly killed the neighborhood.)\"",
"title": ""
},
{
"docid": "28060",
"text": "That is a decision you need to make, but some of the pros and cons you could consider to help your decision making include: Pros: If bought at the right time in the property cycle and in a good growth area, it can help you grow your net worth much quicker than having money in the bank earning near zero interest. You would be replacing rent payments with mortgage payments and if your mortage payments are less than your current rent you will have additional money to pay for any expenses on the property and have a similar cashflow as you do now. You will be able to deduct your interest payments on the mortgage against your income if you are in the USA, thus reducing the tax you pay. You will have the security of your own house and not have to worry about moving if the landlord wants you out after your lease expires. Cons: If bought in a bad area and at the top of the property cycle you may never make any capital gains on the property and in fact may lose money on it long term. If the mortgage payments are more than your current rent you may be paying more especially at the start of your mortgage. If you buy a house you are generally stuck in one spot, it will be harder to move to different areas or states as it can cost a lot of money and time to sell and buy elsewhere, if renting you can generally just give notice and find a new place to rent. Property maintenance costs and taxes could be a drain on your finances, especially if the mortgage repayments are more than your current rent. If your mortgage payments and property expenses are way more than your current rent, it may reduce what you could be investing in other areas to help increase your net worth.",
"title": ""
},
{
"docid": "471686",
"text": "As I understand it (please correct me if i'm wrong, i've looked at this before and i've been a sole trader briefly but I've never formed a LTD company) there are pros and cons to forming a limited company. Pros Cons",
"title": ""
},
{
"docid": "89161",
"text": "\"You ask about the difference between credit and debit, but that may be because you're missing something important. Regardless of credit/debit, there is value in carrying two different cards associated with two different accounts. The reason is simply that because of loss, fraud, or your own mismanagement, or even the bank's technical error, any card can become unusable for some period of time. Exactly how long depends what happened, but just sending you a new card can easily take more than one business day, which might well be longer than you'd like to go without access to any funds. In that situation you would be glad of a credit card, and you would equally be glad of a second debit card on a separate account. So if your question is \"\"I have one bank account with one debit card, and the only options I'm willing to contemplate are (a) do nothing or (b) take a credit card as well\"\", then the answer is yes, take a credit card as well, regardless of the pros or cons of credit vs debit. Even if you only use the credit card in the event that you drop your debit card down a drain. So what you can now consider is the pros and cons of a credit card vs managing an additional bank account -- unless you seriously hate one or more of the cons of credit cards, the credit card is likely to win. My bank has given me a debit card on a cash savings account, which is a little scary, but would cover most emergencies if I didn't have a credit card too. Of course the interest rate is rubbish and I sometimes empty my savings account into a better investment, so I don't use it as backup, but I could. Your final question \"\"can a merchant know if I give him number of debit or credit card\"\" is already asked: Can merchants tell the difference between a credit card and embossed debit card? Yes they can, and yes there are a few things you can't (or might prefer not to) do with debit. The same could even be said of Visa vs. Mastercard, leading to the conclusion that if you have a Visa debit you should look for a Mastercard credit. But that seems to be less of an issue as time goes on and almost everywhere in Europe apparently takes both or neither. If you travel a lot outside the EU then you might want to be loaded down with every card under the sun, and three different kinds of cash, but you'd already know that without asking ;-)\"",
"title": ""
},
{
"docid": "315847",
"text": "Here are the pros and cons and an analytical framework for making a decision. Pros of walking away: Cons: Here's the framework: compare the value of first and second sections for you [1] http://www.nytimes.com/2009/07/30/business/30serviceside.html?_r=0 [2] http://www.mortgagecalculator.org/",
"title": ""
},
{
"docid": "267592",
"text": "In this case can the title of the home still be held by both? Yes, it is possible to have additional people on title that are not on the mortgage. Would the lender (bank) have any reservations about this since a party not on the mortgage has ownership of the property? Possibly, but there is a very simple way to avoid this. Clayton could simply purchase the home himself, and add Emma to the title after closing by recording a quitclaim deed. The lender can't stop that, and from their point of view it's actually better, since they have two people to go after in the case of default. (But despite it being better they often make it difficult to purchase Tip, when you have an attorney draft the quitclaim document, have them draft the reverse document too. (Emma relinquishing the property back to Clayton.) There is usually no extra charge for this and then you have it if you need it. For example, you may need to file the reverse forms if you want to refinance. As a side note, I agree with Grade 'Eh' Bacon's and Pete B.'s in recommending that Clayton and Emma do not do this. Once they are married the property will either be automatically jointly owned, or a spouse can be added to the title easily, and until they are married there are no pros but many cons to doing this. Reasons not to do it: As a side note, in a comment it was proposed: ...suppose Clayton loves Emma so much that he wants her name to be on the house... I understand the desire to do this from an emotional point of view, but realize this does not make sense from a financial point of view.",
"title": ""
},
{
"docid": "110465",
"text": "\"Consider that there are some low-probability, high-impact risk factors involved with property management. For example, an old house has lead paint and may have illegal modifications, unknown to you, that pose some hazard. All of your \"\"pros\"\" are logical, and the cons are relatively minor. Just consult an attorney to look for potential landmines.\"",
"title": ""
},
{
"docid": "457667",
"text": "I've been budgeting with MS Money since 2004 and was pretty disappointed to hear it's being discontinued. Budgeting is actually a stress-relieving hobby for me, and I can be a bit of a control-freak when it comes to finances, so I decided to start early looking for a replacement rather than waiting until MS Money can no longer download transactions. Here are the pros and cons of the ones I've tried (updated 10/2010): You Need A Budget Pro (YNAB) - Based on the old envelopes system, YNAB has you allot money from each paycheck to a specific budget category (envelope). It encourages you to live on last money's income, and if you have trouble with overspending, that can be a great plan. Personally, I'm a big believer in the envelope concept, so that's the biggest pro I found. Also, it's a downloaded software, so once I've bought it (for about $50) it's mine, without forced upgrades as far as I've seen. The big con for me was that it does not automatically download transactions. I would have to sign on to each institution's website and manually download to the program. Also, coming from Money, I'm used to having features that YNAB doesn't offer, like the ability to store information about my accounts. Overall, it's forward-thinking and a good budgeting system, but will take some extra time to download transactions and isn't really a comprehensive management tool for all my financial needs. You can try it out with their free trial. Mint - This is a free online program. The free part was a major pro. It also looks pretty, if that's important to you. Updating is automatic, once you've got it all set up, so that's a pro. Mint's budgeting tools are so-so. Basically, you choose a category and tell it your limit. It yells at you (by text or email) when you cross the line, but doesn't seem to offer any other incentive to stay on budget. When I first looked at Mint, it did not connect with my credit union, but it currently connects to all my banks and all but one of my student loan institutions. Another recent improvement is that Mint now allows you to manually add transactions, including pending checks and cash transactions. The cons for me are that it does not give me a good end-of-the-month report, doesn't allow me to enter details of my paychecks, and doesn't give me any cash-flow forecasting. Overall, Mint is a good casual, retrospective, free online tool, but doesn't allow for much planning ahead. Mvelopes - Here's another online option, but this one is subscription-based. Again, we find the old envelopes system, which I think is smart, so that's a pro for me. It's online, so it downloads transactions automatically, but also allows you to manually add transactions, so another pro. The big con on this one is the cost. Depending on how you far ahead you choose to pay (quarterly, yearly or biannually), you're paying $7.60 to $12 per month. They do offer a free trial for 14 days (plus another 14 days offered when you try to cancel). Another con is that they don't provide meaningful reports. Overall, a good concept, but not worth the cost for me. Quicken - I hadn't tried Quicken earlier because they don't offer a free trial, but after the last few fell short, I landed with Quicken 2009. Pro for Quicken, as an MS Money user is that it is remarkably similar in format and options. The registers and reports are nearly identical. One frustration I'd had with Money was that it was ridiculously slow at start-up, and after a year or so of entering data, Quicken is dragging. Con for Quicken, again as an MS Money user, is that it's budgeting is not as detailed as I would like. Also, it does not download transactions smoothly now that my banks all ask security questions as part of sign-in. I have to sign in to my bank's website and manually download. Quicken 2011 is out now, but I haven't tried it yet. Hopefully they've solved the problem of security questions. Quicken 2011 promises an improved cash-flow forecast, which sounds promising, and was a feature of MS Money that I have very much missed. Haven't decided yet if it's worth the $50 to upgrade to 2011.",
"title": ""
},
{
"docid": "590013",
"text": "This one is pretty interesting in light of this OP's article (bold emphasis mine): >“Mediocre company” Former Employee in Park City, UT – **Reviewed Sep 1, 2010** >Pros – Convenient location, employee covered parking, ski passes (sometimes), competitive pay. >Cons – Corporate Management has no idea what's happening on the local level. **Owner of company sends emails to all employees with his political views, including who you should vote for during election season.** Health insurance premium is more expensive than I have ever paid elsewhere. >**Advice to Senior Management – Keep your political opinions to yourself.** Trust your local GM's and managers.",
"title": ""
},
{
"docid": "344740",
"text": "\"Buying now with a mortgage gets you: Waiting to buy with all cash gets you: These are also some of the pros or cons for the rent or buy dilemma that Paul mentioned in comments to the OP. This is a very complex, multi-faceted question, that would not respond well to being put into any equation or financial model. Most people answer the question with \"\"buy the home now with a mortgage\"\" if they can pay for the down payment. This is why the mortgage industry exists. The people who would want to finance now rather than buy with all cash later would not only be analyzing the question in terms of financial health but also in terms of general well being. They might consider the tremendous pride that comes with home ownership and living under a roof of one's own. Who can say that those people are wrong?\"",
"title": ""
},
{
"docid": "123835",
"text": "\"Canada would most likely not convert any time in the near future. The challenge for Canada converting to the US Dollar or the fictional \"\"Amero\"\" mentioned by JohnFX is that : Some of the benefits would be: The challenge right now for any government would be to sell the pros over the cons and from that viewpoint the cons would appear to have more negative impact to voters. Considering that Canada currently has a minority government with no expected change to that status for some time the risk would be very high. For more details see Pros and Cons of Canadian Monetary Union and to see the Mexican impact see North American Currency Union It is interesting to note that currency union was first proposed in 1999 when the Canadian Dollar fluctuated between $0.64 to $0.69 US. The Canadian Dollar is closer to par with the US Dollar currently (in fact it rose to $1.10 US in Nov. 2007). Look-up historical rates at the Bank of Canada\"",
"title": ""
},
{
"docid": "323214",
"text": "Check with local mechanics which cars they drive and dealers the buy from. Tell them your budget and needs and you'll find they're pretty consistent in their recommendations. Also, don't overlook dealers in favour of buying direct from owners, both have pros and cons. Dealers have to allow you to return the vehicle within a certain time frame, their name is also on the line. Some offer warranties to fix anything that goes wrong in the first x years. Do your research, but for old cars this can be a valuable saving. Also, some dealers offer to provide you with parts at cost for the life of the vehicle, also potential savings. Don't go in on a Saturday, do go in near the end of the month. Go back several times, compare, negotiate.",
"title": ""
},
{
"docid": "542024",
"text": "Will buying a flat which generates $250 rent per month be a good decision? Whether investing in real estate is a good decision or not depends on many things, including the current and future supply/demand for rental units in your particular area. There are many questions on this site about this topic, and another answer to this question which already addresses many risks associated with owning property (though there are also benefits to consider). I just want to focus on this point you raised: I personally think yes, because rent adjusts with inflation and the rise in the price of the property is another benefit. Could this help me become financially independent in the long run since inflation is getting adjusted in it? In my opinion, the fact that rental income general adjusts with 'inflation' is a hedge against some types of economic risk, not an absolute increase in value. First, consider buying a house to live in, instead of to rent: If you pay off your mortgage before your retire, then you have reduced your cost of accommodations to only utilities, property taxes, and repairs. This gives you a (relatively) known, fixed requirement of cash outflows. If the value of property goes up by the time you retire - it doesn't cost you anything extra, because you already own your house. If the value of property goes down by the time you retire, then you don't save anything, because you already own your house. If you instead rent your whole life, and save money each month (instead of paying off a mortgage), then when you retire, you will have a larger amount of savings which you can use to pay your monthly rental costs each month. By the time you retire, your cost of accommodations will be the market price for rent at that time. If the value of property goes up by the time you retire - you will have to pay more on rent. If the value of property goes down by the time you retire, you will save money on rent. You will have larger savings, but your cash outflow will be a little bit less certain, because you don't know what the market price for rent will be. You can see that, because you need to put a roof over your own head, just by existing you bear risk of the cost of property rising. So, buying your own home can be a hedge against that risk. This is called a 'natural hedge', where two competing risks can mitigate each-other just by existing. This doesn't mean buying a house is always the right thing to do, it is just one piece of the puzzle to comparing the two alternatives [see many other threads on buying vs renting on this site, or on google]. Now, consider buying a house to rent out to other people: In the extreme scenario, assume that you do everything you can to buy as much property as possible. Maybe by the time you retire, you own a small apartment building with 11 units, where you live in one of them (as an example), and you have no other savings. Before, owning your own home was, among other pros and cons, a natural hedge against the risk of your own personal cost of accommodations going up. But now, the risk of your many rental units is far greater than the risk of your own personal accommodations. That is, if rent goes up by $100 after you retire, your rental income goes up by $1,000, and your personal cost of accommodations only goes up by $100. If rent goes down by $50 after you retire, your rental income goes down by $500, and your personal cost of accommodations only goes down by $50. You can see that only investing in rental properties puts you at great risk of fluctuations in the rental market. This risk is larger than if you simply bought your own home, because at least in that case, you are guaranteeing your cost of accommodations, which you know you will need to pay one way or another. This is why most investment advice suggests that you diversify your investment portfolio. That means buying some stocks, some bonds, etc.. If you invest to heavily in a single thing, then you bear huge risks for that particular market. In the case of property, each investment is so large that you are often 'undiversified' if you invest heavily in it (you can't just buy a house $100 at a time, like you could a stock or bond). Of course, my above examples are very simplified. I am only trying to suggest the underlying principle, not the full complexities of the real estate market. Note also that there are many types of investments which typically adjust with inflation / cost of living; real estate is only one of them.",
"title": ""
},
{
"docid": "474279",
"text": "Listing on NYSE has more associated overhead costs than listing on NASDAQ. In the case of young technology companies, this makes NASDAQ a more attractive option. Perhaps the most important factor is that NYSE requires that a company has an independent compensation committee and an independent nominating committee while NASDAQ requires only that executive compensation and nominating decisions are made by a majority of independent directors. No self-respecting, would-be-instant-billionare tech entreprenuer is going to want some independent committee lording it over their pay packet. Additionally, listing on NYSE requires a company have stated guidance for corporate governance while NASDAQ imposes no such requirement. Similarly, NYSE requires a company have an internal audit team while NASDAQ imposes no such requirement. Fees on NYSE are also a bit higher than NASDAQ, but the difference is not significant. A good rundown of the pros/cons: http://www.investopedia.com/ask/answers/062215/what-are-advantages-and-disadvantages-listing-nasdaq-versus-other-stock-exchanges.asp",
"title": ""
},
{
"docid": "246547",
"text": "As far as the spam mail goes, I own a rental (in Connecticut) and live in Massachusetts, I get very little mail related to this property. I view this as a non-compelling reason. Your other reasons pick up quick in value. The protection from the rest of your assets is helpful, and the one con for most is the inability to get a loan with such a structure, but in your case, a cash purchase is mentioned. I don't know what the fees are to start an LLC, but overall, I believe the pros outweigh the cons. Yes, your Pro 4 looks good, an ongoing business with a track record will help the next purchase.",
"title": ""
},
{
"docid": "454584",
"text": "Having been both I see the pros and cons Employers: I personally hated all the paperwork. Government forms, legal protection, insurance, taxes, payroll, accounting, year ends, bank accounts, inventory tracking, expenses. The best bosses don't worry about the product, they worry about maintaining an environment that is good for the product. Good employees who are happy will make good products that you can sell to customers who are happy with your company. I personally went back to employee because I wanted to go home at night and forget about work. Employers cannot do that.",
"title": ""
},
{
"docid": "4739",
"text": "\"Some pros and cons to renting vs buying: Some advantages of buying: When you rent, the money you pay is gone. When you buy, assuming you don't have the cash to buy outright but get a mortgage, some of the payment goes to interest, but you are building equity. Ultimately you pay off the mortgage and you can then live rent-free. When you buy, you can alter your home to your liking. You can paint in the colors you like, put in the carpet or flooring you like, heck, tear down walls and alter the floor plan (subject to building codes and safety consideration, of course). If you rent, you are usually sharply limited in what alterations you can make. In the U.S., mortgage interest is tax deductible. Rent is not. Property taxes are deductible from your federal income tax. So if you have, say, $1000 mortgage vs $1000 rent, the mortgage is actually cheaper. Advantages of renting: There are a lot of transaction costs involved in buying a house. You have to pay a realtor's commission, various legal fees, usually \"\"loan origination fees\"\" to the bank, etc. Plus the way mortgages are designed, your total payment is the same throughout the life of the loan. But for the first payment you owe interest on the total balance of the loan, while the last payment you only owe interest on a small amount. So early payments are mostly interest. This leads to the conventional advice that you should not buy unless you plan to live in the house for some reasonably long period of time, exact amount varying with whose giving the advice, but I think 3 to 5 years is common. One mitigating factor: Bear in mind that if you buy a house, and then after 2 years sell it, and you discover that the sale price minus purchase price minus closing costs ends up a net minus, say, $20,000, it's not entirely fair to say \"\"zounds! I lost $20,000 by buying\"\". If you had not bought this house, presumably you would have been renting. So the fair comparison is, mortgage payments plus losses on the resale compared to likely rental payments for the same period.\"",
"title": ""
},
{
"docid": "384626",
"text": "\"A Tweep friend asked me a similar question. In her case it was in the larger context of a marriage and house purchase. In reply I wrote a detail article Student Loans and Your First Mortgage. The loan payment easily fit between the generally accepted qualifying debt ratios, 28% for house/36 for all debt. If the loan payment has no effect on the mortgage one qualifies for, that's one thing, but taking say $20K to pay it off will impact the house you can buy. For a 20% down purchase, this multiplies up to $100k less house. Or worse, a lower down payment percent then requiring PMI. Clearly, I had a specific situation to address, which ultimately becomes part of the list for \"\"pay off student loan? Pro / Con\"\" Absent the scenario I offered, I'd line up debt, highest to lowest rate (tax adjusted of course) and hack away at it all. It's part of the big picture like any other debt, save for the cases where it can be cancelled. Personal finance is exactly that, personal. Advisors (the good ones) make their money by looking carefully at the big picture and not offering a cookie-cutter approach.\"",
"title": ""
},
{
"docid": "574438",
"text": "\"It's a decision that only you can make. What are the chances that you'll want to take another loan (any loan - car, credit card, installment plan for new fridge, whatever else)? What are the chances that with the bad credit you'll find it hard to rent a place (and in Cali it's hard to rent a place right now, believe me, I bought a place just to save on the rent)? What are the chances that the prices will bounce and your \"\"on-paper\"\" loss will be recovered by the time you actually need/want to sell the house? You have to check all these and make a wise decision considering all the pros and cons in your personal case.\"",
"title": ""
},
{
"docid": "202140",
"text": "Is it worth saving HSA funds until retirement? Yes Are there pros and cons from a tax perspective? Mostly pros. This has all of the benefits of an IRA, but if you use it for medical expenses then you get to use the money tax free on the other side. Retirement seems to be the time you are most likely to need money for medical expenses. So why wouldn't you want to start saving tax free to cover those expenses? The cons are similar to other tax advantaged retirement accounts. If you withdraw before retirement time for non-medical purposes, you will pay penalties, but if you withdraw at retirement time, you will pay the same taxes you would pay on an IRA. I should note that I put my money where my mouth is and I max out my contribution to my HSA every year.",
"title": ""
}
] |
126194
|
Alice is a reworking of a film.
|
[
{
"docid": "Alice_(1990_film)",
"text": "Alice is a 1990 American romantic fantasy film written and directed by Woody Allen and starring Mia Farrow , Joe Mantegna and William Hurt . The film is a loose reworking of Federico Fellini 's 1965 film Juliet of the Spirits . Alice received mildly positive reviews .",
"title": ""
}
] |
[
{
"docid": "Alice_Adams",
"text": "Alice Adams may refer to : Alice Adams ( novel ) , a 1921 Pulitzer Prize -- winning novel by Booth Tarkington Alice Adams ( 1923 film ) , a 1923 film based on the novel by Booth Tarkington Alice Adams ( film ) , a 1935 film based on the novel by Booth Tarkington Alice Adams ( writer ) ( 1926 -- 1999 ) , American novelist and writer from Fredericksburg , Virginia Alice Adams ( artist ) ( born 1930 ) , American artist Adams , Alice",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(Disney_film)",
"text": "Alice in Wonderland is the name of several films produced by The Walt Disney Company based on Lewis Carroll 's novels Alice 's Adventures in Wonderland and Through the Looking-Glass : Alice in Wonderland ( 1951 film ) , an animated film directed by Clyde Geronimi , Wilfred Jackson , and Hamilton Luske Alice in Wonderland ( 2010 film ) , a live-action film directed by Tim Burton Alice in Wonderland : Through the Looking Glass , a planned sequel to the 2010 film",
"title": ""
},
{
"docid": "The_Space_Between_Us_(album)",
"text": "The Space Between Us is the debut solo album by Craig Armstrong , originally released in 1998 on Melankolic Records . Elizabeth Fraser of Cocteau Twins contributes vocals to the track `` This Love '' , and The Blue Nile 's Paul Buchanan appears on `` Let 's Go Out Tonight '' , which is a rework of the song of the same name by Blue Nile . The first track , `` Weather Storm '' , is a reworking of a song by the same name which appears on Massive Attack 's 1994 album , Protection , to which Armstrong contributed . Similarly , `` Sly II '' is a reworked version of Massive Attack 's `` Sly '' , also from Protection . `` Balcony Scene '' is a reworked version of `` Time Stands Still , '' from the score of the 1996 film Romeo + Juliet ; it contains elements of `` Kissing You '' by Des ` ree , as well as a quote from the film .",
"title": ""
},
{
"docid": "Black_Alice",
"text": "Black Alice may refer to : Black Alice ( comics ) , a DC Comics character Black Alice ( novel ) , a novel by Thomas M. Disch and John Sladek under the pseudonym Thom Demijohn Black Alice , one of two musical alter-egos of the Japanese group Ali Project Black Alice ( film ) , a 1975 Hong Kong film Black Alice , a character in the sci-fi cult film '' Sons of Steel portrayed by Perth-based singer Rob Hartley",
"title": ""
},
{
"docid": "Alice_(1988_film)",
"text": "Alice is a 1988 dark fantasy film written and directed by Jan Švankmajer . Its original Czech title is Něco z Alenky , which means `` Something from Alice '' . It is a loose adaptation of Lewis Carroll 's first Alice book , Alice 's Adventures in Wonderland ( 1865 ) , about a girl who follows a white rabbit into a bizarre fantasy land . Alice is played by Kristýna Kohoutová . The film combines live action with stop motion animation , and is distinguished by its dark and uncompromising production design . For Švankmajer , a prolific director of short films for more than two decades , Alice became his first venture into feature-length filmmaking . The director had been disappointed by other adaptations of Carroll 's book , which interpret it as a fairy tale . His aim was instead to make the story play out like an amoral dream . The film won the feature film award at the 1989 Annecy International Animated Film Festival .",
"title": ""
},
{
"docid": "Alice_Evans_(disambiguation)",
"text": "Alice Evans is an actress . Alice Evans may also refer to : Alice Catherine Evans , microbiologist Alice Evans , character in 3:10 to Yuma ( 1957 film ) Alice Evans , character in Deadline ( 2009 film )",
"title": ""
},
{
"docid": "Alice,_Sweet_Alice",
"text": "Alice , Sweet Alice ( originally known as Communion and also known as Holy Terror ) is a 1976 American slasher film co-written and directed by Alfred Sole , and starring Linda Miller , Paula Sheppard , and Brooke Shields in her film debut . The narrative focuses on a troubled adolescent girl who becomes a suspect in the brutal murder of her popular younger sister at her first communion . The film premiered at the Chicago International Film Festival under the title Communion in November 1976 , and was released theatrically as Alice , Sweet Alice in 1978 . It was re-released a third time as Holy Terror in 1981 , marketing upon the popularity of Brooke Shields after her notorious performance in Louis Malle 's Pretty Baby ( 1978 ) . The film ranked # 89 on Bravo 's The 100 Scariest Movie Moments for the scene when Alice scares Karen in the warehouse . In 1977 there was a book adaptation of the film titled Communion by Frank Lauria . While not prosecuted for obscenity , the film was seized and confiscated in the UK under Section 3 of the Obscene Publications Act 1959 during the video nasty panic .",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(1951_film)",
"text": "Alice in Wonderland is a 1951 American animated musical fantasy-comedy film produced by Walt Disney Productions and based on the Alice books by Lewis Carroll . The 13th of Disney 's animated features , the film premiered in New York City and London on July 26 , 1951 . The film features the voices of Kathryn Beaumont as Alice , Sterling Holloway as the Cheshire Cat , Verna Felton as the Queen of Hearts , and Ed Wynn as the Mad Hatter . Walt Disney first attempted unsuccessfully to adapt Alice into an animated feature film during the 1930s . However , he finally revived the idea in the 1940s . The film was originally intended to be a live-action/animated film ; however , Disney decided to make it an all-animated feature in 1946 . The theme song of the same name has since become a jazz standard . While the film was critically panned on its initial release , the movie proved to be ahead of its time and has since been regarded as one of Disney 's greatest animated classics , notably one of the biggest cult classics in the animation medium , as well as one of the best film adaptations of Alice .",
"title": ""
},
{
"docid": "Alice's_Wonderland",
"text": "Alice 's Wonderland is a 1923 Walt Disney short silent film , produced in Kansas City , Missouri . The black-and-white short was the first in a series of Walt Disney 's famous Alice Comedies and had a working title of Alice in Slumberland . The film was never shown theatrically , but was instead shown to prospective film distributors . It was included as a bonus feature in the Special `` Un-Anniversary Edition '' of Alice in Wonderland .",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(1976_film)",
"text": "Alice in Wonderland ( sometimes listed as Alice in Wonderland : An X-Rated Musical Comedy ) is a 1976 American musical fantasy adult erotic film , loosely based on Lewis Carroll 's book Alice 's Adventures in Wonderland . It was directed by Bud Townsend and starred Kristine De Bell as Alice . The film was favorably reviewed by film critic Roger Ebert in 1976 . The film initially received an X-rating in 1976 and subsequently , an R-rating a year later with three minutes cut from the film . It was later re-released on VHS with a somewhat grandiose title roll preceding the movie noting that quite a bit of hardcore footage had originally been shot , but `` could not be included '' at the time .",
"title": ""
},
{
"docid": "Alice_Neel_(film)",
"text": "Alice Neel is a 2007 documentary film about the life of Alice Neel , exploring the struggles she faced as a woman artist , a single mother , and a painter who defied convention . The documentary was directed by Neel 's grandson , Andrew Neel . Alice Neel premiered at The Sundance Film Festival in 2007 and later won the Audience Award at the 2007 Newport Beach Film Festival later that year . The film was produced by SeeThink Productions .",
"title": ""
},
{
"docid": "Alice_or_the_Last_Escapade",
"text": "Alice or the Last Escapade ( Alice ou la dernière fugue ) is a 1977 film written and directed by Claude Chabrol . The film is very loosely inspired by Alice 's Adventures in Wonderland by Lewis Carroll , including the protagonist 's name being Alice Carroll ( a combination of the Alice character and the author 's pseudonymous surname ) .",
"title": ""
},
{
"docid": "Alice's_Restaurant_(film)",
"text": "Alice 's Restaurant is a 1969 American comedy film co-written and directed by Arthur Penn. . It is an adaptation of the 1967 folk song `` Alice 's Restaurant Massacree , '' originally written and sung by Arlo Guthrie . The film stars Guthrie as himself , with Pat Quinn as Alice Brock and James Broderick as Ray Brock . Contrary to popular belief , while Arlo Guthrie wrote the lyrics and music for the narrative song `` Alice 's Restaurant Massacree , '' he neither wrote nor co-wrote the screenplay for the film Alice 's Restaurant , which was instead co-written by Venable Herndon and Arthur Penn. . Alice 's Restaurant was released on August 19 , 1969 , a few days after Guthrie appeared at the Woodstock Festival . A soundtrack album for the film was also released by United Artists Records . The soundtrack includes a studio version of the title song , which was originally divided into two parts ( one for each album side ) ; a 1998 CD reissue on the Rykodisc label presents this version of the song in full , and adds several bonus tracks to the original LP .",
"title": ""
},
{
"docid": "Siren_(Ruby_Gloom_song)",
"text": "`` Siren '' is a single released by Nana Kitade under the pseudonym Ruby Gloom . The title track `` Siren '' is being used as the theme song for the Japanese release of the Canadian animation Ruby Gloom . The limited edition of this single comes with a DVD . The single was produced by former Megadeth guitarist , Marty Friedman , who also produced her reworks of `` Kesenai Tsumi '' , and Alice From her `` Berry Berry Singles '' Album .",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(franchise)",
"text": "Alice in Wonderland is a Disney media franchise , commencing in 1951 with the theatrical release of the film Alice in Wonderland . The film is an adaptation of the books by Lewis Caroll , which featured his character Alice . A live-action film directed by Tim Burton was released in 2010 .",
"title": ""
},
{
"docid": "Alice_(Avril_Lavigne_song)",
"text": "`` Alice '' is a song written and performed by Avril Lavigne for Almost Alice , the soundtrack to the 2010 film Alice in Wonderland . An extended version was released as a hidden track on Lavigne 's fourth studio album , Goodbye Lullaby . The song is a mid-tempo ballad sung from the perspective of the film 's lead character , Alice . Lavigne wrote the song after asking Disney executives and film director Tim Burton if she could write a song for the film . The song was produced by Butch Walker and mixed by Lavigne 's former husband Deryck Whibley .",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(1931_film)",
"text": "Alice in Wonderland ( 1931 ) is an independently made black-and-white Pre-Code American film based on Lewis Carroll 's 1865 novel Alice 's Adventures in Wonderland , directed by Bud Pollard , produced by Hugo Maienthau , and filmed at Metropolitan Studios in Fort Lee , New Jersey . This was the first sound version of the story , and therefore the first film in which Carroll 's original dialogue was heard . The film starred Ruth Gilbert as Alice and Leslie King as the Mad Hatter . The film opened at the Warner Theatre in New York City .",
"title": ""
},
{
"docid": "Alice_Through_the_Looking_Glass_(1987_film)",
"text": "Alice Through the Looking Glass is a 1987 Australian-Italian animated film nominally based on the novel Through the Looking-Glass by Lewis Carroll . It was directed by Andrea Bresciani and Richard Slapczynski from a screenplay by Jameson Brewer . The movie starts off with a bored Alice trapped in her house by a snow storm . The film 's voice cast includes Janet Waldo as Alice , Mr. T. as the Jabberwock , Phyllis Diller as the White Queen , Jonathan Winters as Tweedledum and Tweedledee , and Alan Young as the White Knight . Much of the film consists of Alice and a jester named Tom Fool ( Townsend Coleman ) journeying through some of the incidents of the novel , while ultimately , the film is more about Alice finding an imaginary friend in Tom Fool than the novel 's themes of logic , illogic , and reversal . The film also throws in Heffalumps , rock-throwing cavemen , Ed Sullivan , The Marx Brothers ( Hal Rayle ) and Humpty Dumpty ( George Gobel ) . There is also a man made entirely out of newspaper , a talking horse and a talking goat . When Alice wakes up , her father plays a game of chess with her , which her dream journey was based on , walking from square to square on a large chessboard .",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(1988_film)",
"text": "Alice in Wonderland is an Australian 51-minute direct-to-video animated film from Burbank Films Australia . It was originally released in 1988 . The film is based on Lewis Carroll 's classic English novel , Alice 's Adventures in Wonderland , first published in 1865 , and was adapted by Paul Leadon . Unlike many other adaptations of the novel , this one did not borrow elements from its sequel , Through the Looking-Glass ( 1871 ) , combined into one film . The production company produced a 73-minute adaptation of the second novel the year before , in 1987 , entitled Alice : Through the Looking-Glass . The 1988 film was produced by Roz Phillips and directed by Rich Trueblood . Quite uncommon among Burbank Films Australia 's adaptations of classic literary works , Alice in Wonderland featured one original theme song , composed by Mark Isaacs . The copyright in this film is now owned by Pulse Distribution and Entertainment and administered by digital rights management firm NuTech Digital .",
"title": ""
},
{
"docid": "Alice_in_Murderland",
"text": "Alice in Murderland may refer to : Alice in Murderland ( manga ) , a Japanese manga series by Kaori Yuki that began in 2014 Alice in Murderland ( film ) , a 2010 American horror film",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(1949_film)",
"text": "Alice in Wonderland ( Alice au pays des merveilles ) is a 1949 French film based on Lewis Carroll 's fantasy novel Alice 's Adventures in Wonderland . Directed by Dallas Bower , the film stars Carol Marsh as Alice , Stephen Murray as Lewis Carroll , and Raymond Bussières as The Tailor . Most of the Wonderland characters are portrayed by stop-motion animated puppets created by Lou Bunin . All of the other live actors in the film are seen only in the live action scenes . However , they lend their voices to the Wonderland characters , and the staging of the scenes in England vs. the scenes in Wonderland is reminiscent of the Kansas scenes vs. the Oz scenes in The Wizard of Oz , in that several of the live-action characters seem to have counterparts ( of sorts ) in Wonderland . Among the other live actors are Pamela Brown as the Queen and as the voice of the Queen of Hearts . Stephen Murray is seen as Lewis Carroll and provides the voice of the Knave of Hearts , and Felix Aylmer , who played Polonius in Olivier 's Hamlet , plays Dr. Liddell , father of Alice Liddell , the real-life inspiration for Alice ; he also provides the voice of the Cheshire Cat . Carol Marsh was 20 years old when she played the part of Alice - conceived by the novel 's author as 7 years old .",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(1999_film)",
"text": "Alice in Wonderland is a 1999 made-for-television film adaptation of Lewis Carroll 's books Alice 's Adventures in Wonderland and Through the Looking-Glass . It was first broadcast on NBC and then shown on British television on Channel 4 . Tina Majorino played the lead role of Alice , and a number of well-known performers portrayed the eccentric characters whom Alice meets during the course of the story , including Ben Kingsley , Ken Dodd , Martin Short , Whoopi Goldberg , Peter Ustinov , Christopher Lloyd , Gene Wilder , Robbie Coltrane and Miranda Richardson . The film won four Emmy Awards in the categories of costume design , makeup , music composition , and visual effects . The film was re-released as a special edition DVD on March 2 , 2010 , featuring an additional five minutes of footage .",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(1915_film)",
"text": "Alice in Wonderland is a 1915 silent film adaptation of Lewis Carroll 's classic novel , Alice 's Adventures in Wonderland , directed and written by W. W. Young and starring Viola Savoy as Alice . This film version is notable for depicting much of the ` Father William ' poem and it includes footage resembling Tenniel 's illustration of Father William doing his back-somersault at the front door .",
"title": ""
},
{
"docid": "Alice_in_Murderland_(film)",
"text": "Alice in Murderland , also known as The Alice in Wonderland Murders , is a low budget American horror film written and directed by Dennis Devine . The film , produced in 2010 , stars Malerie Grady , Marlene McCohen , Kelly Kula and Christopher Senger . The film has received negative reviews by critics and horror fans .",
"title": ""
},
{
"docid": "Alice_Walker:_Beauty_in_Truth",
"text": "Alice Walker : Beauty in Truth is a documentary film directed by Pratibha Parmar , made by Kali Films production company . The film follows the life of the Pulitzer Prize-winning author , poet and activist Alice Walker . Shooting began in May 2011 . It was aired on the BBC on Monday July 8 , 2013 , and on PBS on February 7 , 2014 . Alice Walker and Pratibha Palmer have previously collaborated on A Place of Rage and Warrior Marks .",
"title": ""
},
{
"docid": "Alice_Through_the_Looking_Glass_(2016_film)",
"text": "Alice Through the Looking Glass is a 2016 American fantasy adventure film directed by James Bobin , written by Linda Woolverton and produced by Tim Burton , Joe Roth , Suzanne Todd and Jennifer Todd . It is based on the characters created by Lewis Carroll and is the sequel to the 2010 film Alice in Wonderland . The film stars Johnny Depp , Anne Hathaway , Mia Wasikowska , Matt Lucas , Rhys Ifans , Helena Bonham Carter and Sacha Baron Cohen and features the voices of Stephen Fry , Michael Sheen , Timothy Spall and Alan Rickman , in his final film role . In the film , Alice comes across a magical looking glass that takes her back to Wonderland , where she finds that the Mad Hatter is acting madder than usual and wants to discover the truth about his family . Alice then travels through time ( with the `` Chronosphere '' ) , comes across friends and enemies at different points of their lives , and embarks on a race to save the Hatter before time runs out . The film premiered in London on May 10 , 2016 , and was theatrically released by Walt Disney Pictures on May 27 , 2016 . It under-performed at the box office in comparison with the first film 's gross .",
"title": ""
},
{
"docid": "Alice_in_Wonderland_(1903_film)",
"text": "Alice in Wonderland is a 1903 British silent film directed by Cecil Hepworth and Percy Stow . Only one copy of the original film is known to exist . The British Film Institute ( BFI ) partially restored the movie and its original film tinting and released it in 2010 . According to BFI , the original film ran about 12 minutes ; the restoration runs 9 minutes and 35 seconds . At the beginning of the restoration , it states that this is the first movie adaptation of Lewis Carroll 's children 's book Alice 's Adventures in Wonderland . The film is memorable for its use of special effects , including Alice 's shrinking in the Hall of Many Doors , and in her large size , stuck inside of White Rabbit 's home , reaching for help through a window . It is now available from several sources , and is included as a bonus feature on a 1996 BBC DVD . It is also included in the Vintage Cinema : Experiments in early film 1900s DVD .",
"title": ""
},
{
"docid": "Dear_Alice",
"text": "Dear Alice ( För kärleken ) is a 2010 Swedish drama film directed by Othman Karim starring Danny Glover , Tuva Novotny and Peter Gardiner . The film is written by Karim and Grace Maharaj-Eriksson . Dear Alice competed at the 2010 Moscow Film Festival .",
"title": ""
},
{
"docid": "Alice_Smith_(disambiguation)",
"text": "Alice Smith ( born 1978 ) is an American singer and songwriter . Alice Smith may also refer to : Alice Smith School , Kuala Lumpur , Malaysia Alice Mary Smith ( 1839 -- 1884 ) , English composer Alice Smith , a character in the 1990 film Alice",
"title": ""
},
{
"docid": "Berry_Berry_Singles",
"text": "Berry Berry Singles is an album by Nana Kitade , released in November 2007 . It is her first compilation album , and it features the singles `` Kesenai Tsumi '' , `` Kiss or Kiss '' , and the single `` Antoinette Blue '' , and more for nine songs total . Also features three bonus tracks including a reworking of `` Kesenai Tsumi '' and `` Alice '' with former Megadeth guitarist Marty Friedman and a cover of Daisy Chainsaw 's `` Love Your Money '' . Limited edition includes bonus DVD with documentary footage of Nana 's performance in Paris and an interview of her and Marty Friedman .",
"title": ""
}
] |
184647
|
Augusto Pinochet remained the Commander-in-Chief of the Chilean Army until the late 1980s.
|
[
{
"docid": "Augusto_Pinochet",
"text": "Augusto José Ramón Pinochet Ugarte ( -LSB- auˈɣusto pinoˈ ( t ) ʃe -RSB- or -LSB- - ˈ ( t ) ʃet -RSB- 25 November 1915 -- 10 December 2006 ) was a Chilean general , politician and the military ruler of Chile between 1973 and 1990 ; he remained the Commander-in-Chief of the Chilean Army until 1998 . He was also president of the Government Junta of Chile between 1973 and 1981 . His rule of Chile was a dictatorship . Pinochet assumed power in Chile following a United States-backed coup d'état on 11 September 1973 that overthrew the democratically elected socialist Unidad Popular government of President Salvador Allende and ended civilian rule . Several academics have stated that the support of the United States was crucial to the coup and the consolidation of power afterward . Pinochet had been promoted to Commander-in-Chief of the Army by Allende on 23 August 1973 , having been its General Chief of Staff since early 1972 . In December 1974 , the ruling military junta appointed Pinochet Supreme Head of the nation by joint decree , although without the support of one of the coup 's instigators , Air Force General Gustavo Leigh . From the start of the new military government harsh measures were implemented . During the period of Pinochet 's rule , various investigations have identified the murder of 1,200 to 3,200 people with up to 80,000 people forcibly interned and as many as 30,000 tortured . According to the Chilean government , the official number of deaths and forced disappearances stands at 3,095 . Under the influence of the free market-oriented neoliberal `` Chicago Boys '' , the military government implemented economic liberalization , including currency stabilization , removed tariff protections for local industry , banned trade unions and privatized social security and hundreds of state-owned enterprises . These policies produced what has been referred to as the `` Miracle of Chile , '' but critics state that economic inequality dramatically increased and attribute the devastating effects of the 1982 monetary crisis on the Chilean economy to these policies . Chile was , for most of the 1990s , the best-performing economy in Latin America , though the legacy of Pinochet 's reforms continues to be in dispute . Pinochet 's 17-year rule was given a legal framework through a controversial 1980 plebiscite , which approved a new Constitution drafted by a government-appointed commission . In a 1988 plebiscite 56 % voted against Pinochet 's continuing as president , which led to democratic elections for the Presidency and Congress . After stepping down in 1990 , Pinochet continued to serve as Commander-in-Chief of the Chilean Army until 10 March 1998 , when he retired and became a senator-for-life in accordance with his 1980 Constitution . However , Pinochet was arrested under an international arrest warrant on a visit to London on 10 October 1998 in connection with numerous human rights violations . Following a legal battle he was released on grounds of ill-health , and returned to Chile on 3 March 2000 . In 2004 , Chilean Judge Juan Guzmán Tapia ruled that Pinochet was medically fit to stand trial and placed him under house arrest . By the time of his death on 10 December 2006 , about 300 criminal charges were still pending against him in Chile for numerous human rights violations during his 17-year rule , and tax evasion and embezzlement during and after his rule ; he was accused of having corruptly amassed at least 28 million USD . Despite the indictment and 300 charges , he only served time in house arrest .",
"title": ""
}
] |
[
{
"docid": "Juan_Emilio_Cheyre",
"text": "Juan Emilio Cheyre Espinoza ( born October 10 , 1947 ) is a retired Chilean Army General . He was Commander-in-Chief of the Chilean Army from 2002 to 2006 . As Commander-in-Chief he attempted to distance the Army from former dictator General Augusto Pinochet , and condemned the human rights abuses of Pinochet 's dictatorship . In 1973 he handed over a two years old child , whose parents had been murdered by the army , to a nunnery . In 2003 , Cheyre as Commander-in-Chief of the Army issued an historically relevant document titled `` Chilean Army : End of a Vision , '' in which he stated that `` never again '' could the circumstances that led Chile to the collapse of its democracy be met . Cheyre was succeeded as Commander-in-Chief by Army General Oscar Izurieta on March 10 , 2006 . He worked later as an academic at the Pontifical Catholic University of Chile . In 2013 he was appointed as president of the `` Servicio de Registro Electoral '' , but few months later he withdraw from his office as consequence of the controverse about his acts in 1973 as he handed over a child .",
"title": ""
},
{
"docid": "Carlos_Prats",
"text": "General Carlos Prats González ( February 24 , 1915 -- September 30 , 1974 ) was a Chilean Army officer and minister in the Salvador Allende 's government , despite being at the time the Commander-in-chief of the Chilean Army . Immediately after General Augusto Pinochet 's September 11 , 1973 coup , Prats went into voluntary exile in Argentina . The following year , he and his wife were assassinated in Buenos Aires by a car bomb , revealed as committed by the DINA .",
"title": ""
},
{
"docid": "Death_of_Salvador_Allende",
"text": "Salvador Allende , President of Chile , died of self-inflicted gunshot wounds on September 11 , 1973 during a coup d'état led by the Chilean Army Commander-in-Chief Augusto Pinochet . After decades of suspicions that Allende might have been assassinated by the Chilean Armed Forces , a Chilean court in May 2011 authorized the exhumation and autopsy of Allende 's remains . A team of international experts examined the remains and concluded that the former president had shot himself with an AK-47 assault rifle . In December 2011 the judge in charge of the investigation affirmed the experts ' findings and ruled Allende 's death a suicide . On September 11 , 2012 , the 39th anniversary of Allende 's death , a Chilean appeals court unanimously upheld the trial court 's ruling , officially closing the case . According to Isabel Allende Bussi -- the daughter of Salvador Allende and currently a member of the Chilean Senate -- the Allende family has long accepted that the former President shot himself , telling the BBC that : `` The report conclusions are consistent with what we already believed . When faced with extreme circumstances , he made the decision of taking his own life , instead of being humiliated . ''",
"title": ""
},
{
"docid": "Marcelo_Moren_Brito",
"text": "Marcelo Luis Manuel Moren Brito ( July 27 , 1935 -- September 11 , 2015 ) was a Chilean retired Army colonel and former agent of the Dirección de Inteligencia Nacional ( DINA ) , the defunct Chilean secret police , during the Pinochet dictatorship from 1973 t0 1990 . During the rule of President Augusto Pinochet , Moren Brito , who was nicknamed `` el Coronta '' and `` el Ronco , '' was the chief of operations at DINA , as well as the head of the Villa Grimaldi , DINA 's feared detention center in Peñalolén , where thousands of political prisoners were interrogated and tortured . He was a member of a death squad of Chilean Army officers who carried out the 1973 , Caravan of Death , in which at least 75 individuals in military custody were executed , including the singer Víctor Jara . Moren Brito was accused of the widespread abductions , disappearances , murder and the torture of political opponents of the Pinochet regime . La Tercera , the daily Chilean newspaper , wrote that Moren Briten was `` associated with some of the cruelest actions of repression against dissidents of the military government of Augusto Pinochet . '' Moren Brito was convicted of crimes against humanity and sentenced to more than 300 years in prison . He was incarcerated for life at Punta Peuco Prison , which was constructed in 1995 specifically for individuals convicted of human rights abuses . He died from multiple organ failure at Hospital Militar de Santiago , where he had been admitted earlier in the week due to declining health , on September 11 , 2015 , at the age of 80 .",
"title": ""
},
{
"docid": "Dirección_de_Inteligencia_Nacional",
"text": "The Dirección de Inteligencia Nacional ( National Intelligence Directorate ) or DINA was the Chilean secret police in the government of Augusto Pinochet , and has been called Pinochet 's Gestapo . The DINA was established in November 1973 , as a Chilean Army intelligence unit headed by Colonel Manuel Contreras and vice-director Raúl Iturriaga . It was separated from the army and made an independent administrative unit in June 1974 , under the aegis of Decree 521 . The DINA existed until 1977 , after which it was renamed the Central Nacional de Informaciones ( CNI ) ( National Information Center ) . In 2008 the Chilean Army presented a list of 1,097 DINA agents to Judge Alejandro Solís .",
"title": ""
},
{
"docid": "Gerardo_Huber",
"text": "Gerardo Huber Olivares ( disappeared 29 January 1992 ; body found 20 February 1992 ) was a Chilean Army Colonel and agent of the DINA , Chile 's intelligence agency . He was in charge of purchasing weapons abroad for the army . Huber was assassinated shortly before he was due to testify before Magistrate Hernán Correa de la Cerda in a case concerning the illegal export of weapons to the Croatian army . That enterprise involved 370 tons of weapons sold to the Croatian government by Chile on 7 December 1991 , when Croatia was under a United Nations embargo arising from the war in Yugoslavia . In January 1992 , Magistrate Correa sought testimony from Huber on the deal . However , Huber may well have been silenced to avoid implicating former Chilean President and then-Commander-in-Chief of the Army Augusto Pinochet , who was himself awaiting trial on related charges .",
"title": ""
},
{
"docid": "Pinocheques",
"text": "Pinocheques were three cheques of total US$ 3,000,000 paid in mid-1989 by the Chilean army to Augusto Pinochet , Jr. , the son of Augusto Pinochet for the purchase of bankrupt `` Valmoval '' , a small rifle company in 1987 . Pinochet 's son was not under the rifle company 's owner and no reason could be found for the payment . The payment was investigated 1990 by a parliamentary investigative committee chaired by Jorge Schaulson . On 19 December 1990 Pinochet stormed into the army headquarters and placed the 57,000 member force in alert , in what the general called a `` ejercicio de enlace '' ( Spanish for Link exercise ) and asked for an end to the investigation . Similar pressure was applied in May 1993 again with boinazo ( Spanish for Putsch with the beret ) . The Chilean justice system continued to investigate the payment , but in 1994 as the Chilean Supreme court had to make a decision , the President of Chile Eduardo Frei Ruiz-Tagle asked them to stop the case for reasons of state . The disclosure of the Riggs Bank accounts reignited in 2005 the case against General Pinochet in Chile . Judge Manuel Valderrama investigated whether the three purchase checks for Valmoval wound up in Pinochet 's secret accounts , but in 2010 the suit was discontinued without results . The armed forces ' ejercicio de enlace-standoff was the worst crisis of the ( then ) 3-year-old coalition government of President Patricio Aylwin .",
"title": ""
},
{
"docid": "Gregorio_Rodríguez_Tascón",
"text": "Gregorio Rodríguez Tascón ( born 1901 ) was a Chilean Army general known for his work on geopolitics and his presidency of the Chilean Commission on Border Limits ( Comisión Chilena de Límites ) where he dealt with the Laguna del Desierto issue . Heading the chair of geography and geopolitics at the Chilean War Academy he lectured several outstanding students like René Schneider , Carlos Prats and Gustavo Serrano Mahns whom he at times invited home for dinner . Another of his students was Augusto Pinochet who given his interest in geopolitics was granted a slot an assistant teacher in the geography and geolitics chair , and later Pinochet succeeded him in the chair . Relatives recall Gregorio Rodríguez Tascón considered that Pinochet 's book Geopolítica ( 1968 ) contained plagiarism of a 1949 conference he had held and left Pinochet 's request for a foreword to the book unanswered . He retired from the army in 1961 but continued to work for the Chilean state as a specialist on border issues , in particular the Laguna del Desierto case .",
"title": ""
},
{
"docid": "José_Toribio_Merino",
"text": "José Toribio Merino Castro ( December 14 , 1915 -- August 30 , 1996 ) was a Chilean admiral who was one of the principal leaders of the 1973 Chilean coup d'état , along with General Augusto Pinochet of the Army , General Gustavo Leigh of the Air Force , and General César Mendoza of the Carabineros ( national police ) . Together they established a military government that ruled Chile from 1973 until 1990 .",
"title": ""
},
{
"docid": "Alejandrina_Cox_incident",
"text": "The Alejandrina Cox Incident was a traffic incident in Santiago , Chile on 27 June 1973 involving Army General Carlos Prats , then Minister of the Interior and commander-in-chief of the Chilean Armed Forces , and a civilian woman named Alejandrina Cox ( born 1921 , died 2015 ) . It is historically significant because , due to the excessive reaction of Carlos Prats to this incident , the general lost the support of the Chilean military , leading to his eventual resignation and replacement by Augusto Pinochet in August 1973 . Prats was a well-known adherent of the Schneider Doctrine , and thus opposed to any sort of military intervention in the civilian government of President Salvador Allende . Due to this incident , the last senior officer opposed to military intervention in the increasingly polarized and disintegrating political situation of the Allende government was forced out , thus paving the way for an eventual coup d'état on September 11 , 1973 , exactly one month after Prats resigned .",
"title": ""
},
{
"docid": "Vivianne_Blanlot",
"text": "Vivianne Amelia Blanlot Soza ( born October 22 , 1956 in La Serena , Chile ) is a Chilean economist and politician . Her father Jorge Enrique Blanlot was an Army captain , and her grandfather General Enrique Blanlot Reisig . She has a degree in economics from the Pontifical Catholic University of Chile and MA in the same discipline applied by the American University in the United States . Between 1980 and 1990 she served as an economist in charge of the evaluation of investments and programs in the area of energy , mining , water and road infrastructure in the Inter-American Development Bank ( IDB ) . She was executive director of the National Environmental Commission ( CONAMA ) between 1995 and 1997 in Chile . In 2000 she took over as executive secretary of the National Energy Commission ( CNE ) , serving until 2003 , after differences of opinion with the minister , Jorge Rodríguez Grossi . In 2005 she joined the board of BancoEstado and worked as a consultant in the areas of energy and environment for telecommunications company IGT . In 2006 President Michelle Bachelet appointed her as Minister of National Defense . She acted as the only government representative at the funeral of former dictator Augusto Pinochet , where she faced boos from Pinochet supporters . She was replaced by Jose Goni Carrasco in March 2007 . In late 2011 she was appointed as a member of the Council for Transparency . In 2012 she joined the board of Colbún , a Chilean power generation and trading company . She married twice , first to Oscar Alvarez ; after his death she married , and later separated from , Enrique Mendez .",
"title": ""
},
{
"docid": "Chilean_constitutional_referendum,_1980",
"text": "A constitutional referendum was held in Chile on 11 September 1980 . The proposed new constitution would replace the 1925 constitution , and was approved by over two-thirds of voters . The new constitution ensured that Augusto Pinochet could remain as President of the Republic for a further eight years with increased powers , after which he would face a re-election referendum . Further reforms , beginning in 1989 and most recently in 2005 , have attempted to make the constitution more democratic .",
"title": ""
},
{
"docid": "Julio_Numhauser",
"text": "Julio Numhauser is a Chilean musician of the Nueva Canción-movement . He founded the folk music group Quilapayún in 1965 together with the brothers , Julio Carrasco and Eduardo Carrasco , where he stayed until 1967 . 1968 he founded the folk music group , Amerindios , together with Mario Salazar . In 1980 he founded the group Somos with Francisco Ibarra and Oscar Salazar . He left chile in 1973 due to the dictatorship of Augusto Pinochet . In 1975 he moved to Sweden where he still is living today . In 2000 he was chosen cultural attaché of the Chilean embassy in Sweden by the Chilean president Ricardo Lagos .",
"title": ""
},
{
"docid": "Chilean_Council_of_State",
"text": "The Chilean Council of State was a body set up by the junta of General Augusto Pinochet to produce a constitution in order to legitimise military rule . The constitution which it produced was approved in a 1980 plebiscite . The President of the Council of State was former President Jorge Alessandri .",
"title": ""
},
{
"docid": "1973_Chilean_coup_d'état",
"text": "The 1973 Chilean coup d'état was a watershed event in both the history of Chile and the Cold War . Following an extended period of social unrest and political tension between the right-controlled Congress of Chile and the socialist President Salvador Allende , as well as economic warfare ordered by US President Richard Nixon , Allende was overthrown by the armed forces and national police . The military deposed Allende 's Popular Unity government and later established a junta that suspended all political activity in Chile and repressed left-wing movements , especially the communist and socialist parties and the Revolutionary Left Movement ( MIR ) . Allende 's appointed army chief , Augusto Pinochet , rose to supreme power within a year of the coup , formally assuming power in late 1974 . The United States government , which had worked to create the conditions for the coup , promptly recognized the junta government and supported it in consolidating power . During the air raids and ground attacks that preceded the coup , Allende gave his last speech , in which he vowed to stay in the presidential palace , refusing offers of safe passage should he choose exile over confrontation . Direct witness accounts of Allende 's death agree that he killed himself in the palace . Before the coup , Chile had for decades been hailed as a beacon of democracy and political stability while the rest of South America had been plagued by military juntas and Caudillismo . The collapse of Chilean democracy ended a streak of democratic governments in Chile , which had held democratic elections since 1932 . Historian Peter Winn characterized the 1973 coup as one of the most violent events in Chile 's history . A weak insurgent movement against the Pinochet regime was maintained inside Chile by elements sympathetic to the former Allende government . An internationally supported plebiscite in 1988 led Pinochet to relinquish power .",
"title": ""
},
{
"docid": "Juan_Bustos",
"text": "Juan Bustos ( December 8 , 1935 , Santiago -- August 7 , 2008 ) was a Chilean politician , law professor and lawyer . He served as the President of the Chamber of Deputies of Chile from March 13 , 2008 until his death on August 7 , 2008 . He was known as an ardent opponent of the Augusto Pinochet dictatorship and the human rights abuses committed by the regime . Bustos lived in exile for 14 years while Chile was ruled by the Pinochet military junta from 1973 until 1990 . After his return he played a major role in uncovering cases of human rights abuses . Bustons , a top Chilean law professor and human rights lawyer , represented many of the families of people killed by the Pinochet government . During the Pinochet regime , nearly 3,000 people disappeared , while tens of thousands were arrested and tortured . Bustos represented the family of former Chilean Foreign Minister Orlando Letelier , an opponent of Pinochet who was killed by a car bomb in Washington D.C. in 1976 . Letelier 's assassination was linked to Pinochet military intelligence officials . Bustos was first elected as a legislator in 1998 as a member of the Socialist Party of Chile . He served as President of the Chamber of Deputies of Chile on March 13 , 2008 , a position he held until his death in August 2008 . He died before gaining congressional approval for the creation of a new institute to be tasked with investigating the disappearance of thousands of opponents of the Pinochet regime . Bustos died of liver cancer in Santiago , Chile , on August 7 , 2008 , at the age of 72 . He was survived by his wife and seven children . Upon learning of Bustos 's death , President Michelle Bachelet declared three days of national mourning .",
"title": ""
},
{
"docid": "No_(2012_film)",
"text": "No is a 2012 internationally co-produced drama film directed by Pablo Larraín . The film is based on the unpublished play El Plebiscito , written by Antonio Skármeta . Mexican actor Gael García Bernal plays René , an in-demand advertising man working in Chile in the late 1980s . The film captures the historical moment of advertising tactics in political campaigns as in the 1988 plebiscite , when the Chilean citizenry decided whether or not dictator Augusto Pinochet should stay in power for another eight years . At the 85th Academy Awards the film was nominated for the Best Foreign Language Film Oscar .",
"title": ""
},
{
"docid": "Ivo_Basay",
"text": "Ivo Alexis Basay Hatibović ( born 13 April 1966 ) is a retired football striker from Chile , who played professional football for seventeen years . Apart from being a regular choice for the Chile national football team in the late 1980s and early 1990s ( 24 caps , six goals ) , he played club football for Magallanes , Curicó Unido , Everton , Colo Colo , Stade Reims , Necaxa and Boca Juniors . During a radio interview with a Buenos Aires sports show , Basay declared his admiration of Chile 's former Dictator Augusto Pinochet . At the end of the interview Basay was asked rapid fire one phrase questions , he was asked by the host of the Radio Sports Show `` De Caño vale doble '' of AM 770 Radio in Buenos Aires , what was his impression of Pinochet , Basay answered that Pinochet was necessary at a time in Chilean history . On 12 April 2012 Amid club president Hernan Levy 's departure and head coach Basay 's dismissal , Colo Colo looks to regain its confidence under interim head coach Luis Pérez .",
"title": ""
},
{
"docid": "Centre_for_Social_Studies",
"text": "Chile 's Centre for Social Studies ( Spanish : Centro de Estudios Sociales , CESOC ) was founded in Rome , Italy , in 1984 , preceded in 1974 by its publication `` ChileAmérica '' . The founders were mainly left-wing Chilean politicians close to the government of ousted President Salvador Allende , and who had fled into exile following the 1973 coup d'état by general Augusto Pinochet . Among them , the most prominent were Pinochet victim Bernardo Leighton and José Antonio Viera-Gallo Quesney , who later became the first post-Pinochet president of Chile 's Chamber of Deputies ( the lower chamber of parliament ) in the government of Patricio Aylwin . The institution , in receipt of funding by leading Italian socialists including Bettino Craxi and Rino Formica , promoted the academic study of Chilean affairs , with the implicit intent of opposing the Pinochet regime , and favouring a return to democracy in the country . From 1989 onwards , the founding exiles started to return to Chile . In 1991 following the exit from power of General Pinochet , the centre was officially established in Chile 's capital Santiago . Whilst remaining firm to its objectives and its political ideology , its academic work gradually left the place to publishing , and the centre established itself as one of Chile 's most prominent publishing houses . Authors published by CESOC include Chilean politicians Patricio Aylwin , Ricardo Lagos , and Andrés Allamand , as well as scholars Maurizio Giuliano and Jorge Edwards .",
"title": ""
},
{
"docid": "António_Augusto_dos_Santos",
"text": "António Augusto dos Santos was a Portuguese General and commander of the Portuguese forces in Mozambique from 1964 until he was relieved of command in 1969 . On the outbreak of the Mozambican War of Independence in 1964 , Augusto dos Santos commanded the Portuguese forces in that Portuguese territory and favored the use of African units trained by Portuguese regulars who fought alongside the Portuguese Army regulars . General Dos Santos believed in a hearts and minds campaign that resulted in the construction of schools and other infrastructure and the training of African Units to build partner capacity ( a technique that is used today by the U.S. Military in Africa ) . He was relieved by General Kaúlza de Arriaga who took over in 1970 and demonstrated poorer success for the Portuguese in the counterinsurgency operations ( Gordian Knot Operation ) in that the scorched earth policy he pursued turned the people against him . For his efforts in Mozambique Gen dos Santos was awarded the Ordem Militar da Torre e Espada . A year later , Augusto dos Santos began serving as the Portuguese Army Chief of Staff ( Chefes do Estado-Maior do Exército ) , a post he held until 1972 . He was retired at the time of the military coup in Lisbon on 25 April 1974 , which overthrew the Portuguese government headed by Marcelo Caetano and would put to an end the Portuguese Colonial War ( 1961-1974 ) shortly after . He refused to participate in the revolution even though he was asked to participate in the revolutionary government . He withdrew from public life and remained a private citizen until his death .",
"title": ""
},
{
"docid": "Julio_Ponce_Lerou",
"text": "Julio Ponce Lerou is a Chilean billionaire who is the principal shareholder of Soquimich . He is a former son-in-law of Augusto Pinochet . Until 1982 he was president of Chilean state-owned forestry company Complejo Forestal y Maderero Panguipulli while he was simultaneously president of CELCO , a wood pulp company . Ponce is currently accused of a millionaire fraud and embezzlement that affects the pension funds of millions of Chilean citizens under what is known as the `` Cascadas '' case .",
"title": ""
},
{
"docid": "Chilean_national_consultation,_1978",
"text": "A national consultation on President Augusto Pinochet 's political program was held in Chile on 4 January 1978 . After being accused of human rights violations by the United Nations , Pinochet announced a national vote to confirm support for his policies . The ` Yes ' field of the ballot featured a Chilean flag , while the ` No ' field featured a solid black rectangle .",
"title": ""
},
{
"docid": "Lucía_Hiriart",
"text": "María Lucía Hiriart Rodríguez ( born December 10 , 1922 ) , also known as Lucía Hiriart de Pinochet , is the widow of former Chilean general Augusto Pinochet .",
"title": ""
},
{
"docid": "Pinochet_in_Suburbia",
"text": "Pinochet in Suburbia ( retitled Pinochet 's Last Stand for US release ) is a 2006 drama about former Chilean dictator Augusto Pinochet and the attempts to extradite him from Great Britain during his visit there in 1998 for medical treatment . It was written and directed by Richard Curson Smith . Pinochet was played by Derek Jacobi , Margaret Thatcher by Anna Massey and Pinochet 's wife Lucía by Phyllida Law , with the cast also including Peter Capaldi , Pip Torrens and Jessica Hynes . It premiered in March 2006 on BBC Two and in September 2007 in the US .",
"title": ""
},
{
"docid": "Human_rights_violations_in_Pinochet's_Chile",
"text": "Human rights violations during the military government of Chile refer to the acts of human rights abuses , persecution of opponents , political repression and state terrorism committed by the Chilean armed forces and the Police , government agents and civilians in the service of security agencies , during the dictatorship of Augusto Pinochet in Chile from September 11 , 1973 , until March 11 , 1990 . According to the Commission of Truth and Reconciliation ( Rettig Commission ) and the National Commission on Political Imprisonment and Torture ( Valech Commission ) , the number of direct victims of human rights violations in Chile accounts for around 30,000 people : 27,255 tortured and 2,279 executed . In addition , some 200,000 people suffered exile and an unknown number went through clandestine centers and illegal detention . -LSB- source ? -RSB- The systematic human rights violations that were committed by the military government of Chile , under General Augusto Pinochet , included gruesome acts of physical and sexual abuse , as well as psychological damage . From September 11 , 1973 to March 11 , 1990 , Chilean armed forces , the police and all those aligned with the military junta were involved in institutionalizing fear and terror in Chile . The most prevalent forms of state-sponsored torture that Chilean prisoners endured were electric shocks , waterboarding , beatings , and sexual abuse . Another common mechanism of torture employed was `` disappearing '' those who were deemed to be potentially subversive because they adhered to leftist political doctrines . The tactic of `` disappearing '' the enemies of the Pinochet regime was systematically carried out during the first four years of military rule . The `` disappeared '' were held in secret , subjected to torture and were often never seen again . Both the National Commission on Political Imprisonment and Torture ( Valech Report ) and the Commission of Truth and Reconciliation ( Rettig Report ) approximate that there were around 30,000 victims of human rights abuses in Chile , with 27,255 tortured and 2,279 executed .",
"title": ""
},
{
"docid": "60_Minutos",
"text": "60 Minutos ( English : 60 Minutes ) was a Chilean TV newscast which aired on TVN during the military government of Augusto Pinochet between 1975 and 1988 . The program was conceived as an attempt to `` reunify the Chilean people '' ; however , the opposition dictatorship criticised it for the lack of independence . For that reason , viewers mainly opted to watch Canal 13 's newscast Teletrece instead , as the content was perceived more open and independent than 60 Minutos 's . At times bias reached substantial levels : a 1984 piece discussed `` socialist '' governments such as those of France and Spain under François Mitterrand and Felipe González in a negative light , focusing on their failure to tackle the industrial crisis of those nations at the time . The program 's most memorable broadcast was the live interview with Augusto Pinochet , immediately after his assassination attempt on 7 September 1986 .",
"title": ""
},
{
"docid": "R_v_Bow_Street_Metropolitan_Stipendiary_Magistrate,_ex_p_Pinochet_(No_3)",
"text": "R v Bow Street Metropolitan Stipendiary Magistrate , Ex Parte Pinochet Ugarte ( No 3 ) was a House of Lords judgment on the state immunity of Chilean President Augusto Pinochet . The judgment was necessary after the House of Lords ruling R v Bow Street Metropolitan Stipendiary Magistrate , Ex Parte Pinochet Ugarte was set aside when one of the judges in the case failed to disclose links to a human rights organization .",
"title": ""
},
{
"docid": "Alberto_Bachelet",
"text": "Alberto Arturo Miguel Bachelet Martínez ( 27 April 1923 -- 13 March 1974 ) was a Brigadier General of the Chilean Air Force . He opposed the 1973 coup of General Augusto Pinochet , and was imprisoned and subject to torture for several months until his death in 1974 of heart disease .",
"title": ""
},
{
"docid": "Chilean_national_plebiscite,_1988",
"text": "The 1988 Chilean national plebiscite was a national referendum held on 5 October 1988 to determine whether Chile 's President , Augusto Pinochet , should extend his rule for another eight years . The `` No '' side won with nearly 56 % of the vote , thus ending the General 's 16 1/2 years in power . The fact the dictatorship respected the results is attributed to pressure from the big business , the international community and unease with extended Pinochet-rule within the dictatorship .",
"title": ""
},
{
"docid": "Caravan_of_Death",
"text": "The Caravan of Death ( Caravana de la Muerte ) was a Chilean Army death squad that , following the Chilean coup of 1973 , flew by helicopters from south to north of Chile between September 30 and October 22 , 1973 . During this foray , members of the squad ordered or personally carried out the execution of at least 75 individuals held in Army custody in certain garrisons . According to the NGO Memoria y Justicia , the squad killed 26 in the South and 71 in the North , making a total of 97 victims . Augusto Pinochet was indicted in December 2002 in this case , but he died four years later without having been judged . His trial , however , is ongoing since his and other military personnel and a former military chaplain have also been indicted in this case .",
"title": ""
}
] |
PLAIN-2191
|
sushi
|
[
{
"docid": "MED-3443",
"text": "Incidence of the metabolic syndrome is increasing worldwide, with notable exceptions of some Asian countries where seaweeds are commonly consumed. 13 men (mean age 47.4+/-9.9 yr) and 14 women (average age 45.6+/-12.2 yr) with at least one symptom of the metabolic syndrome were recruited in Quito Ecuador to a randomized double-blinded placebo-controlled trial. Subjects were assigned to either Group 1 (1 m placebo, followed by 1 m 4 g/d seaweed [Undaria pinnatifida]) or Group 2 (1 m of 4 g/d seaweed, followed by 1 m of 6 g/d of seaweed). Blood pressure, weight, waist circumference, inflammation biomarkers, and lipids were measured monthly. Repeated measures analysis of variance with Tukey's multiple comparison tests were used for statistical analysis. In Group 2, systolic blood pressure decreased 10.5 mmHg after a month of 6 g/d seaweed (95% CI: 4.1, 16.8 mmHg; p<0.05), primarily in subjects with high-normal baseline blood pressure. Waist circumference changed only for women participants, with a 2.4 cm decrease in Group 1 after treatment with placebo (95% CI: 1.0, 3.7 cm; p<0.01). In Group 2, women had a mean decrease of 2.1 cm after 4 g/d (95% CI: 0.4, 3.7 cm; p<0.05) and a further 1.8 cm decrease after 1 m 6 g/d seaweed (95 % CI: 0.1, 3.4, p<0.05). No other changes were observed. Consumption of 4 to 6 g/d seaweed, typical for most people in Japan, may be associated with low metabolic syndrome prevalence.",
"title": "Could dietary seaweed reverse the metabolic syndrome?"
},
{
"docid": "MED-2347",
"text": "Urticaria affects nearly 25% of the population at some time in their lives. In a subset of children, urticaria will develop into a chronic condition that can greatly affect quality of life. Although numerous causes and triggers are proposed for chronic urticaria (CU) in children, ranging from infections, allergens, and medications to physical factors and autoimmune disease, the exact etiology is not always identifiable. Accordingly, a large subset of cases are designated \"chronic idiopathic urticaria.\" Because of the clinical complexities of CU, as well as the confusing literature on this topic, we have developed a conceptual framework based on the cumulative evidence to assist with the categorization, clinical evaluation, and treatment of CU in children. © 2011 Wiley Periodicals, Inc.",
"title": "Evidence-based evaluation and management of chronic urticaria in children."
},
{
"docid": "MED-3441",
"text": "As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Marine edible algae as disease preventers."
},
{
"docid": "MED-4969",
"text": "Transmission of viruses, bacteria, and parasites to food by way of improperly washed hands is a major contributing factor in the spread of foodborne illnesses. Field observers have assessed compliance with hand washing regulations, yet few studies have included consideration of frequency and methods used by sectors of the food service industry or have included benchmarks for hand washing. Five 3-h observation periods of employee (n = 80) hand washing behaviors during menu production, service, and cleaning were conducted in 16 food service operations for a total of 240 h of direct observation. Four operations from each of four sectors of the retail food service industry participated in the study: assisted living for the elderly, childcare, restaurants, and schools. A validated observation form, based on 2005 Food Code guidelines, was used by two trained researchers. Researchers noted when hands should have been washed, when hands were washed, and how hands were washed. Overall compliance with Food Code recommendations for frequency during production, service, and cleaning phases ranged from 5% in restaurants to 33% in assisted living facilities. Procedural compliance rates also were low. Proposed benchmarks for the number of times hand washing should occur by each employee for each sector of food service during each phase of operation are seven times per hour for assisted living, nine times per hour for childcare, 29 times per hour for restaurants, and 11 times per hour for schools. These benchmarks are high, especially for restaurant employees. Implementation would mean lost productivity and potential for dermatitis; thus, active managerial control over work assignments is needed. These benchmarks can be used for training and to guide employee hand washing behaviors.",
"title": "Hand washing frequencies and procedures used in retail food services."
},
{
"docid": "MED-2345",
"text": "Anisakis simplex is a parasite that, if present in uncooked and contaminated saltwater fish, can invade the human gut. Two different clinical situations are recognized: the first, known as a gastrointestinal disease, varying from an asymptomatic episode to vomiting and diarrhea, and the second, classified as an adverse reaction to food, characterized by a wide spectrum of allergic reactions like rhinitis, conjunctivitis, or even anaphylaxis causing hypotension and/or shock. The intestinal epithelium, the major defense system against external molecules, represents an open gate for toxins and allergens if its protective function is compromised. Previous data have demonstrated a strict relationship between an altered intestinal permeability (I.P.) and worsening of the clinical manifestations in patients with adverse reactions to the food. In this article we evaluated the sensitization to A. simplex among patients who referred clinical symptoms of allergy. All subjects underwent commonly used alimentary skin prick test for food allergens, to which Ani s1, an A. simplex allergen, was added. In addition, in A. simplex-sensitized subjects, I.P. was determined upon their enrolment to the study (time 0) and after 6 months of consuming a raw fish-free diet (time 6). Five hundred and forty subjects were screened, and 170 had a positive skin prick test, 87 (51.2%) of whom were positive to Ani s1. Increased I.P. was evidenced in A. simplex-sensitized subjects with worse clinical symptoms, which receded after 6 months' elimination of raw seafood. With our data we demonstrated that the alimentary habit to eat raw fish represents a high risk for the integrity of the intestinal mucosa, and we suggest that this pathological situation may constitute an ideal, under-estimated, open gate for molecules that predispose to other, more important pathologies.",
"title": "Anisakiasis, an underestimated infection: effect on intestinal permeability of Anisakis simplex-sensitized patients."
},
{
"docid": "MED-2350",
"text": "BACKGROUND: The National Electronic Injury Surveillance System (NEISS) captures a nationally representative probability sample from hospital emergency departments (EDs) in the United States. OBJECTIVE: Emergency department data from NEISS were analyzed to assess the magnitude and severity of adverse events attributable to food allergies. METHODS: Emergency department events describing food-related allergic symptomatology were identified from 34 participating EDs from August 1 to September 30, 2003. RESULTS: Extrapolation of NEISS event data predicts a total of 20,821 hospital ED visits, 2333 visits for anaphylaxis, and 520 hospitalizations caused by food allergy in the United States during the 2-month study period. The median age was 26 years; 24% of visits involved children < or =5 years old. Shellfish was the most frequently implicated food in persons > or =6 years old, whereas children < or =5 years old experienced more events from eggs, fruit, peanuts, and tree nuts. There were no reported deaths. Review of medical records found that only 19% of patients received epinephrine, and, using criteria established by a 2005 anaphylaxis symposium, 57% of likely anaphylactic events did not have an ED diagnosis of anaphylaxis. CONCLUSION: Analysis of NEISS data may be a useful tool for assessing the magnitude and severity of food-allergic events. A criteria-based review of medical records suggests underdiagnosis of anaphylactic events in EDs.",
"title": "Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System."
},
{
"docid": "MED-4742",
"text": "Anisakis simplex has been recognized as an important cause of disease in humans and as a food-borne allergen source. Actually, this food-borne parasite was recently identified as an emerging food safety risk. An A. simplex -specific primer-probe system based on a real-time polymerase chain reaction (PCR) detection assay has been successfully optimized and validated with seafood samples. In addition, a DNA extraction procedure has been optimized to detect the presence of the nematode in food samples. The assay is a very reliable, specific, and sensitive methodology to detect the presence of traces of this parasite in seafood products, including highly processed samples. As a result, 13 sequences of cytochrome c oxidase II gene were obtained and scrutinized to calculate intra- and interspecific variabilities of 0 and 35-67%, respectively. Finally, an efficiency of 2.07 +/- 0.14 of the assay was calculated, and a limit of detection of 40 ppm parasite in 25 g of sample was also optimized. Actually, the presence of this parasite in several seafood products has been demonstrated, enforcing the necessity of a design for a good manufacturing practice protocol for the processing industry to minimize the presence of this parasite as a food-borne allergen source in seafood products.",
"title": "Evaluation of a real-time polymerase chain reaction (PCR) assay for detection of anisakis simplex parasite as a food-borne allergen source in seafo..."
},
{
"docid": "MED-2346",
"text": "Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.",
"title": "Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity"
},
{
"docid": "MED-2349",
"text": "PURPOSE OF REVIEW: The present review serves to address urticaria - both acute and chronic - as well as the differential diagnosis of urticarial syndromes in the pediatric population. We also wish to update the reader on progress in the pathophysiology, diagnosis and treatment of urticaria. RECENT FINDINGS: Acute and chronic urticaria represent syndromes caused by a variety of triggers. Recent literature continues to describe subtypes of urticaria that may be differentially responsive to particular therapies. Recent associations highlight the need to fully evaluate patients for allergic and infectious triggers of urticaria. It is important to distinguish idiopathic urticaria from related conditions such as anaphylaxis, systemic conditions and autoimmune urticaria. Although antihistamines remain a cornerstone of therapy, particular urticaria subtypes may also respond to novel therapies such as omalizumab. Chronic urticaria has a significant impact on a patient's quality of life. SUMMARY: Urticaria is a common condition. Our understanding of distinct urticaria subtypes differentially responsive to targeted therapies continues to increase. Due to the myriad of triggers that may cause urticaria, careful individualized patient assessment is necessary to exclude potential etiologies prior to a diagnosis of idiopathic urticaria.",
"title": "An update on childhood urticaria and angioedema."
},
{
"docid": "MED-4743",
"text": "Performance of SBR treatment for nitrogen removal from tannery is evaluated for a wide range of wastewater temperature between 7 and 30 degrees C. A pilot-scale SBR unit fed with plain-settled wastewater is operated on site for this purpose. Effective nitrogen removal is sustained by adjustment of the sludge age from 28 to 5 days. Concentration profiles of nitrogen compounds within a selected complete SBR cycle during the steady state operation at different wastewater temperatures and sludge ages are evaluated by model simulation. System performance is also interpreted in terms of modeling and stoichiometric calculation. Additional nitrate loss was observed during aerobic period when the aeration intensity was reduced by the factor of 50%.",
"title": "Performance evaluation of SBR treatment for nitrogen removal from tannery wastewater."
},
{
"docid": "MED-2341",
"text": "OBJECTIVE: The purposes of this study were to examine milk allergic patients to determine concomitant reactivity between milk, beef, pork and cat and dog dander and other common inhalant allergens. METHODS: 19 patients were selected according to their Immuno-CAP results, which had increased Ig-E levels against milk, pork or beef. Patients were also tested against Johnson grass, short ragweed, cat/dog dander and d. farina. RESULTS: Pearson's test revealed strong correlation between beef and pork, beef and milk, pork and milk Ig-E counts (consecutively r2 = 0.89, r2 = 0.81, r2 = 0.60 and p < 0.01. All cat allergic patients also appeared to be allergic to either beef/pork meat or milk. The correlation between pork and dog dander Ig-E counts was also significant (r2 = 0.38, p < 0.01). No correlation detected between milk-meat-pet and grass-weed-dust allergies. DISCUSSION AND CONCLUSION: Patients who are known to have pet allergies may need to be screened for meat and milk allergy. Milk allergic patients may also need to avoid cows and pork meat.",
"title": "Beef, pork, and milk allergy (cross reactivity with each other and pet allergies)."
},
{
"docid": "MED-3445",
"text": "A population-based case-control interview study was designed to test the hypothesis that dietary iodine or the consumption of goitrogenic vegetables increases the risk of thyroid cancer. A total of 191 histologically confirmed cases (64 percent female) and 441 matched controls from five ethnic groups in Hawaii were available for analysis. Among women, intake of seafood (especially shellfish), harm ha (a fermented fish sauce), and dietary iodine were associated with an increased risk of cancer, whereas consumption of goitrogenic (primarily cruciferous) vegetables was associated with a decreased risk. Non-dietary risk factors included miscarriage (especially at first pregnancy), use of fertility drugs, family history of thyroid disease, obesity, and work as a farm laborer. The odds ratio for the combined effect of a high iodine intake and a first-pregnancy miscarriage was 4.8 (95 percent confidence interval [CI] = 1.2-19.2); and for high iodine intake and use of fertility drugs 7.3 (95 percent CI = 1.5-34.5). Among men, positive associations were found for obesity, work as a farm laborer, and a past history of benign thyroid disease. Although this study identified several dietary and non-dietary risk factors for thyroid cancer, it could not fully explain the exceptionally high incidence rates among Filipino women in Hawaii.",
"title": "An epidemiologic study of thyroid cancer in Hawaii."
},
{
"docid": "MED-2339",
"text": "BACKGROUND: Allergic reactions to food can be produced by contaminants that induce sensitization. Among these, Anisakis simplex can cause seafood infestation, and allergic symptoms (urticaria-angioedema, anaphylaxis, and asthma) can follow the eating or handling of affected fish. Although seafood is the principal source of human infections by this parasite, we have found allergic symptoms in 8 patients previously diagnosed as having A simplex sensitization after they ate chicken meat. Chicken feed usually has a high proportion of fishmeal, which might possibly be contaminated by this nematode. OBJECTIVE: The aim of our study was to determine whether parasite proteins present in chicken meat could be responsible for the symptoms reported by these subjects. METHODS: We carried out in vivo tests (prick, bronchial challenge, and double-blind placebo-controlled challenge with meat chicken) in these 8 patients. We performed immunoblotting using the sera from the 8 patients and controls in order to detect A simplex sensitization. We also investigated the presence of A simplex proteins in sera from chickens fed with fishmeal and in other sera from chickens fed only with cereals. We excluded sensitization to other chicken nematodes by serologic methods. RESULTS: All 8 patients presented positive prick and challenges to A simplex. When we used serum from chickens fed with fishmeal as the antigen in blotting, patients 3, 4, 5, 6, 7, and 8 recognized a band of 16 kd, also obtained when using pools of fish-shellfish and A simplex larva. No detection was observed with sera from chickens fed with only cereals. CONCLUSION: We provide evidence, based on in vivo and in vitro tests, that subjects highly sensitized to A simplex can detect the presence of Anisakis species allergens in chicken meat.",
"title": "Anisakis simplex allergy after eating chicken meat."
},
{
"docid": "MED-2337",
"text": "Urticaria, defined by the presence of wheals and/or angio-edema, is a common condition in children, prompting parents to consult physicians. For its successful management, paediatric-specific features must be taken into account, regarding the identification of eliciting triggers and pharmacological therapy. This review systematically discusses the current best-available evidence on spontaneous acute and chronic urticaria as well as physical and other urticaria types in children. Potential underlying causes, namely infections, food and drug hypersensitivity, autoreactivity and autoimmune or other conditions, and eliciting stimuli are considered, with practical recommendations for specific diagnostic approaches. Second-generation antihistamines are the mainstay of pharmacological treatment aimed at relief of symptoms, which require dose adjustment for pae-diatric use. Other therapeutic interventions are also discussed. In addition, unmet needs are highlighted, aiming to promote research into the paediatric population, ultimately aiming at the effective management of childhood urticaria.",
"title": "Management of childhood urticaria: current knowledge and practical recommendations."
},
{
"docid": "MED-3442",
"text": "Gim (Porphyra sp.) and miyeok (Undaria pinnatifida) are the seaweeds most consumed by Koreans. We investigated the association between the intake of gim and miyeok and the risk of breast cancer in a case-control study. Cases were 362 women aged 30-65 years old, who were histologically confirmed to have breast cancer. Controls visiting the same hospital were matched to cases according to their age (sd 2 years) and menopausal status. Food intake was estimated by the quantitative FFQ with 121 items, including gim and miyeok. Conditional logistic regression analysis was used to obtain the OR and corresponding 95 % CI. The average intake and consumption frequency of gim in cases were lower than in controls. The daily intake of gim was inversely associated with the risk of breast cancer (5th v. 1st quintile, OR, 0.48; 95 % CI, 0.27, 0.86; P for trend, 0.026) after adjustment for potential confounders. After stratification analysis was performed according to menopausal status, premenopausal women (5th v. 1st quintile, OR, 0.44; 95 % CI, 0.24, 0.80; P for trend, 0.007) and postmenopausal women (5th v. 1st quintile, OR, 0.32; 95 % CI, 0.13, 0.80; P for trend, 0.06) showed similar inverse associations between gim intake and the risk of breast cancer after an adjustment for potential confounders except dietary factors. Miyeok consumption did not have any significant associations with breast cancer. These results suggest that high intake of gim may decrease the risk of breast cancer.",
"title": "A case-control study on seaweed consumption and the risk of breast cancer."
},
{
"docid": "MED-4968",
"text": "Vibrios are ubiquitous in the aquatic environment and are commonly present in or on shellfish and other seafood. A small subset of strains/species are able to cause human disease, including the cholera toxin-producing strains of Vibrio cholerae that are responsible for epidemic/pandemic cholera; thermostable direct hemolysin-producing strains of Vibrio parahaemolyticus; and Vibrio vulnificus, which can cause fulminant sepsis. Cholera outbreaks can be initiated by transmission of \"epidemic\" V. cholerae strains from their environmental reservoir to humans through seafood or other environmentally related food or water sources. \"Nonepidemic\" strains of V. cholerae and strains of other Vibrio species, including V. parahaemolyticus and V. vulnificus, are generally acquired by eating seafood (particularly raw oysters/oysters on the half shell). Although the primary clinical manifestation of infection with these strains is gastroenteritis, they can also cause wound infections and (particularly for V. vulnificus) septicemia in persons who have liver disease or are immunocompromised.",
"title": "Cholera and other types of vibriosis: a story of human pandemics and oysters on the half shell."
},
{
"docid": "MED-4966",
"text": "Ciguatera fish poisoning (CFP) is a distinctive type of foodborne disease that results from eating predatory ocean fish contaminated with ciguatoxins. As many as 50,000 cases are reported worldwide annually, and the condition is endemic in tropical and subtropical regions of the Pacific basin, Indian Ocean, and Caribbean. In the United States, 5--70 cases per 10,000 persons are estimated to occur yearly in ciguatera-endemic states and territories. CFP can cause gastrointestinal symptoms (nausea, vomiting, abdominal cramps, or diarrhea) within a few hours of eating contaminated fish. Neurologic symptoms, with or without gastrointestinal disturbance, can include fatigue, muscle pain, itching, tingling, and (most characteristically) reversal of hot and cold sensation. This report describes a cluster of nine cases of CFP that occurred in North Carolina in June 2007. Among the nine patients, six experienced reversal of hot and cold sensations, five had neurologic symptoms only, and overall symptoms persisted for more than 6 months in three patients. Among seven patients who were sexually active, six patients also complained of painful intercourse. This report highlights the potential risks of eating contaminated ocean fish. Local and state health departments can train emergency and urgent care physicians in the recognition of CFP and make them aware that symptoms can persist for months to years.",
"title": "Cluster of ciguatera fish poisoning--North Carolina, 2007."
},
{
"docid": "MED-3447",
"text": "To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4 degrees C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.",
"title": "Seaweed prevents breast cancer?"
},
{
"docid": "MED-2340",
"text": "After observing a patient allergic to cat dander and pork but devoid of other allergies, we prospectively screened patients known to be allergic to cat for a second sensitization to pork. After collecting the sera of 10 young patients found to contain specific IgE to cat dander and pork, we undertook this study to detect the possible cross-reactive allergen, define its molecular characteristics, and evaluate its clinical relevance. Through immunoblotting techniques, cat and porcine serum albumin were found to be jointly recognized molecules. These findings were further analyzed by specific anti-albumin IgE titrations and cross-inhibition experiments. Cat serum albumin cDNA was obtained from cat liver, and the corresponding amino acid sequence was deduced and compared to the known porcine and human serum albumin sequences. Inhibition experiments showed that the spectrum of IgE reactivity to cat serum albumin completely contained IgE reactivity to porcine serum albumin, suggesting that sensitization to cat was the primary event. In two cohorts of cat-allergic persons, the frequency of sensitization to cat serum albumin was found to lie between 14% and 23%. Sensitization to porcine albumin was found to lie between 3% and 10%. About 1/3 of these persons are likely to experience allergic symptoms in relation to pork consumption. Sensitization to cat serum albumin should be considered a useful marker of possible cross-sensitization not only to porcine serum albumin but also to other mammalian serum albumins.",
"title": "Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels."
},
{
"docid": "MED-4967",
"text": "BACKGROUND: From 2003 through 2007, Vibrio cholerae serogroup O75 strains possessing the cholera toxin gene were isolated from 6 patients with severe diarrhea, including 3 in Georgia, 2 in Alabama, and 1 in South Carolina. These reports represent the first identification of V. cholerae O75 as a cause of illness in the United States. V. cholerae O75 was isolated from a water sample collected from a pond in Louisiana in 2004. Subsequently, 3 V. cholerae isolates from Louisiana (2 from patients with diarrhea in 2000 and 1 from a water sample collected in 1978) that had been previously reported as serogroup O141 were also discovered to be serogroup O75. RESULTS: All 8 patients who were infected with V. cholerae O75 were adults who became ill after consuming seafood; 2 had eaten raw oysters traced back to the Gulf Coast of the United States. All 10 isolates possessed the cholera toxin gene and were susceptible to 10 antimicrobials. One clinical isolate and 1 environmental (water) isolate had the same pulsed-field gel electrophoresis pattern; 4 clinical isolates shared a common pulsed-field gel electrophoresis pattern. CONCLUSIONS: The occurrence of these cases over many years and the concurrent identification of V. cholerae O75 in water from a Gulf Coast state suggest that these strains may survive for long periods in this environment. The patients' exposure histories suggest that infection can be acquired from consumption of raw oysters from the Gulf Coast. Clinicians and public health authorities should be vigilant for the occurrence of new toxigenic serogroups of V. cholerae that are capable of causing severe diarrhea.",
"title": "Severe diarrhea caused by cholera toxin-producing vibrio cholerae serogroup O75 infections acquired in the southeastern United States."
},
{
"docid": "MED-5144",
"text": "This study has measured the content of total and inorganic forms of arsenic in seaweed available on retail sale for consumption, to provide data for dietary exposure estimates and to support advice to consumers. A total of 31 samples covering five varieties of seaweed were collected from various retail outlets across London and the internet. All of the samples were purchased as dried product. For four of the five varieties, soaking was advised prior to consumption. The recommended method of preparation for each individual sample was followed, and total and inorganic arsenic were analysed both before and after preparation. The arsenic remaining in the water used for soaking was also measured. Arsenic was detected in all samples with total arsenic at concentrations ranging from 18 to 124 mg/kg. Inorganic arsenic, which can cause liver cancer, was only found in the nine samples of hijiki seaweed that were analysed, at concentrations in the range 67-96 mg/kg. Other types of seaweed were all found to contain less than 0.3mg/kg inorganic arsenic, which was the limit of detection for the method used. Since consumption of hijiki seaweed could significantly increase dietary exposure to inorganic arsenic, the UK Food Standards Agency (FSA) issued advice to consumers to avoid eating it.",
"title": "Arsenic in seaweed--forms, concentration and dietary exposure."
},
{
"docid": "MED-2356",
"text": "Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.",
"title": "The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose"
},
{
"docid": "MED-2355",
"text": "Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.",
"title": "Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)"
},
{
"docid": "MED-4963",
"text": "Because of the worldwide popularization of Japanese cuisine, the traditional Japanese fish dishes sushi and sashimi that are served in Japanese restaurants and sushi bars have been suspected of causing fishborne parasitic zoonoses, especially anisakiasis. In addition, an array of freshwater and brackish-water fish and wild animal meats, which are important sources of infection with zoonotic parasites, are served as sushi and sashimi in rural areas of Japan. Such fishborne and foodborne parasitic zoonoses are also endemic in many Asian countries that have related traditional cooking styles. Despite the recent increase in the number of travelers to areas where these zoonoses are endemic, travelers and even infectious disease specialists are unaware of the risk of infection associated with eating exotic ethnic dishes. The aim of this review is to provide practical background information regarding representative fishborne and foodborne parasitic zoonoses endemic in Asian countries.",
"title": "Sushi delights and parasites: the risk of fishborne and foodborne parasitic zoonoses in Asia."
},
{
"docid": "MED-3448",
"text": "Iodine is a suspected risk factor for thyroid cancer. Seaweed accounts for about 80% of Japanese people's iodine intake. We examined the association between seaweed consumption and the risk of thyroid cancer in Japanese women. Women participating in the Japan Public Health Center-based Prospective Study (n=52 679; age: 40-69 years) were followed up for a mean of 14.5 years; 134 new thyroid cancer cases, including 113 papillary carcinoma cases, were identified. Seaweed consumption was assessed using a food-frequency questionnaire and divided into three categories: 2 days/week or less (reference); 3-4 days/week; and almost daily. The Cox proportional hazards model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Seaweed consumption was clearly associated with an increased risk of papillary carcinoma (HR for almost daily consumption compared with 2 days/week or less=1.71; 95% CI: 1.01-2.90; trend P=0.04). After stratification for menopausal status, an increased risk was observed in postmenopausal women (papillary carcinoma HR for almost daily consumption compared with 2 days/week or less=3.81, 95% CI: 1.67-8.68; trend P<0.01), but not in premenopausal women (HR=0.91, 95% CI: 0.44-1.91; trend P=0.76). This study identified a positive association between seaweed consumption and the risk of thyroid cancer (especially for papillary carcinoma) in postmenopausal women.",
"title": "Seaweed consumption and the risk of thyroid cancer in women: the Japan Public Health Center-based Prospective Study."
},
{
"docid": "MED-5169",
"text": "Fourteen sites evenly divided between the household kitchen and bathroom were monitored on a weekly basis for numbers of faecal coliforms, total coliforms and heterotrophic plate count bacteria. The first 10 weeks comprised the control period, hypochlorite cleaning products were introduced into the household during the second 10 weeks, and a strict cleaning regimen using hypochlorite products was implemented during the last 10 weeks. The kitchen was more heavily contaminated than the bathroom, with the toilet seat being the least contaminated site. The highest concentrations of all three classes of bacteria were found on sites that were moist environments and/or were frequently touched; these included the sponge/dishcloth, the kitchen sink drain area, the bath sink drain area, and the kitchen faucet handle(s). The implementation of a cleaning regimen with common household hypochlorite products resulted in the significant reduction of all three classes of bacteria at these four sites and other household sites.",
"title": "Reduction of faecal coliform, coliform and heterotrophic plate count bacteria in the household kitchen and bathroom by disinfection with hypochlori..."
},
{
"docid": "MED-5143",
"text": "It was previously reported that a methanol extract of Gloiopeltis furcata (MEGF), a kind of edible seaweed, inhibited the growth of several human cancer cell lines. In the present study, the effect of MEGF on the growth of human hepatocarcinoma HepG2 cells and its effect on the cyclooxygenases (COXs) expression were investigated. MEGF markedly reduced the viability of HepG2 cells and induced the G2/M arrest of the cell cycle in a concentration dependent manner. These effects were associated with the down-regulation of cyclin A, up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) and dephosphorylation of Cdc25C. Furthermore, it was found that MEGF decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E(2) (PGE(2)) synthesis. These findings indicate that MEGF may have a possible therapeutic potential in hepatoma cancer patients.",
"title": "Methanol extract of the seaweed Gloiopeltis furcata induces G2/M arrest and inhibits cyclooxygenase-2 activity in human hepatocarcinoma HepG2 cells."
},
{
"docid": "MED-2344",
"text": "The increased consumption of fish and shellfish has resulted in more frequent reports of adverse reactions to seafood, emphasizing the need for more specific diagnosis and treatment of this condition and exploring reasons for the persistence of this allergy. This review discusses interesting and new findings in the area of fish and shellfish allergy. New allergens and important potential cross-reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. The diagnostic approach may require prick to-prick tests using crude extracts of both raw and cooked forms of seafood for screening seafood sensitization before a food challenge or where food challenge is not feasible. Allergen-specific immunotherapy can be important; mutated less allergenic seafood proteins have been developed for this purpose. The persistence of allergy because of seafood proteins' resistance after rigorous treatment like cooking and extreme pH is well documented. Additionally, IgE antibodies from individuals with persistent allergy may be directed against different epitopes than those in patients with transient allergy. For a topic as important as this one, new areas of technological developments will likely have a significant impact, to provide more accurate methods of diagnosing useful information to patients about the likely course of their seafood allergy over the course of their childhood and beyond. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.",
"title": "Fish and shellfish allergy in children: review of a persistent food allergy."
},
{
"docid": "MED-2348",
"text": "BACKGROUND AND OBJECTIVE: Despite a thorough history and comprehensive testing, many children who present with recurrent symptoms consistent with allergic reactions elude diagnosis. Recent research has identified a novel cause for “idiopathic” allergic reactions; immunoglobulin E (IgE) antibody specific for the carbohydrate galactose-α-1,3-galactose (α-Gal) has been associated with delayed urticaria and anaphylaxis that occurs 3 to 6 hours after eating beef, pork, or lamb. We sought to determine whether IgE antibody to α-Gal was present in sera of pediatric patients who reported idiopathic anaphylaxis or urticaria. METHODS: Patients aged 4 to 17 were enrolled in an institutional review board–approved protocol at the University of Virginia and private practice allergy offices in Lynchburg, VA. Sera was obtained and analyzed by ImmunoCAP for total IgE and specific IgE to α-Gal, beef, pork, cat epithelium and dander, Fel d 1, dog dander, and milk. RESULTS: Forty-five pediatric patients were identified who had both clinical histories supporting delayed anaphylaxis or urticaria to mammalian meat and IgE antibody specific for α-Gal. In addition, most of these cases had a history of tick bites within the past year, which itched and persisted. CONCLUSIONS: A novel form of anaphylaxis and urticaria that occurs 3 to 6 hours after eating mammalian meat is not uncommon among children in our area. Identification of these cases may not be straightforward and diagnosis is best confirmed by specific testing, which should certainly be considered for children living in the area where the Lone Star tick is common.",
"title": "Galactose-α-1,3-galactose and Delayed Anaphylaxis, Angioedema, and Urticaria in Children"
},
{
"docid": "MED-3446",
"text": "Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.",
"title": "Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women."
},
{
"docid": "MED-4359",
"text": "Unintentional ingestion of a fishbone (FB) is common, especially in populations with a high consumption of seafood. In most instances, the ingested FB passes uneventfully through the gastrointestinal (GI) tract, usually within a week. However, in certain cases, the FB may become impacted and lead to complications. Awareness of these complications is important as patients usually present with nonspecific symptoms and could be unaware of having ingested an FB.",
"title": "Pictorial essay: Complications of a swallowed fish bone"
},
{
"docid": "MED-4962",
"text": "BACKGROUND: Vibrio species are a rare cause of necrotizing soft-tissue infections and primary septicemia, which are likely to occur in patients with hepatic disease, diabetes, adrenal insufficiency, and immunocompromised conditions. These organisms thrive in warm seawater and are often present in raw oysters, shellfish, and other seafood. This study examined fulminating clinical characteristics of Vibrio vulnificus and Vibrio cholerae non-O1 soft-tissue infections and identified outcome predictors. MATERIALS: Thirty patients with necrotizing fasciitis and sepsis caused by Vibrio species were retrospectively reviewed. Twenty-eight patients had a history of contact with seawater or raw seafood. Eight patients had hepatic disease such as hepatitis or liver cirrhosis, and seven patients had diabetes mellitus. Nine patients had hepatic dysfunction combined with diabetes mellitus. Microbiology laboratory culture studies confirmed V. vulnificus in 23 patients and V. cholerae non-O1 in seven patients. RESULTS: Surgical debridement or immediate limb amputation was initially performed in all patients with necrotizing soft-tissue infections. Eleven patients (37%) died within several days of admission and 19 survived. The mortality of V. cholerae non-O1 group (57%) is higher than that of the V. vulnificus group (30%). A significantly higher mortality rate was noted in patients with initial presentations of a systolic blood pressure of < or =90 mm Hg, leukopenia, decreased platelet counts, and a combination of hepatic dysfunction and diabetes mellitus. CONCLUSIONS: Vibrio necrotizing soft-tissue infections should be suspected in patients with appropriate clinical findings and history of contact with seawater or seafood. V. cholerae non-O1 may cause bacteremia more often than V. vulnificus in patients with liver cirrhosis. Early fasciotomy and culture-directed antimicrobial therapy are aggressively recommended in patients with hypotensive shock, leukopenia, high band forms of white blood cells, decreased platelet counts, severe hypoalbuminemia, and underlying chronic illness, such as hepatic dysfunction and diabetes mellitus.",
"title": "Necrotizing soft-tissue infections and primary sepsis caused by Vibrio vulnificus and Vibrio cholerae non-O1."
},
{
"docid": "MED-3444",
"text": "Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in \"low-risk\" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in \"high-risk\" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.",
"title": "Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study."
},
{
"docid": "MED-4360",
"text": "Ciguatera is a type of food poisoning associated with the consumption of contaminated marine fish. We report two cases in which painful ejaculation in an affected male and dyspareunia in an unaffected female following her partner's ejaculation suggest the sexual transfer of the responsible agent, ciguatoxin (CTX). Immunoassay of semen samples for CTX were not diagnostic, but the sensitivity and timing of the test employed may have precluded detection of small quantities of the toxin. We conclude that CTX may be present in the semen of men affected with ciguatera toxicity and be capable of producing symptomatology in both males and females during sexual intercourse.",
"title": "Can ciguatera be a sexually transmitted disease?"
},
{
"docid": "MED-4964",
"text": "The microbial quality of raw fillets of aquacultured catfish, salmon, tilapia, and trout was evaluated. A total of 272 fillets from nine local and nine Internet retail markets were tested. Mean values were 5.7 log CFU/g for total aerobic mesophiles, 6.3 log CFU/g for psychrotrophs, and 1.9 log most probable number (MPN) per gram for coliforms. Differences in these microbial levels between the two kinds of markets and among the four types of fish were not significant (P > 0.05), except that Internet trout fillets had about 0.8-log higher aerobic mesophiles than did trout fillets purchased locally. Although Escherichia coli was detected in 1.4, 1.5, and 5.9% of trout, salmon, and tilapia, respectively, no sample had > or = 1.0 log MPN/g. However, E. coli was found in 13.2% of catfish, with an average of 1.7 log MPN/g. About 27% of all fillets had Listeria spp., and a positive correlation between the prevalence of Listeria spp. and Listeria monocytogenes was observed. Internet fillets had a higher prevalence of both Listeria spp. and L. monocytogenes than did those fillets purchased locally. L. monocytogenes was present in 23.5% of catfish but in only 5.7, 10.3, and 10.6% of trout, tilapia, and salmon, respectively. Salmonella and E. coli O157 were not found in any sample. A follow-up investigation using catfish operation as a model revealed that gut waste exposed during evisceration is a potential source of coliforms and Listeria spp.",
"title": "Microbial quality of raw aquacultured fish fillets procured from Internet and local retail markets."
},
{
"docid": "MED-5170",
"text": "Sushi is a traditional Japanese food, mostly consisting of rice and raw fish. Fish is considered a healthy food, but as with other animal products, consumption of raw muscle incurs potential health risks such as ingestion of pathogenic bacteria or parasites. In this study, 250 sushi samples were analyzed for their microbiological status and the prevalence of pathogenic bacteria. A comparison was made between frozen sushi from supermarkets and fresh sushi from sushi bars. Aerobic mesophilic bacteria counts differed for sushi from these two sources, with means of 2.7 log CFU/g for frozen sushi and 6.3 log CFU/g for fresh sushi. The prevalence of Escherichia coli and Staphylococcus aureus was higher in the fresh samples. Salmonella was found in four (1.6%) of the sushi samples, and Listeria monocytogenes was found in three (1.2%) of the samples. These results indicate that the microbiological quality of industrially processed sushi is higher than that of freshly prepared sushi. The quality of freshly prepared sushi strongly depends on the skills and habits of the preparation cooks, which may vary.",
"title": "Microbiological quality of sushi from sushi bars and retailers."
},
{
"docid": "MED-2338",
"text": "BACKGROUND: Chronic urticaria (CU) may affect up to 1% of the general population. Anisakis simplex hypersensitivity is frequent in areas where raw fish is consumed and A. simplex allergy represents a relevant cause of acute urticaria. We assessed the possible association between CU and A. simplex sensitization in an area where marinated fish is very frequently eaten. METHODS: A thorough history of CU was sought in 919 adults seen at the Allergy Center, Bari. CU patients and 187 controls underwent skin-prick testing with a commercial extract of A. simplex, and reactors were recommended a 6-month raw-fish-free diet regimen. Responders were followed after a further 3 months. RESULTS: Of 919 subjects, 213 (23%) met the criteria for CU and 106/213 (49.7%) were sensitized to A. simplex with a significant difference between patients aged >65 or <65 years (56 vs. 41%, respectively; p < 0.05). All patients hypersensitive to A. simplex were regular consumers of marinated fish. In a control population without CU, the prevalence of A. simplex sensitization was 16% (p < 0.001). The 6-month diet regimen led to the disappearance of urticaria in 82/106 cases (77%) versus 1/42 (2%) subjects who did not change their dietary habits (p < 0.001). All nonresponders were sensitized to house-dust mites. Of 75 responders who were followed-up after 3 months, CU relapsed in 88% of those who had reintroduced raw fish versus 14% of those who were still on the diet (p < 0.001). CONCLUSION: In areas where raw or marinated fish is frequently eaten, A. simplex hypersensitivity is a frequent cause of CU. Copyright © 2012 S. Karger AG, Basel.",
"title": "Anisakis simplex hypersensitivity is associated with chronic urticaria in endemic areas."
}
] |
[
{
"docid": "MED-1640",
"text": "Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.",
"title": "Effect of coffee on endothelial function in healthy subjects: the role of caffeine."
},
{
"docid": "MED-1695",
"text": "Fruits and vegetables have been thought to be beneficial in cardiovascular disease. The beneficial effects of fruits and vegetables may be explained by the antioxidants and other components contained therein. These nutrients may function individually or in concert to protect lipoproteins and vascular cells from oxidation, or by other mechanisms such as reducing plasma lipid levels (LDL cholesterol, triglycerides), and platelet aggregation response. Kiwi fruit which contains high amounts of vitamin C, vitamin E and polyphenols may be beneficial in cardiovascular disease; however very little is known about its cardioprotective effects. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. To this end, we evaluated whether consuming kiwi fruit modulated platelet activity and plasma lipids in human volunteers in a randomized cross-over study. We report that consuming two or three kiwi fruit per day for 28 days reduced platelet aggregation response to collagen and ADP by 18% compared with the controls (P < 0.05). In addition, consumption of kiwi fruit lowered blood triglycerides levels by 15% compared with control (P < 0.05), whereas no such effects were observed in the case of cholesterol levels. All these data indicate that consuming kiwi fruit may be beneficial in cardiovascular disease.",
"title": "Effects of kiwi fruit consumption on platelet aggregation and plasma lipids in healthy human volunteers."
},
{
"docid": "MED-2124",
"text": "Acne appears to represent a visible indicator disease of over-activated mTORC1 signalling, an unfavour-able metabolic deviation on the road to serious common Western diseases of civilisation associated with increased body mass index and insulin resistance. Exaggerated mTORC1 signalling by Western diet explains the association of acne with increased body mass index, insulin resistance, and early onset of menarche. Both, a high glycaemic load and increased consumption of milk and milk products, staples of Western diet, aggravate mammalian target of rapamycin complex 1 signalling. This review of the literature summarises present evidence for an association between acne, increased body mass index, insulin resistance and Western diet. By dietary intervention with a Palaeolithic-type diet, the dermatologist has the chance to attenuate patients' increased mTORC1 signalling by reducing glycaemic load and milk consumption, which may not only improve acne but may delay the march to more serious mTORC1-driven diseases of civilisation.",
"title": "Acne: risk indicator for increased body mass index and insulin resistance."
},
{
"docid": "MED-4834",
"text": "Soft drinks can be a major source of sucrose, which may influence serum lipid concentration. We have examined the association between intake frequency of various types of soft drinks and the concentration of serum triglycerides (TG) and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol in the cross-sectional Oslo Health Study. A total of 14 188 subjects of the altogether 18,770 participants of the study had data on intake frequency of colas and non-colas, with or without sugar. The population sample consisted of both sexes and 3 age groups: group 1 (30 years of age), group 2 (40 and 45 years of age), and group 3 (59-60 years of age). In both sexes, HDL decreased and TG increased significantly (p < 0.001) with increasing intake frequency of colas. In contrast, no consistent associations were found between the reported intake of non-cola soft drinks and the serum lipids. We found no significant differences related to the reported presence or absence of sugar in the soft drinks. In multiple linear regression analyses, the colas vs. serum lipid associations prevailed (p < 0.001) after including 13 possible confounders: sex; age group; time since last meal; physical activity; intake of alcohol, coffee, cheese, fruit and (or) berries, and fatty fish; smoking; length of education; use of cholesterol-lowering drugs; and intake of non-colas. Thus, the self-reported intake frequency of colas, but not other soft drinks, was negatively associated with serum HDL, and positively associated with TG and LDL.",
"title": "Cola intake and serum lipids in the Oslo Health Study."
},
{
"docid": "MED-3653",
"text": "We previously described how retail meat, particularly chicken, might be a reservoir for extraintestinal pathogenic Escherichia coli (ExPEC) causing urinary tract infections (UTIs) in humans. To rule out retail beef and pork as potential reservoirs, we tested 320 additional E. coli isolates from these meats. Isolates from beef and pork were significantly less likely than those from chicken to be genetically related to isolates from humans with UTIs. We then tested whether the reservoir for ExPEC in humans could be food animals themselves by comparing geographically and temporally matched E. coli isolates from 475 humans with UTIs and from cecal contents of 349 slaughtered animals. We found genetic similarities between E. coli from animals in abattoirs, principally chickens, and ExPEC causing UTIs in humans. ExPEC transmission from food animals could be responsible for human infections, and chickens are the most probable reservoir.",
"title": "Chicken as Reservoir for Extraintestinal Pathogenic Escherichia coli in Humans, Canada"
},
{
"docid": "MED-2669",
"text": "Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular pathology in individuals with CVD, and consumption of such flavonoid-containing foods is associated with a reduced risk for dementia. In addition, preliminary animal data have indicated improvement in memory and motor function with grape juice supplementation, suggesting potential for cognitive benefit in ageing humans. In this initial investigation of neurocognitive effects, we enrolled twelve older adults with memory decline but not dementia in a randomised, placebo-controlled, double-blind trial with Concord grape juice supplementation for 12 weeks. We observed significant improvement in a measure of verbal learning and non-significant enhancement of verbal and spatial recall. There was no appreciable effect of the intervention on depressive symptoms and no effect on weight or waist circumference. A small increase in fasting insulin was observed for those consuming grape juice. These preliminary findings suggest that supplementation with Concord grape juice may enhance cognitive function for older adults with early memory decline and establish a basis for more comprehensive investigations to evaluate potential benefit and assess mechanisms of action.",
"title": "Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment."
},
{
"docid": "MED-3275",
"text": "In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.",
"title": "The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture"
},
{
"docid": "MED-1671",
"text": "BACKGROUND: Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. OBJECTIVE: We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. DESIGN: Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS: In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. CONCLUSIONS: Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.",
"title": "Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women."
},
{
"docid": "MED-4526",
"text": "The sap of Croton lechleri Muell.-Arg (Euphorbiaceae), called Dragon's blood, is used in folk medicine as a cicatrizant, anti-inflammatory and to treat cancer. In this research, the antioxidant activity of Croton lechleri sap was evaluated against the yeast Saccharomyces cerevisiae and against maize plantlets treated with the oxidative agents apomorphine and hydrogen peroxide. The mutagenic activity of the sap was also analyzed using the Salmonella/microsome assay (Salmonella typhimurium TA97a, TA98, TA100, TA102, TA1535) and in cells of the yeast Saccharomyces cerevisiae. The results showed that Croton lechleri sap possesses significant antioxidant activity against the oxidative damages induced by apomorphine in Saccharomyces cerevisiae under all the conditions studied. However, in the case of hydrogen peroxide, antioxidant activity of the sap was detected only in cells in the stationary phase of growth. The sap was also able to protect cells of the maize plantlets from the toxic effect of apomorphine. This sap showed mutagenic activity for strain TA1535 of Salmonella typhimurium in the presence of metabolic activation and a weak mutagenic activity for strain TA98. These strains detect base pair substitutions and frameshift mutations, respectively. Mutagenicity was also observed in a haploid Saccharomyces cerevisiae strain XV185-14c for the lys1-1, his1-7 locus-specific reversion and hom3-10 frameshift mutations.",
"title": "Mutagenic and antioxidant activities of Croton lechleri sap in biological systems."
},
{
"docid": "MED-3492",
"text": "AIM: The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. METHODS: A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. RESULTS: At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. CONCLUSION: The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.",
"title": "Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extrac..."
},
{
"docid": "MED-2893",
"text": "Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.",
"title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis."
},
{
"docid": "MED-3088",
"text": "Elevated serum phosphorus is a major, preventable etiologic factor associated with the increased cardiovascular morbidity and mortality of dialysis patients. An important determinant of serum phosphorus is the dietary intake of this mineral; this makes dietary restriction of phosphorus a cornerstone for the prevention and treatment of hyperphosphatemia. The average daily dietary intake of phosphorus is about 1550 mg for males and 1000 mg for females. In general, foods high in protein are also high in phosphorus. These figures, however, are changing as phosphates are currently being added to a large number of processed foods including meats, cheeses, dressings, beverages, and bakery products. As a result, and depending on the food choices, such additives may increase the phosphorus intake by as a much as 1 g/day. Moreover, nutrient composition tables usually do not include the phosphorus from these additives, resulting in an underestimate of the dietary intake of phosphorus in our patients. Our goal is to convey an understanding of the phosphorus content of the current American diet to better equip nephrologists in their attempt to control hyperphosphatemia.",
"title": "Hidden sources of phosphorus in the typical American diet: does it matter in nephrology?"
},
{
"docid": "MED-1312",
"text": "The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha.",
"title": "Inhibitory effect of oatmeal extract oligomer on vasoactive intestinal peptide-induced inflammation in surviving human skin."
},
{
"docid": "MED-1618",
"text": "To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.",
"title": "A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion..."
},
{
"docid": "MED-3962",
"text": "Pathological colonic tissues were investigated with an Environmental Scanning Electron Microscope technique to verify the presence of inorganic, non-biodegradable pollutants, i.e. micro- and nano-debris of exogenous origin, after debris in liver and kidney had been discovered. In all, 18 samples of colon tissues affected by cancer and Crohn's disease were evaluated and found in all the cases to contain micro- and nano-particles. Their chemistry, detected with an X-ray microprobe, indicated a heterogeneous nature, whereas the size of the particles was homogeneous. Three control samples of healthy, young, cadavers were analysed and showed the absence of debris within the normal, healthy colon mucosa. The study reveals the presence of particulate debris, generally considered as biocompatible, in pathological specimens of human colon. The findings suggest a possible link between the presence of such particles and the underlying pathology in the cases analysed.",
"title": "Biocompatibility of micro- and nano-particles in the colon. Part II."
},
{
"docid": "MED-4114",
"text": "Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..."
},
{
"docid": "MED-2498",
"text": "Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.",
"title": "Dietary Restriction, Growth Factors and Aging: from yeast to humans"
},
{
"docid": "MED-2922",
"text": "Overwhelming evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. The anticancer potential of berries has been related, at least in part, to a multitude of bioactive phytochemicals that these colorful fruits contain, including polyphenols (flavonoids, proanthocyanidins, ellagitannins, gallotannins, phenolic acids), stilbenoids, lignans, and triterpenoids. Studies show that the anticancer effects of berry bioactives are partially mediated through their abilities to counteract, reduce, and also repair damage resulting from oxidative stress and inflammation. In addition, berry bioactives also regulate carcinogen and xenobiotic metabolizing enzymes, various transcription and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and berry fruit consumption may provide protection from therapy-associated toxicities. Although a wide variety of berry fruits are consumed worldwide, this paper focuses on those commonly consumed in North America, namely, blackberries, black raspberries, blueberries, cranberries, red raspberries, and strawberries. In addition, a large body of studies on singly purified berry bioactives is available, but this paper focuses on studies of \"whole berries\" per se, that is, as berry extracts and purified fractions, juices, and freeze-dried powders. Potential mechanisms of anticancer action and bioavailability of berry phenolics, as well as gaps in knowledge and recommendations for future berry research, are also briefly discussed.",
"title": "Berry fruits for cancer prevention: current status and future prospects."
},
{
"docid": "MED-2820",
"text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.",
"title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis"
},
{
"docid": "MED-4422",
"text": "OBJECTIVES: To test the efficacy and safety of oral L-citrulline supplementation in improving erection hardness in patients with mild erectile dysfunction (ED). L-arginine supplementation improves nitric oxide-mediated vasodilation and endothelial function; however, oral administration has been hampered by extensive presystemic metabolism. In contrast, L-citrulline escapes presystemic metabolism and is converted to L-arginine, thus setting the rationale for oral L-citrulline supplementation as a donor for the L-arginine/nitric oxide pathway of penile erection. METHODS: In the present single-blind study, men with mild ED (erection hardness score of 3) received a placebo for 1 month and L-citrulline, 1.5 g/d, for another month. The erection hardness score, number of intercourses per month, treatment satisfaction, and adverse events were recorded. RESULTS: A total of 24 patients, mean age 56.5 ± 9.8 years, were entered and concluded the study without adverse events. The improvement in the erection hardness score from 3 (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01). The mean number of intercourses per month increased from 1.37 ± 0.93 at baseline to 1.53 ± 1.00 at the end of the placebo phase (P = .57) and 2.3 ± 1.37 at the end of the treatment phase (P < .01). All patients reporting an erection hardness score improvement from 3 to 4 reported being very satisfied. CONCLUSIONS: Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychologically fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction."
},
{
"docid": "MED-1928",
"text": "Purpose of review There has been growing evidence that lifestyle factors may affect the health and lifespan of an individual by affecting telomere length. The purpose of this review was to highlight the importance of telomeres in human health and aging and to summarize possible lifestyle factors that may affect health and longevity by altering the rate of telomere shortening. Recent findings Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases. Summary Telomere length shortens with age. Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, affecting the health and lifespan of an individual. Shorter telomeres have been associated with increased incidence of diseases and poor survival. The rate of telomere shortening can be either increased or decreased by specific lifestyle factors. Better choice of diet and activities has great potential to reduce the rate of telomere shortening or at least prevent excessive telomere attrition, leading to delayed onset of age-associated diseases and increased lifespan. This review highlights the role of telomeres in aging and describes the lifestyle factors which may affect telomeres, human health, and aging.",
"title": "Telomeres, lifestyle, cancer, and aging"
},
{
"docid": "MED-3627",
"text": "BACKGROUND: The use of computed tomographic (CT) scans in the United States (US) has increased more than 3-fold since 1993 to approximately 70 million scans annually. Despite the great medical benefits, there is concern about the potential radiation-related cancer risk. We conducted detailed estimates of the future cancer risks from current CT scan use in the US according to age, sex, and scan type. METHODS: Risk models based on the National Research Council's \"Biological Effects of Ionizing Radiation\" report and organ-specific radiation doses derived from a national survey were used to estimate age-specific cancer risks for each scan type. These models were combined with age- and sex-specific scan frequencies for the US in 2007 obtained from survey and insurance claims data. We estimated the mean number of radiation-related incident cancers with 95% uncertainty limits (UL) using Monte Carlo simulations. RESULTS: Overall, we estimated that approximately 29 000 (95% UL, 15 000-45 000) future cancers could be related to CT scans performed in the US in 2007. The largest contributions were from scans of the abdomen and pelvis (n = 14 000) (95% UL, 6900-25 000), chest (n = 4100) (95% UL, 1900-8100), and head (n = 4000) (95% UL, 1100-8700), as well as from chest CT angiography (n = 2700) (95% UL, 1300-5000). One-third of the projected cancers were due to scans performed at the ages of 35 to 54 years compared with 15% due to scans performed at ages younger than 18 years, and 66% were in females. CONCLUSIONS: These detailed estimates highlight several areas of CT scan use that make large contributions to the total cancer risk, including several scan types and age groups with a high frequency of use or scans involving relatively high doses, in which risk-reduction efforts may be warranted.",
"title": "Projected cancer risks from computed tomographic scans performed in the United States in 2007."
},
{
"docid": "MED-2065",
"text": "Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage. Studies on this compound is increasing because its anticarcinogenic and cytoprotective properties in several in vivo experimental paradigms associated with oxidative stress such as focal cerebral ischemia, brain inflammation, intracerebral hemorrhage, ischemia and reperfusion induced acute renal failure, cisplatin induced-nephrotoxicity, streptozotocin-induced diabetes, carbon tetrachloride-induced hepatotoxicity and cardiac ischemia and reperfusion. This protective effect also has been observed in in vitro studies in different cell lines such as human neuroblastoma SH-SY5Y, renal epithelial proximal tubule LLC-PK1 cells and aortic smooth muscle A10 cells. Sulforaphane is considered an indirect antioxidant; this compound is able to induce many cytoprotective proteins, including antioxidant enzymes, through the Nrf2-antioxidant response element pathway. Heme oxygenase-1, NAD(P)H: quinone oxidoreductase, glutathione-S-transferase, gamma-glutamyl cysteine ligase, and glutathione reductase are among the cytoprotective proteins induced by sulforaphane. In conclusion, sulforaphane is a promising antioxidant agent that is effective to attenuate oxidative stress and tissue/cell damage in different in vivo and in vitro experimental paradigms. Copyright © 2010 Elsevier GmbH. All rights reserved.",
"title": "Protective effect of sulforaphane against oxidative stress: recent advances."
},
{
"docid": "MED-2128",
"text": "BACKGROUND: Recipients of organ transplants are susceptible to Kaposi's sarcoma as a result of treatment with immunosuppressive drugs. Sirolimus (rapamycin), an immunosuppressive drug, may also have antitumor effects. METHODS: We stopped cyclosporine therapy in 15 kidney-transplant recipients who had biopsy-proven Kaposi's sarcoma and began sirolimus therapy. All patients underwent an excisional biopsy of the lesion and one biopsy of normal skin at the time of diagnosis. A second biopsy was performed at the site of a previous Kaposi's sarcoma lesion six months after sirolimus therapy was begun. We examined biopsy specimens for vascular endothelial growth factor (VEGF), Flk-1/KDR protein, and phosphorylated Akt and p70S6 kinase, two enzymes in the signaling pathway targeted by sirolimus. RESULTS: Three months after sirolimus therapy was begun, all cutaneous Kaposi's sarcoma lesions had disappeared in all patients. Remission was confirmed histologically in all patients six months after sirolimus therapy was begun. There were no acute episodes of rejection or changes in kidney-graft function. Levels of Flk-1/KDR and phosphorylated Akt and p70S6 kinase were increased in Kaposi's sarcoma cells. The expression of VEGF was increased in Kaposi's sarcoma cells and even more so in normal skin cells around the Kaposi's sarcoma lesions. CONCLUSIONS: Sirolimus inhibits the progression of dermal Kaposi's sarcoma in kidney-transplant recipients while providing effective immunosuppression. Copyright 2005 Massachusetts Medical Society.",
"title": "Sirolimus for Kaposi's sarcoma in renal-transplant recipients."
},
{
"docid": "MED-3423",
"text": "INTRODUCTION: There are no reported studies assessing the relation between diet and sexual function in women with diabetes. AIM: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women. METHODS: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study. MAIN OUTCOME MEASURES: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function. RESULTS: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders. CONCLUSIONS: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.",
"title": "Adherence to Mediterranean diet and sexual function in women with type 2 diabetes."
},
{
"docid": "MED-2093",
"text": "Chlorhexidine (CHX) is one of the most commonly prescribed antiseptic agents in the dental field. It has a long-lasting antibacterial activity with a broad-spectrum of action and it has been shown to reduce plaque, gingival inflammation and bleeding. Its use is considered a powerful adjuvant to mechanical oral hygiene (brushing and flossing), especially in those cases in which it cannot be performed correctly. Available as mouthwash, gel, aerosol, spray and disks, CHX is considered a safe compound, with minimal and transitory local and systemic side effects. Data support its periodic use as an adjuvant to normal brushing and flossing in subjects unable to maintain proper oral hygiene due to physical and/or mental impairment, or lack of motivation, or decreased salivary rate. CHX is also a useful alternative to mechanical oral hygiene procedures in those cases in which they are contraindicated, e.g. after a surgical procedure, or as a preoperative rinse before procedures in which use of a dental dam is not possible. The aim of this article is to offer a complete review of literature regarding the characteristics, the applications and the problems associated with the use of chlorhexidine in the dental field.",
"title": "Chlorhexidine (CHX) in dentistry: state of the art."
},
{
"docid": "MED-2905",
"text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.",
"title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study"
},
{
"docid": "MED-1750",
"text": "The discovery of myostatin and our introduction to the “Mighty Mouse” over a decade ago spurred both basic and applied research and impacted popular culture as well. The myostatin-null genotype produces “double muscling” in mice and livestock and was recently described in a child. The field’s rapid growth is by no means surprising considering the potential benefits of enhancing muscle growth in clinical and agricultural settings. Indeed, several recent studies suggest that blocking myostatin’s inhibitory effects could improve the clinical treatment of several muscle growth disorders, whereas comparative studies suggest that these actions are at least partly conserved. Thus, neutralizing myostatin’s effects could also have agricultural significance. Extrapolating between studies that use different vertebrate models, particularly fish and mammals, is somewhat confusing because whole genome duplication events have resulted in the production and retention of up to four unique myostatin genes in some fish species. Such comparisons, however, suggest that myostatin’s actions may not be limited to skeletal muscle per se, but may additionally influence other tissues including cardiac muscle, adipocytes, and the brain. Thus, therapeutic intervention in the clinic or on the farm must consider the potential of alternative side effects that could impact these or other tissues. In addition, the presence of multiple and actively diversifying myostatin genes in most fish species provides a unique opportunity to study adaptive molecular evolution. It may also provide insight into myostatin’s nonmuscle actions as results from these and other comparative studies gain visibility in biomedical fields.",
"title": "Clinical, Agricultural, and Evolutionary Biology of Myostatin: A Comparative Review"
},
{
"docid": "MED-5247",
"text": "Purpose We investigated whether caffeine, which transiently increases intraocular pressure (IOP) is associated with risk of primary open-angle glaucoma (POAG). Methods We followed 79,120 women from 1980 and 42,052 men from 1986 to 2004 who were 40+ years old, did not have POAG, and reported receiving eye examinations. Information on caffeine consumption, potential confounders and POAG diagnoses were repeatedly updated in validated follow-up questionnaires. We confirmed 1,011 incident POAG cases with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariable rate ratios (RR). Results Compared with daily intake of < 150 mg, the pooled multivariable RRs were 1.05 [95% Confidence Interval (CI), 0.89–1.25] for consuming 150–299 mg, 1.19 [95% CI, 0.99–1.43] for 300 – 449 mg/day, 1.13 [95% CI, 0.89–1.43] for 450–559 mg and 1.17 [95% CI, 0.90, 1.53] for 600+ mg+ [p for trend = 0.11]. However, for consuming 5+ cups of caffeinated coffee daily, RR was 1.61 [95% CI, 1.00, 2.59; p for trend=0.02]; tea or caffeinated cola intake were not associated with risk. Greater caffeine intake was more adversely associated with POAG among those reporting family history of glaucoma, particularly in relation to POAG with elevated IOP (p for trend =0.0009; p-interaction=0.04). Conclusion Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high-tension POAG among those with a family history of glaucoma; this may be due to chance, but warrants further study.",
"title": "Caffeine Consumption and the Risk of Primary Open - Angle Glaucoma: A Prospective Cohort Study"
},
{
"docid": "MED-4749",
"text": "For the first time in the field of steroid residues in humans, demonstration of 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one) excretion in urine subsequent to boar consumption is reported. Three male volunteers agreed to consume 310 g of tissues from the edible parts (meat, liver, heart and kidney) of a boar. The three individuals delivered urine samples before and during 24 h after meal intake. After deconjugation of phase II metabolites, purification and specific derivatisation of target metabolites, the urinary extracts were analysed by mass spectrometry. Identification was carried out using measurements obtained by gas chromatography/high resolution mass spectrometry (GC/HRMS) (R = 7000) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) (positive electrospray ionisation (ESI+)). Quantification was realised using a quadrupole mass filter. 19-NA and 19-NE concentrations in urine reached 3.1 to 7.5 microg/L nearby 10 hours after boar tissue consumption. Levels returned to endogenous values 24 hours after. These two steroids are usually exploited to confirm the exogenous administration of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one), especially in the antidoping field. We have thus proved that eating tissues of non-castrated male pork (in which 17beta-nandrolone is present) might induce some false accusations of the abuse of nandrolone in antidoping. Copyright 2000 John Wiley & Sons, Ltd.",
"title": "Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. I. Mass spectrometric detection and quantification of ..."
}
] |
7640
|
What happens when a company stops trading? (pink sheets)
|
[
{
"docid": "350095",
"text": "\"What will happen if the stock price just continues to decline? Nothing. What would happen if folks just stop trading it? Nothing. What if the company goes private? Then they will have to buy you out based on some agreed upon price, as voted by the board and (potentially) approved by the shareholders. Depending on the corporation charter, the board may not be required to seek the shareholders' approval, but if the price the board agreed upon is unreasonable you can sue and prevent the transaction. How do they decide the fair value of the outstanding stocks? Through a process called \"\"valuation\"\", there are accounting firms which specialize in this area of public accounting.\"",
"title": ""
}
] |
[
{
"docid": "278889",
"text": "\"Changing my answer based on clarification in comments. It appears that some of the securities you mentioned, including GEAPP, are traded on what is colloquially known as the Grey Market. Grey Sheets, and also known as the \"\"Gray Market\"\" is another category of OTC stocks that is completely separate from Pink Sheets and the OTCBB. From investopedia The grey market is an over-the-counter market where dealers may execute orders for preferred customers as well as provide support for a new issue before it is actually issued. This activity allows underwriters and the issuer to determine demand and price the securities accordingly before the IPO. Some additional information on this type of stocks. (Source) Unlike other financial markets... No recent bid or ask quotes are available because no market makers share data or quote such stocks. There is no quoting system available to record and settle trades. All Grey sheet trading is moderated by a broker and done between consenting individuals at a price they agree on. The only documentation that can be publicly found regarding the trades is when the last trade took place. No SEC registration and little SEC regulation. Regulation of Grey Sheet stocks takes place mainly on a state level. Unlike Pink Sheets, these stocks have no SEC registration to possess a stock symbol or to possess shares or trade shares of that stock. Such penny stocks, similar to Pink Sheets, are not required to file SEC (Securities and Exchange Commission) financial and business reports. These stocks may not be solicited or advertised to the public unless a certain number of shares are qualified to be traded publicly under 504 of Regulation D. Extremely Illiquid. Gray sheet trading is infrequent, and for good reason... Difficult to trade, not advertised, difficult to follow the price, the least regulation possible, hard to find any information on the stock, very small market cap, little history, and most such stocks do not yet offer public shares. The lack of information (bids, history, financial reports) alone causes most investors to be very skeptical of Gray Sheets and avoid them altogether. Gray Sheets are commonly associated with Initial public offering (IPO) stocks or start up companies or spin-off companies, even though not all are IPO's, start-ups or spin-offs. Grey Sheets is also Home to delisted stocks from other markets. Some stocks on this financial market were once traded on the NASDAQ, OTCBB, or the Pink Sheets but ran into serious misfortune - usually financial - and thus failed to meet the minimum requirements of the registered SEC filings and/or stock exchange regulations for a financial market. Such stocks were delisted or removed and may begin trading on the Grey Sheets. So to answer your question, I think the cause of the wild swings is that: Great question, BTW.\"",
"title": ""
},
{
"docid": "107227",
"text": "popularity that you are referring to is just known as liquidity when discussing markets. More liquid securities tend to trade more shares per day and have very tight bid/ask spreads as many investors are buying and selling the shares at one time. Some larger securities, especially on exchanges, further enhance liquidity by providing market makers. These are individuals on the NYSE, for example, that will make the market in large securities by handling large orders and providing liquidity through their own book of capital. The individuals on the floor on the NYSE you often see on TV are those market makers. However, as trading becomes more electronic, market markers are becoming less and less required. A previous comment suggested pink sheets are risky companies. This is not entirely factual. While the majority of pink sheets are very highly risky companies, many very solid international companies trade their ADRs (American Depository Receipt) on the pink sheets to avoid the high cost of setting up a large exchange at the NYSE and register and report through the SEC. As a TD Ameritrade user, I would be willing to help you out if you have any other questions.",
"title": ""
},
{
"docid": "261640",
"text": "\"The penny/pink sheet stocks you tend to see promoted are the ones a) with small public floats or, b) they are thinly traded. This means that any appreciable change in buy/sell volume will have an outsized effect on the stock's share price, even when the underlying fundamentals are not so great. Promoters are frequently paid based on how much they can move a stock's price, but such moves are not long-lasting. They peter out when the trading volumes return to more normal ranges for the stock because all of the hype has died out. There are some small-cap NASDAQ stocks which can be susceptible to promotion for the same reason -- they have small floats and/or are thinly traded. Once someone figures out the best targets, they'll accumulate a position and then start posting all kinds of \"\"news\"\" on the web in an effort to drum up interest so they can sell off their position into the buying that follows. The biggest problem with penny/pink sheet stocks is that they frequently fail to publish reliable financial statements, and their ownership is of a dubious nature. In the past, these types of stocks have been targeted by organized crime syndicates, which ran their own \"\"pump and dump\"\" operations as a way to make relatively easy money. This may still be true to some extent today. Be wary of investing in any publicly-traded firm that has to use promoters to drum up investor interest, because it can be a serious red flag. Even if it means missing out on a short-term opportunity, research the company before investing. Read its financials, understand how it has behaved through its trading history, learn about the products/services it is selling. Do your homework. Otherwise you are doing the investing equivalent of taking your money and lighting it on fire. Remember, there's a good reason these companies are trading as penny/pink sheet stocks, and it generally has nothing to do with the notion (the promoters will tell you) that somehow the \"\"market has missed out on this amazing opportunity.\"\" Pump and dump schemes, which lie at the heart of almost all stock promotion, rely on convincing you, the investor, that you're smart enough to see what others haven't. I hope this helps. Good luck!\"",
"title": ""
},
{
"docid": "510163",
"text": "\"The Minnesota Mining and Manufacturing Company was established in 1902 as a private company. It first raised public funds around 1903 but had a limited shareholder base. By around 1929, it was reported as being tradeable as an OTC (over-the-counter) stock but it's likely that shares were traded well before this. On 14 Jan 1946, the stock was listed on NYSE. On 26 Sep 1962 it became a constituent of the the S&P 500 index. On 9 Aug 1976 it became a constituent of the Dow Jones Industrial Average. In 2002, the company's name changed to 3M Co. It appears that the data on Crunchbase's \"\"IPO Date\"\" is wrong on this one. However, there are several companies that appear to do an \"\"IPO\"\" and have trading prices prior. This is quite typical of early-stage biotech companies that trade OTC prior to a major exchange listing and \"\"IPO\"\". An example of an IPO happening after a company became publicly tradeable is NASDAQ:IMRN (Immuron). They had an \"\"IPO\"\" on Nasdaq on 9 Jun 2017, yet they had been trading as an OTC/Pink Sheet stock for months prior. They also have been listed in Australia since 30 Apr 1999. http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-06 Another example is NASDAQ:GNTY (Guaranty Banchshares Inc) which had an \"\"IPO\"\" and NASDAQ listing in May 2017. This was a Nasdaq stock in 1998, went OTC/pink sheet stock in 2005. It has been paying regular dividends since that time. Clearly the word \"\"Initial\"\" is subjective! http://www.nasdaq.com/markets/ipos/activity.aspx?tab=pricings&month=2017-05\"",
"title": ""
},
{
"docid": "165973",
"text": "It depends on what site you're looking on and what exchange they're pulling the data from. Even though funds and stocks are called the same thing, they have different ticker symbols in each country's exchange or could be traded as pink sheet stocks in the US. If a company or fund is based in another country (like Canada or the UK) they probably also trade on that country's exchange (Toronto or London) under a different symbol. This can cause a lot of confusion when researching these tickers.",
"title": ""
},
{
"docid": "253847",
"text": "While most all Canadian brokers allow us access to all the US stocks, the reverse is not true. But some US brokers DO allow trading on foreign exchanges. (e.g. Interactive Brokers at which I have an account). You have to look and be prepared to switch brokers. Americans cannot use Canadian brokers (and vice versa). Trading of shares happens where-ever two people get together - hence the pink sheets. These work well for Americans who want to buy-sell foreign stocks using USD without the hassle of FX conversions. You get the same economic exposure as if the actual stock were bought. But the exchanges are barely policed, and liquidity can dry up, and FX moves are not necessarily arbitraged away by 'the market'. You don't have the same safety as ADRs because there is no bank holding any stash of 'actual' stocks to backstop those traded on the pink sheets.",
"title": ""
},
{
"docid": "291903",
"text": "\"Pink Sheets is not a stock exchange per se, and securities traded through it are not as \"\"safe\"\" as the ones on a stock exchange regulated by SEC. Many companies are traded there because they failed to comply with the SEC regulations, or are bankrupt or don't want the level of reporting to the public that the SEC regulations require. Since you're talking about an ADR of a company traded on LSE, it might be much safer that other, \"\"regular\"\", securities, but still it means that you're buying an unregulated security (even if it is of a company regulated elsewhere). Notice the volume of trades: mere thousands of dollars per day (in a good day, in some days there are no trades at all). It makes it harder to sell the security when needed. Why not buying at LSE?\"",
"title": ""
},
{
"docid": "54257",
"text": "\"If you own 1% of a company, you are technically entitled to 1% of the current value and future profits of that company. However, you cannot, as you seem to imply, just decide at some point to take your ball and go home. You cannot call up the company and ask for 1% of their assets to be liquidated and given to you in cash. What the 1% stake in the company actually entitles you to is: 1% of total shareholder voting rights. Your \"\"aye\"\" or \"\"nay\"\" carries the weight of 1% of the total shareholder voting block. Doesn't sound like much, but when the average little guy has on the order of ten-millionths of a percentage point ownership of any big corporation, your one vote carries more weight than those of millions of single-share investors. 1% of future dividend payments made to shareholders. For every dollar the corporation makes in profits, and doesn't retain for future growth, you get a penny. Again, doesn't sound like much, but consider that the Simon property group, ranked #497 on the Fortune 500 list of the world's biggest companies by revenue, made $1.4 billion in profits last year. 1% of that, if the company divvied it all up, is $14 million. If you bought your 1% stake in March of 2009, you would have paid a paltry $83 million, and be earning roughly 16% on your initial investment annually just in dividends (to say nothing of the roughly 450% increase in stock price since that time, making the value of your holdings roughly $460 million; that does reduce your actual dividend yield to about 3% of holdings value). If this doesn't sound appealing, and you want out, you would sell your 1% stake. The price you would get for this total stake may or may not be 1% of the company's book value. This is for many reasons: Now, to answer your hypothetical: If Apple's stock, tomorrow, went from $420b market cap to zero, that would mean that the market unanimously thought, when they woke up tomorrow morning, that the company was all of a sudden absolutely worthless. In order to have this unanimous consent, the market must be thoroughly convinced, by looking at SEC filings of assets, liabilities and profits, listening to executive statements, etc that an investor wouldn't see even one penny returned of any cash investment made in this company's stock. That's impossible; the price of a share is based on what someone will pay to have it (or accept to be rid of it). Nobody ever just gives stock away for free on the trading floor, so even if they're selling 10 shares for a penny, they're selling it, and so the stock has a value ($0.001/share). We can say, however, that a fall to \"\"effectively zero\"\" is possible, because they've happened. Enron, for instance, lost half its share value in just one week in mid-October as the scope of the accounting scandal started becoming evident. That was just the steepest part of an 18-month fall from $90/share in August '00, to just $0.12/share as of its bankruptcy filing in Dec '01; a 99.87% loss of value. Now, this is an extreme example, but it illustrates what would be necessary to get a stock to go all the way to zero (if indeed it ever really could). Enron's stock wasn't delisted until a month and a half after Enron's bankruptcy filing, it was done based on NYSE listing rules (the stock had been trading at less than a dollar for 30 days), and was still traded \"\"over the counter\"\" on the Pink Sheets after that point. Enron didn't divest all its assets until 2006, and the company still exists (though its mission is now to sue other companies that had a hand in the fraud, get the money and turn it around to Enron creditors). I don't know when it stopped becoming a publicly-traded company (if indeed it ever did), but as I said, there is always someone willing to buy a bunch of really cheap shares to try and game the market (buying shares reduces the number available for sale, reducing supply, increasing price, making the investor a lot of money assuming he can offload them quickly enough).\"",
"title": ""
},
{
"docid": "454465",
"text": "If you are trying to invest in closely held / private companies (things that don't trade on the stock market), you will run into a variety of regulatory problems. For various reasons, most private companies only raise funds with accredited investors. To be an accredited investor you basically have to have $1,000,000 in net worth - NOT including your primary residence, OR you have to make over $200,000 a year for the last two years and expect to keep making that much. This is a class distinction the Federal government created, you will see different but similar wealth and investment classes worldwide. So your best most organized opportunities are left out, unless you do qualify as an accredited investor. There are tons of other companies, things you will find locally, that will let you invest in their smaller time operations. (Think like a local yoga studio looking for $20,000 and willing to split the profits with you). But the problem here is lack of accountability, where partners skip town or just stop answering your calls, and the legal remedies cost you more than your claim. That being said there are people that provide capital to smaller publicly traded companies on the bulletin boards and pink sheets. They have opportunities do much better than the actual stock market investors in these companies, because you can negotiate contracts that let you cash out in their inevitable financing death spirals with very little risk to you. You can do these things as an individual or as a holding company, but the holding company will limit your liability to the amount your holding company invested, instead of your personal assets, in case your financing starts to incur liability with the company.",
"title": ""
},
{
"docid": "404936",
"text": "Depends on the structure of the company and what shares are outstanding. If the pink sheet stock has no voting power then buying all that stock doesn't get you any control at all. On the other hand, if the outstanding shares only represent 20% of the company's overall shares, then buying all the shares isn't likely enough to have a controlling interest. Thus, you'll have to dig into the details. If you want an example of where I'd have my doubts, look at Nestle's stock which has the ticker of NSRGY. There can be companies that are structured with stock on multiple exchanges that can also be a challenge at times. There is also something to be said if you own enough stock in a company that this has to be disclosed to the SEC when you buy more.",
"title": ""
},
{
"docid": "319599",
"text": "Well I'm not going to advise whether it's a good idea to invest in this company (though often OTC is pretty scary), but it DOES have a product (vivio, an ad blocker), it did post financials and it's trading on the OTC-QB (which is better than the pink sheets), so you need to look these over and study up on the product to decide if it is overpriced or not. What might have occurred (viz the Patriot Berry Farm becoming Cyberfort) is that the latter bought up the stock of the former (this is, I believe, called using a shell, which is not necessarily a bad thing) and is using this as a way to be registered, i.e. sell to non-accredited investors via the OTC market. So I'm really just answering your third question: yes, you have to do a lot of due diligence to see if buying this stock is a good deal or not. It might be the next big thing. Or it might not. It certainly is the case that low trading volume allows a relatively small trade to really change the stock price, so the penny stocks do tend to be easier to 'inflate'. Side comment: the bid/ask spreads are pretty big, with a best bid of 0.35 and best ask of 0.44.",
"title": ""
},
{
"docid": "110584",
"text": "For the lazy, Wikipedia says: The term microcap stock (also micro-cap) refers to the stock of public companies in the United States which have a market capitalization of roughly $300 million or less. The shares of companies with a market capitalization of less than $50 million are typically referred to as nano-cap stocks. Many micro-cap and nano-cap stocks are traded over-the-counter with their prices quoted on the OTCBB or the Pink Sheets. A few of the larger, more established microcaps are listed on the NASDAQ Capital Market or American Stock Exchange (AMEX). Micro-cap and especially nano-cap stocks are notorious for their volatility. A high percentage of these companies fail to execute their business plans and go out of business. Fraud and market manipulation are not uncommon, and the transactions costs in trading can be quite high. Pricing is more likely to be inefficient, since fewer institutional investors and analysts operate in this space, due to the relatively small dollar amounts involved and the lack of liquidity.",
"title": ""
},
{
"docid": "495255",
"text": "I'd call it pretty worrisome. HOOB is trading over the counter, in fact, on the pink sheets, so it has been delisted from the major exchanges. It appears that it lacks recent financial disclosures. You'll have to investigate to see if you think it's worth keeping, but trading is thin.",
"title": ""
},
{
"docid": "555047",
"text": "I traded futures for a brief period in school using the BrokersXpress platform (now part of OptionsXpress, which is in turn now part of Charles Schwab). They had a virtual trading platform, and apparently still do, and it was excellent. Since my main account was enabled for futures, this carried over to the virtual account, so I could trade a whole range of futures, options, stocks, etc. I spoke with OptionsXpress, and you don't need to fund your acount to use the virtual trading platform. However, they will cancel your account after an arbitrary period of time if you don't log in every few days. According to their customer service, there is no inactivity fee on your main account if you don't fund it and make no trades. I also used Stock-Trak for a class and despite finding the occasional bug or website performance issue, it provided a good experience. I received a discount because I used it through an educational institution, and customer service was quite good (probably for the same reason), but I don't know if those same benefits would apply to an individual signing up for it. I signed up for top10traders about seven years ago when I was in secondary school, and it's completely free. Unfortunately, you get what you pay for, and the interface was poorly designed and slow. Furthermore, at that time, there were no restrictions that limited the number of shares you could buy to the number of outstanding shares, so you could buy as many as you could afford, even if you exceeded the number that physically existed. While this isn't an issue for large companies, it meant you could earn a killing trading highly illiquid pink sheet stocks because you could purchase billions of shares of companies with only a few thousand shares actually outstanding. I don't know if these issues have been corrected or not, but at the time, I and several other users took advantage of these oversights to rack up hundreds of trillions of dollars in a matter of days, so if you want a realistic simulation, this isn't it. Investopedia also has a stock simulator that I've heard positive things about, although I haven't used it personally.",
"title": ""
},
{
"docid": "390779",
"text": "\"The assumption that companies listed OTC are not serious is far from the truth. Many companies on the OTC are just starting off there because they don't meet the requirements to be listed on the NASDAQ or NYSE. Major stock exchanges like the NASDAQ and the NYSE only want the best companies to trade on their exchanges.The NASDAQ, for example, has three sets of listing requirements. A company must meet at least one of the three requirement sets, as well as the main rules for all companies. These include: Now don't assume that the OTC doesn't have rules either, as this is far from the truth as well. While there are no minimum level of revenue, profits or assets required to get listed on the OTC there are requirements for audited financial statements and ongoing filing and reporting to the SEC and NASD. Additionally there are several different levels of the OTC, including the OTCQX, the OTCCB and the OTC Pink, each with their own set of requirements. For more information about what it takes to be listed on OTC look here: http://www.otcmarkets.com/learn/otc-trading A company deciding to trade on the OTC is making the decision to take their company public, and they are investing to make it happen. Currently the fees to get listed on the OTC range from $30,000 to $150,000 depending on the firm you decide to go with and the services they offer as part as their package. Now, I know I wouldn't consider $30K (or more) to not be serious money! When I looked into the process of getting a company listed on the TSX the requirements seemed a lot more relaxed than those of the major U.S. markets as well, consisting of an application, records submission and then a decision made by a TSX committee about whether you get listed. More information about the TSX here: http://apps.tmx.com/en/listings/listing_with_us/process/index.html I think the way that the OTC markets have gotten such a bad reputation is from these \"\"Get Rich on Penny Stock\"\" companies that you see pumping up OTC company stocks and getting massive amounts of people to buy without doing their due diligence and investigating the company and reading its prospectus. Then when they loose a bunch of money on an ill-informed investment decision they blame it on the company being an OTC stock. Whether you decide to trade the OTC market or not, I wouldn't make a decision based on how many exchanges the company is listed on, but rather based on the research you do into the company.\"",
"title": ""
},
{
"docid": "129481",
"text": "I'm going to guess that you found this because of a stock screener. This company went through a 1:20 reverse split on June 30, so every 20 shares outstanding became a single share. Where before you had 20 shares worth $100 you now have 1 share worth $100, the value of the company doesn't change because of a split. This company was never trading for $30+ per share. Reverse splits are typical of a floundering company trading on an exchange that has a minimum share price requirement. While reverse splits don't change the value of the company, just the number of shares outstanding and the price per share, no healthy company performs a reverse split. Reverse splits are generally a massive signal to jump ship... The company seems to be trading for $1 right now, why the value fell from a pre-split $1.65 ($33/20) to $1 is anyone's guess; how the company ever got to $1.65 is also anyone's guess. But looking at the most recent 10-Q there are numerous causes for concern: Note 2. Capital Stock On March 6, 2017, the Company issued as compensation for services provided a total of 650,000 common shares with a fair value of $390,000 to a third party. The fair value of the shares was based on the price quoted on the OTC pink sheets on the grant date. this indicates a share price of $0.60 ($390,000/650,000) as of 3/6/2017, just to reinforce that the google price chart doesn't show the true past but a past adjusted for the split Results of Operations The three months ended March 31, 2017 compared to the three months ended March 31, 2016 For the three months ended March 31, 2017 compared to the three months ended March 31, 2016, total revenues were $0 and $0, respectively, and net losses from operations were $414,663 and $26,260, respectively. The net losses were attributable to costs attributable to operating as a public company, in particular, common stock with a valuation of $390,000 that was issued to an investor relations firm in the first quarter of 2017. Going Concern As of March 31, 2017, there is substantial doubt regarding our ability to continue as a going concern as we have not generated sufficient cash flow to fund our proposed business. We have suffered recurring losses from operations since our inception. In addition, we have yet to generate an internal cash flow from our business operations or successfully raised the financing required to develop our proposed business. As a result of these and other factors, our independent auditor has expressed substantial doubt about our ability to continue as a going concern. Liquidity and Capital Resources We had no cash as of the date of March 31, 2017. Additionally, since there is no balance sheet in the last 10-Q (another bad sign), the last annual report 10-K has this balance sheet: So the company: So why did the stock value plummet? It's anyones' guess but there is no shortage of ways to justify it. In fact, it's reasonable to ask how is this company still worth $3mm ($1 * 3mm shares outstanding)...",
"title": ""
},
{
"docid": "151871",
"text": "\"Their is no arbitrage opportunity with \"\"buying dividends.\"\" You're buying a taxable event. This is a largely misunderstood topic. The stock always drops by the amount if the dividend on the ex date. The stock opens that day trading \"\"ex\"\" (excluding) the dividend. It then pays out later based in the shareholders on record. There is a lot of talk about price movement and value here. That can happen but it's from trading not from the dividend per se. Yes sometimes you do see a stock pop the day prior to ex date because people are buying the stock for the dividend but the trading aspect of a stock is determined by supply and demand from people trading the stock. The dividends are paid out from the owners equity section of the balance sheet. This is a return of equity to shareholders. The idea is to give owners of the company some of their investment back (from when they bought the stock) without having the owners sell the shares of the company. After all if it's a good company you want to keep holding it so it will appreciate. Another similar way to think of it is like a bonds interest payment. People sometimes forget when trading that these are actual companies meant to be invested in. Your buying an ownership in the company with your cash. It really makes no difference to buy the dividend or not, all other things constant. Though market activity can add or lose value from trading as normal.\"",
"title": ""
},
{
"docid": "506460",
"text": "First, I want to point out that your question contains an assumption. Does anyone make significant money trading low volume stocks? I'm not sure this is the case - I've never heard of a hedge fund trading in the pink sheets, for example. Second, if your assumption is valid, here are a few ideas how it might work: Accumulate slowly, exit slowly. This won't work for short-term swings, but if you feel like a low-volume stock will be a longer-term winner, you can accumulate a sizable portion in small enough chunks not to swing the price (and then slowly unwind your position when the price has increased sufficiently). Create additional buyers/sellers. Your frustration may be one of the reasons low-volume stock is so full of scammers pumping and dumping (read any investing message board to see examples of this). If you can scare holders of the stock into selling, you can buy significant portions without driving the stock price up. Similarly, if you can convince people to buy the stock, you can unload without destroying the price. This is (of course) morally and legally dubious, so I would not recommend this practice.",
"title": ""
},
{
"docid": "160421",
"text": "When I read that part of his post, it reminded me more of credit companies rather than banks. People default on credit all the time. I have no idea what the regulations are on the amount of credit that a company can issue, though. And this is sort of part of what actually happened in the beginning of the economic crunch. A bunch of people began to trade for credit (debt) against what they thought the *future* value of their house or other real estate would be. After a while, people stopped being able to afford property at its future value, so they stopped buying it. When people then tried to sell their property for the future value that they had borrowed against, they couldn't, so they couldn't pay back their debt. Because real estate had become a popular investment vehicle for the middle class, this was able to reach a kind of critical mass, and shortly afterward the effects rippled back into the credit market, which also had its own crunch -- a bunch of credit just disappeared overnight because so many people had assumed a level of debt that they could not actually fulfill their promises on once the future value of their home became completely imaginary.",
"title": ""
},
{
"docid": "365465",
"text": "\"Very simple. You open an account with a broker who will do the trades for you. Then you give the broker orders to buy and sell (and the money to pay for the purchases). That's it. In the old days, you would call on the phone (remember, in all the movies, \"\"Sell, sell!!!!\"\"? That's how), now every decent broker has an online trading platform. If you don't want to have \"\"additional value\"\" and just trade - there are many online discount brokers (ETrade, ScotTrade, TD Ameritrade, and others) who offer pretty cheap trades and provide decent services and access to information. For more fees, you can also get advices and professional management where an investment manager will make the decisions for you (if you have several millions to invest, that is). After you open an account and login, you'll find a big green (usually) button which says \"\"BUY\"\". Stocks are traded on exchanges. For example the NYSE and the NASDAQ are the most common US exchanges (there's another one called \"\"pink sheets\"\", but its a different kind of animal), there are also stock exchanges in Europe (notably London, Frankfurt, Paris, Moscow) and Asia (notably Hong Kong, Shanghai, Tokyo). Many trading platforms (ETrade, that I use, for example) allow investing on some of those as well.\"",
"title": ""
},
{
"docid": "593644",
"text": "NSCC illiquid charges are charges that apply to the trading of low-priced over-the counter (OTC) securities with low volumes. Open net buy quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net buy quantity must be less than 5,000,000 shares per stock for your entire firm Basically, you can't hold a long position of more than 5 million shares in an illiquid OTC stock without facing a fee. You'll still be assessed this fee if you accumulate a long position of this size by breaking your purchase up into multiple transactions. Open net sell quantity represents the total unsettled share amount per stock at any given time during a 3-day settlement cycle. Open net sell quantity must be less than 10% percent of the 20-day average volume If you attempt to sell a number of shares greater than 10% of the stock's average volume over the last 20 days, you'll also be assessed a fee. The first link I included above is just an example, but it makes the important point: you may still be assessed a fee for trading OTC stocks even if your account doesn't meet the criteria because these restrictions are applied at the level of the clearing firm, not the individual client. This means that if other investors with your broker, or even at another broker that happens to use the same clearing firm, purchase more than 5 million shares in an individual OTC stock at the same time, all of your accounts may face fees, even though individually, you don't exceed the limits. Technically, these fees are assessed to the clearing firm, not the individual investor, but usually the clearing firm will pass the fees along to the broker (and possibly add other charges as well), and the broker will charge a fee to the individual account(s) that triggered the restriction. Also, remember that when buying OTC/pink sheet stocks, your ability to buy or sell is also contingent on finding someone else to buy from/sell to. If you purchase 10,000 shares one day and attempt to sell them sometime in the future, but there aren't enough buyers to buy all 10,000 from you, you might not be able to complete your order at the desired price, or even at all.",
"title": ""
},
{
"docid": "61418",
"text": "\">BPI took such a hard hit because they showed the world that they're the type of company willing to sell people really nasty shit just to make a buck (in my opinion). Honestly, if there was a news expose on 90% of the processed food that is on grocery store shelves, people would have the same reaction. You would be shocked as to what happens in food manufacturing facilities. Yes, there are FDA, USDA, and many other agencies that do both announced and surprise audits of food manufacturers to ensure food safety, but this is just a snapshot in time, and the food is only deemed as safe as to the standards of that company and what the definition of \"\"safe\"\" is. IMO, yes, BPI took a huge hit because of this being called pink slime. Are they manufacturing something that is potentially dangerous for consumption? Possibly. That all depends on who you ask what \"\"safe for consumption\"\" means. Are lobbyists involved? Bet your ass they are. But the market at the time was demanding a type of beef that was super lean. All BPI did was find a way to fulfill that need. I don't know what the outcome of this will be, but I can absolutely see both sides of the argument. The press needs to be free to report on anything and everything. However, there needs to be regulation regarding what they can and can not say from a slander standpoint. Coming up with a cute catch phrase such as \"\"pink slime\"\" is slanderous, and potentially damaging. That's where I agree with you and believe that they should have reported on the factual inclusions in the finished product. /rant\"",
"title": ""
},
{
"docid": "393925",
"text": "Many of the major indices retreated today because of this news. Why? How do the rising budget deficits and debt relate to the stock markets? It does seem strange that there is a correlation between government debt and the stock market. But I could see many reasons for the reaction. The downgrade by S&P may make it more expensive for the government to borrow money (i.e. higher interest rates). This means it becomes more expensive for the government to borrow money and the government will probably need to raise taxes to cover the cost of borrowing. Rising taxes are not good for business. Also, many banks in the US hold US government debt. Rising yields will push down the value of their holdings which in turn will reduce the value of US debt on the businesses' balance sheets. This weakens the banks' balance sheets. They may even start to unload US bonds. Why is there such a large emphasis on the S&P rating? I don't know. I think they have proven they are practically useless. That's just my opinion. Many, though, still think they are a credible ratings agency. What happens when the debt ceiling is reached? Theoretically the government has to stop borrowing money once the debt ceiling is reached. If this occurs and the government does not raise the debt ceiling then the government faces three choices:",
"title": ""
},
{
"docid": "542765",
"text": "Using Fundamental and Technical Analysis together is actually a good idea for longer term trading of up to 6 months or longer. The whole idea behind trading with Technical Analysis is to increase the probabilities of a trade going in the desired direction by using uncorrelated indicators that produce the same signal to buy or sell at the same time. For example, you might use a Moving Average (MA) as a buy signal when the price falls for a few days, hits the MA and then reverses and starts moving back up. If however, you also include a Stochastic Oscillator (SO) to indicate when the stock is oversold (under 20%), and if the price rebounds from the MA average at the same time as the Stochastic is crossing over in the oversold position, then this may be a higher probability trade. If you also only trade stocks that are Fundamentally healthy (as fundamentally good stocks are more likely to go up than fundamentally bad stocks) then this might increase the probabilities again. Then if you only buy when the market as a whole is moving up, then this will increase your chances again. A few weeks ago at a seminar, the presenter totalled the men in the room to be 76 and the women in the room to be 8. He then asked what will most likely be the next person to walk in the room - a man or a woman? The statistics are on the side of a wan walking in next. This is what we try to do with Technical Analysis, increase our chances when we take a trade. Of course a woman could be the next person to walk in the room, just like any trade can go against you, and this is why we use money management and risk management and take a small loss when a trade does go against you. Lets look at an example where you could incorporate FA with TA to increase your chances of profits: Above is a candlestick chart of Select Harvest (SHV), the green line above the price is the perceived value, the pink line is the 40 day MA, the blue line is the EPS, and the white lines is the Stochastic Oscillator (above 80% being overbought and below 20% is oversold). From Feb 2015 to start of Aug 2015 the stock was uptrending, since then the price reversed and started to downtrend. The stock was determined to be fundamentally good early in 2015 with the perceived value gradually increasing and greater than the share price, and the EPS starting to increase regularly from mid April. Thus, as the stock is seen as fundamentally healthy any price reversal in the vicinity of the MA could be seen as a buy opportunity. In fact there where 2 such opportunities on 31st March and 11th June where price had reversed and rebounded off the MA whist the SO crossed over in or near the oversold area. The price did reverse and then rebounded off the MA again on 9th July, however the SO was not in or near the oversold area on this occasion, so not as high in probability terms. The price still rebounded and went up again, however another momentum indicator (not shown here) shows some bearish divergence in this case - so another reason to possibly keep away at this point in time. A good signal to get out of the trade, that is your stop loss has not already taken you out, is when the price breaks and closes below the MA line. This occurred on 7th August. So if we had bought on the first signal on 31st March for $7.41 and sold when the priced broke through the MA on 7th August for $11.76, we would have made a profit of approx. 59% in just over 4 months. If bought on the second signal on 11th June for $9.98 and again sold on 7th August for $11.76, we would have made about 18% in under 2 months. So the fundamentals, the Price (in relation to MA) and the SO where all lining up to provide two high probability trades. Of course you would need to incorporate you risk management (including stops) in case the price did not continue upwards after you bought. If the market is also moving up on the day of the signal this will further increase your chances. Unless you day trade, which I would avoid, a good way to enter your trades after a signal is to enter a stop buy order after market close to buy if the price moves above the high of the signal day. That way if the market and the stock open and move lower during the day after the signal you avoid entering the trade altogether. This can be incorporated as part of your risk management and trading rules. After the price broke down through the MA we can see that a downtrend commenced which is still current today (in fact I just took a short trade on this stock yesterday). We can also see that the perceived value, whilst still above the price, has reached a peak and is currently moving downwards and the EPS after being flat for a few months has just moved down for the first time in 10 months. So maybe the fundamentals are starting to waver a bit on this stock. It may be a good stock to continue shorting into the future. So basically you can continue using Fundamental Analysis to select which stocks to buy, place them in a watch-list, and then use Technical Analysis to determine when these stocks are starting to uptrend and use a combination of uncorrelated indicators to produce higher probability signals for when to enter your trades.",
"title": ""
},
{
"docid": "565971",
"text": ">PI’s attorney, Dan Webb, said in court Monday that ABC used the term “pink slime” 350 times over the course of its reporting, and that ABC willfully spread this preconceived, negative message. Webb also showed the jurors a picture of lean finely textured beef. “It physically doesn’t look like slime,” he said. It physically doesn't look like slime, and presumably it isn't slime chemically. What's their reason for calling it 'pink slime'? >In fact, the term “pink slime” was coined by one of the segment’s whistleblowing USDA scientists in a 2002 email to colleagues, and a 2009 New York Times piece using the term to describe BPI’s meat product won a Pulitzer Prize. So, they coined a word to describe something that was intentionally designed to sensationalize it, in a negative way. If I were on the jury this is the point of fact that I'd base my vote on. The media needs to be slapped pretty hard when they start actively damaging people and companies to sell stories.",
"title": ""
},
{
"docid": "287325",
"text": "\"What could the tax issues with the IRS be? I thought (but not totally certain) that the tax treatment of an ISO option was based on difference between exercise price and FMV at the time of the sale. This is an accounting issue. There were times not so long ago that companies actually did these things on purpose, to boost the stock grant values for their employees (especially senior employees). They would give a grant but date it with an earlier date with a more favorable valuation. This is called \"\"backdating\"\", and it brought companies down and CEOs into criminal courts. In addition, only reasonable compensation is allowed as a deduction for the company, and incorrectly set strike price may be deemed unreasonable. Thus, the deduction the company would take for your compensation can be denied, leading to loss of tax benefit (this was also a weapon used by the IRS at the time against companies doing backdating). Last but not least, company that has intentions of going public cannot allow itself such a blatant disregard of the accounting rules. Even if the mistake was not made on purpose (as it sounds), it is a mistake that has to be corrected. What should I take into consideration to determine whether a 27% increase in shares is a fair exchange for an increase in 270% increase in strike price. Did you know the strike price when you signed the contract? Was it a consideration for you? For most people, the strike price is determined at the board approval, since the valuations are not public and are not disclosed before you actually join, which is already after you've agreed to the terms. So basically, you agreed to get 100 sheets of toilet paper, and instead getting 127 sheets. So you're getting 27 sheets more than you initially agreed to. Why are you complaining? In other words, options are essentially random numbers which are quite useless. By the time you get to exercise them, they'll be diluted through a bunch of additional financing rounds, and their value will be determined for real only after the IPO, or at least when your company's stocks are trading OTC with some reasonable volume. Until then - it's just a number with not much of a meaning. The FMV does matter for early exercise and 83(b) election, if that is an option, but even then - I doubt you can actually negotiate anything.\"",
"title": ""
},
{
"docid": "316673",
"text": "We constantly hear that there are not enough trades-people to fill manufacturing roles. This is what happens when you offshore everything possible for the last 30 years. No one wants to go into a trade that will be offshored plus there are too few of those positions to apprentice in. Stop the boo-hooing big business, man-up and invest in some of your fellow citizens.",
"title": ""
},
{
"docid": "312811",
"text": "\"Share sales & purchases are accounted only on the balance sheet & cash flow statement although their effects are seen on the income statement. Remember, the balance sheet is like a snapshot in time of all accrued accounts; it's like looking at a glass of water and noting the level. The cash flow and income statements are like looking at the amount of water, \"\"actually\"\" and \"\"imaginary\"\" respectively, pumped in and out of the glass. So, when a corporation starts, it sells shares to whomever. The amount of cash received is accounted for in the investing section of the cash flow statement under the subheading \"\"issuance (retirement) of stock\"\" or the like, so when shares are sold, it is \"\"issuance\"\"; when a company buys back their shares, it's called \"\"retirement\"\", as cash inflows and outflows respectively. If you had a balance sheet before the shares were sold, you'd see under the \"\"equity\"\" heading a subheading common stock with a nominal (irrelevant) par value (this is usually something obnoxiously low like $0.01 per share used for ease of counting the shares from the Dollar amount in the account) under the subaccount almost always called \"\"common stock\"\". If you looked at the balance sheet after the sale, you'd see the number of shares in a note to the side. When shares trade publicly, the corporation usually has very little to do with it unless if they are selling or buying new shares under whatever label such as IPO, secondary offering, share repurchase, etc, but the corporation's volume from such activity would still be far below the activity of the third parties: shares are trading almost exclusively between third parties. These share sales and purchases will only be seen on the income statement under earnings per share (EPS), as EPS will rise and fall with stock repurchases and sales assuming income is held constant. While not technically part of the income statement but printed with it, the \"\"basic weighted average\"\" and \"\"diluted weighted average\"\" number of shares are also printed which are the weighted average over the reporting period of shares actually issued and expected if all promises to issue shares with employee stock options, grants, convertibles were made kept. The income statement is the accrual accounts of the operations of the company. It has little detail on investing (depreciation & appreciation) or financing (interest expenses & preferred dividends).\"",
"title": ""
},
{
"docid": "407274",
"text": "There are lots of good points here already, but something that hasn't been mentioned yet is what would happen if the purchased items break or are somehow defective? Depending on the warranty and how trustworthy the company is, there could be an advantage to not having fully paid for the item yet when a defect is discovered, as it might incentivize the company to be more attentive to your warranty claim, since they are faced with knowing that you could stop making payments if they don't act in a timely manner. Note I'm not suggesting you stop making payments in this case, just that companies (and banks) are oftentimes more willing to work with you when you owe them money.",
"title": ""
},
{
"docid": "301547",
"text": "\"To my knowledge, there's no universal equation, so this could vary by individual/company. The equation I use (outside of sentiment measurement) is the below - which carries its own risks: This equations assumes two key points: Anything over 1.2 is considered oversold if those two conditions apply. The reason for the bear market is that that's the time stocks generally go on \"\"sale\"\" and if a company has a solid balance sheet, even in a downturn, while their profit may decrease some, a value over 1.2 could indicate the company is oversold. An example of this is Warren Buffett's investment in Wells Fargo in 2009 (around March) when WFC hit approximately 7-9 a share. Although the banking world was experiencing a crisis, Buffett saw that WFC still had a solid balance sheet, even with a decrease in profit. The missing logic with many investors was a decrease in profits - if you look at the per capita income figures, Americans lost some income, but not near enough to justify the stock falling 50%+ from its high when evaluating its business and balance sheet. The market quickly caught this too - within two months, WFC was almost at $30 a share. As an interesting side note on this, WFC now pays $1.20 dividend a year. A person who bought it at $7 a share is receiving a yield of 17%+ on their $7 a share investment. Still, this equation is not without its risks. A company may have a solid balance sheet, but end up borrowing more money while losing a ton of profit, which the investor finds out about ad-hoc (seen this happen several times). Suddenly, what \"\"appeared\"\" to be a good sale, turns into a person buying a penny with a dollar. This is why, to my knowledge, no universal equation applies, as if one did exist, every hedge fund, mutual fund, etc would be using it. One final note: with robotraders becoming more common, I'm not sure we'll see this type of opportunity again. 2009 offered some great deals, but a robotrader could easily be built with the above equation (or a similar one), meaning that as soon as we had that type of environment, all stocks fitting that scenario would be bought, pushing up their PEs. Some companies might be willing to take an \"\"all risk\"\" if they assess that this equation works for more than n% of companies (especially if that n% returns an m% that outweighs the loss). The only advantage that a small investor might have is that these large companies with robotraders are over-leveraged in bad investments and with a decline, they can't make the good investments until its too late. Remember, the equation ultimately assumes a person/company has free cash to use it (this was also a problem for many large investment firms in 2009 - they were over-leveraged in bad debt).\"",
"title": ""
}
] |
9971
|
ESPP advantages and disadvantages
|
[
{
"docid": "11675",
"text": "It would be difficult to answer without knowing specifics about a particular offer. In certain cases, it's definitely great and one could become a millionaire [Google for example]. In other cases one could lose money. In most cases one makes a decent return. As the specifics are not available, in general look out for: Most of these would determine if the plan is good for you to get into.",
"title": ""
},
{
"docid": "294573",
"text": "You should always always enroll in an espp if there is no lockup period and you can finance the contributions at a non-onerous rate. You should also always always sell it right away regardless of your feelings for the company. If you feel you must hold company stock to be a good employee buy some in your 401k which has additional advantages for company stock. (Gains treated as gains and not income on distribution.) If you can't contribute at first, do as much as you can and use your results from the previous offering period to finance a greater contribution the next period. I slowly went from 4% to 10% over 6 offering periods at my plan. The actual apr on a 15% discount plan is ~90% if you are able to sell right when the shares are priced. (Usually not the case, but the risk is small, there usually is a day or two administrative lockup (getting the shares into your account)) even for ESPP's that have no official lockup period. see here for details on the calculation. http://blog.adamnash.com/2006/11/22/your-employee-stock-purchase-plan-espp-is-worth-a-lot-more-than-15/ Just a note For your reference I worked for Motorola for 10 years. A stock that fell pretty dramatically over those 10 years and I always made money on the ESPP and more than once doubled my money. One additional note....Be aware of tax treatment on espp. Specifically be aware that plans generally withhold income tax on gains over the purchase price automatically. I didn't realize this for a couple of years and double taxed myself on those gains. Fortunately I found out my error in time to refile and get the money back, but it was a headache.",
"title": ""
},
{
"docid": "457795",
"text": "The typical deal is you can put 10% of your gross pay into the ESPP. The purchase will occur on the last deposit date, usually a 6 month period, at a 15% discount to the market price. So, the math is something like this: Your return if sold the day it's purchased is not 15%, it's 100/85 or 17.6%. Minor nitpick on my part, I suppose. Also the return is not a 6 month return, as the weekly or bi-weekly deductions are the average between the oldest (6 mo) and the most recent (uh, zero time, maybe a week.) This is closer to 3 months. The annualized rate is actually pretty meaningless since you don't have 4 opportunities to achieve this return, it's important only if the cash flow hit causes you to borrow to support the ESPP purchases. The risk is whether the stock drops the 15% before you can execute the sell to take advantage of the gain. Of course the return is gross, you need to net for taxes. Edit to respond to comment below - When I said meaningless, I meant that you can't take the 17.6%, annualize it to 91.2% per year and think your $1000 will compound to $1912. It's as meaningless as when an investor gets a 10% gain on a stock in one day, and (with 250 trading days per year) decides his $1000 will be worth $2 quadrillion dollars after a year. The 17.6% is significant in that it's available twice per year, for a true 38% return over a year, but if borrowing to help the cash flow, that rate is really over 3 months.",
"title": ""
},
{
"docid": "15030",
"text": "Advantage: more money. The financial tradeoff is usually to your benefit: Given these, for having your money locked up for the average length of the vesting periods (some is locked up for 3 months, some is locked up for nearly 0), you get a 10% return. Overall, it's like a 1.5% bonus for the year, assuming you were to sell everything right away. Of course, whether or not you wish to keep the stock depends on how you value MSFT as an investment. The disadvantage lies in a couple parts:",
"title": ""
},
{
"docid": "54064",
"text": "The answer is simple. If your employer is offering you a discount, that is free money. You always take free money, always.",
"title": ""
}
] |
[
{
"docid": "534887",
"text": "\"Typical Human Advisor: Advantages: They can recommend funds and allocations that fit to your portfolio. Disadvantages: Those who are just fund salespeople in disguise will usually recommend poor-performing funds for higher commission pay. Their advice will not be much different from random person internet advice. When your portfolio drops, they still get paid, and they don't care because they are not a fiduciary. Robo-Advisor: Advantages: Rules are automated, and typically based on crunched numbers. Somebody else executes the trades, and remembers to rebalance your portfolio when you'd usually forget to. Disadvantages: Not always accurate, usually relies on momentum from popularity. No one at the helm to adjust for risk. If you follow, you'll usually just lag behind. Yet, those with simple, low-cost diversified ETF portfolios can be attractive. Market ETFs: Advantages: Low cost funds that typically match the market. High performance. Easy to sell when you need to, zero decision making required, and you will be sure to nearly match the general market. Disadvantages: Boring. You need to enter your own orders, but you won't be doing that too often. No thrill except counting all the commas in your account. No wacky stories to wow your friends and family about your gambling addiction. Seriously, some people just can't help but take the high risk route. Newsletter / Portfolio / Online \"\"Expert\"\": Advantages: They usually have some idea of what indicators to look for and can make predictions about price movements. Disadvantages: Predictions are as frequently wrong as they are right. Good ones won't have much to say, and incompetent ones will write multi-paragraph essays about Fibonacci sequences, resistance levels, trends RSI, ROIT, everything that might show an indicator in some direction maybe... and it's usually forgotten by the next newsletter.\"",
"title": ""
},
{
"docid": "107152",
"text": "From my experience and friends' experiences, I can say that there are advantages and disadvantages for paying off your mortgage quickly. Basically, it depends on these factors: the type of the mortgage, its interest rate, your financial stability, your skills in making investments and other outside factors, such as inflation, liquidity, oppurtunity cost, etc. Paying it off means you save on interest ratings, you decrease investment risks and your investment rates are taxable. Disadvantages are that you cannot use this money for investing, you cannot use this money for tax deductions and that in a state of inflation, not paying it off in advance could save you a lot of money. However, I always recommend to read some more on websites that deal with mortgages, and speak with the mortgage expert in your bank.Just acquire enough information to make a good assessment. An interesting article on this topic - The Advantages and Disadvantages of Paying Off Your Mortgage",
"title": ""
},
{
"docid": "568006",
"text": "Another disadvantage is the inability to value commodities in an accounting sense. In contrast with stocks, bonds and real estate, commodities don't generate cash flows and so any valuation methodology is by definition speculative. But as rhaskett notes, there are diversification advantages. The returns for gold, for instance, tend to exhibit low/negative correlation with the performance of stocks. The question is whether the diversification advantage, which is the primary reason to hold commodities in a multi-asset class portfolio through time, overcomes the disadvantages? The answer... maybe.",
"title": ""
},
{
"docid": "469100",
"text": "You didn't give enough information. What is your goal? What is your financial situation? A discount to buy company stock can seem very tempting. I was tempted by it myself, gee, almost 20 years ago. I still own some of the stock. But I held mutual funds first. There are two disadvantages that have disuaded me from partaking in the ESPP of my subsequent employers (one of which was a spin-out company of the stock-issuing company, the other having bought the spin-out). First, putting a bunch of money in a single stock is rather risky. single stocks will drop dramatically due to market conditions. Generally market conditions don't act so dramatically on all stock. Second, is it wise to put not only your salary but also your saved wealth all in one basket? It worked out reasonably well for me. The stock doubled right before my division was spun out -- I sold half of my position. And the resulting stock has continued to provide opportunities to diversify. However, it could have just as easily dropped in half instead of doubled. What is your timeline for holding the stock -- for realizing any gain? Can you afford patience if the stock value should drop in half? I have co-workers who continue to invest through our new company's ESPP. At least one co-worker has the stated goal to sell after every purchase -- he holds the stock long enough to make a long-term gain instead of short term, but he sells after every purchase. And it seems to him that the stock always drops right when he wants to sell.",
"title": ""
},
{
"docid": "441893",
"text": "Not really my field but this is how I see the impact Disadvantages for banks : not being able to chose where they park assets/cash they have been trusted with which mean lower income from investing those disadvantage for banks shareholders : less earnings disadvantage for the economy : harder criteria to lend, lower loan growth advantage for the economy : (theoretically) less risks of liquidity crunch and financial crisis",
"title": ""
},
{
"docid": "402939",
"text": "This is more of an economics question than personal finance. That said, I already started writing an answer before I noticed, so here are a few points. I'll leave it open for others to expand the list. Advantages Disadvantages Advantages Disadvantages The flip-side to the argument that more users means more stability is that the impact of a strong economy (on the value of the currency) is diluted somewhat by all the other users. Indeed, if adopted by another country with similar or greater GDP, that economy could end up becoming the primary driver of the currency's value. It may be harder to control counterfeiting. Perhaps not in the issuing country itself, but in foreign countries that do not adopt new bills as quickly.",
"title": ""
},
{
"docid": "127689",
"text": "\"I think this is a good question with no single right answer. For a conservative investor, possible responses to low rates would be: Probably the best response is somewhere in the middle: consider riskier investments for a part of your portfolio, but still hold on to some cash, and in any case do not expect great results in a bad economy. For a more detailed analysis, let's consider the three main asset classes of cash, bonds, and stocks, and how they might preform in a low-interest-rate environment. (By \"\"stocks\"\" I really mean mutual funds that invest in a diversified mixture of stocks, rather than individual stocks, which would be even riskier. You can use mutual funds for bonds too, although diversification is not important for government bonds.) Cash. Advantages: Safe in the short term. Available on short notice for emergencies. Disadvantages: Low returns, and possibly inflation (although you retain the flexibility to move to other investments if inflation increases.) Bonds. Advantages: Somewhat higher returns than cash. Disadvantages: Returns are still rather low, and more vulnerable to inflation. Also the market price will drop temporarily if rates rise. Stocks. Advantages: Better at preserving your purchasing power against inflation in the long term (20 years or more, say.) Returns are likely to be higher than stocks or bonds on average. Disadvantages: Price can fluctuate a lot in the short-to-medium term. Also, expected returns are still less than they would be in better economic times. Although the low rates may change the question a little, the most important thing for an investor is still to be familiar with these basic asset classes. Note that the best risk-adjusted reward might be attained by some mixture of the three.\"",
"title": ""
},
{
"docid": "106684",
"text": "I'm not sure 1099-MISC is what you should expect. Equity means ownership, and in LLC context it means membership. As an LLC member, you'll get distributions and should receive a K-1 form for tax treatment, not 1099 or W2. If the CEO is talking about 1099 it means he's going to hire you as a contractor which contradicts the statement about equity allocation. That's an entirely different situation. 1) Specifically, would the 1099-MISC form be used in this case? 1099-MISC is used to describe various payments. Depending on which box is filled, the tax treatment may be as of employment income (subject to SE taxes) or passive income (royalties, rents, etc - subject to various limitations in the tax code). 3) If this is the only logical method of compensation (receiving a % of real estate sales), how would it be taxed? That would probably be a commission and taxed as employment income. I suggest to get a professional tax adviser consultation on this issue, with specific details, numbers, and kinds of deals involved. You can get gain or lose a lot of money just because you're characterized as a contractor and not LLC member or employee (each has its own benefits and disadvantages, and you have to consider them all). 4) Are there any advantages/disadvantages to acquiring and selling properties through the company as opposed to receiving a % of sales? Yes. There are advantages and there are disadvantages. For example, if you're using a corporation, you can get salary, if you're a contractor you cannot. There are a lot of issues hidden in this distinction (which I've just discussed with KeithS in this argument).",
"title": ""
},
{
"docid": "444095",
"text": "No, there is no advantage. There may be some peace of mind at no cost if you are already in the lowest tax bracket. Otherwise, it is actually disadvantageous. Consider the following scenario: RRSP HBP withdrawal $15000 ($1000/y repayment), You are required to pay back $1000 a year with no tax advantage. Any additional RRSP payments can be designated as HBP (no tax advantage) or as a regular RRSP contribution Tax = (Taxable Income - contributions) * rate. So, you are forgoing the tax benefit for no advantage.",
"title": ""
},
{
"docid": "186071",
"text": "\"It very much comes down to question of semantics and your particular situation. Some people do not view a house (and most upgrades) as an investment, but rather an expense. I certainly agree that this is probably the case if you pay someone else to make the repairs and upgrades. However, if you are a serious DIYer, that may not be the case. Of course, if the house is a money pit and/or you were unfortunate to buy when prices where ridiculously high, you'll have a hard time making any money on this \"\"investment.\"\" To continue this game of semantics, you may also consider the value you extract from your home while you are living in it. On to the mortgage itself. Chances are that it is a long term, relatively low rate loan and that the interest is deductible. So, there are some disadvantages to paying it down early, even without early payment penalties. Paying down early on the principal is a disadvantage from a tax perspective. How much of a disadvantage hinges on the rate. Now, a debt is a liability on your personal balance sheet. It drags down any returns you may have from investing. However, a home lone is not generally subject to the cardinal rule of paying off your high interest debt before investing. It should not be relatively high and it pays for something necessary. It may be that any credit card debt you have may have paid for something considered necessary. However, with the relatively high interest rates, you have to question just how necessary any credit card debt really is. Not to mention that there is no tax advantage. So, it comes down to the fact that a home loan should be relatively low interest, paying for something you must have and that you hopefully have some tax advantage from the interest you pay on it.\"",
"title": ""
},
{
"docid": "443903",
"text": "Advantage of cash: You can spend the money without having to pay any fees or taxes to get it out. Disadvantage: When inflation is greater than zero, which it has been for many decades, your cash is continually losing value. Advantages of an IRA (Roth or classic): Your money will usually grow as the investments return a profit. You get special tax benefits. Disadvantages: There's risk -- you may lose money. There are tax penalties for withdrawing the money before retirement. In general, you should only put money in an IRA if you expect to leave it there until you retire. Or at least, for a long time. Whole life is a combination of a life insurance policy and an investment. Advantages: Combines insurance and investment into one convenient monthly payment. Disadvantages: The investment portion typically has lower returns than you could get elsewhere. If you have no need for life insurance -- if you're not supporting anyone or you're confidant they could get along without you or you don't like them and don't care what happens to them when you're gone or whatever -- then there's no point buying life insurance, whole or term. You're paying for a product that you don't need. It's pretty common advice to tell people that instead of buying a whole life policy, they should buy a term policy with the same coverage, and then invest the difference in the premium. For example, if you were considering getting a $100,000 whole life policy that costs $50 per month (just making up numbers, of course it depends on your age, health, etc), and you see you could get a $100,000 term life policy for $30 per month, you will almost certainly do better in the long run to buy the $30 term policy and put the other $20 into investments. The catch to this plan is that there are usually transaction costs to investing. Even a discount broker like Ameritrade or Scott Trade charges around $10 per transaction. So if you tried to invest $20 each month, you'd lose half of it to transaction fees. Which means that in practice, you'd have to save that money up until you had at least a few hundred. And at that point many people find other things always seem to come up to spend the money on, so that while they start out with every intention of investing this money, they don't.",
"title": ""
},
{
"docid": "79378",
"text": "\"1) Don't buy a house as an investment. Buy a house because you've reached the point in your life where you don't expect to move in the next five years and you'd prefer to own a house (with its advantages/disadvantages) than to rent (with its advantages/disadvantages). Thinking of houses primarily as investments is what caused the housing bubble, crash, and Great Recession. 2) Before buying a house for cash, look at the available mortgage interest rates versus market rate of return. Owning the house outright is slightly lower stress, but using the house as the basis for a \"\"leveraged investment\"\" may be financially wiser. (I compromised; I paid 50% down and took a mortgage for the other 50%.) 3) 1 year is short-term. Your money doesn't belong in the market if you're going to need it in the short term. If you really intend to pull it back out that soon, I'd stick with CD/money-market kinds of instruments. 4) Remember that while a house is illiquid, it is possible to take out home equity loans... so money you put into a house isn't completely inaccessible. You just can't move elsewhere as easily.\"",
"title": ""
},
{
"docid": "201019",
"text": "\"A subsidy is a benefit. While you're right most of the time it is a crude \"\"transfer of wealth by the US government\"\" the formal intent of a subsidy is to assist so as to confer an advantage or mitigate a disadvantage. If as you say \"\"discounting the risk premium\"\" actively by the US government so as to confer, in the words of Ueda and Di Mauro, a \"\"funding cost advantage [to] SIFIs [of] around 60bp in 2007 and 80bp in 2009\"\" is not a subsidy, then what is it?\"",
"title": ""
},
{
"docid": "266323",
"text": "The main advantage of commodities to a largely stock and bond portfolio is diversification and the main disadvantages are investment complexity and low long-term returns. Let's start with the advantage. Major commodities indices and the single commodities tend to be uncorrelated to stocks and bonds and will in general be diversifying especially over short periods. This relationship can be complex though as Supply can be even more complicated (think weather) so diversification may or may not work in your favor over long periods. However, trading in commodities can be very complex and expensive. Futures need to be rolled forward to keep an investment going. You really, really don't want to accidentally take delivery of 40000 pounds of cattle. Also, you need to properly take into account roll premiums (carry) when choosing the closing date for a future. This can be made easier by using commodities index ETFs but they can also have issues with rolling and generally have higher fees than stock index ETFs. Most importantly, it is worth understanding that the long-term return from commodities should be by definition (roughly) the inflation rate. With stocks and bonds you expect to make more than inflation over the long term. This is why many large institutions talk about commodities in their portfolio they often actually mean either short term tactical/algorithmic trading or long term investments in stocks closely tied to commodities production or processing. The two disadvantages above are why commodities are not recommended for most individual investors.",
"title": ""
},
{
"docid": "127702",
"text": "I don't think you are reading the stock chart right. ORCL has a beta of 1.12 which means it has more volatility than the market as a whole. See image below for a fairly wild stock chart for a year. I would not truly consider ESPP participation investing, unless you intend to buy and hold the stock. If you intend to sell the stock soon after you are able, it is more speculation. ESPP's are okay based upon the terms. If the stock was a constant price, and you could sell right away, then an ESPP plan would be easy money. Often, employees are often given a 15% discount to purchase the stock. If you can sell it before any price drop, then you are guaranteed to make 15% on the money invested minus any commissions. Some employers make ESPP participants hold the stock for a year. This makes such a plan less of a value. The reasons are the stock can drop in price during that time, you could need the money, or (in the best case) your money is tied up longer making the ROI less. The reasons people invest in stock are varied and is far to much to discuss in a single post. Some of your colleagues are using the ESPP solely to earn the discount in their money.",
"title": ""
},
{
"docid": "4612",
"text": "A few thoughts off the top of my head: Advantages of more than 20% down: Disadvantages of more than 20% down:",
"title": ""
},
{
"docid": "466742",
"text": "Disadvantages: Advantages: In my opinion, the convenience and price (free!) of online options make doing your taxes online worth the negligible risks.",
"title": ""
},
{
"docid": "317037",
"text": "I would use student loans and avoid credit card debt if debt is your only option. Here are the advantages I see: Disadvantages:",
"title": ""
},
{
"docid": "44187",
"text": "You can't max out your retirement savings. There are vehicles that aren't tax-advantaged that you can fund after you've exhausted the tax-advantaged ones. Consider how much you want to put into these vehicles. There are disadvantages as well as advantages. The rules on these can change at any time and can make it harder for you to get your money out. How's your liquid (cash) emergency fund? It sounds like you're in a position to amass a good one. Don't miss this opportunity. Save like crazy while you can. Kids make this harder. Paying down your mortgage will save you interest, of course, but make sure you're not cash-poor as a result. If something happens to your income(s), the bank will still foreclose on you even if you only owe $15,000. A cash cushion buys you time.",
"title": ""
},
{
"docid": "512827",
"text": "As with most strategies there are pros and cons associated with this approach: Advantages of using LEAPS: Disadvantages of using LEAPS: Read more about it in great detail on my blog: http://www.thebluecollarinvestor.com/leaps-and-covered-call-writing-2/",
"title": ""
},
{
"docid": "143020",
"text": "I want to mention I've found 2 options for more powerful tools that can be used to manage asset allocation: Advantages/Disadvantages: Vanguard Morningstar X-ray I hope this helps others struggling with asset allocation.",
"title": ""
},
{
"docid": "348927",
"text": "The main advantage and disadvantage I can see in a scenario like this are - how savvy and good an investor are you? It's a good way to create below-market average returns if you're not that good at investing and returns way above market average if you are...",
"title": ""
},
{
"docid": "123929",
"text": "How was Scunthorpe steelworks sold for £1? I have £1, what is to stop me from buying a hyper distressed company like this for so cheaply? Why doesn't this happen more often? What are the advantages and disadvantages of the sale to the buyers and sellers?",
"title": ""
},
{
"docid": "122794",
"text": "Group RESPs are a bit like a true mutual insurance company. You all pay into the fund, and then, depending on the number of kids that are in school that particular year, you get paid a certain amount. Advantages could be that if you end up with one or two years of only your kid in school and nobody else's in that age bracket, you get more money. Disadvantage for the same-reverse reason also could be true. Another advantage of regular programs, unlike pooled, is that if you do not use all the money, then some/all of the remaining funds may be transferable to an RRSP. Personally I would not invest in one, unless it was more like a specific investment-club that I knew everybody.",
"title": ""
},
{
"docid": "12488",
"text": "easier access to your money That can be a disadvantage for some people. Based on the number of people who tap their 401K for non-retirement reasons, or just cash it in when they change jobs; making it painful to use before retirement age does keep some people from spending it too early. They need to be able to compartmentalize the funds in order to understand the difference between funds spending, saving and investing for retirement. Roth 401K One advantage that the 401K may have is that you can in many plans invest the funds in a Roth 401K. This allows you to go beyond the Roth IRA limits. You are currently investing the maximum amount in your Roth IRA, so this could be a big advantage.",
"title": ""
},
{
"docid": "233751",
"text": "If you are just starting out, I would say there is no disadvantage to using a personal card for business expenses. In fact, the advantage of doing so is that the consumer protections are better on personal cards than on business cards. One possible advantage to business credit cards, is that many (but not all) will not show up on your personal credit report unless you default. This might help with average age of accounts if you have a thin credit file, but otherwise it won't make much difference. Issuers also expect higher charge volumes on business cards, so as your business grows might question a lot of heavy charges on a personal card. Whether this would ever happen is speculation, but it's worth being aware of it.",
"title": ""
},
{
"docid": "434812",
"text": "ESPP is common among US companies, often with a framework similar to your outline. In the US, some ESPPs allow sales of shares to be considered qualifying (subject to capital gains rather than ordinary income tax) if they are sold at least 2 years after the enrollment date and at least 1 year after the purchase date. These details can vary from one plan to another and will be stated in the company's ESPP enrollment documents. Do look at the high and low values of the stock over the last year. If it swings up and down more than 15% (or whatever the discount is), then that risk should be a factor in your decision. If the stock is trending upward over the long term and you are confident in the durability of the company, then you might favor holding.",
"title": ""
},
{
"docid": "70315",
"text": "Despite the ACA offering generous deductions, a lot of small businesses still cannot afford the initial capital involved in offering health insurance plan to their employees... Therefore we cannot take advantage of these deductions... Putting us at a disadvantage for finding low-to-mid skilled workers, to the larger corporations that are now mandated to offer the benefits..",
"title": ""
},
{
"docid": "164628",
"text": "This answer assumes that your purpose for using the ESPP is to generate a relatively safe 15% return on that portion of your income. Frequently before there were Roth 401K options the advice was: This advice was especially good for the younger workers because they wanted to have a Roth account but didn't want to miss the 401K match. As Roth 401K accounts were introduced that advice changed somewhat because it was possible to get the benefit of the Roth and still get the maximum match. for your situation what I would propose is: contribute to the 401K enough to get the maximum match. Contribute as much as you want or are allowed into the ESPP. Take the proceeds and contribute to an IRA or Roth IRA. If you reach the IRA max you have to decide if you will scale back the ESPP to contribute more to the 401K.",
"title": ""
},
{
"docid": "315286",
"text": "Advantages of Gold IRA (regardless of where you're holding it): Disadvantages of Gold IRA: Instead, you can invest in trust funds like SLV (The ETF for silver) or GLD in your regular brokerage IRA. These funds negotiate their prices of storage, are relatively liquid, and shield you from the dangers of owning physical metal while providing opportunity to invest in it at market prices.",
"title": ""
}
] |
1075
|
How do you compare the sales of a company like Coca Cola against another company like JPMorgan Chase to figure out the best investment opportunity?
|
[
{
"docid": "438392",
"text": "The question isn't sales but profits. Banks traditionally profit by making loans. Just as with a physical product, there are costs involved, income produced, and the difference between the two is gross profit. From there you can get net profit, and from there you can look at efficiency or profit per share or whatever other metric floats your boat. Or you can just buy index funds, get average rates of return, and not have to think about it.",
"title": ""
}
] |
[
{
"docid": "198895",
"text": "OCTOBER 18, 2017 by John Gapper Goldman Sachs making too little money is not the worst of the world’s problems. But inside the investment bank’s New York headquarters, it feels like an insult. Goldman is not suffering a financial crisis, as it did in 2008 when it officially converted to being a bank holding company amid panic that the whole of Wall Street could collapse. It faces something deeper: an identity crisis. It used to be the role model for many rival banks — envied even while resented for its single-minded focus on investment banking and trading. But as Tuesday’s disclosure of a 26 per cent fall in its bond trading revenues confirmed, banking has changed. Instead of lenders such as JPMorgan Chase wanting to become as glamorous as Goldman, it needs to be more like them. This is a telling moment, albeit less dramatic than 2008. Investment banking enjoyed a lucrative two decades, spurred by globalisation and financial liberalisation. Goldman’s revenues rose briskly from its initial public offering in 1999 to 2007, and boomed in 2009. It could do no wrong financially, although it turned out to have done wrong to some of its customers. But guess what? Regulation works. Governments and central bank supervisors set out to make complex trading in bonds and derivatives, the securities business in which Goldman specialised, more expensive and less profitable. The rules now favour deposit taking and lending instead of wizardry. No one really planned the second aspect of the bank’s difficulty. The huge dose of monetary easing since the crisis has damped volatility and made markets more predictable. Hedge funds, themselves under pressure, no longer need to reward Goldman and others for taking on financial risk. Goldman’s bond and commodities trading division — from which emerged a cadre of leaders including Lloyd Blankfein, its chairman and chief executive — tells its own story. It used to occupy two floors of the New York office but has shrunk to one as Wall Street’s total bond trading revenues have halved since 2009. More prices are calculated by computers than humans. When you rely heavily on one engine and that engine sputters, you are in trouble. The bank’s financial advisory and capital raising division is performing well and it has an investment management arm. But it lacks a consumer powerhouse like Morgan Stanley’s wealth management operation, or the lending and credit card activities that drive banks such as JPMorgan. The humbling truth for Goldman is that US retail banking has become not only more reliable than investment banking, but more profitable. JPMorgan’s balance sheet is three times the size of Goldman’s and its retail banking arm made a 19 per cent return on equity in the third quarter, compared with Goldman’s 11 per cent. The best historical comparison for Goldman’s predicament is, ironically, the JPMorgan of the 1990s. JPMorgan was a blue-chip corporate bank but found that this business was no longer profitable enough as lending margins fell. It launched an effort to return to investment banking, having been separated from Morgan Stanley in 1935 by the Glass-Steagall Act. JPMorgan had a good stab at it, compensating for the fact that Goldman and others dominated Wall Street’s “bulge bracket” by pioneering credit derivatives (which later turned out badly). But it could not make enough progress alone and settled for being bought by Chase Manhattan in 2000. “Both [banks] have struggled to keep pace with the rapid growth of the leading investment banks, which are in businesses that have been far more lucrative than the lending business at the core of commercial banking,” the New York Times noted in its account of the merger. Seventeen years and one financial crisis later, JPMorgan has reversed this order of profitability. So Goldman is now trying to do the opposite of the old JPMorgan by adding banking to investment banking. JPMorgan’s former dilemma has not gone away — lending to blue-chip companies is not much of a moneymaker. A more tempting target is the high margins that banks make on credit cards. Hence Marcus, Goldman’s online lender (named after its founder Marcus Goldman), which offers loans to prime US consumers as an alternative to credit card debt. Marcus, which will launch next year in the UK, accounts for $12bn of the $28bn in new lending and financing planned by Goldman in the next three years as it diversifies. But it is no simpler for Goldman to break into Main Street than it was for the old JPMorgan to break back into Wall Street: $12bn on a balance sheet of $930bn is an interesting financial experiment, not a revolution. It would need to inflict on consumer banking with technology what Amazon did to the retail industry to rival fully JPMorgan and Bank of America. “We’re a bank and we’re committed to being a bank,” says one partner firmly. But selling personal loans and mortgages, which could be Marcus’s next target, is not a job designed for masters of the universe. This is Goldman’s identity crisis: regulation and economics are rendering it ordinary.",
"title": ""
},
{
"docid": "285185",
"text": "\"First of all, congratulations on saving some money. So many people these days do not even get that far. As far as investments, what is best for you depends heavily on your: Here is a quick summary of types of assets that are likely available to you, and my thoughts on why they may or may not be a good fit for your situation. Cash Equivalents Cash Equivalents are highly liquid, meaning you can get cash for them on fairly short notice. In particular, Money Markets and Certificates of Deposit (CDs) are also considered very safe when issued by a bank, as they are often insured against loss by the government up to a certain amount (this varies quite a lot by country within Europe, see the Wikipedia article here for additional detail. Please note that in the case of a CD, you are usually unable to get access to your money for the length of the investment period, which is usually a short period of time such as 3 months, 6 months, or 1 year. This is a good choice if you may need your money back on short notice, and your main goal is to preserve your principal. However, the returns tend to be very low and often do not keep pace with inflation, meaning that over several years, you may lose \"\"real\"\" purchasing power, even if you don't lose nominal value in your account. Special Note on Cash Equivalents If the money you want to invest is also your Emergency Fund, or you do not have an Emergency Fund, I would highly recommend Cash Equivalents. They will provide the highest level of Liquidity along with a short Time Horizon so that you can get your money as needed in the case of unforeseen expenses such as if your car breaks down. Debt Debt investments include government and corporate bonds. They are still considered relatively safe, as the issuer would need to default (usually this means they are in bankruptcy) in order for you not to be paid back. For example, German bonds have been considered safer than Greek bonds recently based on the underlying strength of the government. Unlike Cash Equivalents, these are not guaranteed against loss, which means that if the issuer defaults, you could lose up to 100% of your investment. Bonds have several new features you will need to consider. One is interest rate risk. One reason bonds perform better than cash equivalents is that you are taking on the risk that if interest rates rise, the fixed payments the bond promises will be worth less, and the face value of your bond will fall. While most bonds are still very Liquid, this means that if you need to sell the bond before it matures, you could lose money. As mentioned earlier, some bonds are riskier than others. Given that you are looking for a low-risk investment, you would want to select a bond that is considered \"\"invesment grade\"\" rather than a riskier \"\"junk\"\" bond. Debt investments are a good choice if you can afford to do without this money for a few years, and you want to balance safety with somewhat better returns than Cash Equivalents. Again though, I would not recommend investing in Debt until you have also built up a separate Emergency Fund. If you do choose to invest in bonds, I recommend that you diversify your risks by investing in a bond fund, rather than in just one company's or government's debt. This will reduce the likelihood that you will experience a catastrophic loss. Ownership Ownership assets includes stocks and other assets such as real estate and precious metals such as gold. While these investments can have high returns, in your situation I would strongly recommend that you not invest in these types of investments, for the following reasons: For these reasons, debt is considered a safer investment than equity for any particular company, government, or the market as a whole. Ownership assets are a good choice for people who have a high Risk Tolerance, long Time Horizon, low Liquidity needs, and will not be bothered by larger potential changes in the value of the investment at any given time. Special Note on Gold I would consider Gold a very risky investment and not a good fit for you at the moment based on what you've shared in your question. Gold is considered \"\"safe\"\" in the sense that people believe that if the economy goes into recession, depression, or collapses entirely, gold will continue to be valuable. In a post-apocalyptic world where paper money became worthless, it is still a good bet that gold will always be considered valuable within human society as a store of value. That being said, the price of gold fluctuates almost entirely based on how bad people think things are going to get. Think about the difference between gold and a company like Coca-Cola. Would you like to own 100% of Coca-Cola? Of course, because you know there is a very good chance that people will continue to spend money all over the world on their products. On the other hand, gold itself produces no products, no sales, no profits, and no cash flow. As such, if you buy gold, you are really making a speculative bet that gold will be in higher demand tomorrow than it is today. You are buying an asset (the gold) rather than part of a company's equity or debt that is designed to throw off payments to its investors in the form of bond payments or dividends. So, if people decide next year that things are improving, it is possible that gold could lose value, given that gold prices are at historically high levels. Gold could be a good choice for someone who has a large, well-diversified investment portfolio, and who is looking for a hedge to protect against inflation and other risks that they have taken on via their other investments. I hope that is helpful - best of luck in your choices. Let us know what you decide!\"",
"title": ""
},
{
"docid": "451178",
"text": "\"The way the post is worded, coca cola wouldn't count towards either, although it's not entirely clear. If the dividends are considered under capital gains (which isn't technically an appropriate term) he's earning only 500Million a year from his stake in coca cola. If he sold his shares, he'd receive capital gains of ~15Billion, which would probably outpace his operations business. The best graph would probably be something like \"\"net worth of operations vs net worth of equity in other companies\"\"\"",
"title": ""
},
{
"docid": "9672",
"text": "\"You're talking about money in a savings account, and avoiding the risks posed by an ongoing crisis, and avoiding risk. If you are risk-averse, and likely to need your money in the short term, you should not put your money in the stock market, even in \"\"safe\"\" stocks like P&G/Coca-Cola/etc. Even these safe stocks are at risk of wild price swings in the short- to intermediate-term, especially in the event of international crises such as major European debt defaults and the like. These stocks are suitable for long-term growth objectives, but they are not as a replacement for a savings account. Coca-Cola lost a third of its value between 2007 and 2009. (It's recovered, and is currently doing better than ever.) P&G went from $74/share to $46/share. (It's partially recovered and back at $63). On the other hand, these stocks may indeed be suitable as long-term investments to protect you against local currency inflation. And yes, they even pay dividends. If you're after this investment, a good option is probably a sector-specific exchange-traded fund, such as a consumer-staples ETF. It will likely be more diversified and safer than anything you could come up with using a list of individual stocks. You can also investigate recommendations that show up when you search for a \"\"defensive ETF\"\". If you do not wish to buy the ETF directly, you can also look at listings of the ETF's holdings. Read the prospectus for an idea of the risks associated with these funds. You can buy these funds with any brokerage that gives you access to US stock exchanges.\"",
"title": ""
},
{
"docid": "265314",
"text": "It is not so useful because you are applying it to large capital. Think about Theory of Investment Value. It says that you must find undervalued stocks with whatever ratios and metrics. Now think about the reality of a company. For example, if you are waiting KO (The Coca-Cola Company) to be undervalued for buying it, it might be a bad idea because KO is already an international well known company and KO sells its product almost everywhere...so there are not too many opportunities for growth. Even if KO ratios and metrics says it's a good time to buy because it's undervalued, people might not invest on it because KO doesn't have the same potential to grow as 10 years ago. The best chance to grow is demographics. You are better off either buying ETFs monthly for many years (10 minimum) OR find small-cap and mid-cap companies that have the potential to grow plus their ratios indicate they might be undervalued. If you want your investment to work remember this: stock price growth is nothing more than You might ask yourself. What is your investment profile? Agressive? Speculative? Income? Dividends? Capital preservation? If you want something not too risky: ETFs. And not waste too much time. If you want to get more returns, you have to take more risks: find small-cap and mid-companies that are worth. I hope I helped you!",
"title": ""
},
{
"docid": "152286",
"text": "I don't want to get involved in trading chasing immediate profit That is the best part. There is an answer in the other question, where a guy only invested in small amounts and had a big sum by the time he retired. There is good logic in the answer. If you put in lump sum in a single stroke you will get at a single price. But if you distribute it over a time, you will get opportunities to buy at favorable prices, because that is an inherent behavior of stocks. They inherently go up and down, don't remain stable. Stock markets are for everybody rich or poor as long as you have money, doesn't matter in millions or hundreds, to invest and you select stocks with proper research and with a long term view. Investment should always start in small amounts before you graduate to investing in bigger amounts. Gives you ample time to learn. Where do I go to do this ? To a bank ? To the company, most probably a brokerage firm. Any place to your liking. Check how much they charge for brokerage, annual charges and what all services they provide. Compare them online on what services you require, not what they provide ? Ask friends and colleagues and get their opinions. It is better to get firsthand knowledge about the products. Can the company I'm investing to be abroad? At the moment stay away from it, unless you are sure about it because you are starting. Can try buying ADRs, like in US. This is an option in UK. But they come with inherent risk. How much do you know about the country where the company does its business ? Will I be subject to some fees I must care about after I buy a stock? Yes, capital gains tax will be levied and stamp duties and all.",
"title": ""
},
{
"docid": "133943",
"text": "\"You're missing a very important thing: YEAR END values in (U.S.) $ millions unless otherwise noted So 7098 is not $7,098. That would be a rather silly amount for Coca Cola to earn in a year don't you think? I mean, some companies might happen upon random small income amounts, but it seems pretty reasonable to assume they'll earn (or lose) millions or billions, not thousands. This is a normal thing to do on reports like this; it's wasteful to calculate to so many significant digits, so they divide everything by 1000 or 1000000 and report at that level. You need to look on the report (usually up top left, but it can vary) to see what factor they're dividing by. Coca Cola's earnings per share are $1.60 for FY 2014, which is 7,098/4450 (use the whole year numbers, not the quarter 4 numbers; and here they're both in millions, so they divide out evenly). You also need to understand that \"\"Dividend on preferred stock\"\" is not the regular dividend; I don't see it explicitly called out on the page you reference. They may not have preferred stock and/or may not pay dividends on it in excess of common stock (or at all).\"",
"title": ""
},
{
"docid": "496921",
"text": "\"The hardest part seems to be knowing exactly when to sell the stock. Well yes, that's the problem with all stock investing. Reports come out all the time, sometimes even from very smart people with no motivation to lie, about expected earnings for this company, or for that industry. Whether those predictions come true is something you will only find out with time. What you are considering is using financial information available to you (and equally available to the public) to make investment choices. This is called 'fundamental analysis'; that is, the analysis of the fundamentals of a business and what it should be worth. It forms the basis of how many investment firms decide where to put their money. In a perfectly 'efficient' market, all information available to the public is immediately factored into the market price for that company's stock. ie: if a bank report states with absolute certainty (through leaked documents) that Coca-Cola is going to announce 10% revenue growth tomorrow, then everyone will immediately buy Coca-Cola stock today, and then tomorrow there would be no impact. Even if PwC is 100% accurate in its predictions, if the rest of the market agrees with them, then the price at the time of IPO would equal the future value of the cashflows, meaning there would be no gain unless results surpassed expectations. So what you are proposing is to take one sliver of the information available to the public (have you also read all publicly available reports on those businesses and their industries?), and using that to make a high risk investment. Are you going to do better than the investment firms that have teams of researchers and years of experience in the investment world? You can do quite well by picking individual stocks, but you can also lose a lot of money if you do it haphazardly. Be aware that there is risk in doing any type of investing. There is higher than average risk if you invest in equities ('the stock market'). There is higher risk still, if you pick individual stocks. There is yet even higher risk, if you pick small startup companies. There are some specific interesting side-elements with your proposal to purchase stock about to have an IPO - those are better dealt with in a separate question if you want more information; search this site for 'IPO' and you should find a good starting point. In short, the company about to go public will hire a firm of analysts who will try to calculate the best price the public will accept for an offering of shares. Stock often goes up after IPO, but not always. Sometimes the company doesn't even fill its full IPO order, adding a new type of risk to a potential investor, that the stock will drop on day 1. Consider an analogy outside the investing world: Let's say Auto Trader magazine prints an article that says \"\"all 2015 Honda Civics are worth $15,000 if they have less than 50,000 Miles.\"\" Assume you have no particular knowledge about cars. If you read this article, and you see an ad in the paper the next day for a Honda Civic with 40k miles, should you buy it for $14k? The answer is not without more research. And even if you determine enough about cars to find one for $14k that you can reasonably sell for $15k, there's a whole world of mechanics out there who buy and sell cars for a living, and they have an edge both because they can repair the cars themselves to sell for more, and also because they have experience to spot low-offers faster than you. And if you pick a clunker (or a stock that doesn't perform even when everyone expected it would), then you could lose some serious money. As with buying and selling individual stocks, there is money to be made from car trading, but that money gets made by people who really know what they're doing. People who go in without full information are the ones who lose money in the long run.\"",
"title": ""
},
{
"docid": "391323",
"text": "You can get no load annuities through some no-load financial companies like Vanguard so to start with I'd see how what she is being offered compares with something that comes free of a sales load. I'd also question that fixed rate, seems pretty impossible to me, which makes me think there is some catch or 'gotcha' that we are not seeing that either brings down that rate, or makes it delusional (they are kidding themselves) or deceptive in some way. In any case it's setting off my 'too good to be true' alarm at full volume, along with the 'shark attack' alarm as well. (I would strongly suspect the 'advisor' is advising the product that makes the most money for him, NOT what is in your mother's best interest) A fixed annuity is an insurance product, not a security, because the insurance company must credit the annuity holder’s account with the specified interest rate for the contractually-stipulated time period, regardless of market fluctuations in actual interest rates. It is the insurance company that bears the investment risk, which it does by investing the annuity holder’s purchase proceeds in fixed-income instruments that the company hopes will provide sufficient return to fulfill its contractual representations to the holder. THIS is why there is no prospectus (it's not a 'security' they are not required to provide one by SEC) because the risk is entirely with the company. Obviously as pointed out in the comments, the company could easily go out of business (especially of they sell a lot of these and can't find a way to get that kind of return on the invested money). Now, ask yourself, if I was the insurance company, would I be comfortable guaranteeing that level of return over that much time if I intend to make a profit from it, pay sales comissions, and stay in business? In terms of 'will they stay in business' I'd have a hard look at their ratings, and go compare where that is on the total range for AM Best (they are lowest 'secure' rating, next thing down is in the 'vulnerable' category) and Standard and Poors (4 places down from their best rating, next thing down is 'marginal' followed by 'poor') You might also want to see if you can get any idea of historical ratings, is this company's ratings falling, or rising? Personally, for the amount of money involved, I'd want a company with MUCH higher ratings than these guys.. THEN maybe someone could say 'no risk', but with those ratings? an no, I don't think so! BTW I'd check over what this bozo (um sorry, that's not fair to clowns) is recommending she do with her own funds as well. For example is he recommending she take something that is already tax sheltered such as an IRA and investing the stuff inside that in an annuity (kind of pointless to 'double shelter' the money, or lock it up for a period of time when she may be required to make withdrawals) make sure you don't see something there that is actually against what is in her best interest and is only done to make him a comission.",
"title": ""
},
{
"docid": "350110",
"text": "\"Because I feel the answers given do not wholely represent the answer you are expecting, I'd like to re-iterate but include more information. When you own stock in a company, you OWN some of that company. When that company makes profit, you usually receive a dividend of those profits. If you owned 1% of the company stock, you (should) recieve 1% of the profits. If your company is doing well, someone might ask to buy your stock. The price of that stock is (supposed) to be worth a value representative of the expected yield or how much of a dividend you'd be getting. The \"\"worth\"\" of that, is what you're betting on when you buy the stock, if you buy $100 worth of coca cola stock and they paid $10 as dividend, you'd be pretty happy with a 10% growth in your wealth. Especially if the banks are only playing 3%. So maybe some other guy sees your 10% increase and thinks, heck.. 10% is better than 3%, if I buy your stocks, even as much as 6% more than they are worth ($106) I'm still going to be better off by that extra 1% than I would be if I left it in the bank.. so he offers you $106.. and you think.. awesome.. I can sell my $100 of cola shares now, make a $6 profit and buy $100 worth of some other share I think will pay a good dividend. Then cola publicises their profits, and they only made 2% profit, that guy that bought your shares for $106, only got a dividend of $2 (since their 'worth' is still $100, and effectively he lost $4 as a result. He bet on a better than 10% profit, and lost out when it didn't hit that. Now, (IMHO) while the stock market was supposed to be about buying shares, and getting dividends, people (brokers) discovered that you could make far more money buying and selling shares for 'perceived value' rather than waiting for dividends to show actual value, especially if you were not the one doing the buying and selling (and risk), but instead making a 0.4% cut off the difference between each purchase (broker fees). So, TL;DR, Many people have lost money in the market to those who made money from them. But only the traders and gamblers.\"",
"title": ""
},
{
"docid": "546548",
"text": "\"From The Coca-Cola Company website, section for Investors: Stock History, Issues Year 1919 Original issue -- 600,000 shares 100,000 preferred, par $100 each 500,000 common, without nominal or par value 1926 Eliminated 100,000 preferred in November. This means there were preferred shares issued in 1919. However, all preferred shares were \"\"eliminated\"\" (not sure what that means) as of 1926. There has been no subsequent reissuance of preferred shares of Coca-Cola since then. I think the company is still authorized to issue them, should they choose to do so in the future.\"",
"title": ""
},
{
"docid": "380402",
"text": "It shouldn't, really. Investors and companies thinking about an IPO shouldn't be scared. I mean, Facebook is a company with no real way to profit from its technology. They have the user base, but has no way of profiting off them. Yet anyways. For them to come out with a near $100 bln valuation, only making a few bln in revenue last year (and little profit), it seems that the market is just adjusting to their respective value to investors. Now, if a company wants to IPO that's awesome, just make sure: * The company will be relevant to daily life in 10-25-50-100 years, etc. * The company can turn a profit without uncertainty. * A company that can grow. Meaning if you buy into a $100 bln valuation, that it can be realistically seen as to growing into a $200 bln company in the next few years. * Preferably, traditional investors like companies that make or deal with a physical product. * The company has leadership. CEO Zuckerberg of (FB) may have created the social network technology, but that doesn't mean he's fit to run a $100 bln public company. I mean, the guy couldn't even dress in a suit for his important meetings pre-IPO. * Preferably companies that can/will enter emerging markets. Cue Coca-Cola and bottlers. * The list goes on but I'm bored of typing. Anyone can add/argue or critique anything if they would like to. If you have all that, you shouldn't be scared of IPO'ing or investing in at IPO.",
"title": ""
},
{
"docid": "94900",
"text": "Buy a share - not a penny stock; rather a well known company like Coca-Cola, Kelloggs, Exxon, etc. Follow the company. Understand their business model. See the share price fall and rise. You will learn a lot having your own money at risk.",
"title": ""
},
{
"docid": "407505",
"text": "\"This answer will expand a bit on the theory. :) A company, as an entity, represents a pile of value. Some of that is business value (the revenue stream from their products) and some of that is assets (real estate, manufacturing equipment, a patent portfolio, etc). One of those assets is cash. If you own a share in the company, you own a share of all those assets, including the cash. In a theoretical sense, it doesn't really matter whether the company holds the cash instead of you. If the company adds an extra $1 billion to its assets, then people who buy and sell the company will think \"\"hey, there's an extra $1 billion of cash in that company; I should be willing to pay $1 billion / shares outstanding more per share to own it than I would otherwise.\"\" Granted, you may ultimately want to turn your ownership into cash, but you can do that by selling your shares to someone else. From a practical standpoint, though, the company doesn't benefit from holding that cash for a long time. Cash doesn't do much except sit in bank accounts and earn pathetically small amounts of interest, and if you wanted pathetic amounts of interests from your cash you wouldn't be owning shares in a company, you'd have it in a bank account yourself. Really, the company should do something with their cash. Usually that means investing it in their own business, to grow and expand that business, or to enhance profitability. Sometimes they may also purchase other companies, if they think they can turn a profit from the purchase. Sometimes there aren't a lot of good options for what to do with that money. In that case, the company should say, \"\"I can't effectively use this money in a way which will grow my business. You should go and invest it yourself, in whatever sort of business you think makes sense.\"\" That's when they pay a dividend. You'll see that a lot of the really big global companies are the ones paying dividends - places like Coca-Cola or Exxon-Mobil or what-have-you. They just can't put all their cash to good use, even after their growth plans. Many people who get dividends will invest them in the stock market again - possibly purchasing shares of the same company from someone else, or possibly purchasing shares of another company. It doesn't usually make a lot of sense for the company to invest in the stock market themselves, though. Investment expertise isn't really something most companies are known for, and because a company has multiple owners they may have differing investment needs and risk tolerance. For instance, if I had a bunch of money from the stock market I'd put it in some sort of growth stock because I'm twenty-something with a lot of savings and years to go before retirement. If I were close to retirement, though, I would want it in a more stable stock, or even in bonds. If I were retired I might even spend it directly. So the company should let all its owners choose, unless they have a good business reason not to. Sometimes companies will do share buy-backs instead of dividends, which pays money to people selling the company stock. The remaining owners benefit by reducing the number of shares outstanding, so they own more of what's left. They should only do this if they think the stock is at a fair price, or below a fair price, for the company: otherwise the remaining owners are essentially giving away cash. (This actually happens distressingly often.) On the other hand, if the company's stock is depressed but it subsequently does better than the rest of the market, then it is a very good investment. The one nice thing about share buy-backs in general is that they don't have any immediate tax implications for the company's owners: they simply own a stock which is now more valuable, and can sell it (and pay taxes on that sale) whenever they choose.\"",
"title": ""
},
{
"docid": "451688",
"text": "The idea here is to get an idea of how to value each business and thus normalize how highly prized is each dollar that a company makes. While some companies may make millions and others make billions, how does one put these in proper context? One way is to consider a dollar in earnings for the company. How does a dollar in earnings for Google compare to a dollar for Coca-cola for example? Some companies may be valued much higher than others and this is a way to see that as share price alone can be rather misleading since some companies can have millions of shares outstanding and split the shares to keep the share price in a certain range. Thus the idea isn't that an investor is paying for a dollar of earnings but rather how is that perceived as some companies may not have earnings and yet still be traded as start-ups and other companies may be running at a loss and thus the P/E isn't even meaningful in this case. Assuming everything but the P/E is the same, the lower P/E would represent a greater value in a sense, yes. However, earnings growth rate can account for higher P/Es for some companies as if a company is expected to grow at 40% for a few years it may have a higher P/E than a company growing earnings at 5% for example.",
"title": ""
},
{
"docid": "466835",
"text": "\"This is several questions wrapped together: How can I diplomatically see the company's financial information? How strong a claim does a stockholder or warrantholder have to see the company's financials? What information do I need to know about the company financials before deciding to buy in? I'll start with the easier second question (which is quasi implicit). Stockholders typically have inspection rights. For example, Delaware General Corporate Law § 220 gives stockholders the right to inspect and copy company financial information, subject to certain restrictions. Check the laws and corporate code of your company's state of incorporation to find the specific inspection right. If it is an LLC or partnership, then the operating agreement usually controls and there may be no inspection rights. If you have no corporate stock, then of course you have no statutory inspection rights. My (admittedly incomplete) understanding is that warrantholders generally have no inspection rights unless somehow contracted for. So if you vest as a corporate stockholder, it'll be your right to see the financials—which may make even a small purchase valuable to you as a continuing employee with the right to see the financials. Until then, this is probably a courtesy and not their obligation. The first question is not easy to answer, except to say that it's variable and highly personal for small companies. Some people interpret it as prying or accusatory, the implication being that the founders are either hiding something or that you need to examine really closely the mouth of their beautiful gift horse. Other people may be much cooler about the question, understanding that small companies are risky and you're being methodical. And in some smaller companies, they may believe giving you the expenses could make office life awkward. If you approach it professionally, directly, and briefly (do not over-explain yourself) with the responsible accountant or HR person (if any), then I imagine it should not be a problem for them to give some information. Conversely, you may feel comfortable enough to review a high-level summary sheet with a founder, or to find some other way of tactfully reviewing the right information. In any case, I would keep the request vague, simple, and direct, and see what information they show you. If your request is too specific, then you risk pushing them to show information A, which they refuse to do, but a vague request would've prompted them to show you information B. A too-specific request might get you information X when a vague request could have garnered XYZ. Vague requests are also less aggressive and may raise fewer objections. The third question is difficult to say. My personal understanding is some perspective of how venture capitalists look at the investment opportunity (you didn't say how new this startup is or what series/stage they are on, so I'll try to stay vague). The actual financials are less relevant for startups than they are for other investments because the situation will definitely change. Most venture capital firms like to look at the burn rate or amount of cash spent, usually at a monthly rate. A high burn rate relative to infusions of cash suggests the company is growing rapidly but may have a risk of toppling (i.e. failing before exit). Burn rate can change drastically during the early life of the startup. Of course burn rate needs the context of revenues and reserves (and latest valuation is helpful as a benchmark, but you may be able to calculate that from the restricted share offer made to you). High burn rate might not be bad, if the company is booming along towards a successful exit. You might also want to look at some sort of business plan or info sheet, rather than financials alone. You want to gauge the size of the market (most startups like to claim 9- or 10-figure markets, so even a few percentage points of market share will hit revenue into the 8-figures). You'll also have to have a sense for the business plan and model and whether it's a good investment or a ridiculous rehash (\"\"it's Twitter for dogs meets Match.com for Russian Orthodox singles!\"\"). In other words, appraise it like an investor or VC and figure out whether it's a prospect for decent return. Typical things like competition, customer acquisition costs, manufacturing costs are relevant depending on the type of business activity. Of course, I wouldn't ignore psychology (note that economists and finance people don't generally condone the following sort of emotional thinking). If you don't invest in the company and it goes big, you'll kick yourself. If it goes really big, other people will either assume you are rich or feel sad for you if you say you didn't get rich. If you invest but lose money, it may not be so painful as not investing and losing out the opportunity. So if you consider the emotional aspect of personal finance, it may be wise to invest at least a little, and hedge against \"\"woulda-shoulda\"\" syndrome. That's more like emotional advice than hard-nosed financial advice. So much of the answer really depends on your particular circumstances. Obviously you have other considerations like whether you can afford the investment, which will be on you to decide. And of course, the § 83(b) election is almost always recommended in these situations (which seems to be what you are saying) to convert ordinary income into capital gain. You may also need cash to pay any up-front taxes on the § 83(b) equity, depending on your circumstances.\"",
"title": ""
},
{
"docid": "499166",
"text": "It's all about risk. These guidelines were all developed based on the risk characteristics of the various asset categories. Bonds are ultra-low-risk, large caps are low-risk (you don't see most big stocks like Coca-Cola going anywhere soon), foreign stocks are medium-risk (subject to additional political risk and currency risk, especially so in developing markets) and small-caps are higher risk (more to gain, but more likely to go out of business). Moreover, the risks of different asset classes tend to balance each other out some. When stocks fall, bonds typically rise (the recent credit crunch being a notable but temporary exception) as people flock to safety or as the Fed adjusts interest rates. When stocks soar, bonds don't look as attractive, and interest rates may rise (a bummer when you already own the bonds). Is the US economy stumbling with the dollar in the dumps, while the rest of the world passes us by? Your foreign holdings will be worth more in dollar terms. If you'd like to work alternative asset classes (real estate, gold and other commodities, etc) into your mix, consider their risk characteristics, and what will make them go up and down. A good asset allocation should limit the amount of 'down' that can happen all at once; the more conservative the allocation needs to be, the less 'down' is possible (at the expense of the 'up'). .... As for what risks you are willing to take, that will depend on your position in life, and what risks you are presently are exposed to (including: your job, how stable your company is and whether it could fold or do layoffs in a recession like this one, whether you're married, whether you have kids, where you live). For instance, if you're a realtor by trade, you should probably avoid investing too much in real estate or it'll be a double-whammy if the market crashes. A good financial advisor can discuss these matters with you in detail.",
"title": ""
},
{
"docid": "288756",
"text": "He owns the majoirty of berkshire hathaway which owns a lot of big companies outright as well as fractions of other big public companies. For example, his holding company berkshire hathaway which lets say he owns 50% of, owns 10% of coca cola. This means that every can or bottle of coke sold, berkshire hathaway gets 10% of the profit so say .01 per can. Thats a lot given the millions of cans sold. Since he owns 50% of berkshire hathaway that means he is getting half a penny of every can of coke sold. Do this with all of his companies and investment holdings and you get to billions of dollars.",
"title": ""
},
{
"docid": "137746",
"text": "Problem with deciding investments in a company is that you have multiple potential options, each with their projected returns, but each also has some hard-to-estimate risks. A further problem is that these opportunities arrive one-by-one, so you usually cannot compare project A vs. project B to decide which one is better. The internal rate of return is a rule-of-thumb like way to make these decisions. The company board may set an IRR target of e.g. 15%, and each executive will compare their projects against that target. They'll execute only the projects that are projected to give a good return, but some of these projects will end up failing. Thus the real average profit will not be equal to IRR. Important thing is that this target number gives ways to compare projects, and also for the board to control the investments. If the company has a good track record of being successful at projects, the board might set an IRR target of 10% and expect to get e.g. 8% return on their investment. However, if the company has a much larger risk of projects failing, they might demand a predicted IRR of 20% to account for the risk. Ultimately if the IRR target is set too high, the company will find no projects it considers profitable to invest in. In practice if this happens, the company owners are better off taking out the cash as dividends and investing it elsewhere.",
"title": ""
},
{
"docid": "403514",
"text": "\"How will contribution limits rise? Contribution limits are raised based on COLA. COLA (Cost of Living Adjustment) is a number based on CPI (Consumer Price Index) which is published by the Bureau of Labor Statistics. The IRS publishes these limits annually and a simple search term to find them each year is \"\"415 limits\"\" because section 415 lists how much the various qualified plans can set aside each year. CPI is a heavily managed and very political number. It is the number that is cited when the media talks about \"\"inflation.\"\" Since it drives increases in salaries, deductions, Social Security and pension payments, there is very heavy pressure to keep the number smaller than it really is. My next step was to calculate how long that money will last One traditional rule-of-thumb is to withdraw 4% of your balance each year. Another alternative is to purchase annuities. While younger people think that annuities are horrible investments, they appeal to older people because they protect the annuitant from excessive risk of losing your capital. When you are 30, and another 2008 comes along wiping out half your savings, you have time to re-earn that money. When you are 60, and another 2008 comes along wiping out half your savings, you have very few years to recover that money. So an annuity pushes that risk onto insurance companies. If you think you will die in your 90s, then an annuity is going to be a good investment (the insurance company will be betting that you won't be living that long). I have a simple spreadsheet that I use to calculate estimated projected balances and compare them to actual performance. Don't forget that when you reach 50, the amount you can contribute goes up due to \"\"catch up contributions.\"\" There are 2 views of the same tab in this picture. There are 3 growth rates: pessimistic, nominal and optimistic. You can change the numbers to suit your own projections of future growth. Other tabs on this spreadsheet include measurements of actual performance by my 401k and IRA accounts. At the end of the year, I replace the numbers in columns F, G & H with the actual end-of-year dollar amounts. This way, future estimates do not get too far unhinged from reality. If you need more sophisticated planning, such as Monte Carlo analysis to attempt to cope with inflation, I recommend the book Engineering Your Retirement. The book is aimed at younger engineers, so there is a bit more math than the average person would want.\"",
"title": ""
},
{
"docid": "61787",
"text": "I think Wikipedia offers a very good explanation: A dividend reinvestment program or dividend reinvestment plan (DRIP) is an equity investment option offered directly from the underlying company. The investor does not receive quarterly dividends directly as cash; instead, the investor's dividends are directly reinvested in the underlying equity. The investor must still pay tax annually on his or her dividend income, whether it is received or reinvested. This allows the investment return from dividends to be immediately invested for the purpose of price appreciation and compounding, without incurring brokerage fees or waiting to accumulate enough cash for a full share of stock. So essentially, a dividend reinvestment plan is offered by companies directly, allowing investors to bypass brokerages, and immediately re-invests dividends rather than paying them out in cash. Investopedia also gives a straighforward definition: A plan offered by a corporation that allows investors to reinvest their cash dividends by purchasing additional shares or fractional shares on the dividend payment date. A DRIP is an excellent way to increase the value of your investment. Most DRIPs allow you to buy shares commission free and at a significant discount to the current share price. Most DRIPS don't allow reinvestments much lower than $10. I had a hard time finding a comprehensive listing of companies that offered DRPs (or DRIPs), but MyDollarPlan.com offers these suggestions: Finding a Dividend Reinvestment Plan: Computershare offers one-stop shopping for hundreds of dividend reinvestment plans. They offer a searchable list that can be filtered to easily find a dividend reinvestment plan that fits your needs. You can also use OneShare. Probably the best way to find out if a company offers a dividend reinvestment plan is to visit the company website. Most companies have an Investor Relations area that will highlight the various options available to shareowners. For example: Coca-Cola, Disney, and Wal-Mart. Hope this helps! @YMCbuzz",
"title": ""
},
{
"docid": "422183",
"text": "\"I don't agree that the market as a whole is a ponzi scheme, but there are some ponzi-like aspects to it. If you buy high quality stocks like Coca Cola, Johnson and Johnson, AT&T, Verizon, Kraft, Wells Fargo (the vanilla bank, not one of the crazy ones), IBM, Berkshire Hathaway etc and simply hold onto them for the next 10-20 years, you will make money. Even over the last decade, when stocks \"\"went nowhere\"\", you still came out ahead through the dividend payments. It was just at an unsatisfactory rate of return. Also \"\"the market\"\" consists of a lot more than just stocks. Corporate bonds are a big market and I always recommend people to look at bonds. If you cannot judge whether a company is credit worthy, how can you invest in the common stock? I've made a lot more money myself in the bond market than in the stock market. However, for many stocks, they do look a lot like ponzi schemes. This is true, in particular, with many of the tech stocks (Cuban was a tech investor, so that is probably where his sentiment is coming from). You have many of these companies that create great products. However, they never have positive cash flow because all the money is spent to develop new products. As the share price goes up, the company issues new shares to fund research, stock options to employees to enrich them, etc. However, eventually, they run into a string of bad research that do not yield a new product and the share price plunges. Perhaps the company goes bankrupt. So you have a company that developed great products, but the shareholders never got a penny in dividends and the final shareholders have paper worth zero. Take a look at Research in Motion for example. Creating the Blackberry has to be one of the biggest successes in tech over the last decade. However, has the shareholders gotten any richer? Only if they traded amongst themselves, nobody got a dividend. What happened to the many billions of dollars they made during the peak popularity years of Blackberry? It went to executives, employees, and was squandered on development that did not effectively defend the phone's dominant market position. Now the stock price is back down to the pre-prime years, and if a shareholder held onto it throughout the entire period, he would not have received a single penny. And this is a profitable enterprise, things look even more bizarre when you start looking at the tech companies that have NEVER had a positive earnings quarter and no plans to ever have positive earnings (something like Pandora comes to mind). Often, management at these more bizarre companies run the company as a toy - to play with their own ideas and to issue themselves stock as compensation. And of course, they sell a lot of the stock to cash in before they delve into the next risky venture. They have no intention of ever enriching anybody who holds into the stock in the long run. If for some reason they make money, they will put it all into their next toy project until one of them fails and wipes everything out. If you invest in a profitable business with reasonable management, you will generally come out ahead. Some businesses get displaced by unpredictable circumstances and they go bankrupt. But on average, if a company is good at doing something and they pay out the earnings, you come out ahead. You get in trouble when businesses are good at something, and they take all the money they make and put it into doing something they are not good at. A business might only provide good cashflow for 10-20 years when the product is popular and before competitors cut into margins. If that money is squandered, the long term shareholder may ultimately have very terrible results. The long term shareholder ends up being the guy who keeps going all-in on a 80%-chance-to-win bet (that is what management is doing when they bet the company on the next unproven product), but eventually he gets zeroed out on one loss. This is why if you look at Buffett's investments, they are all in simple businesses that spits off cash to the owner/shareholder. Businesses like soft drinks, snacks, rail roads, vanilla banking, utility-like energy companies, insurance, etc. You might be good at judging the odds of whether a business will succeed or not (aka make more money than your original investment or not). But you don't want management of that company to make a wildly different bet for you. Just because they are great at operating a company doesn't mean they are good enough at judging odds or disciplined enough to make those bets for you. I may have predicted accurately that Business X will be a great success, but if manage takes those profits and goes all in on Business Y, without giving me a chance to cash out, that may have disasterous results.\"",
"title": ""
},
{
"docid": "577370",
"text": "\"Yes and no. Any great idea, excluding new technologies/discoveries, usually involves a trade-off. Good ideas taken to their extremes usually are pathological. I've generally worked in the open communication environment Musk describes for most of my career for 25 years and I've seen where it works and where it doesn't, and what Musk's email misses is where it doesn't work. It is a good *starting point*. For one thing, there need to be filters. A VP, Director, Senior Manager, CEO, or other higher up cannot deal with 1000 emails per day for ideas, criticisms, etc. He does mention avoiding \"\"chit chat\"\", but employees with \"\"good ideas\"\" for technology or business do not see their suggestions as \"\"chit chat\"\". Most actual *good* ideas from juniors are too low level for senior management, such as different platforms, coding methods, etc. Most ideas that senior management are needed, like company direction, organization, etc., require a sophisticated knowledge and experience of business, contracts, etc. Most of the junior ideas I've seen, including my own, were bad ideas that came from lack of experience in business. Or take some new HR policy. Imagine the thousands of direct responses of people straight to HR on the policy. That would grind things to a halt. The whole purpose of direct managers and supervisors is to filter information down, up, and sideways so that other people can do their jobs. You don't want to have high-value people (knowledge, experience, specialties) spending their day dealing with emails and other people's ideas. You want them providing that value to the business. So you need filters -- people who can recognize the good from the bad and pass on the bad. That could be direct managers at the employee's side, or it could be administrative help at the department's side. Either way, it's necessary to be efficient. Then there's the problem of including all stakeholders. If you are junior and work out a solution to a problem with a junior in another problem, but in implementing it you break a whole system (which I've seen happen), you've just caused a lot of harm to the organization. Neither of you may fully understand the implications of your solution on other things. People with responsibility for those things need to be included in the discussion and take responsibility for any implementation. I hate bureaucracy and sometimes it can be a major inefficiency and roadblock for getting simple and obvious things done. But bureaucracy can also improve efficiency and value and a lack of it can be pathological. I've seen marketing and sales people continually take engineers off of important development work in order to build demos for potential new clients, all of which failed to materialize. Why? Because the marketing and sales people were chasing *leads* for contracts without any review of the technical solution, the ideal one, what the solution to the customer needs *really* involves. What was needed to improve efficiency was a \"\"bureaucratic\"\" process that reviewed the market opportunities with the technical offerings of the company and either reject opportunities early on or plan and schedule how best to chase the leads. In my experience, what works best in most cases is open communication but clear guidelines (a) on what is appropriate or not to go direct, (b) that the communications are about ideas only and coming up with solutions, and (c) that actions or implementations require bringing the \"\"chain of command\"\" into the loop for comment or objection before doing anything. Complaining to management isn't usually of much value and doesn't change much. But, identifying the problem (that is part of the complaint), identifying a workable solution with stakeholders, and asking for permission via the chain of command is usually a good way to get things done without creating the problems of a free-for-all.\"",
"title": ""
},
{
"docid": "100283",
"text": "\"I hate to point this out, but have you heard of this guy Trump, or Warren Buffet (although his son seems to be very competent and grounded, to some degree). The US is also plagued with this problem where family companies remain so through leadership, they also tend to fail at greater rates than our publicly ran companies. I suppose Samsung is public company, but why having stock on the open KRX doesn’t lead to better leadership is beyond me to understand? EDIT:My bad for bringing Trump into this, it was meant as an example of wealth distribution which translates into capacity for business options, and he's well known. However you guys need to do some more research before throwing shade, Howard Buffet has taken over Berkshire Hathaway in a non-executive role, while also holding board positions on a multitude of companies in which BH own significant portions including coca-cola. I wasn't pointing out Warren is incompetent in any way, just he passed the reins off to family too in many ways. \"\"In December 2011, Warren Buffett told CBS News that he would like his son Howard to succeed him as Berkshire Hathaway's non-executive chairman.\"\" Apologies for lack of clarity in my statement.\"",
"title": ""
},
{
"docid": "439404",
"text": "Whether it's wise or not depends on what you think and what you should consider are the risks both ways. What are the risks? For Let's say that the company produces great value and its current price and initial price are well below what it's worth. By investing some of your money in the company, you can take advantage of this value and capitalize off of it if the market recognizes this value too, or when the market does (if it's a successful company it will be a matter of when). Other reasons to be for it are that the tech industry is considered a solid industry and a lot of money is flowing into it. Therefore, if this assumption is correct, you may assume that your job is safe even if your investment doesn't pay off (meaning, you don't lose income, but your investment may not be a great move). Against Let's say that you dump a lot of money into your company and invest in the stock. You're being paid by the company, you're taking some of that money and investing it in the company, meaning that, depending on how much you make outside the company, you are increasing your risk of loss if something negative happens to the company (ie: it fails). Other reasons to be against it are just the opposite as above: due to the NSA, some analysts (like Mish, ZeroHedge, and others) think that the world will cut back on doing IT business with the United States, thus the tech industry will take a major hit over the next decade. In addition to that, Jesse Colombo (@TheBubbleBubble) on Twitter is predicting that there's another tech bubble and it will make a mess when it pops (to be fair to Colombo, he was one of analysts who predicted the housing bubble and his predictions on trading are often right). Finally, there is a risk of lost money and there is also a risk of lost opportunity. Looking at your past investments, which generally hurt more? That might give you a clue what to do.",
"title": ""
},
{
"docid": "123226",
"text": "\"The first thing you have to do is to decided what area in finance you want to get into. For example, investment banking and quant are very different jobs. Learning all the CFA material is useful, so you might as well take the exams too while you are at it. You may be able to get into financial IT or some type of financial programming job. That is one step closer to your goal because at least you will be at a finance company and you can network with people that are in the field. Also, if you want to go into the buy side like I did, I recommend you invest your own money and manage your own portfolio. That way you would have some intimate familiarity with some companies/strategies. You can't get this from a textbook. There is something a little wrong with someone who wants to manage other people's money when he doesn't manage his own. That is a tough sell. You can't be too picky about where you get in. Getting in the door is the most important. I got a lot of quant interviews because I was an engineer. Those interviews consist of a lot of math and brain teaser type questions. For fundamental analyst positions, they will typically want to figure out how you think about businesses/companies. You can typically steer the interview any way you want, which is why I think it is important that you invest your own money. If you say \"\"the largest position I hold is in XYZ company\"\", you can be 99% certain that they will be asking about that investment for the next 15 minutes (at least). That is your opportunity to show how you can add value. Most companies prefer students for entry level, because why hire a guy who is already working in another field when you can get someone fresh? I stood out in the interviews because I could say \"\"I put $50k into this position because...\"\". It's not the only way to do it, but I can only provide you with my anedoctal experience.\"",
"title": ""
},
{
"docid": "444581",
"text": "This. Best Buy doesn't sell cases of water...they are shrinkwrapped like this from the Coke distributor and meant to go in coolers by the registers and such. There was no price gouging here...hell, the price of the products might not even be set by Best Buy (they likely get a cut from Coca cola when they are actually sold). But...they shouldn't have ended up on the floor like this in the first place, it just looks bad.",
"title": ""
},
{
"docid": "440091",
"text": "Companies typically release their earnings before the market opens, and then later host an analyst/investor conference call to discuss the results. Here's a link to an interesting article abstract on the subject: Disclosure Rules For Earnings Releases And Calls | Bowne Digest. Excerpt: In the aftermath of the Sarbanes-Oxley Act, the SEC changed regulations to bring quarterly earnings announcements in line with the generally heightened sensitivity to adequate disclosure. New regulations required that issuers file or furnish their earnings press releases on Form 8-K and conduct any related oral presentations promptly thereafter, to avoid a second 8-K. [...] Sample from a news release by The Coca Cola Company: ATLANTA, September 30, 2009 - The Coca-Cola Company will release third quarter and year-to-date 2009 financial results on Tuesday, October 20, before the stock market opens. The Company will host an investor conference call at 9:30 a.m. ( EDT ), on October 20. [...] Sample from a news release by Apple, Inc.: CUPERTINO, California—January 21, 2009—Apple® today announced financial results for its fiscal 2009 first quarter ended December 27, 2008. The Company posted record revenue of [...] Apple will provide live streaming of its Q1 2009 financial results conference call utilizing QuickTime®, Apple’s standards-based technology for live and on-demand audio and video streaming. The live webcast will begin at [...]",
"title": ""
},
{
"docid": "135411",
"text": "\"I think your question might be coming from a misunderstanding of how corporate structures work - specifically, that a corporation is a legal entity (sort of like a person) that can have its own assets and debts. To make it clear, let's look at your example. We have two founders, Albert and Brian, and they start a corporation called CorpTech. When they start the company, it has no assets - just like you would if you owned nothing and had no bank account. In order to do anything, CorpTech is going to need some money. So Albert and Brian give it some. They can give it as much as they want - they can give it property if they want, too. Usually, people don't just put money into a corporation without some sort of agreement in place, though. In most cases, the agreement says something like \"\"Each member will own a fraction of the company that is in proportion to this initial investment.\"\" The way that is done varies depending on the type of corporation, but in general, if Albert ends up owning 75% and Brian ends up owning 25%, then they probably valued their contributions at 75% and 25% of the total value. These contributions don't have to be money or property, though. They could just be general \"\"know-how,\"\" or \"\"connections,\"\" or \"\"an expectation that they will do some work.\"\" The important thing is that they agree on the value of these contributions and assign ownership of the company according to that agreement. If they don't have an agreement, then the laws of the state that the company is registered in will say how the ownership is assigned. Now, what \"\"ownership\"\" means can be different depending on the context. When it comes to decision-making, you could \"\"own\"\" one percentage of the company in terms of votes, but when it comes to shares of future profits, you could own a different amount. This is why you can have voting and non-voting versions of a company's stock, for example. So this is a critical point - the ownership of a company is independent of the individual contributions to the company. The next part of your question is related to this: what happens when CorpTech sees an opportunity to make an investment? If it has enough cash on hand (because of the initial investment, or through financing, or reinvested profits), then the decision to make the investment is made according to Albert and Brian's ownership agreement, and they spend it. The money doesn't belong to them individually anymore, it belongs to CorpTech, and so CorpTech is spending it. They are just making the decision for CorpTech to spend it. This is why people say the owners are not financially liable beyond their initial investment. If the deal is bad, and they lose the money, the most they can lose is what they initially put in. On the other hand, if CorpTech doesn't have the money, then they have to figure out a way to get it. They might decide to each put in an amount in proportion to their ownership, so that their stake doesn't change. Or, Albert might agree to finance the deal 100% in exchange for a larger share of ownership. Or, he could agree to fund all of it without a larger stake, because Brian is the one who set the deal up. Or, they might take out a loan, and not need to invest any new money. Or, they might find an investor who agrees to put in the needed money in exchange for a a 51% share, in which case Albert and Brian will have to figure out how to split the remaining 49% if they agree to the deal. The details of how all of this would work depend on the structure (LLC, LLP, C-corp, S-corp, etc), but in general, the idea is that the company has assets and debts, and the owners can have voting rights, equity rights, and rights to future profits in any type of split that they want, regardless of what the companies assets and debts are, or what their initial investment was.\"",
"title": ""
},
{
"docid": "209349",
"text": "\"I'll take a stab at this question and offer a disclosure: I recently got in RING (5.1), NEM (16.4), ASX:RIO (46.3), and FCX (8.2). While I won't add to my positions at current prices, I may add other positions, or more to them if they fall further. This is called catching a falling dagger and it's a high risk move. Cons (let's scare everyone away) Pros The ECB didn't engage in as much QE as the market hoped and look at how it reacted, especially commodities. Consider that the ECB's actions were \"\"tighter\"\" than expected and the Fed plans to raise rates, or claims so. Commodities should be falling off a cliff on that news. While most American/Western attention is on the latest news or entertainment, China has been seizing commodities around the globe like crazy, and the media have failed to mention that even with its market failing, China is still seizing commodities. If China was truly panicked about its market, it would stop investing in other countries and commodities and just bail out its own country. Yet, it's not doing that. The whole \"\"China crisis\"\" is completely oversold in the West; China is saying one thing (\"\"oh no\"\"), but doing another (using its money to snap up cheap commodities). Capitalism works because hard times strengthen good companies. You know how many bailouts ExxonMobil has received compared to Goldman Sachs? You know who owns more real wealth? Oil doesn't get bailed out, banks do, and banks can't innovate to save their lives, while oil innovates. Hard times strengthen good companies. This means that this harsh bust in commodities will separate the winners from the losers and history shows the winners do very well in the long run. Related to the above point: how many bailouts from tax payers do you think mining companies will get? Zero. At least you're investing in companies that don't steal your money through government confiscation. If you're like me, you can probably find at least 9 people out of 10 who think \"\"investing in miners is a VERY BAD idea.\"\" What do they think is a good idea? \"\"Duh, Snapchat and Twitter, bruh!\"\" Then there's the old saying, \"\"Be greedy when everyone's fearful and fearful when everyone's greedy.\"\" Finally, miners own hard assets. Benjamin Graham used to point this out with the \"\"dead company\"\" strategy like finding a used cigarette with one more smoke. You're getting assets cheap, while other investors are overpaying for stocks, hoping that the Fed unleashes moar QE! Think strategy here: seize cheap assets, begin limiting the supply of these assets (if you're the saver and not borrowing), then watch as the price begins to rise for them because of low supply. Remember, investors are part owners in companies - take more control to limit the supply. Using Graham's analogy, stock pile those one-puff cigarettes for a day when there's a low supply of cigarettes. Many miners are in trouble now because they've borrowed too much and must sell at a low profit, or in some cases, must lose. When you own assets debt free, you can cut the supply. This will also help the Federal Reserve, who's been desperately trying to figure out how to raise inflation. The new patriotic thing to do is stimulate the economy by sending inflation up, and limiting the supply here is key.\"",
"title": ""
}
] |
335
|
Deregulation of HAND2 is a crucial step in endometrial carcinogenesis in mice.
|
[
{
"docid": "1780819",
"text": "BACKGROUND Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. METHODS AND FINDINGS Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. CONCLUSIONS HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary.",
"title": "Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development"
}
] |
[
{
"docid": "4767806",
"text": "Maintenance and accurate propagation of the genetic material are key features for physiological development and wellbeing. The replication licensing machinery is crucial for replication precision as it ensures that replication takes place once per cell cycle. Thus, the expression status of the components comprising the replication licensing apparatus is tightly regulated to avoid re-replication; a form of replication stress that leads to genomic instability, a hallmark of cancer. In the present review we discuss the mechanistic basis of replication licensing deregulation, which leads to systemic effects, exemplified by its role in carcinogenesis and a variety of genetic syndromes. In addition, new insights demonstrate that above a particular threshold, the replication licensing factor Cdc6 acts as global transcriptional regulator, outlining new lines of exploration. The role of the putative replication licensing factor ChlR1/DDX11, mutated in the Warsaw Breakage Syndrome, in cancer is also considered. Finally, future perspectives focused on the potential therapeutic advantage by targeting replication licensing factors, and particularly Cdc6, are discussed.",
"title": "Exploring and exploiting the systemic effects of deregulated replication licensing."
},
{
"docid": "6121668",
"text": "OBJECTIVES To investigate the expressions of survivin and Cyclooxygenase-2 (COX-2), and their possible correlations in the development of endometrial adenocarcinoma (EC). We also looked at their association with classical prognostic factors in EC. To our knowledge, this is the first time survivin expression is investigated in terms of its relation to COX-2 in the developmental pathway of EC. METHODS Archived tissue samples of 50 EC, 30 endometrial hyperplasia and 20 proliferative endometrium were selected and immunohistochemically analyzed for survivin and COX-2 expression. RESULTS Both survivin and COX-2 were overexpressed in hyperplasia and endometrial adenocarcinoma cases compared to proliferative endometrium, which was statistically significant (p=0.01, p=0.02, respectively). Among EC cases, survivin and COX-2 were strongly positive in 38 (76%) and 30 (60%) patients, respectively. Furthermore, we found survivin and COX-2 to be positively correlated, which was also statistically significant (p=0.0001, r=0.46). Neither survivin nor COX-2 expression was correlated with classical prognostic factors of endometrial carcinoma such as myometrial invasion, grade or lymph node metastasis (p>0.05). Neither COX-2 nor survivin had an impact on overall survival (p>0.05). CONCLUSIONS Both survivin and COX-2 are overexpressed, and they seem to be early events in the occurrence of EC. Moreover, protein products of these two genes are positively correlated. COX-2 and survivin might share a common molecular pathway or enhance each other's actions in the developmental pathway of EC. Molecular basis of such a relationship should be further investigated in endometrial carcinogenesis.",
"title": "COX-2 and survivin are overexpressed and positively correlated in endometrial carcinoma."
},
{
"docid": "9634465",
"text": "Direct reprogramming is a promising approach in regenerative medicine. Overexpression of the cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2 (GHMT) directly reprogram fibroblasts into cardiomyocyte-like cells (iCMs). However, the critical timing of transgene expression and the molecular mechanisms for cardiac reprogramming remain unclear. The conventional doxycycline (Dox)-inducible temporal transgene expression systems require simultaneous transduction of two vectors (pLVX-rtTA/pLVX-cDNA) harboring the reverse tetracycline transactivator (rtTA) and the tetracycline response element (TRE)-controlled transgene, respectively, leading to inefficient cardiac reprogramming. Herein, we developed a single-construct-based polycistronic Dox-inducible vector (pDox-cDNA) expressing both the rtTA and TRE-controlled transgenes. Fluorescence activated cell sorting (FACS) analyses, quantitative RT-PCR, and immunostaining revealed that pDox-GMT increased cardiac reprogramming three-fold compared to the conventional pLVX-rtTA/pLVX-GMT. After four weeks, pDox-GMT-induced iCMs expressed multiple cardiac genes, produced sarcomeric structures, and beat spontaneously. Co-transduction of pDox-Hand2 with retroviral pMX-GMT increased cardiac reprogramming three-fold compared to pMX-GMT alone. Temporal Dox administration revealed that Hand2 transgene expression is critical during the first two weeks of cardiac reprogramming. Microarray analyses demonstrated that Hand2 represses cell cycle-promoting genes and enhances cardiac reprogramming. Thus, we have developed an efficient temporal transgene expression system, which could be invaluable in the study of cardiac reprogramming.",
"title": "Single-Construct Polycistronic Doxycycline-Inducible Vectors Improve Direct Cardiac Reprogramming and Can Be Used to Identify the Critical Timing of Transgene Expression"
},
{
"docid": "8133180",
"text": "Germline mutations in the RET tyrosine kinase gene are responsible for the development of multiple endocrine neoplasia 2A and 2B (MEN2A and MEN2B). However, knowledge of the fundamental principles that determine the mutant RET-mediated signaling remains elusive. Here, we report increased expression of mitogen-activated protein kinase phosphatase-2 (MKP-2) in carcinomas developed in transgenic mice carrying RET with the MEN2A mutation (RET-MEN2A). The expression of MKP-2 was not only induced by RET-MEN2A or RET-MEN2B mutant proteins but also by the activation of endogenous RET by its ligand, glial cell line-derived neurotrophic factor (GDNF). MKP-2 expression was also evident in the MKK-f cell line, which was established from a mammary tumor developed in a RET-MEN2A transgenic mouse. Inhibition of MKP-2 attenuated the in vitro and in vivo proliferation of MKK-f cells, which was mediated by the suppression of cyclin B1 expression. Furthermore, we found that MKP-2 is highly expressed in medullary thyroid carcinomas derived from MEN2A patients. These findings suggest that the increased expression of MKP-2 may play a crucial role in oncogenic signaling downstream of mutant RET, leading to deregulation of cell cycle.",
"title": "Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice"
},
{
"docid": "42279414",
"text": "For more than 60 years, the chemical induction of tumors in mouse skin has been used to study mechanisms of epithelial carcinogenesis and evaluate modifying factors. In the traditional two-stage skin carcinogenesis model, the initiation phase is accomplished by the application of a sub-carcinogenic dose of a carcinogen. Subsequently, tumor development is elicited by repeated treatment with a tumor-promoting agent. The initiation protocol can be completed within 1–3 h depending on the number of mice used; whereas the promotion phase requires twice weekly treatments (1–2 h) and once weekly tumor palpation (1–2 h) for the duration of the study. Using the protocol described here, a highly reproducible papilloma burden is expected within 10–20 weeks with progression of a portion of the tumors to squamous cell carcinomas within 20–50 weeks. In contrast to complete skin carcinogenesis, the two-stage model allows for greater yield of premalignant lesions, as well as separation of the initiation and promotion phases.",
"title": "Multi-stage chemical carcinogenesis in mouse skin: Fundamentals and applications"
},
{
"docid": "10024681",
"text": "Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.",
"title": "Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer"
},
{
"docid": "23122306",
"text": "In an experiment to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), we found that there is a strong relation between lung tumor response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated intratracheal instillation. Repeated intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a representative enzyme of superoxide generation, and two types of nitric oxide (NO) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of CuZn-superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depressed by the instillation of DEP. These results suggest that generation of superoxide, hydroxyI radical, and nitric oxide are increased in epithelial cells in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO(-)). The peroxynitrite also produce hydroxyI radical. The hydroxyl radical may play an important role in carcinogenesis by DEP.",
"title": "Lung Carcinogenesis by Diesel Exhaust Particles and the Carcinogenic Mechanism Via Active Oxygens."
},
{
"docid": "25263942",
"text": "Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.",
"title": "Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia"
},
{
"docid": "5271210",
"text": "MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs involved in the regulation of gene expression and protein translation. Many studies have shown that they play a crucial role in driving organ and tissue differentiation during embryogenesis and in the fine-tuning of fundamental biological processes, such as proliferation and apoptosis. Growing evidence indicates that their deregulation plays an important role in cancer onset and progression as well, where they act as oncogenes or oncosuppressors. In this review, we highlight the most recent findings regarding the role of miRNAs in hepatocellular carcinoma (HCC) by analyzing the possible mechanisms by which they contribute to this neoplasm. Moreover, we discuss the possible role of circulating miRNAs as biomarkers, a field that needs urgent improvement in the clinical surveillance of HCC, and the fascinating possibility of using them as therapeutic targets or drugs themselves.",
"title": "MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma?"
},
{
"docid": "15928989",
"text": "Successful pregnancy requires coordination of an array of signals and factors from multiple tissues. One such element, liver receptor homolog-1 (Lrh-1), is an orphan nuclear receptor that regulates metabolism and hormone synthesis. It is strongly expressed in granulosa cells of ovarian follicles and in the corpus luteum of rodents and humans. Germline ablation of Nr5a2 (also called Lrh-1), the gene coding for Lrh-1, in mice is embryonically lethal at gastrulation. Depletion of Lrh-1 in the ovarian follicle shows that it regulates genes required for both steroid synthesis and ovulation. To study the effects of Lrh-1 on mouse gestation, we genetically disrupted its expression in the corpus luteum, resulting in luteal insufficiency. Hormone replacement permitted embryo implantation but was followed by gestational failure with impaired endometrial decidualization, compromised placental formation, fetal growth retardation and fetal death. Lrh-1 is also expressed in the mouse and human endometrium, and in a primary culture of human endometrial stromal cells, reduction of NR5A2 transcript abundance by RNA interference abrogated decidualization. These findings show that Lrh-1 is necessary for maintenance of the corpus luteum, for promotion of decidualization and for formation of the placenta. It therefore has multiple, indispensible roles in establishing and sustaining pregnancy.",
"title": "Liver receptor homolog-1 is essential for pregnancy"
},
{
"docid": "16346504",
"text": "BACKGROUND Growth arrest-specific 5 (GAS5) was reported to be implicated and aberrantly express in multiple cancers. However, the expression and mechanism of action of GAS5 were largely poor understood in endometrial carcinoma. RESULTS According to the result of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and flow cytometry analysis, we identified that GAS5 was down-regulated in endometrial cancer cells and stimulated the apoptosis of endometrial cancer cells. To investigate the expression of GAS5, PTEN and miR-103, RT-PCR was performed. And we found that the expression of PTEN was up-regulated when endometrial cancer cells overexpressed GAS5. The prediction of bioinformatics online revealed that GAS5 could bind to miR-103, which was further found to be regulated by GAS5. Finally, we found that miR-103 mimic could decrease the mRNA and protein levels of PTEN through luciferase reporter assay and western blotting, and GAS5 plasmid may reverse this regulation effect in endometrial cancer cells. CONCLUSION In summary, we demonstrate that GAS5 acts as an tumor suppressor lncRNA in endometrial cancer. Through inhibiting the expression of miR-103, GAS5 significantly enhanced the expression of PTEN to promote cancer cell apoptosis, and, thus, could be an important mediator in the pathogenesis of endometrial cancer.",
"title": "LncRNA-GAS5 induces PTEN expression through inhibiting miR-103 in endometrial cancer cells"
},
{
"docid": "23577867",
"text": "Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.",
"title": "Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer."
},
{
"docid": "9239963",
"text": "Excessive exposure to estradiol represents the main risk factor for endometrial cancer. The abnormally high estradiol levels in the endometrium of women with endometrial cancer are most likely due to overproduction by the tumour itself. Endometrial cancer cells express the genes encoding the steroidogenic enzymes involved in estradiol synthesis. Here we used RT-PCR and Western blot to show that the nuclear receptors SF1 and LRH1, two well-known regulators of steroidogenic gene expression in gonadal and adrenal cells, are also expressed in endometrial cancer cell lines. By transient transfections, we found that SF1 and LRH1, but not the related nuclear receptor NUR77, can activate the promoters of three human steroidogenic genes: STAR, HSD3B2, and CYP19A1 PII. Similarly, forskolin but not PMA, could activate all three promoters. In addition, we found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters. All together, our data provide novel insights into the mechanisms of steroidogenic gene expression in endometrial cancer cells and thus in the regulation of estradiol biosynthesis by tumour cells.",
"title": "The nuclear receptors SF1 and LRH1 are expressed in endometrial cancer cells and regulate steroidogenic gene transcription by cooperating with AP-1 factors."
},
{
"docid": "8774475",
"text": "Loss of cell polarity proteins such as Scribble induces neoplasia in Drosophila by promoting uncontrolled proliferation. In mammals, the role that polarity proteins play during tumorigenesis is not well understood. Here, we demonstrate that depletion of Scribble in mammary epithelia disrupts cell polarity, blocks three-dimensional morphogenesis, inhibits apoptosis, and induces dysplasia in vivo that progress to tumors after long latency. Loss of Scribble cooperates with oncogenes such as c-myc to transform epithelial cells and induce tumors in vivo by blocking activation of an apoptosis pathway. Like depletion, mislocalization of Scribble from cell-cell junction was sufficient to promote cell transformation. Interestingly, spontaneous mammary tumors in mice and humans possess both downregulated and mislocalized Scribble. Thus, we demonstrate that scribble inhibits breast cancer formation and that deregulation of polarity pathways promotes dysplastic and neoplastic growth in mammals by disrupting morphogenesis and inhibiting cell death.",
"title": "Deregulation of Scribble Promotes Mammary Tumorigenesis and Reveals a Role for Cell Polarity in Carcinoma"
},
{
"docid": "11359243",
"text": "Altered DNA methylation occurs ubiquitously in human cancer from the earliest measurable stages. A cogent approach to understanding the mechanism and timing of altered DNA methylation is to analyze it in the context of carcinogenesis by a defined agent. Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma, but also used commonly in the laboratory to immortalize human B-cells in culture. Here we have performed whole-genome bisulfite sequencing of normal B-cells, activated B-cells, and EBV-immortalized B-cells from the same three individuals, in order to identify the impact of transformation on the methylome. Surprisingly, large-scale hypomethylated blocks comprising two-thirds of the genome were induced by EBV immortalization but not by B-cell activation per se. These regions largely corresponded to hypomethylated blocks that we have observed in human cancer, and they were associated with gene-expression hypervariability, similar to human cancer, and consistent with a model of epigenomic change promoting tumor cell heterogeneity. We also describe small-scale changes in DNA methylation near CpG islands. These results suggest that methylation disruption is an early and critical step in malignant transformation.",
"title": "Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization."
},
{
"docid": "2389574",
"text": "PURPOSE Overexpression of the oncogen Stathmin has been linked to aggressive endometrial carcinoma and a potential for PI3Kinase inhibitors in this disease. We wanted to validate the prognostic value of Stathmin expression in a large prospective multicenter setting. As lymph node sampling is part of current surgical staging, we also aimed to test if Stathmin expression in endometrial curettage specimens could predict lymph node metastasis. EXPERIMENTAL DESIGN A total of 1,076 endometrial cancer patients have been recruited from 10 centers to investigate the biological tumor marker Stathmin in relation to clinicopathologic variables, including lymph node status and survival. Stathmin immunohistochemical staining was carried out in 477 hysterectomy and 818 curettage specimens. RESULTS Seventy-one percent of the patients (n = 763) were subjected to lymph node sampling, of which 12% had metastatic nodes (n = 94). Overexpression of Stathmin was detected in 37% (302 of 818) of the curettage and in 18% (84 of 477) of the hysterectomy specimens investigated. Stathmin overexpression in curettage and hysterectomy specimens were highly correlated and significantly associated with nonendometrioid histology, high grade, and aneuploidy. Stathmin analysis in preoperative curettage samples significantly correlated with, and was an independent predictor of, lymph node metastases. High Stathmin expression was associated with poor disease-specific survival (P ≤ 0.002) both in curettage and hysterectomy specimens. CONCLUSIONS Stathmin immunohistochemical staining identifies endometrial carcinomas with lymph node metastases and poor survival. The value, as a predictive marker for response to PI3Kinase inhibition and as a tool to stratify patients for lymph node sampling in endometrial carcinomas, remains to be determined.",
"title": "Stathmin overexpression identifies high-risk patients and lymph node metastasis in endometrial cancer."
},
{
"docid": "45015767",
"text": "BACKGROUND Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH). METHODS This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses. RESULTS Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens. CONCLUSIONS The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.",
"title": "Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study."
},
{
"docid": "43014661",
"text": "Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer. Consistent with the ability of Pol eta to efficiently bypass UV light-induced cyclobutane pyrimidine dimers, XPV cells lacking Pol eta have diminished capacity to replicate UV-damaged DNA and are sensitive to UV light-induced killing and mutagenesis. To better understand these and other Pol eta functions, we generated Pol eta-deficient mice. Mice homozygous for a null mutation in pol eta are viable, fertile, and do not show any obvious spontaneous defects during the first year of life. However, fibroblasts derived from these mutant mice are sensitive to killing by exposure to UV light, and all Pol eta-deficient mice develop skin tumors after UV irradiation, in contrast to the wild-type littermate controls that did not develop such tumors. These results and biochemical studies of translesion synthesis by mouse Pol eta indicate that Pol eta-dependent bypass of cyclobutane pyrimidine dimers suppresses UV light-induced skin cancer in mice. Moreover, 37.5% of pol eta heterozygous mice also developed skin cancer during 5 months after a 5-month exposure to UV light, suggesting that humans who are heterozygous for mutations in pol eta may also have an increased risk of skin cancer.",
"title": "Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice."
},
{
"docid": "3210545",
"text": "BACKGROUND Three quarter of endometrial carcinomas are treated at early stage. Still, 15 to 20% of these patients experience recurrence, with little effect from systemic therapies. Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogenes homologue (KRAS) mutations have been reported to have an important role in tumorigenesis for human cancers, but there is limited knowledge regarding clinical relevance of KRAS status in endometrial carcinomas. METHODS We have performed a comprehensive and integrated characterisation of genome-wide expression related to KRAS mutations and copy-number alterations in primary- and metastatic endometrial carcinoma lesions in relation to clinical and histopathological data. A primary investigation set and clinical validation set was applied, consisting of 414 primary tumours and 61 metastatic lesions totally. RESULTS Amplification and gain of KRAS present in 3% of the primary lesions and 18% of metastatic lesions correlated significantly with poor outcome, high International Federation of Gynaecology and Obstetrics stage, non-endometrioid subtype, high grade, aneuploidy, receptor loss and high KRAS mRNA levels, also found to be associated with aggressive phenotype. In contrast, KRAS mutations were present in 14.7% of primary lesions with no increase in metastatic lesions, and did not influence outcome, but was significantly associated with endometrioid subtype, low grade and obesity. CONCLUSION These results support that KRAS amplification and KRAS mRNA expression, both increasing from primary to metastatic lesions, are relevant for endometrial carcinoma disease progression.",
"title": "KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer"
},
{
"docid": "21502234",
"text": "BACKGROUND The association between the deficiency in mismatch repair (MMR) genes and prognosis in women with endometrial cancer is unclear. Here we report a systematic review and meta-analysis exploring this association. METHODS We searched literature databases (MEDLINE, EMBASE, and Cochrane) from 1980 until December 2011 to identify studies evaluating the association between MMR status and clinical outcome in endometrial cancer. The main outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS Twenty-three studies met the inclusion criteria. The median sample size of studies was 112, 74% were retrospective case-series and 70% performed microsatellite instability (MSI) analysis to evaluate the status of MMR. Only 22% of studies used the panel of five microsatellite markers recommended by the National Cancer Institute. Seven studies used immunohistochemistry to define MMR deficiency, but only two of them determined the expression of all four MMR proteins. Overall, significant associations between MMR and outcome were observed in 32% of studies. There was marked inter-study heterogeneity for estimates of OS and DFS. Pooled analysis did not show any significant association between deficiency in MMR and worse OS (6 studies, hazard ratio [HR] 2.0, p=0.11) or DFS (4 studies, HR ratio 1.31, p=0.66). CONCLUSION There is no definitive evidence of a significant association between MMR status and detrimental survival in endometrial cancer.",
"title": "Mismatch repair status and clinical outcome in endometrial cancer: a systematic review and meta-analysis."
},
{
"docid": "32721137",
"text": "Although 75% of endometrial cancers are treated at an early stage, 15% to 20% of these recur. We performed an integrated analysis of genome-wide expression and copy-number data for primary endometrial carcinomas with extensive clinical and histopathological data to detect features predictive of recurrent disease. Unsupervised analysis of the expression data distinguished 2 major clusters with strikingly different phenotypes, including significant differences in disease-free survival. To identify possible mechanisms for these differences, we performed a global genomic survey of amplifications, deletions, and loss of heterozygosity, which identified 11 significantly amplified and 13 significantly deleted regions. Amplifications of 3q26.32 harboring the oncogene PIK3CA were associated with poor prognosis and segregated with the aggressive transcriptional cluster. Moreover, samples with PIK3CA amplification carried signatures associated with in vitro activation of PI3 kinase (PI3K), a signature that was shared by aggressive tumors without PIK3CA amplification. Tumors with loss of PTEN expression or PIK3CA overexpression that did not have PIK3CA amplification also shared the PI3K activation signature, high protein expression of the PI3K pathway member STMN1, and an aggressive phenotype in test and validation datasets. However, mutations of PTEN or PIK3CA were not associated with the same expression profile or aggressive phenotype. STMN1 expression had independent prognostic value. The results affirm the utility of systematic characterization of the cancer genome in clinically annotated specimens and suggest the particular importance of the PI3K pathway in patients who have aggressive endometrial cancer.",
"title": "Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation."
},
{
"docid": "33677323",
"text": "MicroRNAs are frequently deregulated in cancer. Here we show that miR-22 is upregulated in myelodysplastic syndrome (MDS) and leukemia and its aberrant expression correlates with poor survival. To explore its role in hematopoietic stem cell function and malignancy, we generated transgenic mice conditionally expressing miR-22 in the hematopoietic compartment. These mice displayed reduced levels of global 5-hydroxymethylcytosine (5-hmC) and increased hematopoietic stem cell self-renewal accompanied by defective differentiation. Conversely, miR-22 inhibition blocked proliferation in both mouse and human leukemic cells. Over time, miR-22 transgenic mice developed MDS and hematological malignancies. We also identify TET2 as a key target of miR-22 in this context. Ectopic expression of TET2 suppressed the miR-22-induced phenotypes. Downregulation of TET2 protein also correlated with poor clinical outcomes and miR-22 overexpression in MDS patients. Our results therefore identify miR-22 as a potent proto-oncogene and suggest that aberrations in the miR-22/TET2 regulatory network are common in hematopoietic malignancies.",
"title": "The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation."
},
{
"docid": "11271123",
"text": "Endometrial cancer is associated with numeric and structural chromosomal abnormalities, microsatellite instability (MSI), and alterations that activate oncogenes and inactivate tumor suppressor genes. The aim of this study was to characterize a set of endometrial cancers using multiple molecular genetic and immunohistochemical techniques. Ninety-six cases were examined for genomic alterations by MSI, MLH1 promoter hypermethylation, p53 and mismatch repair protein expression (MLH1, MSH2, MSH6, PMS2), and PTEN, PIK3CA, KRAS, and BRAF mutation analysis. At least 1 alteration was identified in 48 of 87 (55%) specimens tested for PTEN, making it the most common abnormality in this study. A PIK3CA alteration was observed in 16 (17%) specimens. Twenty-nine of 94 (31%) MSI tested tumors exhibited an MSI-H phenotype. Of the 29 MSI-H cases, 24 (83%) were positive for methylation of the MLH1 promoter region. Twenty-three (82%) of the 28 MSI-H cases with immunohistochemistry results showed loss of expression of MLH1/PMS2 (n=19), MSH2/MSH6 (n=2), or MSH6 only (n=2). Of the 19 MSI-H cases with loss of MLH1/PMS2 on immunohistochemistry, 18 were positive, and 1 was equivocal for MLH1 promoter hypermethylation. Twelve of 94 cases (13%) analyzed for KRAS mutations were found to have a mutation. No BRAF V600E mutations were indentified. This study provides a comprehensive molecular genetic analysis of commonly analyzed targets in a large cohort of endometrial cancers.",
"title": "Molecular characterization of endometrial cancer: a correlative study assessing microsatellite instability, MLH1 hypermethylation, DNA mismatch repair protein expression, and PTEN, PIK3CA, KRAS, and BRAF mutation analysis."
},
{
"docid": "18734652",
"text": "Classifying endometrial hyperplasia (EH) according to the severity of glandular crowding (simple hyperplasia (SH) vs complex hyperplasia (CH)) and nuclear atypia (simple atypical hyperplasia (SAH) vs complex atypical hyperplasia (CAH)) should predict subsequent endometrial carcinoma risk, but data on progression are lacking. Our nested case–control study of EH progression included 138 cases, who were diagnosed with EH and then with carcinoma (1970–2003) at least 1 year (median, 6.5 years) later, and 241 controls, who were individually matched on age, date, and follow-up duration and counter-matched on EH classification. After centralised pathology panel and medical record review, we generated rate ratios (RRs) and 95% confidence intervals (CIs), adjusted for treatment and repeat biopsies. With disordered proliferative endometrium (DPEM) as the referent, AH significantly increased carcinoma risk (RR=14, 95% CI, 5–38). Risk was highest 1–5 years after AH (RR=48, 95% CI, 8–294), but remained elevated 5 or more years after AH (RR=3.5, 95% CI, 1.0–9.6). Progression risks for SH (RR=2.0, 95% CI, 0.9–4.5) and CH (RR=2.8, 95% CI, 1.0–7.9) were substantially lower and only slightly higher than the progression risk for DPEM. The higher progression risks for AH could foster management guidelines based on markedly different progression risks for atypical vs non-atypical EH.",
"title": "Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan"
},
{
"docid": "4418878",
"text": "The development of an oncogenic state is a complex process involving the accumulation of multiple independent mutations that lead to deregulation of cell signalling pathways central to the control of cell growth and cell fate. The ability to define cancer subtypes, recurrence of disease and response to specific therapies using DNA microarray-based gene expression signatures has been demonstrated in multiple studies. Various studies have also demonstrated the potential for using gene expression profiles for the analysis of oncogenic pathways. Here we show that gene expression signatures can be identified that reflect the activation status of several oncogenic pathways. When evaluated in several large collections of human cancers, these gene expression signatures identify patterns of pathway deregulation in tumours and clinically relevant associations with disease outcomes. Combining signature-based predictions across several pathways identifies coordinated patterns of pathway deregulation that distinguish between specific cancers and tumour subtypes. Clustering tumours based on pathway signatures further defines prognosis in respective patient subsets, demonstrating that patterns of oncogenic pathway deregulation underlie the development of the oncogenic phenotype and reflect the biology and outcome of specific cancers. Predictions of pathway deregulation in cancer cell lines are also shown to predict the sensitivity to therapeutic agents that target components of the pathway. Linking pathway deregulation with sensitivity to therapeutics that target components of the pathway provides an opportunity to make use of these oncogenic pathway signatures to guide the use of targeted therapeutics.",
"title": "Oncogenic pathway signatures in human cancers as a guide to targeted therapies"
},
{
"docid": "12869200",
"text": "We performed this meta-analysis of epidemiologic studies to investigate the associations between circulating adiponectin, leptin and adiponectin-leptin (A/L) ratio and endometrial cancer risk. Relevant manuscripts were identified by searching PubMed and ISI Web of Science databases as well as by manual searching the references cited in retrieved manuscripts. Random-effects models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned associations. Fourteen manuscripts with 13 studies (five nested case-control and eight case-control studies) cumulatively involving a total of 1,963 endometrial cancer cases and 3,503 noncases were included in the analyses. Overall, comparing persons with circulating concentrations of adiponectin, leptin and A/L ratio in the top tertile with persons with concentrations of these biomarkers in the bottom tertile yielded SORs of 0.47 (95% CI: 0.34-0.65; I(2) = 63.7%; n = 13), 2.19 (95% CI: 1.44-3.31; I(2) = 64.2%; n = 7),and 0.45 (95% CI: 0.24-0.86; I(2) = 90.1%; n = 5), respectively. Notably, there was an 18% reduction in risk for per each 5 μg/mL increment in circulating adiponectin concentrations (SOR = 0.82; 95% CI: 0.74-0.90; I(2) = 49%; n = 8). Stratifying by study characteristics and whether these studies considered or adjusted for potential confounders, the findings were robust in the analyses of circulating adiponectin and leptin. No evidence of publication bias was detected. In conclusion, the findings from this meta-analysis suggest that increased circulating adiponectin and A/L ratio or decreased leptin concentrations were associated with reduced risk of endometrial cancer. Further prospective designed studies are warranted to confirm our findings.",
"title": "Circulating adiponectin, leptin and adiponectin-leptin ratio and endometrial cancer risk: Evidence from a meta-analysis of epidemiologic studies."
},
{
"docid": "9604301",
"text": "UNLABELLED Cryptococcosis is a multifaceted fungal infection with variable clinical presentation and outcome. As in many infectious diseases, this variability is commonly assigned to host factors. To investigate whether the diversity of Cryptococcus neoformans clinical (ClinCn) isolates influences the interaction with host cells and the clinical outcome, we developed and validated new quantitative assays using flow cytometry and J774 macrophages. The phenotype of ClinCn-macrophage interactions was determined for 54 ClinCn isolates recovered from cerebrospinal fluids (CSF) from 54 unrelated patients, based on phagocytic index (PI) and 2-h and 48-h intracellular proliferation indexes (IPH2 and IPH48, respectively). Their phenotypes were highly variable. Isolates harboring low PI/low IPH2 and high PI/high IPH2 values were associated with nonsterilization of CSF at week 2 and death at month 3, respectively. A subset of 9 ClinCn isolates with different phenotypes exhibited variable virulence in mice and displayed intramacrophagic expression levels of the LAC1, APP1, VAD1, IPC1, PLB1, and COX1 genes that were highly variable among the isolates and correlated with IPH48. Variation in the expression of virulence factors is thus shown here to depend on not only experimental conditions but also fungal background. These results suggest that, in addition to host factors, the patient's outcome can be related to fungal determinants. Deciphering the molecular events involved in C. neoformans fate inside host cells is crucial for our understanding of cryptococcosis pathogenesis. IMPORTANCE Cryptococcus neoformans is a life-threatening human fungal pathogen that is responsible for an estimated 1 million cases of meningitis/year, predominantly in HIV-infected patients. The diversity of infecting isolates is well established, as is the importance of the host factors. Interaction with macrophages is a major step in cryptococcosis pathogenesis. How the diversity of clinical isolates influences macrophages' interactions and impacts cryptococcosis outcome in humans remains to be elucidated. Using new assays, we uncovered how yeast-macrophage interactions were highly variable among clinical isolates and found an association between specific behaviors and cryptococcosis outcome. In addition, gene expression of some virulence factors and intracellular proliferation were correlated. While many studies have established that virulence factors can be differentially expressed as a function of experimental conditions, our study demonstrates that, under the same experimental conditions, clinical isolates behaved differently, a diversity that could participate in the variable outcome of infection in humans.",
"title": "Dynamics of Cryptococcus neoformans-Macrophage Interactions Reveal that Fungal Background Influences Outcome during Cryptococcal Meningoencephalitis in Humans"
},
{
"docid": "10485142",
"text": "Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC. Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or nonnasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase-immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16(INK4A) locus and downregulation of RASSF1A expression. The deletion of the p16(INK4A) locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array-based CGH revealed a gain of a 17q21-q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16(INK4A) locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF-kappaB was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development.",
"title": "Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase."
},
{
"docid": "1428840",
"text": "BACKGROUND It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. PURPOSE We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. METHODS The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. RESULTS High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. CONCLUSION High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. IMPLICATIONS Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.",
"title": "Case-control study of endogenous steroid hormones and endometrial cancer."
},
{
"docid": "7438803",
"text": "Archaea constitute a considerable fraction of the microbial biomass on Earth. Like Bacteria they have evolved a variety of energy metabolisms using organic and/or inorganic electron donors and acceptors, and many of them are able to fix carbon from inorganic sources. Archaea thus play crucial roles in the Earth's global geochemical cycles and influence greenhouse gas emissions. Methanogenesis and anaerobic methane oxidation are important steps in the carbon cycle; both are performed exclusively by anaerobic archaea. Oxidation of ammonia to nitrite is performed by Thaumarchaeota. They represent the only archaeal group that resides in large numbers in the global aerobic terrestrial and marine environments on Earth. Sulfur-dependent archaea are confined mostly to hot environments, but metal leaching by acidophiles and reduction of sulfate by anaerobic, nonthermophilic methane oxidizers have a potential impact on the environment. The metabolisms of a large number of archaea, in particular those dominating the subsurface, remain to be explored.",
"title": "Archaea in biogeochemical cycles."
}
] |
626
|
Induction of urokinase receptor signaling in podocytes causes foot process effacement and proteinuria.
|
[
{
"docid": "16355392",
"text": "Podocyte dysfunction, represented by foot process effacement and proteinuria, is often the starting point for progressive kidney disease. Therapies aimed at the cellular level of the disease are currently not available. Here we show that induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via a mechanism that includes lipid-dependent activation of αvβ3 integrin. Mice lacking uPAR (Plaur−/−) are protected from lipopolysaccharide (LPS)-mediated proteinuria but develop disease after expression of a constitutively active β3 integrin. Gene transfer studies reveal a prerequisite for uPAR expression in podocytes, but not in endothelial cells, for the development of LPS-mediated proteinuria. Mechanistically, uPAR is required to activate αvβ3 integrin in podocytes, promoting cell motility and activation of the small GTPases Cdc42 and Rac1. Blockade of αvβ3 integrin reduces podocyte motility in vitro and lowers proteinuria in mice. Our findings show a physiological role for uPAR signaling in the regulation of kidney permeability.",
"title": "Modification of kidney barrier function by the urokinase receptor"
}
] |
[
{
"docid": "22241778",
"text": "The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.",
"title": "Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus."
},
{
"docid": "10574949",
"text": "Laminin β2 is a component of laminin-521, which is an important constituent of the glomerular basement membrane (GBM). Null mutations in laminin β2 (LAMB2) cause Pierson syndrome, a severe congenital nephrotic syndrome with ocular and neurologic defects. In contrast, patients with LAMB2 missense mutations, such as R246Q, can have less severe extrarenal defects but still exhibit congenital nephrotic syndrome. To investigate how such missense mutations in LAMB2 cause proteinuria, we generated three transgenic lines of mice in which R246Q-mutant rat laminin β2 replaced the wild-type mouse laminin β2 in the GBM. These transgenic mice developed much less severe proteinuria than their nontransgenic Lamb2-deficient littermates; the level of proteinuria correlated inversely with R246Q-LAMB2 expression. At the onset of proteinuria, expression and localization of proteins associated with the slit diaphragm and foot processes were normal, and there were no obvious ultrastructural abnormalities. Low transgene expressors developed heavy proteinuria, foot process effacement, GBM thickening, and renal failure by 3 months, but high expressors developed only mild proteinuria by 9 months. In vitro studies demonstrated that the R246Q mutation results in impaired secretion of laminin. Taken together, these results suggest that the R246Q mutation causes nephrotic syndrome by impairing secretion of laminin-521 from podocytes into the GBM; however, increased expression of the mutant protein is able to overcome this secretion defect and improve glomerular permselectivity.",
"title": "A missense LAMB2 mutation causes congenital nephrotic syndrome by impairing laminin secretion."
},
{
"docid": "21369472",
"text": "Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.",
"title": "TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function"
},
{
"docid": "41599676",
"text": "Congenital nephrotic syndrome, Finnish type (CNF or NPHS1), is an autosomal recessive disease characterized by massive proteinuria and development of nephrotic syndrome shortly after birth. The disease is most common in Finland, but many patients have been identified in other populations. The disease is caused by mutations in the gene for nephrin which is a key component of the glomerual ultrafilter, the podocyte slit diaphragm. A total of 30 mutations have been reported in the nephrin gene in patients with congenital nephrotic syndrome worldwide. In the Finnish population, two main mutations have been found. These two nonsense mutations account for over 94% of all mutations in Finland. Most mutations found in non-Finnish patients are missense mutations, but they include also nonsense and splice site mutations, as well as deletions and insertions. This mutation update summarizes the nature of all previously reported nephrin mutations and, additionally, describes 20 novel mutations recently identified in our laboratory.",
"title": "Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome."
},
{
"docid": "28207326",
"text": "Vascular endothelial growth factor-A (VEGF-A) is a protein secreted by podocytes that is necessary for survival of endothelial cells, podocytes, and mesangial cells. VEGF-A regulates slit-diaphragm signaling and podocyte shape via VEGF-receptor 2-nephrin-nck-actin interactions. Chronic hyperglycemia-induced excess podocyte VEGF-A and low endothelial nitric oxide drive the development and the progression of diabetic nephropathy. The abnormal cross-talk between VEGF-A and nitric oxide pathways is fueled by the diabetic milieu, resulting in increased oxidative stress. Recent findings on these pathogenic molecular mechanisms provide new potential targets for therapy for diabetic renal disease.",
"title": "VEGF and podocytes in diabetic nephropathy."
},
{
"docid": "13070316",
"text": "Tumor angiogenesis is an essential process for supplying rapidly growing malignant tissues with essential nutrients and oxygen. An angiogenic switch allows tumor cells to survive and grow, and provides them access to vasculature resulting in metastatic disease. Monocyte-derived macrophages recruited and reprogrammed by tumor cells serve as a major source of angiogenic factors boosting the angiogenic switch. Tumor endothelium releases angiopoietin-2 and further facilitates recruitment of TIE2 receptor expressing monocytes (TEM) into tumor sites. Tumor-associated macrophages (TAM) sense hypoxia in avascular areas of tumors, and react by production of angiogenic factors such as VEGFA. VEGFA stimulates chemotaxis of endothelial cells (EC) and macrophages. In some tumors, TAM appeared to be a major source of MMP9. Elevated expression of MMP9 by TAM mediates extracellular matrix (ECM) degradation and the release of bioactive VEGFA. Other angiogenic factors released by TAM include basic fibroblast growth factor (bFGF), thymidine phosphorylase (TP), urokinase-type plasminogen activator (uPA), and adrenomedullin (ADM). The same factors used by macrophages for the induction of angiogenesis [like vascular endothelial growth factor A (VEGF-A) and MMP9] support lymphangiogenesis. TAM can express LYVE-1, one of the established markers of lymphatic endothelium. TAM support tumor lymphangiogenesis not only by secretion of pro-lymphangiogenic factors but also by trans-differentiation into lymphatic EC. New pro-angiogenic factor YKL-40 belongs to a family of mammalian chitinase-like proteins (CLP) that act as cytokines or growth factors. Human CLP family comprises YKL-40, YKL-39, and SI-CLP. Production of all three CLP in macrophages is antagonistically regulated by cytokines. It was recently established that YKL-40 induces angiogenesis in vitro and in animal tumor models. YKL-40-neutralizing monoclonal antibody blocks tumor angiogenesis and progression. The role of YKL-39 and SI-CLP in tumor angiogenesis and lymphangiogenesis remains to be investigated.",
"title": "Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis"
},
{
"docid": "13492264",
"text": "Glomerular basement membrane (GBM) and podocalyxin are essential for podocyte morphology. We provide evidence of functional interconnections between basement membrane components (collagen IV and laminin), the expression of podocalyxin and the morphology of human glomerular epithelial cells (podocytes). We demonstrated that GBM and laminin, but not collagen IV, up-regulated the expression of podocalyxin. Scanning electron microscopy revealed that laminin induced a modified morphology of podocytes with process formation, which was more extensive in the presence of GBM. Under high magnification, podocytes appeared ruffled. Using transmission electron microscopy we observed that raised areas occurred in the basal cell surface. Furthermore, the presence of anti-podocalyxin antibody increased the extent of adhesion and spreading of podocytes to both collagen IV and laminin, thus podocalyxin apparently inhibits cell-matrix interactions. We also performed adhesion and spreading assays on podocytes grown under increased glucose concentration (25 mM). Under these conditions, the expression of podocalyxin was almost totally suppressed. The cells adhered and spread to basement membrane components but there was no increase in the extent of adhesion and spreading in the presence of anti-podocalyxin antibody, or ruffling of the cell edges. Additionally, in podocytes expressing podocalyxin, the presence of anti-podocalyxin antibody partially reversed the inhibition of adhesion to collagen IV provoked by anti-beta1 integrin antibody, thus podocalyxin should compete with beta1-related cell adhesion. We suggest that the observed podocalyxin-mediated inhibition of binding to the matrix could be in part responsible for the specialized conformation of the basal surface of podocytes.",
"title": "Summary"
},
{
"docid": "39291138",
"text": "Cells develop by reading mixed signals. Nowhere is this clearer than in the highly dynamic processes that propel embryogenesis, when critical cell-fate decisions are made swiftly in response to well-orchestrated growthfactor combinations. Learning how diverse signaling pathways are integrated is therefore essential for understanding physiology. This requires the identification, in tangible molecular terms, of key nodes for pathway integration that operate in vivo. A report in this issue, on the integration of Smad and Ras/MAPK pathways during neural induction (Pera et al. 2003), provides timely insights into the relevance of one such node. Pera et al. (2003) report that FGF8 and IGF2—two growth factors that activate the Ras/MAPK pathway— favor neural differentiation and mesoderm dorsalization in Xenopus by inhibiting BMP (Bone Morphogenetic Protein) signaling. Mesoderm is formed from ectoderm in response to Nodal-related signals from the endoderm at the blastula stage and beyond (Fig. 1; for review, see De Robertis et al. 2000). BMP induces differentiation of ectoderm into epidermal cell fates at the expense of neural fates, and it ventralizes the mesoderm at the expense of dorsal fates (for review, see Weinstein and HemmatiBrivanlou 1999; De Robertis et al. 2000). Accordingly, neural differentiation and dorsal mesoderm formation are favored when BMP signaling is attenuated. Noggin, Chordin, Cerberus, and Follistatin, secreted by the Spemann organizer on the dorsal side at the gastrula stage, facilitate the formation of neural tissue by sequestering BMP (Weinstein and Hemmati-Brivanlou 1999; De Robertis et al. 2000). Experimentally blocking BMP signaling with a dominant-negative BMP receptor has a similar effect of promoting ectoderm neuralization (Weinstein and Hemmati-Brivanlou 1999). As it turns out, neural induction can also be achieved with FGF (fibroblast growth factor; Kengaku and Okamoto 1993; Lamb and Harland 1995; Hongo et al. 1999; Hardcastle et al. 2000; Streit et al. 2000; Wilson et al. 2000) and IGF (insulin-like growth factor; Pera et al. 2001; Richard-Parpaillon et al. 2002). Injection of transcripts encoding FGF8 or IFG2 into one animal-pole blastomere of a fourto eight-cell embryo results in an expanded neural plate at the injected side (Pera et al. 2003). Surprisingly, expression of a dominant-negative FGF receptor prevents neuralization of ectoderm explants by the BMP blocker Noggin (Launay et al. 1996). Likewise, the potent neuralizing effect of Chordin can be blocked by a dominant-negative FGF receptor or a morpholino oligonucleotide targeting the IGF receptor (Pera et al. 2003). Thus, the neuralizing effect of BMP inhibitors is somehow tied to FGF and IFG signaling. The question is, how? Because FGF8 and IFG2 activate MAPK, Pera et al. (2003) took heed from previous work showing that MAPK inhibits the BMP signal-transduction factor Smad1 (Kretzschmar et al. 1997a). Smad1 is directly phosphorylated by the BMP receptor, resulting in Smad1 activation (Kretzschmar et al. 1997b), and by MAPK in response to EGF, resulting in Smad1 inhibition (Kretzschmar et al. 1997a; Fig. 2). Smad transcription factors mediate gene responses to the entire TGF (Transforming Growth Factor) family, to which the BMPs belong (for review, see Massague 2000; Derynck and Zhang 2003). Smads 1, 5, and 8 act primarily downstream of BMP receptors and Smads 2 and 3 downstream of TGF , Activin and Nodal receptors. Smad proteins have two conserved globular domains—the MH1 and MH2 domains (Fig. 2). The MH1 domain is involved in DNA binding and the MH2 domain in binding to cytoplasmic retention factors, activated receptors, nucleoporins in the nuclear pore, and DNA-binding cofactors, coactivators, and corepressors in the nucleus (for review, see Shi and Massague 2003). Receptor-mediated phosphorylation occurs at the carboxy-terminal sequence SXS. This enables the nuclear accumulation of Smads and their association with the shared partner Smad4 to form transcriptional complexes that are interpreted by the cell as a function of the context (Massague 2000). Between the MH1 and MH2 domains lies a linker region of variable sequence and length. Attention was drawn to this region when it was found that EGF (epidermal growth factor), a classical activator of the Ras/ MAPK pathway, causes phosphorylation of the Smad1 linker at four MAPK sites (PXSP sequences; Kretzschmar et al. 1997a). This prevents the nuclear localization of Smad1 and inhibits BMP signaling. Mutation of these E-MAIL [email protected]; FAX (212) 717-3298. Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/ gad.1167003.",
"title": "Integration of Smad and MAPK pathways: a link and a linker revisited."
},
{
"docid": "26990001",
"text": "A murine whole organ metanephric culture system was designed to study the developmental aspects of mammalian nephrogenesis. Metanephros and ureteric bud were removed from CFI albino mouse embryos at 13.5 +/- 0.4 days gestation, and grown in Dulbecco's modified Eagle's Minimal Essential Medium supplemented with 20 per cent donor bovine serum at 37C in a mixed air--5 per cent CO2 environment. Under the experimental conditions employed, the metanephric explants showed organotypic tubular and glomerular epithelial development. A well-developed proximal tubule with microvilli, and characteristic intracellular organelles and intercellular junctions developed by 72 hours of culture. By 120 hours of culture, unique devascularized glomeruli consisting of parietal and visceral epithelial layers formed. The glomerular visceral epithelial cells formed foot processes and slit pore diaphragms, and produced islands of basement membrane. No endothelial or mesangial elements were present at any stage in organ culture development, indicating that advanced nephrogenesis can occur following initial epithelial-mesenchymal induction despite the absence of vascularization. The whole organ culture model system isolates renal structural development from the influences of perfusion and urine formation. The system thus affords the opportunity to study normal, as well as abnormal mammalian renal development under highly controlled experimental conditions.",
"title": "An organ culture model for the study of metanephric development."
},
{
"docid": "26688294",
"text": "Hypofunction of the N-methyl D-aspartate subtype of glutamate receptor (NMDAR) is hypothesized to be a mechanism underlying cognitive dysfunction in individuals with schizophrenia. For the schizophrenia-linked genes NRG1 and ERBB4, NMDAR hypofunction is thus considered a key detrimental consequence of the excessive NRG1-ErbB4 signaling found in people with schizophrenia. However, we show here that neuregulin 1β–ErbB4 (NRG1β-ErbB4) signaling does not cause general hypofunction of NMDARs. Rather, we find that, in the hippocampus and prefrontal cortex, NRG1β-ErbB4 signaling suppresses the enhancement of synaptic NMDAR currents by the nonreceptor tyrosine kinase Src. NRG1β-ErbB4 signaling prevented induction of long-term potentiation at hippocampal Schaffer collateral–CA1 synapses and suppressed Src-dependent enhancement of NMDAR responses during theta-burst stimulation. Moreover, NRG1β-ErbB4 signaling prevented theta burst–induced phosphorylation of GluN2B by inhibiting Src kinase activity. We propose that NRG1-ErbB4 signaling participates in cognitive dysfunction in schizophrenia by aberrantly suppressing Src-mediated enhancement of synaptic NMDAR function.",
"title": "Schizophrenia susceptibility pathway neuregulin 1–ErbB4 suppresses Src upregulation of NMDA receptors"
},
{
"docid": "13639330",
"text": "Nuclear receptors undergo ligand-dependent conformational changes that are required for corepressor-coactivator exchange, but whether there is an actual requirement for specific epigenetic landmarks to impose ligand dependency for gene activation remains unknown. Here we report an unexpected and general strategy that is based on the requirement for specific cohorts of inhibitory histone methyltransferases (HMTs) to impose gene-specific gatekeeper functions that prevent unliganded nuclear receptors and other classes of regulated transcription factors from binding to their target gene promoters and causing constitutive gene activation in the absence of stimulating signals. This strategy, based at least in part on an HMT-dependent inhibitory histone code, imposes a requirement for specific histone demethylases, including LSD1, to permit ligand- and signal-dependent activation of regulated gene expression. These events link an inhibitory methylation component of the histone code to a broadly used strategy that circumvents pathological constitutive gene induction by physiologically regulated transcription factors.",
"title": "Histone Methylation-Dependent Mechanisms Impose Ligand Dependency for Gene Activation by Nuclear Receptors"
},
{
"docid": "123859",
"text": "Podocytes are critical in the maintenance of a healthy glomerular filter; however, they have been difficult to study in the intact kidney because of technical limitations. Here we report the development of serial multiphoton microscopy (MPM) of the same glomeruli over several days to visualize the motility of podocytes and parietal epithelial cells (PECs) in vivo. In podocin-GFP mice, podocytes formed sporadic multicellular clusters after unilateral ureteral ligation and migrated into the parietal Bowman's capsule. The tracking of single cells in podocin-confetti mice featuring cell-specific expression of CFP, GFP, YFP or RFP revealed the simultaneous migration of multiple podocytes. In phosphoenolpyruvate carboxykinase (PEPCK)-GFP mice, serial MPM found PEC-to-podocyte migration and nanotubule connections. Our data support a highly dynamic rather than a static nature of the glomerular environment and cellular composition. Future application of this new approach should advance our understanding of the mechanisms of glomerular injury and regeneration.",
"title": "Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in novel mouse models with fluorescent lineage tags"
},
{
"docid": "6076903",
"text": "Embryos have the ability to self-regulate and regenerate normal structures after being sectioned in half. How is such a morphogenetic field established? We discovered that quadruple knockdown of ADMP and BMP2/4/7 in Xenopus embryos eliminates self-regulation, causing ubiquitous neural induction throughout the ectoderm. ADMP transcription in the Spemann organizer is activated at low BMP levels. When ventral BMP2/4/7 signals are depleted, Admp expression increases, allowing for self-regulation. ADMP has BMP-like activity and signals via the ALK-2 receptor. It is unable to signal dorsally because of inhibition by Chordin. The ventral BMP antagonists Sizzled and Bambi further refine the pattern. By transplanting dorsal or ventral wild-type grafts into ADMP/BMP2/4/7-depleted hosts, we demonstrate that both poles serve as signaling centers that can induce histotypic differentiation over considerable distances. We conclude that dorsal and ventral BMP signals and their extracellular antagonists expressed under opposing transcriptional regulation provide a molecular mechanism for embryonic self-regulation.",
"title": "Regulation of ADMP and BMP2/4/7 at Opposite Embryonic Poles Generates a Self-Regulating Morphogenetic Field"
},
{
"docid": "38727075",
"text": "The neural crest is a multipotent, migratory cell population arising from the border of the neural and surface ectoderm. In mouse, the initial migratory neural crest cells occur at the five-somite stage. Bone morphogenetic proteins (BMPs), particularly BMP2 and BMP4, have been implicated as regulators of neural crest cell induction, maintenance, migration, differentiation and survival. Mouse has three known BMP2/4 type I receptors, of which Bmpr1a is expressed in the neural tube sufficiently early to be involved in neural crest development from the outset; however, earlier roles in other domains obscure its requirement in the neural crest. We have ablated Bmpr1a specifically in the neural crest, beginning at the five-somite stage. We find that most aspects of neural crest development occur normally; suggesting that BMPRIA is unnecessary for many aspects of early neural crest biology. However, mutant embryos display a shortened cardiac outflow tract with defective septation, a process known to require neural crest cells and to be essential for perinatal viability. Surprisingly, these embryos die in mid-gestation from acute heart failure, with reduced proliferation of ventricular myocardium. The myocardial defect may involve reduced BMP signaling in a novel, minor population of neural crest derivatives in the epicardium, a known source of ventricular myocardial proliferation signals. These results demonstrate that BMP2/4 signaling in mammalian neural crest derivatives is essential for outflow tract development and may regulate a crucial proliferation signal for the ventricular myocardium.",
"title": "BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium."
},
{
"docid": "21439640",
"text": "Tumor-associated macrophages and high levels of cyclooxygenase-2 (COX-2) are associated with poor prognosis in breast cancer patients, but their potential interdependence has not been evaluated. The objective of this study was to determine whether macrophages regulate COX-2 expression in breast cancer cells. For this purpose, THP-1 cells were cocultured with HCC1954 breast cancer cells. Coculture led to increased COX-2 expression in the HCC1954 cells and elevated prostaglandin E(2) levels in conditioned media. Similar results were observed when THP-1 cells were incubated with HCC1937 breast cancer cells or when human monocyte-derived macrophages were cocultured with HCC1954 cells. Coculture triggered production of reactive oxygen species (ROS) in HCC1954 cells. COX-2 induction was blocked in cells preincubated with an reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor or by silencing p67PHOX, a subunit of NADPH oxidase. ROS production triggered activation of Src and mitogen-activated protein kinases (MAPKs). Blocking Src or MAPK activities or antagonizing the activator protein-1 (AP-1) transcription factor attenuated COX-2 induction in HCC1954 cells. Coculture caused rapid induction of interleukin-1β (IL-1β) in both breast cancer cells and macrophages. Increased IL-1β expression was blocked by an interleukin-1 receptor antagonist (IL-1Ra), suggesting autocrine and paracrine effects. Importantly, macrophage-induced COX-2 expression was blocked in HCC1954 cells preincubated with IL-1Ra or anti-IL-1β IgG. Together, these results indicate that macrophage-mediated induction of COX-2 in breast cancer cells is a consequence of IL-1β-mediated stimulation of ROS→Src→MAPK→AP-1 signaling. IL-1β-dependent induction of COX-2 in breast cancer cells provides a mechanism whereby macrophages contribute to tumor progression and potential therapeutic targets in breast cancer.",
"title": "Macrophages induce COX-2 expression in breast cancer cells: role of IL-1β autoamplification."
},
{
"docid": "25816994",
"text": "BACKGROUND Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. METHODS The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. FINDINGS 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril. INTERPRETATION In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.",
"title": "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial."
},
{
"docid": "24185667",
"text": "The stress-activated kinase JNK mediates key cellular responses to oxidative stress. Here we show that DAP kinase (DAPk), a cell death promoting Ser/Thr protein kinase, plays a main role in oxidative stress-induced JNK signaling. We identify protein kinase D (PKD) as a novel substrate of DAPk and demonstrate that DAPk physically interacts with PKD in response to oxidative stress. We further show that DAPk activates PKD in cells and that induction of JNK phosphorylation by ectopically expressed DAPk can be attenuated by knocking down PKD expression or by inhibiting its catalytic activity. Moreover, knockdown of DAPk expression caused a marked reduction in JNK activation under oxidative stress, indicating that DAPk is indispensable for the activation of JNK signaling under these conditions. Finally, DAPk is shown to be required for cell death under oxidative stress in a process that displays the characteristics of caspase-independent necrotic cell death. Taken together, these findings establish a major role for DAPk and its specific interaction with PKD in regulating the JNK signaling network under oxidative stress.",
"title": "DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress"
},
{
"docid": "7039855",
"text": "Myelin regeneration can occur spontaneously in demyelinating diseases such as multiple sclerosis (MS). However, the underlying mechanisms and causes of its frequent failure remain incompletely understood. Here we show, using an in-vivo remyelination model, that demyelinated axons are electrically active and generate de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which, early after lesion induction, sense neuronal activity by expressing AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptors. Blocking neuronal activity, axonal vesicular release or AMPA receptors in demyelinated lesions results in reduced remyelination. In the absence of neuronal activity there is a ∼6-fold increase in OPC number within the lesions and a reduced proportion of differentiated oligodendrocytes. These findings reveal that neuronal activity and release of glutamate instruct OPCs to differentiate into new myelinating oligodendrocytes that recover lost function. Co-localization of OPCs with the presynaptic protein VGluT2 in MS lesions implies that this mechanism may provide novel targets to therapeutically enhance remyelination.",
"title": "Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors"
},
{
"docid": "35008773",
"text": "In vertebrates, the development of the nervous system is triggered by signals from a powerful 'organizing' region of the early embryo during gastrulation. This phenomenon--neural induction--was originally discovered and given conceptual definition by experimental embryologists working with amphibian embryos. Work on the molecular circuitry underlying neural induction, also in the same model system, demonstrated that elimination of ongoing transforming growth factor-β (TGFβ) signaling in the ectoderm is the hallmark of anterior neural-fate acquisition. This observation is the basis of the 'default' model of neural induction. Endogenous neural inducers are secreted proteins that act to inhibit TGFβ ligands in the dorsal ectoderm. In the ventral ectoderm, where the signaling ligands escape the inhibitors, a non-neural fate is induced. Inhibition of the TGFβ pathway has now been demonstrated to be sufficient to directly induce neural fate in mammalian embryos as well as pluripotent mouse and human embryonic stem cells. Hence the molecular process that delineates neural from non-neural ectoderm is conserved across a broad range of organisms in the evolutionary tree. The availability of embryonic stem cells from mouse, primates, and humans will facilitate further understanding of the role of signaling pathways and their downstream mediators in neural induction in vertebrate embryos.",
"title": "Neural induction and early patterning in vertebrates."
},
{
"docid": "9614443",
"text": "The anti-inflammatory eicosanoid lipoxin A(4) (LXA(4)), aspirin-triggered 15-epi-LXA(4), and their stable analogs down-regulate IL-8 secretion and subsequent recruitment of neutrophils by intestinal epithelia. In an effort to elucidate the mechanism by which these lipid mediators modulate cellular proinflammatory programs, we surveyed global epithelial gene expression using cDNA microarrays. LXA(4) analog alone did not significantly affect expression of any of the >7000 genes analyzed. However, LXA(4) analog pretreatment attenuated induction of approximately 50% of the 125 genes up-regulated in response to the gastroenteritis-causing pathogen Salmonella typhimurium. A major subset of genes whose induction was reduced by LXA(4) analog pretreatment is regulated by NF-kappaB, suggesting that LXA(4) analog was influencing the activity of this transcription factor. Nanomolar concentrations of LXA(4) analog reduced NF-kappaB-mediated transcriptional activation in a LXA(4) receptor-dependent manner and inhibited induced degradation of IkappaBalpha. LXA(4) analog did not affect earlier stimulus-induced signaling events that lead to IkappaBalpha degradation, such as S. typhimurium-induced epithelial Ca(2+) mobilization or TNF-alpha-induced phosphorylation of IkappaBalpha. To establish the in vivo relevance of these findings, we examined whether LXA(4) analogs could affect intestinal inflammation in vivo using the mouse model of DSS-induced inflammatory colitis. Oral administration of LXA(4) analog (15-epi-16-para-fluoro-phenoxy-LXA(4), 10 microg/day) significantly reduced the weight loss, hematochezia, and mortality that characterize DSS colitis. Thus, LXA(4) analog-mediated down-regulation of proinflammatory gene expression via inhibition of the NF-kappaB pathway can be therapeutic for diseases characterized by mucosal inflammation.",
"title": "Lipoxin a4 analogs attenuate induction of intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis."
},
{
"docid": "17188921",
"text": "Cell migration is a process which is essential during embryonic development, throughout adult life and in some pathological conditions. Cadherins, and more specifically the neural cell adhesion molecule N-cadherin, play an important role in migration. In embryogenesis, N-cadherin is the key molecule during gastrulation and neural crest development. N-cadherin mediated contacts activate several pathways like Rho GTPases and function in tyrosine kinase signalling (for example via the fibroblast growth factor receptor). In cancer, cadherins control the balance between suppression and promotion of invasion. E-cadherin functions as an invasion suppressor and is downregulated in most carcinomas, while N-cadherin, as an invasion promoter, is frequently upregulated. Expression of N-cadherin in epithelial cells induces changes in morphology to a fibroblastic phenotype, rendering the cells more motile and invasive. However in some cancers, like osteosarcoma, N-cadherin may behave as a tumour suppressor. N-cadherin can have multiple functions: promoting adhesion or induction of migration dependent on the cellular context.",
"title": "N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling."
},
{
"docid": "9185195",
"text": "AIMS The vascular endothelial growth factor (VEGF) stimulates angiogenesis by induction of vessel permeability, proliferation, and migration of endothelial cells, an important process in ischaemic diseases. ADP-ribosylation factor (ARF) nucleotide-binding site opener (ARNO) (cytohesin-2) is a guanine exchange factor important for cellular signalling through ARF GTPases. However, a role for ARNO in VEGF-dependent endothelial processes has so far not been documented. Therefore, we investigated whether ARNO has a role in VEGF-dependent activation of endothelial cells and thus vessel permeability. METHODS AND RESULTS ARNO expression was observed in endothelial cells in vitro by RT-PCR, western blotting, and immunofluorescence as well as ex vivo by immunohistochemical staining of mouse aorta. Treatment with the cytohesin inhibitor SecinH3 or with an ARNO siRNA prevented VEGF-dependent Akt activation, assessed by detection of phosphorylated Akt, and proliferation of endothelial cells in vitro, measured by methylthiazoletetrazolium (MTT) reduction. In addition, ARNO suppression reduced VEGF-induced permeability in vessels of the mouse (C57BL/6) cremaster muscle in vivo, as measured by extravasation of fluorescein isothiocyanate (FITC)-dextran. Moreover, ARNO knock-down accelerated ligand-induced reduction in vascular endothelial growth factor receptor-2 (VEGFR-2) surface expression, internalization, and degradation, as assessed by flow cytometry and western blotting, respectively. CONCLUSION Our findings indicate an important and novel role for endothelial ARNO in VEGF-dependent initiation of angiogenesis by regulation of VEGFR-2 internalization in endothelial cells, resulting in the activation of the Akt pathway, vessel permeability, and ultimately endothelial proliferation. Thus, ARNO may be a new essential player in endothelial signalling and angiogenesis.",
"title": "ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression."
},
{
"docid": "34445160",
"text": "BACKGROUND & AIMS Hepatic stellate cell activation is a wound-healing response to liver injury. However, continued activation of stellate cells during chronic liver damage causes excessive matrix deposition and the formation of pathological scar tissue leading to fibrosis and ultimately cirrhosis. The importance of sustained stellate cell activation for this pathological process is well recognized, and several signalling pathways that can promote stellate cell activation have been identified, such as the TGFβ-, PDGF-, and LPS-dependent pathways. However, the mechanisms that trigger and drive the early steps in activation are not well understood. METHODS AND RESULTS We identified the Hippo pathway and its effector YAP as a key pathway that controls stellate cell activation. YAP is a transcriptional co-activator and we found that it drives the earliest changes in gene expression during stellate cell activation. Activation of stellate cells in vivo by CCl4 administration to mice or activation in vitro caused rapid activation of YAP as revealed by its nuclear translocation and by the induction of YAP target genes. YAP was also activated in stellate cells of human fibrotic livers as evidenced by its nuclear localization. Importantly, knockdown of YAP expression or pharmacological inhibition of YAP prevented hepatic stellate cell activation in vitro and pharmacological inhibition of YAP impeded fibrogenesis in mice. CONCLUSIONS YAP activation is a critical driver of hepatic stellate cell activation and inhibition of YAP presents a novel approach for the treatment of liver fibrosis.",
"title": "The Hippo pathway effector YAP controls mouse hepatic stellate cell activation."
},
{
"docid": "26071782",
"text": "Latent membrane protein 1 (LMP1), an oncoprotein encoded by Epstein–Barr virus (EBV), is an integral membrane protein, which acts like a constitutively active receptor. LMP1 is critical for some facet of EBV's induction and maintenance of proliferation of infected B cells. It, in part, mimics signaling by the CD40 receptor and has been implicated in regulating proliferation, survival, or both properties of EBV-infected cells. We established a conditional LMP1 allele in the context of the intact EBV genome to define the immediate-early cellular target genes regulated by LMP1 in order to assess its contributions to infected human B cells. The functional analysis of this conditional system indicated that LMP1 specifically induces mitogenic B-cell activation through c-myc and Jun/AP1 family members and confirms its direct role in upregulating expression of multiple genes with opposing activities involved in cell survival. LMP1's signals were found to be essential for the G1/S transition in human B cells; cells lacking LMP1's signals are cell cycle arrested and survive quiescently. LMP1's activities are therefore not required to maintain survival in nonproliferating cells. LMP1 does induce both pro- and antiapoptotic genes whose balance seems to permit survival during LMP1's induction and maintenance of proliferation.",
"title": "Latent membrane protein 1 of Epstein–Barr virus coordinately regulates proliferation with control of apoptosis"
},
{
"docid": "11557602",
"text": "LXR alpha is a nuclear receptor that has previously been shown to regulate the metabolic conversion of cholesterol to bile acids. Here we define a role for this transcription factor in the control of cellular cholesterol efflux. We demonstrate that retroviral expression of LXR alpha in NIH 3T3 fibroblasts or RAW264.7 macrophages and/or treatment of these cells with oxysterol ligands of LXR results in 7- to 30-fold induction of the mRNA encoding the putative cholesterol/phospholipid transporter ATP-binding cassette (ABC)A1. In contrast, induction of ABCA1 mRNA in response to oxysterols is attenuated in cells that constitutively express dominant-negative forms of LXR alpha or LXR beta that lack the AF2 transcriptional activation domain. We further demonstrate that expression of LXR alpha in NIH 3T3 fibroblasts and/or treatment of these cells with oxysterols is sufficient to stimulate cholesterol efflux to extracellular apolipoprotein AI. The ability of oxysterol ligands of LXR to stimulate efflux is dramatically reduced in Tangier fibroblasts, which carry a loss of function mutation in the ABCA1 gene. Taken together, these results indicate that cellular cholesterol efflux is controlled, at least in part, at the level of transcription by a nuclear receptor-signaling pathway. They suggest a model in which activation of LXRs by oxysterols in response to cellular sterol loading leads to induction of the ABCA1 transporter and the stimulation of lipid efflux to extracellular acceptors. These findings have important implications for our understanding of mammalian cholesterol homeostasis and suggest new opportunities for pharmacological regulation of cellular lipid metabolism.",
"title": "Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha."
},
{
"docid": "994800",
"text": "T cell receptor (TCR) ligation is required for the extrathymic differentiation of forkhead box p3(+) (Foxp3(+)) regulatory T cells. Several lines of evidence indicate that weak TCR stimulation favors induction of Foxp3 in the periphery; however, it remains to be determined how TCR ligand potency influences this process. We characterized the density and affinity of TCR ligand favorable for Foxp3 induction and found that a low dose of a strong agonist resulted in maximal induction of Foxp3 in vivo. Initial Foxp3 induction by weak agonist peptide could be enhanced by disruption of TCR-peptide major histocompatibility complex (pMHC) interactions or alteration of peptide dose. However, time course experiments revealed that Foxp3-positive cells induced by weak agonist stimulation are deleted, along with their Foxp3-negative counterparts, whereas Foxp3-positive cells induced by low doses of the strong agonist persist. Our results suggest that, together, pMHC ligand potency, density, and duration of TCR interactions define a cumulative quantity of TCR stimulation that determines initial peripheral Foxp3 induction. However, in the persistence of induced Foxp3(+) T cells, TCR ligand potency and density are noninterchangeable factors that influence the route to peripheral tolerance.",
"title": "TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo"
},
{
"docid": "23076291",
"text": "We recently identified a novel mechanism for modulation of the phosphorylation state and function of the N-methyl-d-aspartate (NMDA) receptor via the scaffolding protein RACK1. We found that RACK1 binds both the NR2B subunit of the NMDA receptor and the nonreceptor protein-tyrosine kinase, Fyn. RACK1 inhibits Fyn phosphorylation of NR2B and decreases NMDA receptor-mediated currents in CA1 hippocampal slices (Yaka, R., Thornton, C., Vagts, A. J., Phamluong, K., Bonci, A., and Ron, D. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 5710-5715). Here, we identified the signaling cascade by which RACK1 is released from the NMDA receptor complex and identified the consequences of the dissociation. We found that activation of the cAMP/protein kinase A pathway in hippocampal slices induced the release of RACK1 from NR2B and Fyn. This resulted in the induction of NR2B phosphorylation and the enhancement of NMDA receptor-mediated activity via Fyn. We identified the neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP(1-38)), as a ligand that induced phosphorylation of NR2B and enhanced NMDA receptor potentials. Finally, we found that activation of the cAMP/protein kinase A pathway induced the movement of RACK1 to the nuclear compartment in dissociated hippocampal neurons. Nuclear RACK1 in turn was found to regulate the expression of brain-derived neurotrophic factor induced by PACAP(1-38). Taken together our results suggest that activation of adenylate cyclase by PACAP(1-38) results in the release of RACK1 from the NMDA receptor and Fyn. This in turn leads to NMDA receptor phosphorylation, enhanced activity mediated by Fyn, and to the induction of brain-derived neurotrophic factor expression by RACK1.",
"title": "Pituitary adenylate cyclase-activating polypeptide (PACAP(1-38)) enhances N-methyl-D-aspartate receptor function and brain-derived neurotrophic factor expression via RACK1."
},
{
"docid": "5828251",
"text": "During Drosophila myogenesis, Notch signalling acts at multiple steps of the muscle differentiation process. In vertebrates, Notch activation has been shown to block MyoD activation and muscle differentiation in vitro, suggesting that this pathway may act to maintain the cells in an undifferentiated proliferative state. In this paper, we address the role of Notch signalling in vivo during chick myogenesis. We first demonstrate that the Notch1 receptor is expressed in postmitotic cells of the myotome and that the Notch ligands Delta1 and Serrate2 are detected in subsets of differentiating myogenic cells and are thus in position to signal to Notch1 during myogenic differentiation. We also reinvestigate the expression of MyoD and Myf5 during avian myogenesis, and observe that Myf5 is expressed earlier than MyoD, consistent with previous results in the mouse. We then show that forced expression of the Notch ligand, Delta1, during early myogenesis, using a retroviral system, has no effect on the expression of the early myogenic markers Pax3 and Myf5, but causes strong down-regulation of MyoD in infected somites. Although Delta1 overexpression results in the complete lack of differentiated muscles, detailed examination of the infected embryos shows that initial formation of a myotome is not prevented, indicating that exit from the cell cycle has not been blocked. These results suggest that Notch signalling acts in postmitotic myogenic cells to control a critical step of muscle differentiation.",
"title": "Notch signalling acts in postmitotic avian myogenic cells to control MyoD activation."
},
{
"docid": "2266471",
"text": "Lymphangioleiomyomatosis (LAM), a multisystem disease of women, is manifest by the proliferation of smooth muscle-like cells in the lung resulting in cystic lung destruction. Women with LAM can also develop renal angiomyolipomas. LAM is caused by mutations in the tuberous sclerosis complex genes (TSC1 or TSC2), resulting in hyperactive mammalian Target of Rapamycin (mTOR) signaling. The mTOR inhibitor, Rapamycin, stabilizes lung function in LAM and decreases the volume of renal angiomyolipomas, but lung function declines and angiomyolipomas regrow when treatment is discontinued, suggesting that factors induced by mTORC1 inhibition may promote the survival of TSC2-deficient cells. Whether microRNA (miRNA, miR) signaling is involved in the response of LAM to mTORC1 inhibition is unknown. We identified Rapamycin-dependent miRNA in LAM patient angiomyolipoma-derived cells using two separate screens. First, we assayed 132 miRNA of known significance to tumor biology. Using a cut-off of >1.5-fold change, 48 microRNA were Rapamycin-induced, while 4 miRs were downregulated. In a second screen encompassing 946 miRNA, 18 miRs were upregulated by Rapamycin, while eight were downregulated. Dysregulation of miRs 29b, 21, 24, 221, 106a and 199a were common to both platforms and were classified as candidate \"RapamiRs. \" Validation by qRT-PCR confirmed that these microRNA were increased. miR-21, a pro-survival miR, was the most significantly increased by mTOR-inhibition (p<0.01). The regulation of miR-21 by Rapamycin is cell type independent. mTOR inhibition promotes the processing of the miR-21 transcript (pri-miR-21) to a premature form (pre-miR-21). In conclusion, our findings demonstrate that Rapamycin upregulates multiple miRs, including pro-survival miRs, in TSC2-deficient patient-derived cells. The induction of miRs may contribute to the response of LAM and TSC patients to Rapamycin therapy.",
"title": "MicroRNA-21 is Induced by Rapamycin in a Model of Tuberous Sclerosis (TSC) and Lymphangioleiomyomatosis (LAM)"
},
{
"docid": "15669393",
"text": "Transient activation of estrogen receptors (ER) in the developing brain during a limited perinatal \"window of time\" is recognized as a key mechanism of defeminization of neural control of reproductive function and sexual behavior. Two major ER isoforms, alpha and beta, are present in neural circuits that govern ovarian cycle and sexual behavior. Using highly selective ER agonists, this study provides the first evidence for distinct contribution of individual ER isoforms to the process of estrogen dependent defeminization. Neonatal activation of the ERalpha in female rats resulted in abrogation of cyclic ovarian activity and female sexual behavior in adulthood. These effects are associated with male-like alterations in the morphology of the anteroventral periventricular (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN-POA), as well as refractoriness to estrogen-mediated induction of sexual receptivity. Exposure to an ERbeta-selective agonist induced persistent estrus and had a strong defeminizing effect on the hypothalamic gonadotropin \"surge generator\" AVPV. However, neonatal ERbeta activation failed to alter female sexual behavior, responsiveness to estrogens and morphometric features of the behaviorally relevant SDN-POA. Thus, although co-present in several brain regions involved in the control of female reproductive function, ER isoforms convey different, and probably not synergistic, chemical signals in the course of neonatal sex-specific brain organization.",
"title": "brain organization"
}
] |
73
|
Activator-inhibitor pairs are provided ventrally by Xrl-sizzled.
|
[
{
"docid": "6076903",
"text": "Embryos have the ability to self-regulate and regenerate normal structures after being sectioned in half. How is such a morphogenetic field established? We discovered that quadruple knockdown of ADMP and BMP2/4/7 in Xenopus embryos eliminates self-regulation, causing ubiquitous neural induction throughout the ectoderm. ADMP transcription in the Spemann organizer is activated at low BMP levels. When ventral BMP2/4/7 signals are depleted, Admp expression increases, allowing for self-regulation. ADMP has BMP-like activity and signals via the ALK-2 receptor. It is unable to signal dorsally because of inhibition by Chordin. The ventral BMP antagonists Sizzled and Bambi further refine the pattern. By transplanting dorsal or ventral wild-type grafts into ADMP/BMP2/4/7-depleted hosts, we demonstrate that both poles serve as signaling centers that can induce histotypic differentiation over considerable distances. We conclude that dorsal and ventral BMP signals and their extracellular antagonists expressed under opposing transcriptional regulation provide a molecular mechanism for embryonic self-regulation.",
"title": "Regulation of ADMP and BMP2/4/7 at Opposite Embryonic Poles Generates a Self-Regulating Morphogenetic Field"
}
] |
[
{
"docid": "1031534",
"text": "Spemann's organizer plays a key role in dorsal-ventral (DV) patterning in the amphibian embryo by secreting diffusible proteins such as Chordin, an antagonist to ventralizing bone morphogenetic proteins (BMPs). The DV patterning is so robust that an amphibian embryo with its ventral half surgically removed can develop into a smaller but proportionally patterned larva. Here, we show that this robust patterning depends on facilitated Chordin degradation and requires the expression of the Chordin-proteinase inhibitor Sizzled on the opposite side. Sizzled, which is stable and diffuses widely along the DV axis, stabilizes Chordin and expands its distribution in the ventral direction. This expanded Chordin distribution, in turn, limits BMP-dependent Sizzled production, forming an axis-wide feedback loop for shaping Chordin's activity. Using bisection assays, we demonstrate that Chordin degradation is dynamically controlled by embryo-size-coupled Sizzled accumulation. We propose a scaling model that enables the DV pattern to adjust proportionally to embryonic axis size.",
"title": "Scaling of Dorsal-Ventral Patterning by Embryo Size-Dependent Degradation of Spemann’s Organizer Signals"
},
{
"docid": "38380061",
"text": "As organisms develop, their tissues can become separated into distinct cell populations through the establishment of compartment boundaries. Compartment boundaries have been discovered in a wide variety of tissues, but in many cases the molecular mechanisms that separate cells remain poorly understood. In the Drosophila wing, a stripe of Notch activation maintains the dorsal-ventral compartment boundary, through a process that depends on the actin cytoskeleton. Here, we show that the dorsal-ventral boundary exhibits a distinct accumulation of Myosin II, and that this accumulation is regulated downstream of Notch signaling. Conversely, the dorsal-ventral boundary is depleted for the Par-3 homologue Bazooka. We further show that mutations in the Myosin heavy chain subunit encoded by zipper can impair dorsal-ventral compartmentalization without affecting anterior-posterior compartmentalization. These observations identify a distinct accumulation and requirement for Myosin activity in dorsal-ventral compartmentalization, and suggest a novel mechanism in which contractile tension along an F-actin cable at the compartment boundary contributes to compartmentalization.",
"title": "Localization and requirement for Myosin II at the dorsal-ventral compartment boundary of the Drosophila wing."
},
{
"docid": "17119869",
"text": "The pancreas emerges independently from dorsal and ventral domains of embryonic gut endoderm. Gene inactivation experiments in mice have identified factors required for dorsal pancreas development, but factors that initiate the ventral pancreas have remained elusive. In this study, we investigated the hypothesis that the emergence of the ventral pancreas is related to the emergence of the liver. We find that the liver and ventral pancreas are specified at the same time and in the same general domain of cells. Using embryo tissue explantation experiments, we find that the default fate of the ventral foregut endoderm is to activate the pancreas gene program. FGF signalling from the cardiac mesoderm diverts this endoderm to express genes for liver instead of those for pancreas. No evidence was found to indicate that the cell type choice for pancreas or liver involves a selection for growth or viability. Cardiac mesoderm or FGF induces the local expression of sonic hedgehog, which in turn is inhibitory to pancreas but not to liver. The bipotential precursor cell population for pancreas and liver in embryonic development and its fate selection by FGF has features that appear to be recapitulated in the adult pancreas and are reflected in the evolution of these organs.",
"title": "A bipotential precursor population for pancreas and liver within the embryonic endoderm."
},
{
"docid": "14492964",
"text": "Signals released by the Spemann organizer of the amphibian gastrula can directly induce neural tissue from ectoderm and can dorsalize ventral mesoderm to form muscle. The secreted polypeptide noggin mimics these activities and is expressed at the appropriate time and place to participate in the organizer signal. Neural induction and mesoderm dorsalization are antagonized by bone morphogenetic proteins (BMPs), which induce epidermis and ventral mesoderm instead. Here we report that noggin protein binds BMP4 with high affinity and can abolish BMP4 activity by blocking binding to cognate cell-surface receptors. These data suggest that noggin secreted by the organizer patterns the embryo by interrupting BMP signaling.",
"title": "The Spemann Organizer Signal noggin Binds and Inactivates Bone Morphogenetic Protein 4"
},
{
"docid": "14333540",
"text": "Neural crest (NC) cells arise in the dorsal neural tube (NT) and migrate into the embryo to develop into many different cell types. A major unresolved question is when and how the fate of NC cells is decided. There is widespread evidence for multipotential NC cells, whose fates are decided during or after migration. There is also some evidence that the NC is already divided into subpopulations of discrete precursors within the NT. We have investigated this question in the mouse embryo. We find that a subpopulation of cells on the most dorsomedial aspect of the NT express the receptor tyrosine kinase Kit (previously known as c-kit), emigrate exclusively into the developing dermis, and then express definitive markers of the melanocyte lineage. These are thus melanocyte progenitor cells. They are generated predominantly at the midbrain-hindbrain junction and cervical trunk, with significant numbers also in lower trunk. Other cells within the dorsal NT are Kit-, migrate ventrally, and, from embryonic day 9.5, express the neurotrophin receptor p75. These cells most likely only give rise to ventral NC derivatives such as neurons and glia. The p75+ cells are located ventrolateral to the Kit+ cells in areas of the NT where these two cell types are found. These data provide direct in vivo evidence for NC lineage segregation within the mouse neural tube.",
"title": "Neural crest cell lineage segregation in the mouse neural tube."
},
{
"docid": "6969753",
"text": "Metastatic tumor cells that actively migrate and invade surrounding tissues rely on invadopodia to degrade extracellular matrix (ECM) barriers. Invadopodia are membrane protrusions that localize enzymes required for ECM degradation. Little is known about the formation, function, and regulation of invadopodia. Here, we show that invadopodia have two distinct aspects: (a) structural for organizing the cellular actin cytoskeleton to form membrane protrusions and (b) functional for using proteolytic enzyme(s) for ECM degradation. Small interfering RNA (siRNA) inhibition established that organization of invadopodia structure requires cortactin, whereas protease inhibitor studies identified membrane type 1 matrix metalloproteinase (MT1-MMP) as the key invadopodial enzyme responsible for gelatin matrix degradation in the breast carcinoma cell line MDA-MB-231. The inhibition of invadopodial structure assembly by cortactin depletion resulted in a block of matrix degradation due to failure of invadopodia formation. Either protease inhibition or MT1-MMP siRNA depletion moderately decreased the formation of invadopodial structures that were identified as actin-cortactin accumulations at the ventral cell membrane adherent to matrix. The invadopodia that were able to form upon MT1-MMP inhibition or depletion retained actin-cortactin accumulations but were unable to degrade matrix. Examination of cells at different time points as well as live-cell imaging revealed four distinct invadopodial stages: membrane cortactin aggregation at membranes adherent to matrix, MT1-MMP accumulation at the region of cortactin accumulation, matrix degradation at the invadopodia region, and subsequent cortactin dissociation from the area of continued MT1-MMP accumulation associated with foci of degraded matrix. Based on these results, we propose a stepwise model of invadopodia formation and function.",
"title": "Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function."
},
{
"docid": "2682997",
"text": "Despite the importance of CNS blood vessels, the molecular mechanisms that regulate CNS angiogenesis and blood-brain barrier (BBB) formation are largely unknown. Here we analyze the role of Wnt/beta-catenin signaling in regulating the formation of CNS blood vessels. First, through the analysis of TOP-Gal Wnt reporter mice, we identify that canonical Wnt/beta-catenin signaling is specifically activated in CNS, but not non-CNS, blood vessels during development. This activation correlates with the expression of different Wnt ligands by neural progenitor cells in distinct locations throughout the CNS, including Wnt7a and Wnt7b in ventral regions and Wnt1, Wnt3, Wnt3a, and Wnt4 in dorsal regions. Blockade of Wnt/beta-catenin signaling in vivo specifically disrupts CNS, but not non-CNS, angiogenesis. These defects include reduction in vessel number, loss of capillary beds, and the formation of hemorrhagic vascular malformations that remain adherent to the meninges. Furthermore, we demonstrate that Wnt/beta-catenin signaling regulates the expression of the BBB-specific glucose transporter glut-1. Taken together these experiments reveal an essential role for Wnt/beta-catenin signaling in driving CNS-specific angiogenesis and provide molecular evidence that angiogenesis and BBB formation are in part linked.",
"title": "Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis."
},
{
"docid": "24249915",
"text": "To gain insights into the possible role of oestrogen receptor (ER) beta in breast carcinogenesis, immunohistochemical analysis of ER beta was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real-time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER beta gene in the ER beta negative breast cancer cell lines SkBr3 and MDA-MB-435. A gradual reduction in, but not a complete loss of, ER beta expression was observed during the transition from normal and pre-invasive lesions to invasive cancers, where ER beta was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER beta-positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER beta was present in the primary tumour, it persisted in the metastasis. Treatment of ER beta-negative cell lines with DNA methyl transferase inhibitors restored ER beta expression, providing experimental evidence that silencing of ER beta in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER beta expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation.",
"title": "Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model."
},
{
"docid": "35008773",
"text": "In vertebrates, the development of the nervous system is triggered by signals from a powerful 'organizing' region of the early embryo during gastrulation. This phenomenon--neural induction--was originally discovered and given conceptual definition by experimental embryologists working with amphibian embryos. Work on the molecular circuitry underlying neural induction, also in the same model system, demonstrated that elimination of ongoing transforming growth factor-β (TGFβ) signaling in the ectoderm is the hallmark of anterior neural-fate acquisition. This observation is the basis of the 'default' model of neural induction. Endogenous neural inducers are secreted proteins that act to inhibit TGFβ ligands in the dorsal ectoderm. In the ventral ectoderm, where the signaling ligands escape the inhibitors, a non-neural fate is induced. Inhibition of the TGFβ pathway has now been demonstrated to be sufficient to directly induce neural fate in mammalian embryos as well as pluripotent mouse and human embryonic stem cells. Hence the molecular process that delineates neural from non-neural ectoderm is conserved across a broad range of organisms in the evolutionary tree. The availability of embryonic stem cells from mouse, primates, and humans will facilitate further understanding of the role of signaling pathways and their downstream mediators in neural induction in vertebrate embryos.",
"title": "Neural induction and early patterning in vertebrates."
},
{
"docid": "39291138",
"text": "Cells develop by reading mixed signals. Nowhere is this clearer than in the highly dynamic processes that propel embryogenesis, when critical cell-fate decisions are made swiftly in response to well-orchestrated growthfactor combinations. Learning how diverse signaling pathways are integrated is therefore essential for understanding physiology. This requires the identification, in tangible molecular terms, of key nodes for pathway integration that operate in vivo. A report in this issue, on the integration of Smad and Ras/MAPK pathways during neural induction (Pera et al. 2003), provides timely insights into the relevance of one such node. Pera et al. (2003) report that FGF8 and IGF2—two growth factors that activate the Ras/MAPK pathway— favor neural differentiation and mesoderm dorsalization in Xenopus by inhibiting BMP (Bone Morphogenetic Protein) signaling. Mesoderm is formed from ectoderm in response to Nodal-related signals from the endoderm at the blastula stage and beyond (Fig. 1; for review, see De Robertis et al. 2000). BMP induces differentiation of ectoderm into epidermal cell fates at the expense of neural fates, and it ventralizes the mesoderm at the expense of dorsal fates (for review, see Weinstein and HemmatiBrivanlou 1999; De Robertis et al. 2000). Accordingly, neural differentiation and dorsal mesoderm formation are favored when BMP signaling is attenuated. Noggin, Chordin, Cerberus, and Follistatin, secreted by the Spemann organizer on the dorsal side at the gastrula stage, facilitate the formation of neural tissue by sequestering BMP (Weinstein and Hemmati-Brivanlou 1999; De Robertis et al. 2000). Experimentally blocking BMP signaling with a dominant-negative BMP receptor has a similar effect of promoting ectoderm neuralization (Weinstein and Hemmati-Brivanlou 1999). As it turns out, neural induction can also be achieved with FGF (fibroblast growth factor; Kengaku and Okamoto 1993; Lamb and Harland 1995; Hongo et al. 1999; Hardcastle et al. 2000; Streit et al. 2000; Wilson et al. 2000) and IGF (insulin-like growth factor; Pera et al. 2001; Richard-Parpaillon et al. 2002). Injection of transcripts encoding FGF8 or IFG2 into one animal-pole blastomere of a fourto eight-cell embryo results in an expanded neural plate at the injected side (Pera et al. 2003). Surprisingly, expression of a dominant-negative FGF receptor prevents neuralization of ectoderm explants by the BMP blocker Noggin (Launay et al. 1996). Likewise, the potent neuralizing effect of Chordin can be blocked by a dominant-negative FGF receptor or a morpholino oligonucleotide targeting the IGF receptor (Pera et al. 2003). Thus, the neuralizing effect of BMP inhibitors is somehow tied to FGF and IFG signaling. The question is, how? Because FGF8 and IFG2 activate MAPK, Pera et al. (2003) took heed from previous work showing that MAPK inhibits the BMP signal-transduction factor Smad1 (Kretzschmar et al. 1997a). Smad1 is directly phosphorylated by the BMP receptor, resulting in Smad1 activation (Kretzschmar et al. 1997b), and by MAPK in response to EGF, resulting in Smad1 inhibition (Kretzschmar et al. 1997a; Fig. 2). Smad transcription factors mediate gene responses to the entire TGF (Transforming Growth Factor) family, to which the BMPs belong (for review, see Massague 2000; Derynck and Zhang 2003). Smads 1, 5, and 8 act primarily downstream of BMP receptors and Smads 2 and 3 downstream of TGF , Activin and Nodal receptors. Smad proteins have two conserved globular domains—the MH1 and MH2 domains (Fig. 2). The MH1 domain is involved in DNA binding and the MH2 domain in binding to cytoplasmic retention factors, activated receptors, nucleoporins in the nuclear pore, and DNA-binding cofactors, coactivators, and corepressors in the nucleus (for review, see Shi and Massague 2003). Receptor-mediated phosphorylation occurs at the carboxy-terminal sequence SXS. This enables the nuclear accumulation of Smads and their association with the shared partner Smad4 to form transcriptional complexes that are interpreted by the cell as a function of the context (Massague 2000). Between the MH1 and MH2 domains lies a linker region of variable sequence and length. Attention was drawn to this region when it was found that EGF (epidermal growth factor), a classical activator of the Ras/ MAPK pathway, causes phosphorylation of the Smad1 linker at four MAPK sites (PXSP sequences; Kretzschmar et al. 1997a). This prevents the nuclear localization of Smad1 and inhibits BMP signaling. Mutation of these E-MAIL [email protected]; FAX (212) 717-3298. Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/ gad.1167003.",
"title": "Integration of Smad and MAPK pathways: a link and a linker revisited."
},
{
"docid": "15953181",
"text": "Receiver operating characteristic (ROC) curves are used to describe and compare the performance of diagnostic technology and diagnostic algorithms. This paper refines the statistical comparison of the areas under two ROC curves derived from the same set of patients by taking into account the correlation between the areas that is induced by the paired nature of the data. The correspondence between the area under an ROC curve and the Wilcoxon statistic is used and underlying Gaussian distributions (binormal) are assumed to provide a table that converts the observed correlations in paired ratings of images into a correlation between the two ROC areas. This between-area correlation can be used to reduce the standard error (uncertainty) about the observed difference in areas. This correction for pairing, analogous to that used in the paired t-test, can produce a considerable increase in the statistical sensitivity (power) of the comparison. For studies involving multiple readers, this method provides a measure of a component of the sampling variation that is otherwise difficult to obtain.",
"title": "A method of comparing the areas under receiver operating characteristic curves derived from the same cases."
},
{
"docid": "3095620",
"text": "The homologues of the two distinct architectonic areas 44 and 45 that constitute the anterior language zone (Broca's region) in the human ventrolateral frontal lobe were recently established in the macaque monkey. Although we know that the inferior parietal lobule and the lateral temporal cortical region project to the ventrolateral frontal cortex, we do not know which of the several cortical areas found in those regions project to the homologues of Broca's region in the macaque monkey and by means of which white matter pathways. We have used the autoradiographic method, which permits the establishment of the cortical area from which axons originate (i.e., the site of injection), the precise course of the axons in the white matter, and their termination within particular cortical areas, to examine the parietal and temporal connections to area 44 and the two subdivisions of area 45 (i.e., areas 45A and 45B). The results demonstrated a ventral temporo-frontal stream of fibers that originate from various auditory, multisensory, and visual association cortical areas in the intermediate superolateral temporal region. These axons course via the extreme capsule and target most strongly area 45 with a more modest termination in area 44. By contrast, a dorsal stream of axons that originate from various cortical areas in the inferior parietal lobule and the adjacent caudal superior temporal sulcus was found to target both areas 44 and 45. These axons course in the superior longitudinal fasciculus, with some axons originating from the ventral inferior parietal lobule and the adjacent superior temporal sulcus arching and forming a simple arcuate fasciculus. The cortex of the most rostral part of the inferior parietal lobule is preferentially linked with the ventral premotor cortex (ventral area 6) that controls the orofacial musculature. The cortex of the intermediate part of the inferior parietal lobule is linked with both areas 44 and 45. These findings demonstrate the posterior parietal and temporal connections of the ventrolateral frontal areas, which, in the left hemisphere of the human brain, were adapted for various aspects of language production. These precursor circuits that are found in the nonlinguistic, nonhuman, primate brain also exist in the human brain. The possible reasons why these areas were adapted for language use in the human brain are discussed. The results throw new light on the prelinguistic precursor circuitry of Broca's region and help understand functional interactions between Broca's ventrolateral frontal region and posterior parietal and temporal association areas.",
"title": "Distinct Parietal and Temporal Pathways to the Homologues of Broca's Area in the Monkey"
},
{
"docid": "25787749",
"text": "The evolutionarily conserved G-quadruplexes (G4s) are faithfully inherited and serve a variety of cellular functions such as telomere maintenance, gene regulation, DNA replication initiation, and epigenetic regulation. Different from the Watson-Crick base-pairing found in duplex DNA, G4s are formed via Hoogsteen base pairing and are very stable and compact DNA structures. Failure of untangling them in the cell impedes DNA-based transactions and leads to genome instability. Cells have evolved highly specific helicases to resolve G4 structures. We used a recombinant nuclear form of Saccharomyces cerevisiae Pif1 to characterize Pif1-mediated DNA unwinding with a substrate mimicking an ongoing lagging strand synthesis stalled by G4s, which resembles a replication origin and a G4-structured flap in Okazaki fragment maturation. We find that the presence of G4 may greatly stimulate the Pif1 helicase to unwind duplex DNA. Further studies reveal that this stimulation results from G4-enhanced Pif1 dimerization, which is required for duplex DNA unwinding. This finding provides new insights into the properties and functions of G4s. We discuss the observed activation phenomenon in relation to the possible regulatory role of G4s in the rapid rescue of the stalled lagging strand synthesis by helping the replicator recognize and activate the replication origin as well as by quickly removing the G4-structured flap during Okazaki fragment maturation.",
"title": "G-quadruplexes significantly stimulate Pif1 helicase-catalyzed duplex DNA unwinding."
},
{
"docid": "41774099",
"text": "We propose a Medicare Demonstration Project to develop a standard acquisition charge for kidney paired donation. A new payment strategy is required because Medicare and commercial insurance companies may not directly pay living donor costs intended to lead to transplantation of a beneficiary of a different insurance provider. Until the 1970s, when organ procurement organizations were empowered to serve as financial intermediaries to pay the upfront recovery expenses for deceased donor kidneys before knowing the identity of the recipient, there existed similar limitations in the recovery and placement of deceased donor organs. Analogous to the recovery of deceased donor kidneys, kidney paired donation requires the evaluation of living donors before identifying their recipient. Tissue typing, crossmatching and transportation of living donors or their kidneys represent additional financial barriers. Finally, the administrative expenses of the organizations that identify and coordinate kidney paired donation transplantation require reimbursement akin to that necessary for organ procurement organizations. To expand access to kidney paired donation for more patients, we propose a model to reimburse paired donation expenses analogous to the proven strategy used for over 30 years to pay for deceased donor solid organ transplantation in America.",
"title": "Call to Develop a Standard Acquisition Charge Model for Kidney Paired Donation"
},
{
"docid": "11420613",
"text": "The 137 ribosomal protein genes (RPGs) of Saccharomyces provide a model for gene coregulation. We examined the positional and functional organization of their regulators (Rap1 [repressor activator protein 1], Fhl1, Ifh1, Sfp1, and Hmo1), the transcription machinery (TFIIB, TFIID, and RNA polymerase II), and chromatin at near-base-pair resolution using ChIP-exo, as RPGs are coordinately reprogrammed. Where Hmo1 is enriched, Fhl1, Ifh1, Sfp1, and Hmo1 cross-linked broadly to promoter DNA in an RPG-specific manner and demarcated by general minor groove widening. Importantly, Hmo1 extended 20-50 base pairs (bp) downstream from Fhl1. Upon RPG repression, Fhl1 remained in place. Hmo1 dissociated, which was coupled to an upstream shift of the +1 nucleosome, as reflected by the Hmo1 extension and core promoter region. Fhl1 and Hmo1 may create two regulatable and positionally distinct barriers, against which chromatin remodelers position the +1 nucleosome into either an activating or a repressive state. Consistent with in vitro studies, we found that specific TFIID subunits, in addition to cross-linking at the core promoter, made precise cross-links at Rap1 sites, which we interpret to reflect native Rap1-TFIID interactions. Our findings suggest how sequence-specific DNA binding regulates nucleosome positioning and transcription complex assembly >300 bp away and how coregulation coevolved with coding sequences.",
"title": "Molecular mechanisms of ribosomal protein gene coregulation."
},
{
"docid": "18473550",
"text": "Bisphosphonates are widely used agents for the treatment of malignant bone disease. They inhibit osteoclast-mediated bone resorption and can have direct effects on cancer cells. In this study, we investigated whether the anticancer activity of the third-generation bisphosphonate zoledronic acid (ZOL) could be enhanced by combination with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). We found that ZOL and SAHA cooperated to induce cell death in the prostate cancer cell lines LNCaP and PC-3. The effect was synergistic, as evidenced by combination index isobologram analysis. ZOL and SAHA synergized to induce dissipation of the mitochondrial transmembrane potential, to activate caspase-3, and to trigger DNA fragmentation, showing that the combination of ZOL and SAHA resulted in the initiation of apoptosis. Because ZOL acts by inhibiting the mevalonate pathway, thereby preventing protein prenylation, we explored whether the mevalonate pathway was also the target of the cooperative action of ZOL and SAHA. We found that geranylgeraniol, but not farnesol, significantly reduced ZOL/SAHA-induced cell death, indicating that the synergistic action of the agents was due to the inhibition of geranylgeranylation. Consistently, a direct inhibitor of geranylgeranylation, GGTI-298, synergized with SAHA to induce cell death, whereas an inhibitor of farnesylation, FTI-277, had no effect. In addition, SAHA synergized with mevastatin, an inhibitor of the proximal enzyme in the mevalonate pathway. These in vitro findings provide a rationale for an in vivo exploration into the potential of combining SAHA and ZOL, or other inhibitors of the mevalonate pathway, as an effective strategy for anticancer therapy.",
"title": "Synergistic activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid and the bisphosphonate zoledronic acid against prostate cancer cells in vitro."
},
{
"docid": "22711954",
"text": "OBJECTIVE Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. DESIGN Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. MAIN OUTCOME MEASURE Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. RESULTS In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. CONCLUSIONS A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.",
"title": "Bias in meta-analysis detected by a simple, graphical test."
},
{
"docid": "4067274",
"text": "Differential splice site pairing establishes alternative splicing patterns resulting in the generation of multiple mRNA isoforms. This process is carried out by the spliceosome, which is activated by a series of sequential structural rearrangements of its five core snRNPs. To determine when splice sites become functionally paired, we carried out a series of kinetic trap experiments using pre-mRNAs that undergo alternative 5' splice site selection or alternative exon inclusion. We show that commitment to splice site pairing in both cases occurs in the A complex, which is characterized by the ATP-dependent association of the U2 snRNP with the branch point. Interestingly, the timing of splice site pairing is independent of the intron or exon definition modes of splice site recognition. Using the ATP analog ATPgammaS, we showed that ATP hydrolysis is required for splice site pairing independent from U2 snRNP binding to the pre-mRNA. These results identify the A complex as the spliceosomal assembly step dedicated to splice site pairing and suggest that ATP hydrolysis locks splice sites into a splicing pattern after stable U2 snRNP association to the branch point.",
"title": "Spliceosome assembly pathways for different types of alternative splicing converge during commitment to splice site pairing in the A complex."
},
{
"docid": "39763465",
"text": "We have demonstrated previously that a combination of signals from the neural tube and the floor plate/notochord complex synergistically induce the expression of myogenic bHLH genes and myogenic differentiation markers in unspecified somites. In this study we demonstrate that Sonic hedgehog (Shh), which is expressed in the floor plate/notochord, and a subset of Wnt family members (Wnt-1, Wnt-3, and Wnt-4), which are expressed in dorsal regions of the neural tube, mimic the muscle inducing activity of these tissues. In combination, Shh and either Wnt-1 or Wnt-3 are sufficient to induce myogenesis in somitic tissue in vitro. Therefore, we propose that myotome formation in vivo may be directed by the combinatorial activity of Shh secreted by ventral midline tissues (floor plate and notochord) and Wnt ligands secreted by the dorsal neural tube.",
"title": "Combinatorial signaling by Sonic hedgehog and Wnt family members induces myogenic bHLH gene expression in the somite."
},
{
"docid": "49432306",
"text": "The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. MicroRNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules, mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer: (1) imprecise therapeutic indication, (2) difficult response evaluation, (3) numerous immunologic adverse-events, and (4) the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.",
"title": "Key questions about the checkpoint blockade-are microRNAs an answer?"
},
{
"docid": "13963620",
"text": "Dorsal closure is a paradigm epithelial fusion episode that occurs late in Drosophila embryogenesis and leads to sealing of a midline hole by bonding of two opposing epithelial sheets. The leading edge epithelial cells express filopodia and fusion is dependent on interdigitation of these filopodia to prime formation of adhesions. Since the opposing epithelia are molecularly patterned there must exist some mechanism for accurately aligning the two sheets across this fusion seam. To address this, we generated a fly in which RFP-Moesin and GFP-Moesin are expressed in mutually exclusive stripes within each segment using the engrailed and patched promoters. We observe mutually exclusive interactions between the filopodia of engrailed and patched cells. Interactions between filopodia from matching cells leads to formation of tethers between them, and these tethers can pull misaligned epithelial sheets into alignment. Filopodial matching also occurs during repair of laser wounds in the ventral epithelium, and so this behaviour is not restricted to leading edge cells during dorsal closure. Finally, we characterise the behaviour of a patched-expressing cell that we observe within the engrailed region of segments A1-A5, and provide evidence that this cell contributes to cell matching.",
"title": "Dynamic analysis of filopodial interactions during the zippering phase of Drosophila dorsal closure."
},
{
"docid": "19308127",
"text": "BACKGROUND P2Y12 inhibitor switching has appeared in clinical practice as a consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for use in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS In the context of the GReek AntiPlatelet REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing PCI. RESULTS Switching occurred in 636 (35.5%) patients of which in the form of clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively. Presentation to non PCI-capable hospital, bivalirudin use, age ≥75 years (inverse predictor), and regional trends emerged as predictive factors of switching to a novel agent. At combined in-hospital and one-month follow-up, propensity matched pairs analysis showed no differences in major adverse cardiovascular (MACE) or bleeding events between switching from clopidogrel to a novel agent vs novel agent constant administration. More Bleeding Academic Research Consortium type 1, type 2 and any type events and fewer MACE were seen when switching from clopidogrel to a novel agent vs only clopidogrel administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P < .001, P = .03, P < .001 and P = .03 respectively). CONCLUSIONS In a real-life experience with contemporary antiplatelet treatment in ACS patients undergoing PCI, in-hospital switching represents common clinical practice. Clinical factors and regional practice differences seem to affect this strategy's choice, while switching to a novel agent may be associated with higher risk of bleeding.",
"title": "In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: prevalence, predictors and short-term outcome."
},
{
"docid": "18276599",
"text": "Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells.",
"title": "Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation"
},
{
"docid": "26491450",
"text": "Kinase inhibitors are a new class of therapeutics with a propensity to inhibit multiple targets. The biological consequences of multi-kinase activity are poorly defined, and an important step toward understanding the relationship between selectivity, efficacy and safety is the exploration of how inhibitors interact with the human kinome. We present interaction maps for 38 kinase inhibitors across a panel of 317 kinases representing >50% of the predicted human protein kinome. The data constitute the most comprehensive study of kinase inhibitor selectivity to date and reveal a wide diversity of interaction patterns. To enable a global analysis of the results, we introduce the concept of a selectivity score as a general tool to quantify and differentiate the observed interaction patterns. We further investigate the impact of panel size and find that small assay panels do not provide a robust measure of selectivity.",
"title": "A quantitative analysis of kinase inhibitor selectivity"
},
{
"docid": "12631697",
"text": "Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission. We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease. Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates. Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis. Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.",
"title": "Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases"
},
{
"docid": "23160444",
"text": "Neuronal growth cones move forward by dynamically connecting actin-based motility to substrate adhesion, but the mechanisms at the individual molecular level remain unclear. We cultured primary neurons on N-cadherin-coated micropatterned substrates, and imaged adhesion and cytoskeletal proteins at the ventral surface of growth cones using single particle tracking combined to photoactivated localization microscopy (sptPALM). We demonstrate transient interactions in the second time scale between flowing actin filaments and immobilized N-cadherin/catenin complexes, translating into a local reduction of the actin retrograde flow. Normal actin flow on micropatterns was rescued by expression of a dominant negative N-cadherin construct competing for the coupling between actin and endogenous N-cadherin. Fluorescence recovery after photobleaching (FRAP) experiments confirmed the differential kinetics of actin and N-cadherin, and further revealed a 20% actin population confined at N-cadherin micropatterns, contributing to local actin accumulation. Computer simulations with relevant kinetic parameters modeled N-cadherin and actin turnover well, validating this mechanism. Such a combination of short- and long-lived interactions between the motile actin network and spatially restricted adhesive complexes represents a two-tiered clutch mechanism likely to sustain dynamic environment sensing and provide the force necessary for growth cone migration.",
"title": "Two-tiered coupling between flowing actin and immobilized N-cadherin/catenin complexes in neuronal growth cones."
},
{
"docid": "243694",
"text": "The ontogeny of haematopoietic stem cells (HSCs) during embryonic development is still highly debated, especially their possible lineage relationship to vascular endothelial cells. The first anatomical site from which cells with long-term HSC potential have been isolated is the aorta-gonad-mesonephros (AGM), more specifically the vicinity of the dorsal aortic floor. But although some authors have presented evidence that HSCs may arise directly from the aortic floor into the dorsal aortic lumen, others support the notion that HSCs first emerge within the underlying mesenchyme. Here we show by non-invasive, high-resolution imaging of live zebrafish embryos, that HSCs emerge directly from the aortic floor, through a stereotyped process that does not involve cell division but a strong bending then egress of single endothelial cells from the aortic ventral wall into the sub-aortic space, and their concomitant transformation into haematopoietic cells. The process is polarized not only in the dorso-ventral but also in the rostro-caudal versus medio-lateral direction, and depends on Runx1 expression: in Runx1-deficient embryos, the exit events are initially similar, but much rarer, and abort into violent death of the exiting cell. These results demonstrate that the aortic floor is haemogenic and that HSCs emerge from it into the sub-aortic space, not by asymmetric cell division but through a new type of cell behaviour, which we call an endothelial haematopoietic transition.",
"title": "Blood stem cells emerge from aortic endothelium by a novel type of cell transition"
},
{
"docid": "21859699",
"text": "Providing transplantation opportunities for patients with incompatible live donors through kidney paired donation (KPD) is seen as one of the important strategies for easing the crisis in organ availability. It has been estimated that an additional 1000-2000 transplants per year could be accomplished if a national KPD program were implemented in the United States. While most of these transplants could be arranged within the participants' local or regional area, patients with hard-to-match blood types or broad HLA sensitization would benefit from matching across larger geographic areas. In this case, either patients or organs would need to travel in order to obtain maximum benefit from a national program. In this study, we describe how a triple KPD enabled a highly sensitized patient (PRA 96%) to receive a well-matched kidney from a live donor on the opposite coast. The kidney was removed in San Francisco and transported to Baltimore where it was reperfused 8 h later. The patient had prompt function and 1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint for solving some of the complexities that are inherent in the implementation of a national KPD program in a large country like the United States.",
"title": "Successful three-way kidney paired donation with cross-country live donor allograft transport."
},
{
"docid": "4392608",
"text": "Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive. To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors. Advanced quantitative analysis identified low-methylated regions (LMRs) with an average methylation of 30%. These represent CpG-poor distal regulatory regions as evidenced by location, DNase I hypersensitivity, presence of enhancer chromatin marks and enhancer activity in reporter assays. LMRs are occupied by DNA-binding factors and their binding is necessary and sufficient to create LMRs. A comparison of neuronal and stem-cell methylomes confirms this dependency, as cell-type-specific LMRs are occupied by cell-type-specific transcription factors. This study provides methylome references for the mouse and shows that DNA-binding factors locally influence DNA methylation, enabling the identification of active regulatory regions.",
"title": "DNA-binding factors shape the mouse methylome at distal regulatory regions"
},
{
"docid": "2319305",
"text": "Drug resistance-associated mutations in HIV-1 reverse transcriptase (RT) can affect the balance between polymerase and ribonuclease H (RNase H) activities of the enzyme. We have recently demonstrated that the N348I mutation in the connection domain causes selective dissociation from RNase H-competent complexes, whereas the functional integrity of the polymerase-competent complex remains largely unaffected. N348I has been associated with resistance to the non-nucleoside RT inhibitor (NNRTI), nevirapine; however, a possible mechanism that links changes in RNase H activity to changes in NNRTI susceptibility remains to be established. To address this problem, we consider recent findings suggesting that NNRTIs may affect the orientation of RT on its nucleic acid substrate and increase RNase H activity. Here we demonstrate that RNase H-mediated primer removal is indeed more efficient in the presence of NNRTIs; however, the N348I mutant enzyme is able to counteract this effect. Efavirenz, a tight binding inhibitor, restricts the influence of the mutation. These findings provide strong evidence to suggest that N348I can thwart the inhibitory effects of nevirapine during initiation of (+)-strand DNA synthesis, which provides a novel mechanism for resistance. The data are in agreement with clinical data, which demonstrate a stronger effect of N348I on susceptibility to nevirapine as compared with efavirenz.",
"title": "N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation."
}
] |
226
|
Cancer-associated fibroblasts (CAFs) interact with cancer cells to mediate formation and activation of CAFs.
|
[
{
"docid": "6944800",
"text": "Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.",
"title": "Microenvironmental regulation of tumor progression and metastasis"
}
] |
[
{
"docid": "3727986",
"text": "Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.",
"title": "A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion"
},
{
"docid": "9648896",
"text": "Lung cancer is the leading cause of cancer-related mortality in humans worldwide. Moreover, the overall 5-year survival rate is only 15%. Pathologically almost 80% of all lung cancer cases are non-small cell lung cancer (NSCLC). Cancer-associated fibroblasts (CAFs) have been found to exist in a large number of NSCLCs. CAFs have been proven to promote tumor progression, metastasis and resistance to therapy through paracrine effects in most solid tumors. In the present study, firstly we isolated CAFs from patient tissues and demonstrated that they promoted cell proliferation and chemoresistance to cisplatin in the lung cancer cell lines A549 and 95D in a paracrine manner. Secondly, using ELISA and quantative PCR, we found that a higher amount of stromal cell-derived factor 1 (SDF-1) existed in the CAFs rather than that observed in the normal fibroblasts (NFs). Thirdly, we detected that SDF-1 facilitated lung cancer cell proliferation and drug resistance via the CXCR4-mediated signaling pathway which involved NF-κB and Bcl-xL. Moreover, we also confirmed that the expression level of SDF-1 in the CAFs was negatively regulated by microRNA mir-1 through microRNA overexpression and quantitative PCR. Overall, our data provide one explanation for the effects of CAFs on lung cancer cells. Meanwhile, our results also suggest CAFs as a potential therapeutic target in tumor treatment.",
"title": "mir-1-mediated paracrine effect of cancer-associated fibroblasts on lung cancer cell proliferation and chemoresistance."
},
{
"docid": "32742683",
"text": "Among cells present in the tumor microenvironment, activated fibroblasts termed cancer-associated fibroblasts (CAFs), play a critical role in the complex process of tumor-stroma interaction. CAFs, one of the prominent stromal cell populations in most types of human carcinomas, have been involved in tumor growth, angiogenesis, cancer stemness, extracellular matrix remodeling, tissue invasion, metastasis, and even chemoresistance. During the past decade, these activated tumor-associated fibroblasts have also been involved in the modulation of the anti-tumor immune response on various levels. In this review, we describe our current understanding of how CAFs accomplish this task as well as their potential therapeutic implications.",
"title": "Alteration of the Antitumor Immune Response by Cancer-Associated Fibroblasts"
},
{
"docid": "952111",
"text": "Cancer associated fibroblasts (CAFs) is one of the most crucial components of the tumor microenvironment which promotes the growth and invasion of cancer cells by various mechanisms. CAFs demonstrate a high degree of heterogeneity due to their various origins; however, many distinct morphological features and physiological functions of CAFs have been identified. It is becoming clear that the crosstalk between the cancer cells and the CAFs plays a key role in the progression of cancer, and understanding this mutual relationship would eventually enable us to treat cancer patients by targeting CAFs. In this review, we will discuss the latest findings on the role of CAFs in tumorigenesis and metastasis as well as potential therapeutic implication of CAFs.",
"title": "Cancer associated fibroblasts (CAFs) in tumor microenvironment."
},
{
"docid": "35993767",
"text": "Fibroblasts are rich in the surrounding microenvironment of hepatocellular carcinoma (HCC) because most HCCs occur in fibrotic or cirrhotic livers. However, the role of cancer-associated fibroblasts (CAFs) in HCC metastasis remains obscure. Here, we reported that CAFs promote the migration and invasion of HCC cells in vitro and facilitate the HCC metastasis to the bone, brain and lung in NOD/SCID mice. The RayBio human chemokine antibody array revealed that CAFs secret higher levels of CCL2, CCL5, CCL7 and CXCL16 than peri-tumor fibroblasts. CCL2 and CCL5 increase the migration but not the invasion of HCC cells, while CCL7 and CXCL16 promote both migration and invasion of HCC cells. Moreover, CCL2 and CCL5 stimulate the activation of the hedgehog (Hh) pathway, while CCL7 and CXCL16 enhance the activity of the transforming growth factor-β (TGF-β) pathway in HCC cells. The neutralizing antibodies of chemokines notably attenuate the effect of CAFs on HCC metastasis and compromised the activation of Hh and TGF-β pathways in HCC cells. In summary, CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells.",
"title": "Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways."
},
{
"docid": "8702697",
"text": "AIMS Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer-associated fibroblasts (CAFs) elicit a redox-dependent epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-κB pathway and enhancing tumor aggressiveness. Here, we investigated the involvement of microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to counteract oxidative stress and metastasis dissemination. RESULTS We found that miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to direct transcriptional repression by HIF-1, a known redox-sensitive transcription factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity, and metastatic dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding fibroblasts by reducing pro-inflammatory cytokine secretion. INNOVATION Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma. CONCLUSION The evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert the oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale for developing miRNA-based approaches to prevent and treat metastatic disease.",
"title": "miR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts."
},
{
"docid": "10812605",
"text": "Fibroblasts regulate the structure and function of healthy tissues, participate transiently in tissue repair after acute inflammation, and assume an aberrant stimulatory role during chronic inflammatory states including cancer. Such cancer-associated fibroblasts (CAFs) modulate the tumor microenvironment and influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. These pleiotropic functions highlight the inherent plasticity of fibroblasts and may provide new avenues to understand and therapeutically intervene in malignancies. We discuss the emerging themes of CAF biology in the context of tumorigenesis and therapy.",
"title": "Fibroblast heterogeneity in the cancer wound"
},
{
"docid": "3559136",
"text": "Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with a CXCR2 antagonist blocked granulocyte infiltration of tumors and showed strong anti-tumor effects.",
"title": "Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors."
},
{
"docid": "1727493",
"text": "Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. These data suggest that the malignant phenotype of metastatic ovarian cancer cells can be altered by miR21 delivered by exosomes derived from neighbouring stromal cells in the omental tumour microenvironment, and that inhibiting the transfer of stromal-derived miR21 is an alternative modality in the treatment of metastatic and recurrent ovarian cancer.",
"title": "Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1"
},
{
"docid": "15832146",
"text": "Fibroblasts often constitute the majority of the stromal cells within a breast carcinoma, yet the functional contributions of these cells to tumorigenesis are poorly understood. Using a coimplantation tumor xenograft model, we demonstrate that carcinoma-associated fibroblasts (CAFs) extracted from human breast carcinomas promote the growth of admixed breast carcinoma cells significantly more than do normal mammary fibroblasts derived from the same patients. The CAFs, which exhibit the traits of myofibroblasts, play a central role in promoting the growth of tumor cells through their ability to secrete stromal cell-derived factor 1 (SDF-1); CAFs promote angiogenesis by recruiting endothelial progenitor cells (EPCs) into carcinomas, an effect mediated in part by SDF-1. CAF-secreted SDF-1 also stimulates tumor growth directly, acting through the cognate receptor, CXCR4, which is expressed by carcinoma cells. Our findings indicate that fibroblasts within invasive breast carcinomas contribute to tumor promotion in large part through the secretion of SDF-1.",
"title": "Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion"
},
{
"docid": "11291348",
"text": "The Maf oncoproteins are b-Zip transcription factors of the AP-1 superfamily. They are involved in developmental, metabolic, and tumorigenic processes. Maf proteins are overexpressed in about 50% of human multiple myelomas. Here, we show that Maf-transforming activity is controlled by GSK-3-dependent phosphorylation and that phosphorylation by GSK-3 can increase the oncogenic activity of a protein. Using microarray analysis, we identify a gene-expression subprogram regulated by GSK-3-mediated Maf phosphorylation involved in extracellular matrix remodeling and relevant to cancer progression. We also demonstrate that GSK-3 triggers MafA sequential phosphorylation on residues S61, T57, T53, and S49, inducing its ubiquitination and degradation. Paradoxically, this phosphorylation increases MafA-transcriptional activity through the recruitment of the coactivator P/CAF. We further demonstrate that P/CAF protects MafA from ubiquitination and degradation, suggesting that, upon the release of the coactivator complex, MafA becomes polyubiquitinated and degraded to allow the response to terminate.",
"title": "GSK-3-mediated phosphorylation enhances Maf-transforming activity."
},
{
"docid": "195680777",
"text": "BACKGROUND Moderate differences in efficacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could affect treatment choices. We sought any such differences. METHODS We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plus-anthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44,000); one anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide, methotrexate, and fluorouracil (CMF; n=18,000); and polychemotherapy versus no chemotherapy (n=32,000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported. FINDINGS In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided significance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no significant difference (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little affected by age, nodal status, tumour diameter or differentiation (moderate or poor; few were well differentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality differences paralleled breast cancer mortality differences, despite taxane, anthracycline, and other toxicities. INTERPRETATION 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute benefit, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both. FUNDING Cancer Research UK; British Heart Foundation; UK Medical Research Council.",
"title": "Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials."
},
{
"docid": "12588500",
"text": "Chromatin assembly factor 1 (CAF-1) and Rtt106 participate in the deposition of newly synthesized histones onto replicating DNA to form nucleosomes. This process is critical for the maintenance of genome stability and inheritance of functionally specialized chromatin structures in proliferating cells. However, the molecular functions of the acetylation of newly synthesized histones in this DNA replication-coupled nucleosome assembly pathway remain enigmatic. Here we show that histone H3 acetylated at lysine 56 (H3K56Ac) is incorporated onto replicating DNA and, by increasing the binding affinity of CAF-1 and Rtt106 for histone H3, H3K56Ac enhances the ability of these histone chaperones to assemble DNA into nucleosomes. Genetic analysis indicates that H3K56Ac acts in a nonredundant manner with the acetylation of the N-terminal residues of H3 and H4 in nucleosome assembly. These results reveal a mechanism by which H3K56Ac regulates replication-coupled nucleosome assembly mediated by CAF-1 and Rtt106.",
"title": "Acetylation of Histone H3 Lysine 56 Regulates Replication-Coupled Nucleosome Assembly"
},
{
"docid": "15727984",
"text": "Non-small cell lung cancer (NSCLC) cells with somatic mutations in K-ras recruit to the tumor a variety of cell types (hereafter collectively termed \"stromal cells\") that can promote or inhibit tumorigenesis by mechanisms that have not been fully elucidated. Here, we postulated that stromal cells in the tumor microenvironment alter the tumor cell secretome, including those proteins required for tumor growth and dissemination, and we developed an in vitro model to test this hypothesis. Coculturing a murine K-ras mutant lung adenocarcinoma cell line (LKR-13) with a murine lung stromal cell (macrophage, endothelial cell, or fibroblast) enhanced stromal cell migration, induced endothelial tube formation, increased LKR-13 cell proliferation, and regulated the secretion of proteins involved in angiogenesis, inflammation, cell proliferation, and epithelial-to-mesenchymal transition. Among these proteins, CXCL1 has been reported to promote NSCLC development, whereas interleukin-18 (IL-18) has an undefined role. Genetic and pharmacologic strategies to inhibit CXCL1 and IL-18 revealed that stromal cell migration, LKR-13 cell proliferation, and LKR-13 cell tumorigenicity required one or both of these proteins. We conclude that stromal cells enhanced LKR-13 cell tumorigenicity partly through their effects on the secretome of LKR-13 cells. Strategies to inhibit tumor/stromal cell interactions may be useful as therapeutic approaches in NSCLC patients.",
"title": "Identification of secreted proteins that mediate cell-cell interactions in an in vitro model of the lung cancer microenvironment."
},
{
"docid": "2727303",
"text": "Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca(2+) storage sensor that promotes cell growth, migration, and angiogenesis in breast and cervical cancers. Here, we report that the microtubule-associated histone deacetylase 6 (HDAC6) differentially regulates activation of STIM1-mediated store-operated Ca(2+) entry (SOCE) between cervical cancer cells and normal cervical epithelial cells. Confocal microscopy of living cells indicated that microtubule integrity was necessary for STIM1 trafficking to the plasma membrane and interaction with Orai1, an essential pore subunit of SOCE. Cancer cells overexpressed both STIM1 and Orai1 compared with normal cervical epithelial cells. HDAC6 upregulation in cancer cells was accompanied by hypoacetylated α-tubulin. Tubastatin-A, a specific HDAC6 inhibitor, inhibited STIM1 translocation to plasma membrane and blocked SOCE activation in cancer cells but not normal epithelial cells. Genetic or pharmacologic inhibition of HDAC6 blocked STIM1 membrane trafficking and downstream Ca(2+) influx, as evidenced by total internal reflection fluorescent images and intracellular Ca(2+) determination. In contrast, HDAC6 inhibition did not affect interactions between STIM1 and the microtubule plus end-binding protein EB1. Analysis of surgical specimens confirmed that most cervical cancer tissues overexpressed STIM1 and Orai1, accompanied by hypoacetylated α-tubulin. Together, our results identify HDAC6 as a candidate target to disrupt STIM1-mediated SOCE as a general strategy to block malignant cell behavior.",
"title": "Microtubule-associated histone deacetylase 6 supports the calcium store sensor STIM1 in mediating malignant cell behaviors."
},
{
"docid": "6807122",
"text": "Activated fibroblasts are associated with many different tumors. Myofibroblasts, activated fibroblasts, and perivascular mesenchymal cells such as pericytes play a role in cancer progression. Many studies suggest that myofibroblasts facilitate tumor growth and cancer progression. The source for myofibroblasts and other activated fibroblasts within the tumors is still debated. Although de novo activation of quiescent fibroblasts into alpha-smooth muscle actin (alpha SMA)-positive myofibroblasts is one likely source, epithelial to mesenchymal transition and bone marrow recruitment are also evolving as possible mechanisms for the emergence of a heterogeneous population of carcinoma-associated fibroblasts. Here, we show that transforming growth factor-beta1 could induce proliferating endothelial cells to undergo a phenotypic conversion into fibroblast-like cells. Such endothelial to mesenchymal transition (EndMT) is associated with the emergence of mesenchymal marker fibroblast-specific protein-1 (FSP1) and down-regulation of CD31/PECAM. Additionally, we show EndMT in tumors using the B16F10 melanoma model and the Rip-Tag2 spontaneous pancreatic carcinoma model. Crossing Tie2-Cre mice with R26Rosa-lox-Stop-lox-LacZ mice allows for irreversible tagging of endothelial cells. We provide unequivocal evidence for EndMT at the invasive front of the tumors in these transgenic mice. Collectively, our results show that EndMT is a unique mechanism for the accumulation of carcinoma-associated fibroblasts and suggest that antiangiogenic treatment of tumors may have a direct effect in decreasing activated fibroblasts that likely facilitate cancer progression.",
"title": "Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts."
},
{
"docid": "20183360",
"text": "Transforming growth factor β (TGFβ) is a potent and context-dependent regulator of tumor progression. TGFβ promotes the lung metastasis of basal-like (but not the luminal-like) breast cancer. Here, we demonstrated that fascin, a pro-metastasis actin bundling protein, was a direct target of the canonical TGFβ-Smad4 signaling pathway in basal-like breast cancer cells. TGFβ and Smad4 induced fascin overexpression by directly binding to a Smad binding element on the fascin promoter. We identified GATA3, a transcription factor crucial for mammary gland morphogenesis and luminal differentiation, as a negative regulator of TGFβ- and Smad4-induced fascin overexpression. When ectopically expressed in basal-like breast cancer cells, GATA-3 abrogated TGFβ- and Smad4-mediated overexpression of fascin and other TGFβ response genes, invadopodium formation, cell migration, and invasion, suggesting suppression of the canonical TGFβ-Smad signaling axis. Mechanistically, GATA3 abrogated the canonical TGFβ-Smad signaling by abolishing interactions between Smad4 and its DNA binding elements, potentially through physical interactions between the N-terminal of GATA3 and Smad3/4 proteins. Our findings provide mechanistic insight into how TGFβ-mediated cell motility and invasiveness are differentially regulated in breast cancer.",
"title": "GATA3 transcription factor abrogates Smad4 transcription factor-mediated fascin overexpression, invadopodium formation, and breast cancer cell invasion."
},
{
"docid": "24349992",
"text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.",
"title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells."
},
{
"docid": "52925737",
"text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.",
"title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration"
},
{
"docid": "13889430",
"text": "There is a growing interest in the cell-cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated α-smooth muscle actin expression and other changes consistent with the process of fibroblast differentiation into myofibroblasts. We show that TGF-β is expressed at the exosome surface in association with the transmembrane proteoglycan betaglycan. Although existing in a latent state, this complex was fully functional in eliciting SMAD-dependent signaling. Inhibiting either signaling or betaglycan expression attenuated differentiation. While the kinetics and overall magnitude of the response were similar to that achieved with soluble TGF-β, we identified important qualitative differences unique to the exosomal route of TGF-β delivery, as exemplified by a significant elevation in fibroblast FGF2 production. This hitherto unknown trigger for instigating cellular differentiation in a distinctive manner has major implications for mechanisms underlying cancer-recruited stroma, fibrotic diseases, and wound-healing responses.",
"title": "Cancer exosomes trigger fibroblast to myofibroblast differentiation."
},
{
"docid": "13007205",
"text": "Stromal fibroblasts can contribute to tumor invasion through the release of matrix metalloproteinases (MMPs). Population studies have suggested that single nucleotide polymorphisms (SNPs) in MMP genes influence levels of expression and may be associated with breast cancer risk and with disease progression. This study directly examined the impact of MMP SNP genotype on the ability of host fibroblasts to promote tumor cell invasion. Primary breast fibroblasts were isolated from patients with (n = 13) or without (n = 19) breast cancer, and their ability to promote breast cancer cell invasion was measured in in vitro invasion assays. Fibroblast invasion-promoting capacity (IPC) was analyzed in relation to donor type (tumor or non-tumor patient), MMP-1, MMP-3, and MMP-9 SNP genotype and MMP activity using independent samples t test and analysis of variance. All statistical tests were two-sided. Tumor-derived fibroblasts promoted higher levels of invasion than normal fibroblasts (p = 0.041). When IPC was related to genotype, higher levels of IPC were generated by tumor fibroblasts with the high-expressing MMP-3 5A/5A genotype compared with the 5A/6A and 6A/6A genotypes (p = 0.05 and 0.07, respectively), and this was associated with enhanced MMP-3 release. The functional importance of MMP-3 was demonstrated by enhanced invasion in the presence of recombinant MMP-3, whereas reduction occurred in the presence of a specific MMP-3 inhibitor. An inverse relationship was demonstrated between fibroblast IPC and the high-expressing MMP-1 genotype (p = 0.031), but no relationship was seen with MMP-9 SNP status. In contrast, normal fibroblasts showed no variation in IPC in relation to MMP genotype, with MMP-3 5A/5A fibroblasts exhibiting significantly lower levels of IPC than their tumor-derived counterparts (p = 0.04). This study has shown that tumor-derived fibroblasts exhibit higher levels of IPC than normal fibroblasts and that the MMP-3 5A/5A genotype contributes to this through enhanced MMP-3 release. Despite a high-expressing genotype, normal fibroblasts do not exhibit higher IPC or enhanced MMP release. This suggests that more complex changes occur in tumor-derived fibroblasts, enabling full expression of the MMP SNP genotype and these possibly are epigenetic in nature. The results do suggest that, in women with breast cancer, a high-expressing MMP-3 genotype may promote tumor progression more effectively.",
"title": "Intrinsic genetic characteristics determine tumor-modifying capacity of fibroblasts: matrix metalloproteinase-3 5A/5A genotype enhances breast cancer cell invasion"
},
{
"docid": "7736860",
"text": "Store-operated Ca(2+) entry (SOCE) is the principal Ca(2+) entry mechanism in nonexcitable cells. Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca(2+) sensor that triggers SOCE activation. However, the role of STIM1 in regulating cancer progression remains controversial and its clinical relevance is unclear. Here we show that STIM1-dependent signaling is important for cervical cancer cell proliferation, migration, and angiogenesis. STIM1 overexpression in tumor tissue is noted in 71% cases of early-stage cervical cancer. In tumor tissues, the level of STIM1 expression is significantly associated with the risk of metastasis and survival. EGF-stimulated cancer cell migration requires STIM1 expression and EGF increases the interaction between STIM1 and Orai1 in juxta-membrane areas, and thus induces Ca(2+) influx. STIM1 involves the activation of Ca(2+)-regulated protease calpain, as well as Ca(2+)-regulated cytoplasmic kinase Pyk2, which regulate the focal-adhesion dynamics of migratory cervical cancer cells. Because of an increase of p21 protein levels and a decrease of Cdc25C protein levels, STIM1-silencing in cervical cancer cells significantly inhibits cell proliferation by arresting the cell cycle at the S and G2/M phases. STIM1 also regulates the production of VEGF in cervical cancer cells. Interference with STIM1 expression or blockade of SOCE activity inhibits tumor angiogenesis and growth in animal models, confirming the crucial role of STIM1-mediated Ca(2+) influx in aggravating tumor development in vivo. These results make STIM1-dependent signaling an attractive target for therapeutic intervention.",
"title": "Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis."
},
{
"docid": "27647593",
"text": "Cancer cells do not exist as pure homogeneous populations in vivo. Instead they are embedded in \"cancer cell nests\" that are surrounded by stromal cells, especially cancer associated fibroblasts. Thus, it is not unreasonable to suspect that stromal fibroblasts could influence the metabolism of adjacent cancer cells, and visa versa. In accordance with this idea, we have recently proposed that the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria. An in depth analysis of this phenomenon reveals that aggressive cancer cells are \"parasites\" that use oxidative stress as a \"weapon\" to extract nutrients from surrounding stromal cells. Oxidative stress in fibroblasts induces the autophagic destruction of mitochondria, by mitophagy. Then, stromal cells are forced to undergo aerobic glycolysis, and produce energy-rich nutrients (such as lactate and ketones) to \"feed\" cancer cells. This mechanism would allow cancer cells to seed anywhere, without blood vessels as a food source, as they could simply induce oxidative stress wherever they go, explaining how cancer cells survive during metastasis. We suggest that stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm \"The Autophagic Tumor Stroma Model of Cancer Metabolism\", or the \"Reverse Warburg Effect\". We also discuss how glutamine addiction (glutaminolysis) in cancer cells fits well with this new model, by promoting oxidative mitochondrial metabolism in aggressive cancer cells.",
"title": "Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment."
},
{
"docid": "3590806",
"text": "BACKGROUND Colorectal cancer remains one of the most common malignant tumors worldwide. Colorectal cancer initiating cells (CCICs) are a small subpopulation responsible for malignant behaviors of colorectal cancer. Aberrant activation of the Wnt pathways regulates the self-renewal of CCIC. However, the underlying mechanism(s) remain poorly understood. METHODS Via retroviral library screening, we identified Nuclear Receptor-Interacting Protein 2 (NRIP2) as a novel interactor of the Wnt pathway from enriched colorectal cancer colosphere cells. The expression levels of NRIP2 and retinoic acid-related orphan receptor β (RORβ) were further examined by FISH, qRT-PCR, IHC and Western blot. NRIP2 overexpressed and knockdown colorectal cancer cells were produced to study the role of NRIP2 in Wnt pathway. We also verified the binding between NRIP2 and RORβ and investigated the effect of RORβ on CCICs both in vitro and in vivo. Genechip-scanning speculated downstream target HBP1. Western blot, ChIP and luciferase reporter were carried to investigate the interaction between NRIP2, RORβ, and HBP1. RESULTS NRIP2 was significantly up-regulated in CCICs from both cell lines and primary colorectal cancer tissues. Reinforced expression of NRIP2 increased Wnt activity, while silencing of NRIP2 attenuated Wnt activity. The transcription factor RORβ was a key target through which NRIP2 regulated Wnt pathway activity. RORβ was a transcriptional enhancer of inhibitor HBP1 of the Wnt pathway. NRIP2 prevented RORβ to bind with downstream HBP1 promoter regions and reduced the transcription of HBP1. This, in turn, attenuated the HBP1-dependent inhibition of TCF4-mediated transcription. CONCLUSIONS NRIP2 is a novel interactor of the Wnt pathway in colorectal cancer initiating cells. interactions between NRIP2, RORβ, and HBP1 mediate a new mechanism for CCIC self-renewal via the Wnt activity.",
"title": "Up-regulated NRIP2 in colorectal cancer initiating cells modulates the Wnt pathway by targeting RORβ"
},
{
"docid": "25915873",
"text": "PURPOSE Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. RESULTS Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. EXPERIMENTAL DESIGN We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. CONCLUSION Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.",
"title": "Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation."
},
{
"docid": "3376731",
"text": "Various factors and cellular components in the tumor microenvironment are key drivers associated with drug resistance in many cancers. Here, we analyzed the factors and molecular mechanisms involved in chemoresistance in patients with esophageal squamous cell carcinoma (ESCC). We found that interleukin 6 (IL6) derived mainly from cancer-associated fibroblasts played the most important role in chemoresistance by upregulating C-X-C motif chemokine receptor 7 (CXCR7) expression through signal transducer and activator of transcription 3/nuclear factor-κB pathway. CXCR7 knockdown resulted in the inhibition of IL6-induced proliferation and chemoresistance. In addition, CXCR7 silencing significantly decreased gene expression associated with stemness, chemoresistance and epithelial–mesenchymal transition and suppressed the proliferation ability of ESCC cells in three-dimensional culture systems and angiogenesis assay. In clinical samples, ESCC patients with high expression of CXCR7 and IL6 presented a significantly worse overall survival and progression-free survival upon receiving cisplatin after operation. These results suggest that the IL6–CXCR7 axis may provide a promising target for the treatment of ESCC.",
"title": "IL6 derived from cancer-associated fibroblasts promotes chemoresistance via CXCR7 in esophageal squamous cell carcinoma"
},
{
"docid": "7165938",
"text": "PURPOSE The circadian clock gene Bmal1 is involved in cancer cell proliferation and DNA damage sensitivity. The aim of this study was to explore the effect of Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in colorectal cancer. EXPERIMENTAL DESIGN Three colorectal cancer cell lines, HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal cancer cell proliferation was tested in vitro and in vivo. MTT and colony formation assays were performed to determine the sensitivity of colorectal cancer cells to oxaliplatin. Flow cytometry was used to examine changes in the cell-cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1 upon its overexpression were determined by Western blotting. Immunohistochemistry was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from patients treated with oxaliplatin-based regimens. RESULTS Bmal1 overexpression inhibited colorectal cancer cell proliferation and increased colorectal cancer sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells model in vivo. Furthermore, the overall survival of patients with colorectal cancer with high Bmal1 levels in their primary tumors was significantly longer than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The progression-free survival of patients with high Bmal1 expression was also significantly longer than that of patients with low Bmal1 expression (11 vs. 5 months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its ability to regulate G2-M arrest by activating the ATM pathway. CONCLUSION Bmal1 shows the potential as a novel prognostic biomarker and may represent a new therapeutic target in colorectal cancer.",
"title": "Overexpression of the circadian clock gene Bmal1 increases sensitivity to oxaliplatin in colorectal cancer."
},
{
"docid": "17188921",
"text": "Cell migration is a process which is essential during embryonic development, throughout adult life and in some pathological conditions. Cadherins, and more specifically the neural cell adhesion molecule N-cadherin, play an important role in migration. In embryogenesis, N-cadherin is the key molecule during gastrulation and neural crest development. N-cadherin mediated contacts activate several pathways like Rho GTPases and function in tyrosine kinase signalling (for example via the fibroblast growth factor receptor). In cancer, cadherins control the balance between suppression and promotion of invasion. E-cadherin functions as an invasion suppressor and is downregulated in most carcinomas, while N-cadherin, as an invasion promoter, is frequently upregulated. Expression of N-cadherin in epithelial cells induces changes in morphology to a fibroblastic phenotype, rendering the cells more motile and invasive. However in some cancers, like osteosarcoma, N-cadherin may behave as a tumour suppressor. N-cadherin can have multiple functions: promoting adhesion or induction of migration dependent on the cellular context.",
"title": "N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling."
},
{
"docid": "38252314",
"text": "The minichromosome maintenance protein homologs MCM8 and MCM9 have previously been implicated in DNA replication elongation and prereplication complex (pre-RC) formation, respectively. We found that MCM8 and MCM9 physically associate with each other and that MCM8 is required for the stability of MCM9 protein in mammalian cells. Depletion of MCM8 or MCM9 in human cancer cells or the loss of function MCM9 mutation in mouse embryo fibroblasts sensitizes cells to the DNA interstrand cross-linking (ICL) agent cisplatin. Consistent with a role in the repair of ICLs by homologous recombination (HR), knockdown of MCM8 or MCM9 significantly reduces HR repair efficiency. Chromatin immunoprecipitation analysis using human DR-GFP cells or Xenopus egg extract demonstrated that MCM8 and MCM9 proteins are rapidly recruited to DNA damage sites and promote RAD51 recruitment. Thus, these two metazoan-specific MCM homologs are new components of HR and may represent novel targets for treating cancer in combination with DNA cross-linking agents.",
"title": "The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination."
},
{
"docid": "8764879",
"text": "Leukemias and other cancers possess self-renewing stem cells that help to maintain the cancer. Cancer stem cell eradication is thought to be crucial for successful anticancer therapy. Using an acute myeloid leukemia (AML) model induced by the leukemia-associated monocytic leukemia zinc finger (MOZ)-TIF2 fusion protein, we show here that AML can be cured by the ablation of leukemia stem cells. The MOZ fusion proteins MOZ-TIF2 and MOZ-CBP interacted with the transcription factor PU.1 to stimulate the expression of macrophage colony–stimulating factor receptor (CSF1R, also known as M-CSFR, c-FMS or CD115). Studies using PU.1-deficient mice showed that PU.1 is essential for the ability of MOZ-TIF2 to establish and maintain AML stem cells. Cells expressing high amounts of CSF1R (CSF1Rhigh cells), but not those expressing low amounts of CSF1R (CSF1Rlow cells), showed potent leukemia-initiating activity. Using transgenic mice expressing a drug-inducible suicide gene controlled by the CSF1R promoter, we cured AML by ablation of CSF1Rhigh cells. Moreover, induction of AML was suppressed in CSF1R-deficient mice and CSF1R inhibitors slowed the progression of MOZ-TIF2–induced leukemia. Thus, in this subtype of AML, leukemia stem cells are contained within the CSF1Rhigh cell population, and we suggest that targeting of PU.1-mediated upregulation of CSF1R expression might be a useful therapeutic approach.",
"title": "PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2"
}
] |
844
|
Neutrophil extracellular trap (NET) antigens may contain the targeted autoantigens PR3 and MPO.
|
[
{
"docid": "17741440",
"text": "Small-vessel vasculitis (SVV) is a chronic autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). Here we show that chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). Deposition of NETs in inflamed kidneys and circulating MPO-DNA complexes suggest that NET formation triggers vasculitis and promotes the autoimmune response against neutrophil components in individuals with SVV.",
"title": "Netting neutrophils in autoimmune small-vessel vasculitis"
}
] |
[
{
"docid": "11328820",
"text": "The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.",
"title": "NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis."
},
{
"docid": "30041340",
"text": "BACKGROUND Histone deimination regulates gene function and contributes to antimicrobial response, allowing the formation of neutrophil extracellular traps (NETs). Deiminated proteins are target of anti-citrullinated peptides antibodies (ACPA) in rheumatoid arthritis (RA). OBJECTIVE The objective of this paper is to test the hypothesis that RA sera react with deiminated histones contained in NETs. METHODS Neutrophils from peripheral blood were stimulated with A23187 and acid treated; NETosis was induced by phorbol myristate acetate, and NET proteins were isolated. Sera were tested by immunoblot on acid extracted proteins from neutrophils and from NETs, and by ELISA on deiminated histone H4 or H4-derived peptides. Bands reactive with RA sera were excised from gels, digested with trypsin and subjected to matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) analysis, before and after derivatisation to detect citrullinated peptides. RESULTS RA sera reacted with a deiminated antigen of 11 KDa from activated neutrophils, recognised also by anti-H4 and antideiminated H4 antibodies. A similar reactivity was observed with NET proteins. The antigen from neutrophils or NETs was identified as citrullinated H4 by MALDI-TOF analysis. By ELISA, RA sera bound in vitro citrullinated H4. Citrullinated H4 14-34 and 31-50 peptides detected antibodies in 67% and 63% of RA sera and in less than 5% of controls; antibody titre was correlated with anti-CCP2. CONCLUSIONS Citrullinated H4 from activated neutrophils and NETs is a target of antibodies in RA, and synthetic citrullinated H4-derived peptides are a new substrate for ACPA detection. As NETosis can generate antigens for ACPA, these data suggest a novel connection between innate and adaptive immunity in RA.",
"title": "Antibodies from patients with rheumatoid arthritis target citrullinated histone 4 contained in neutrophils extracellular traps."
},
{
"docid": "14853989",
"text": "Autoantibodies to DNA and histones (chromatin) are the defining antigen specificity in systemic lupus erythematosus (SLE) and related musculoskeletal disorders but the mechanisms responsible for their induction remain mysterious. That situation rapidly changed once neutrophil extracellular chromatin traps (NETs) were discovered and observed to play a conserved role in innate immune responses to a broad variety of microbial pathogens. At the center of an infectious process, neutrophils exert various antimicrobial defenses, including the release of nuclear chromatin into the extracellular space. The externalized NETs, a complex meshwork of nuclear chromatin and antimicrobial proteins, serve to immobilize and degrade microbial pathogens. Here, we critically evaluate the evidence supporting NETs versus apoptotic bodies as a source for nuclear antigens in autoimmunity. We also discuss the possibility that NET chromatin forms an essential component of immune deposits in the pathogenesis of glomerulonephritis in SLE and other autoimmune immune complex diseases.",
"title": "Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity"
},
{
"docid": "9878167",
"text": "Neutrophil extracellular traps (NETs) represent extracellular structures able to bind and kill microorganisms. It is believed that they are generated by neutrophils undergoing cell death, allowing these dying or dead cells to kill microbes. We show that, following priming with granulocyte/macrophage colony-stimulating factor (GM-CSF) and subsequent short-term toll-like receptor 4 (TLR4) or complement factor 5a (C5a) receptor stimulation, viable neutrophils are able to generate NETs. Strikingly, NETs formed by living cells contain mitochondrial, but no nuclear, DNA. Pharmacological or genetic approaches to block reactive oxygen species (ROS) production suggested that NET formation is ROS dependent. Moreover, neutrophil populations stimulated with GM-CSF and C5a showed increased survival compared with resting neutrophils, which did not generate NETs. In conclusion, mitochondrial DNA release by neutrophils and NET formation do not require neutrophil death and do also not limit the lifespan of these cells.",
"title": "Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps"
},
{
"docid": "6251620",
"text": "Antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker for ANCA-associated systemic vasculitis. Using indirect immunofluorescence on ethanol-fixed neutrophils, two major fluoroscopic patterns can be recognised: a diffuse cytoplasmic staining (C-ANCA), and a perinuclear/nuclear staining (P-ANCA). In patients with vasculitis, more of 90% of C-ANCA are directed against proteinase 3 (PR3-ANCA) whereas approximately 80-90% of P-ANCA recognise myelperoxidase (MPO-ANCA). Although C-ANCA (PR3-ANCA) is preferentially associated with Wegener's granulomatosis (WG), and P-ANCA (MPO-ANCA) with microscopic polyangiitis (MPA), idiopathic necrotising crescentic glomerulonephritis (iNCGN) and Churg-Strauss syndrome (CSS), there is not absolute specificity. Between 10-20% of patients with classical WG show P-ANCA (MPO-ANCA), and even a larger percentage of patients with MPA or CSS have C-ANCA (PR3-ANCA). Furthermore, it should be stressed that approximately 10-20% of patients with WG or MPA (and 40-50% of cases of CSS) have negative assay for ANCA. The best diagnostic performance is obtained when indirect immunofluorescence is combined with PR3 and MPO-specific ELISAs. ANCA with different and unknown antigen specificity are found in a variety of conditions other than AASV, including inflammatory bowel diseases, other autoimmune diseases, and infections where their clinical significance is unclear. ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatment. A significant increase in ANCA titres, or the reappearance of ANCA, should alert the clinicians and lead to a stricter patient control.",
"title": "Antineutrophil cytoplasmic antibodies (ANCA)."
},
{
"docid": "28015516",
"text": "Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a breakdown of tolerance to nuclear antigens and the development of immune complexes. Genomic approaches have shown that human SLE leukocytes homogeneously express type I interferon (IFN)-induced and neutrophil-related transcripts. Increased production and/or bioavailability of IFN-α and associated alterations in dendritic cell (DC) homeostasis have been linked to lupus pathogenesis. Although neutrophils have long been shown to be associated with lupus, their potential role in disease pathogenesis remains elusive. Here, we show that mature SLE neutrophils are primed in vivo by type I IFN and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). SLE NETs contain DNA as well as large amounts of LL37 and HMGB1, neutrophil proteins that facilitate the uptake and recognition of mammalian DNA by plasmacytoid DCs (pDCs). Indeed, SLE NETs activate pDCs to produce high levels of IFN-α in a DNA- and TLR9 (Toll-like receptor 9)-dependent manner. Our results reveal an unsuspected role for neutrophils in SLE pathogenesis and identify a novel link between nucleic acid-recognizing antibodies and type I IFN production in this disease.",
"title": "Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus."
},
{
"docid": "36089763",
"text": "Neutrophils phagocytose and kill microbes upon phagolysosomal fusion. Recently we found that activated neutrophils form extracellular fibres that consist of granule proteins and chromatin. These neutrophil extracellular traps (NETs) degrade virulence factors and kill Gram positive and negative bacteria. Here we show for the first time that Candida albicans, a eukaryotic pathogen, induces NET-formation and is susceptible to NET-mediated killing. C. albicans is the predominant aetiologic agent of fungal infections in humans, particularly in immunocompromised hosts. One major virulence trait of C. albicans is its ability to reversibly switch from singular budding cells to filamentous hyphae. We demonstrate that NETs kill both yeast-form and hyphal cells, and that granule components mediate fungal killing. Taken together our data indicate that neutrophils trap and kill ascomycetous yeasts by forming NETs.",
"title": "Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms."
},
{
"docid": "17967608",
"text": "Neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs). We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation. However, the role of PAD4 in NET-mediated bacterial trapping and killing has not been tested. Here, we use PAD4 knockout mice to show that PAD4 is essential for NET-mediated antibacterial function. Unlike PAD4(+/+) neutrophils, PAD4(-/-) neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. In a mouse infectious disease model of necrotizing fasciitis, PAD4(-/-) mice are more susceptible to bacterial infection than PAD4(+/+) mice due to a lack of NET formation. Moreover, we found that citrullination decreased the bacterial killing activity of histones and nucleosomes, which suggests that PAD4 mainly plays a role in chromatin decondensation to form NETs instead of increasing histone-mediated bacterial killing. Our results define a role for histone hypercitrullination in innate immunity during bacterial infection.",
"title": "PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps"
},
{
"docid": "43054703",
"text": "Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.",
"title": "A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus."
},
{
"docid": "28149602",
"text": "PURPOSE OF REVIEW Recent discoveries implicate neutrophils as important regulators of innate and adaptive immunity and in the development of organ damage in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). RECENT FINDINGS Various putative SLE biomarkers are neutrophil-related, including neutrophil granular proteins and histones undergoing post-translational modifications during neutrophil extracellular trap (NET) formation. In the bone marrow, lupus neutrophils can drive B and T cell abnormalities, at least in part, by their enhanced production of type-I interferons, tumor necrosis factor-alpha (TNFα) and the B-cell stimulating factors B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Lupus neutrophils and, in particular, lupus low-density granulocytes (a distinct pathogenic subset) display epigenetic modifications and genomic alterations that may be relevant to their deleterious roles in SLE. Proteins and enzymes externalized by lupus NETs can affect vascular health by inducing endothelial apoptosis and oxidizing lipoproteins. Hampering NET formation through peptidylarginine deiminase inhibitors abrogates lupus phenotype and atherosclerosis in murine studies. SUMMARY Recent discoveries support the notion that neutrophils, low-density granulocytes and aberrant NET formation and clearance play important roles in lupus pathogenesis. Future studies should focus on how to selectively target these immunostimulatory pathways in this disease.",
"title": "The role of neutrophils in the pathogenesis of systemic lupus erythematosus."
},
{
"docid": "1800734",
"text": "Upon activation, neutrophils release DNA fibers decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). Although NETs are bactericidal and contribute to innate host defense, excessive NET formation has been linked to the pathogenesis of autoinflammatory diseases. However, the mechanisms regulating NET formation, particularly during chronic inflammation, are poorly understood. Here we show that the G protein–coupled receptor (GPCR) CXCR2 mediates NET formation. Downstream analyses showed that CXCR2-mediated NET formation was independent of NADPH oxidase and involved Src family kinases. We show the pathophysiological relevance of this mechanism in cystic fibrosis lung disease, characterized by chronic neutrophilic inflammation. We found abundant NETs in airway fluids of individuals with cystic fibrosis and mouse cystic fibrosis lung disease, and NET amounts correlated with impaired obstructive lung function. Pulmonary blockade of CXCR2 by intra-airway delivery of small-molecule antagonists inhibited NET formation and improved lung function in vivo without affecting neutrophil recruitment, proteolytic activity or antibacterial host defense. These studies establish CXCR2 as a receptor mediating NADPH oxidase–independent NET formation and provide evidence that this GPCR pathway is operative and druggable in cystic fibrosis lung disease.",
"title": "CXCR2 mediates NADPH oxidase–independent neutrophil extracellular trap formation in cystic fibrosis airway inflammation"
},
{
"docid": "29399239",
"text": "Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed \"NETosis. \" Here we review our understanding of how NETs are made, their function in infections and as danger signals, and their emerging importance in autoimmunity and coagulation.",
"title": "Neutrophil extracellular traps: Is immunity the second function of chromatin?"
},
{
"docid": "2236768",
"text": "Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask.",
"title": "Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo"
},
{
"docid": "1049501",
"text": "Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.",
"title": "Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease"
},
{
"docid": "46517055",
"text": "Uncontrolled proteolysis by neutrophil serine proteases (NSPs) in lung secretions is a hallmark of cystic fibrosis (CF). We have shown that the active neutrophil elastase, protease 3, and cathepsin G in CF sputum resist inhibition in part by exogenous protease inhibitors. This resistance may be due to their binding to neutrophil extracellular traps (NETs) secreted by the activated neutrophils in CF sputum and to genomic DNA released from senescent and dead neutrophils. Treating CF sputum with DNase dramatically increases its elastase activity, which can then be stoichiometrically inhibited by exogenous elastase inhibitors. However, DNase treatment does not increase the activities of protease 3 and cathepsin G, indicating their different distribution and/or binding in CF sputum. Purified blood neutrophils secrete NETs when stimulated by the opportunistic CF bacteria Pseudomonas aeruginosa and Staphylococcus aureus. The activities of the three proteases were unchanged in these conditions, but subsequent DNase treatment produced a dramatic increase in all three proteolytic activities. Neutrophils activated with a calcium ionophore did not secrete NETs but released huge amounts of active proteases whose activities were not modified by DNase. We conclude that NETs are reservoirs of active proteases that protect them from inhibition and maintain them in a rapidly mobilizable status. Combining the effects of protease inhibitors with that of DNA-degrading agents could counter the deleterious proteolytic effects of NSPs in CF lung secretions.",
"title": "Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum."
},
{
"docid": "12489688",
"text": "Neutrophilic polymorphonuclear leukocytes (neutrophils) are highly specialized for their primary function, the phagocytosis and destruction of microorganisms. When coated with opsonins (generally complement and/or antibody), microorganisms bind to specific receptors on the surface of the phagocyte and invagination of the cell membrane occurs with the incorporation of the microorganism into an intracellular phagosome. There follows a burst of oxygen consumption, and much, if not all, of the extra oxygen consumed is converted to highly reactive oxygen species. In addition, the cytoplasmic granules discharge their contents into the phagosome, and death of the ingested microorganism soon follows. Among the antimicrobial systems formed in the phagosome is one consisting of myeloperoxidase (MPO), released into the phagosome during the degranulation process, hydrogen peroxide (H2O2), formed by the respiratory burst and a halide, particularly chloride. The initial product of the MPO-H2O2-chloride system is hypochlorous acid, and subsequent formation of chlorine, chloramines, hydroxyl radicals, singlet oxygen, and ozone has been proposed. These same toxic agents can be released to the outside of the cell, where they may attack normal tissue and thus contribute to the pathogenesis of disease. This review will consider the potential sources of H2O2 for the MPO-H2O2-halide system; the toxic products of the MPO system; the evidence for MPO involvement in the microbicidal activity of neutrophils; the involvement of MPO-independent antimicrobial systems; and the role of the MPO system in tissue injury. It is concluded that the MPO system plays an important role in the microbicidal activity of phagocytes.",
"title": "Myeloperoxidase: friend and foe."
},
{
"docid": "13106686",
"text": "Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3' repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.",
"title": "Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing."
},
{
"docid": "3330111",
"text": "Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, more recent evidence has extended the functions of these cells. The newly discovered repertoire of effector molecules in the neutrophil armamentarium includes a broad array of cytokines, extracellular traps and effector molecules of the humoral arm of the innate immune system. In addition, neutrophils are involved in the activation, regulation and effector functions of innate and adaptive immune cells. Accordingly, neutrophils have a crucial role in the pathogenesis of a broad range of diseases, including infections caused by intracellular pathogens, autoimmunity, chronic inflammation and cancer.",
"title": "Neutrophils in the activation and regulation of innate and adaptive immunity"
},
{
"docid": "10284593",
"text": "Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain elusive. Here we provide experimental and clinical evidence for the mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of atrial fibrillation. MPO-deficient mice pretreated with angiotensin II (AngII) to provoke leukocyte activation showed lower atrial tissue abundance of the MPO product 3-chlorotyrosine, reduced activity of matrix metalloproteinases and blunted atrial fibrosis as compared to wild-type mice. Upon right atrial electrophysiological stimulation, MPO-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored. Humans with atrial fibrillation had higher plasma concentrations of MPO and a larger MPO burden in right atrial tissue as compared to individuals devoid of atrial fibrillation. In the atria, MPO colocalized with markedly increased formation of 3-chlorotyrosine. Our data demonstrate that MPO is a crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation.",
"title": "Myeloperoxidase acts as a profibrotic mediator of atrial fibrillation"
},
{
"docid": "20459964",
"text": "Neutrophil is a key cell in pathophysiology of granulomatosis with polyangiitis. Recently, neutrophil extracellular traps were described in this disease. Mitochondrial DNA is also released during traps formation. We measured circulating cell-free mitochondrial and genomic DNA in serum of patients with granulomatosis with polyangiitis. Subjects with the disease (14 active and 11 in remission stage) and 10 healthy controls were enrolled. Quantitative real-time polymerase chain reaction (PCR) was used to measure 79 base pairs (bp) and 230 bp mtDNA fragments. Alu repeats were quantified to evaluate abundance of nuclear DNA in serum at the presence of plasmid control. Both fragments of mtDNA (79 bp and 230 bp) and genomic DNA were elevated significantly in granulomatosis with polyangiitis compared to controls. Only the shorter 79 bp mtDNA correlated with active stage of granulomatosis with polyangiitis and clinical symptoms. A mechanism of extracellular release of mitochondrial DNA accompanies the active stage of the disease. Circulating mtDNA is extremely high in untreated patients. This suggests that biomarker properties of mtDNA are useful for monitoring of treatment.",
"title": "Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis."
},
{
"docid": "18592108",
"text": "The sampling efficiency of light trap catches relative to human bait catches in estimating biting rates of the mosquito Anopheles gambiae Giles was investigated in two types of community in southern Sierra Leone: (i) where most of the inhabitants slept under treated bed nets; and (ii) where most of the inhabitants slept without bed nets. The number of female A. gambiae mosquitoes caught in these communities by light trap was strongly correlated (r > or = 0.72) with those from corresponding human biting catches performed either on the same or adjacent nights. It was found that the relative sampling efficiency of light traps varied slightly but significantly with mosquito abundance in villages with treated bed nets, but not in those without them. Nevertheless, the relationship between relative sampling efficiency and mosquito abundance did not differ significantly between the two types of village. Overall, there was insufficient evidence to show that the presence of treated nets altered the relative efficiency of light traps and any bias was only slight, and unlikely to be of any practical importance. Hence, it was concluded that light traps can be used as a surrogate for human bait catches in estimating biting rates of A. gambiae mosquitoes in the two communities.",
"title": "How reliable are light traps in estimating biting rates of adult Anopheles gambiae s.l. (Diptera: Culicidae) in the presence of treated bed nets?"
},
{
"docid": "25319221",
"text": "INTRODUCTION The GOLD guidelines advocate not to institute inhaled corticosteroids (ICS) in patients with mild-to-moderate COPD. However, many patients do use ICS and in some patients, withdrawal is associated with deteriorating lung function and increased exacerbation rates. Unfortunately, physicians do not know in which patients they can stop ICS treatment safely. AIM To identify predictors of COPD exacerbations after ICS withdrawal. METHODS During ICS treatment, post-bronchodilator spirometry, body plethysmography, and health status assessment were performed in 68 COPD patients using ICS. Additionally, sputum cell differentials, supernatant leukotriene B(4), eosinophilic cationic protein, and myeloperoxidase, serum C-reactive protein and soluble intracellular adhesion molecule, and urinary desmosine were assessed. Sputum was also analysed for mRNA levels of haemoxygenase-1, tumour necrosis factor-α, RANTES, interleukin 5(IL-5), IL-10, IL-12, IL-13, transforming growth factor-β, and interferon-γ. STATISTICS Cox regression analyses were performed using time to exacerbation as outcome variable to identify significant hazards for a COPD exacerbation after ICS withdrawal. RESULTS Higher sputum % eosinophils, higher sputum MPO/neutrophil level, longer duration of COPD symptoms, <40 packyears smoking, and ICS withdrawal in November, December or January were significant hazards (all p<0.05) for experiencing a COPD exacerbation after ICS withdrawal in a monovariate model. In a multivariate model, all factors proved independent predictors except for sputum MPO/neutrophil level. CONCLUSIONS Decisions on whether or not inhaled corticosteroids can be safely withdrawn in mild-to-moderate COPD can be facilitated by assessment of sputum inflammation, particularly eosinophil numbers, next to packyears smoking, season, and duration of COPD symptoms.",
"title": "Sputum inflammation predicts exacerbations after cessation of inhaled corticosteroids in COPD."
},
{
"docid": "4380287",
"text": "Immune homeostasis in tissues is achieved through a delicate balance between pathogenic T-cell responses directed at tissue-specific antigens and the ability of the tissue to inhibit these responses. The mechanisms by which tissues and the immune system communicate to establish and maintain immune homeostasis are currently unknown. Clinical evidence suggests that chronic or repeated exposure to self antigen within tissues leads to an attenuation of pathological autoimmune responses, possibly as a means to mitigate inflammatory damage and preserve function. Many human organ-specific autoimmune diseases are characterized by the initial presentation of the disease being the most severe, with subsequent flares being of lesser severity and duration. In fact, these diseases often spontaneously resolve, despite persistent tissue autoantigen expression. In the practice of antigen-specific immunotherapy, allergens or self antigens are repeatedly injected in the skin, with a diminution of the inflammatory response occurring after each successive exposure. Although these findings indicate that tissues acquire the ability to attenuate autoimmune reactions upon repeated responses to antigens, the mechanism by which this occurs is unknown. Here we show that upon expression of self antigen in a peripheral tissue, thymus-derived regulatory T cells (Treg cells) become activated, proliferate and differentiate into more potent suppressors, which mediate resolution of organ-specific autoimmunity in mice. After resolution of the inflammatory response, activated Treg cells are maintained in the target tissue and are primed to attenuate subsequent autoimmune reactions when antigen is re-expressed. Thus, Treg cells function to confer ‘regulatory memory’ to the target tissue. These findings provide a framework for understanding how Treg cells respond when exposed to self antigen in peripheral tissues and offer mechanistic insight into how tissues regulate autoimmunity.",
"title": "Response to self antigen imprints regulatory memory in tissues"
},
{
"docid": "22937651",
"text": "Epstein-Barr virus (EBV) is associated with multiple sclerosis (MS), and antibodies to the EBV nuclear antigen-1 (EBNA-1) are consistently increased in MS patients. The hypothesis of this study is that anti-EBNA-1 antibodies cross-react with a self antigen in MS patients. We affinity purified anti-EBNA-1 antibodies from human plasma, used the anti-EBNA-1 to immunoprecipitate antigens from human brain, and identified bound antigens with mass spectrometry. Anti-EBNA-1 consistently bound heterogeneous nuclear ribonucleoprotein L (HNRNPL). We expressed both the long and short isoforms of this protein, and verified with Western blots and ELISA that the long isoform cross-reacts with EBNA-1. Immunohistochemistry demonstrated that anti-EBNA-1 bound to an antigen in the nucleus of cultured rat central nervous system cells. ELISA demonstrated the presence of antibodies to HNRNPL in the plasma of both healthy controls and MS patients, but anti-HNRNPL was not increased in MS patients. We conclude that HNRNPL is an autoantigen which cross-reacts with EBNA-1. The relevance of this autoantigen to MS and other autoimmune diseases remains to be investigated.",
"title": "Antibodies specific for Epstein-Barr virus nuclear antigen-1 cross-react with human heterogeneous nuclear ribonucleoprotein L."
},
{
"docid": "15707049",
"text": "Interstitial lung disease (ILD) is a common manifestation of systemic autoimmunity characterized by progressive inflammation or scarring of the lungs. Patients who develop these complications can exhibit significantly impaired gas exchange that may result in hypoxemia, pulmonary hypertension, and even death. Unfortunately, little is understood about how these diseases arise, including the role of specific defects in immune tolerance. Another key question is whether autoimmune responses targeting the lung parenchyma are critical to ILD pathogenesis, including that of isolated idiopathic forms. We show that a specific defect in central tolerance brought about by mutations in the autoimmune regulator gene (Aire) leads to an autoreactive T cell response to a lung antigen named vomeromodulin and the development of ILD. We found that a human patient and mice with defects in Aire develop similar lung pathology, demonstrating that the AIRE-deficient model of autoimmunity is a suitable translational system in which to unravel fundamental mechanisms of ILD pathogenesis.",
"title": "Identification of an autoantigen demonstrates a link between interstitial lung disease and a defect in central tolerance."
},
{
"docid": "15248287",
"text": "Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.",
"title": "Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival"
},
{
"docid": "3761017",
"text": "BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.",
"title": "Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion"
},
{
"docid": "1855679",
"text": "It was recently demonstrated that interleukin (IL)-23–driven IL-17–producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases. We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I–deficient (IL-1RI−/−) mice. Furthermore, the incidence of experimental autoimmune encephalomyelitis (EAE) was significantly lower in IL-1RI−/− compared with wild-type mice, and this correlated with a failure to induce autoantigen-specific ThIL-17 cells, whereas induction of Th1 and Th2 responses was not substantially different. However, EAE was induced in IL-1RI−/− mice by adoptive transfer of autoantigen-specific cells from wild-type mice with EAE. IL-23 alone did not induce IL-17 production by T cells from IL-1RI−/− mice, and IL-23–induced IL-17 production was substantially enhanced by IL-1α or IL-1β, even in the absence of T cell receptor stimulation. We demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor κB, and novel protein kinase C isoforms in IL-1– and IL-23–mediated IL-17 production. Tumor necrosis factor α also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent. Our findings demonstrate that IL-1 functions upstream of IL-17 to promote pathogenic ThIL-17 cells in EAE.",
"title": "A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis"
},
{
"docid": "27789588",
"text": "Little is known about the etiologies of diseases associated with circulating antineutrophil cytoplasm autoantibodies (ANCA), such as primary vasculitides and inflammatory bowel diseases. However, the understanding of immune mechanisms supposedly involved in the pathogenesis of these diseases is still growing. In the present review, we first focus on the mechanisms triggering the development of ANCA, including the potential role of microbial superantigens and the possible defect(s) in the progression of apoptosis or in the removal of apoptotic cells. We next concentrate on the contribution of ANCA to the clinical symptoms and on the pathogenic role of ANCA, including the accessibility of ANCA antigens as targets for circulating antibodies and the mode of action of ANCA. Mechanisms of neutrophil activation by ANCA include the engagement of Fcgamma receptors, the possible mechanisms of neutrophil-mediated tissue damage, and the neutrophil-endothelial interaction.",
"title": "Pathogenesis of diseases associated with antineutrophil cytoplasm autoantibodies."
},
{
"docid": "28392393",
"text": "Local presentation of autoantigen by organ-resident cells inappropriately expressing Ia determinants has been implicated in organ-specific autoimmunity. Experimental autoimmune uveoretinitis, induced in rats by immunization with retinal soluble antigen, is used as a model of organ-specific autoimmunity. In an in vitro system derived from this model, uveitogenic rat T-helper lymphocytes specific to the retinal soluble antigen, or control T-helper lymphocytes reactive to the purified protein derivative of tuberculin, were cocultured with Ia-expressing syngeneic retinal glial cells (Müller cells) in the presence of specific antigen. Antigen presentation was not apparent under ordinary culture conditions, and the Müller cells profoundly suppressed the proliferative response of primed T-helper lymphocytes to antigen presented on conventional antigen-presenting cells, as well as their subsequent interleukin-2 (IL-2)-dependent expansion. Suppression of proliferation was accompanied by inhibition of IL-2 production in response to antigen, as well as by reduction in high-affinity IL-2 receptor expression, and proceeded via a contact-dependent mechanism. These results suggest a role for locally acting suppression mechanisms in immune regulation and maintenance of tissue homeostasis.",
"title": "Organ-resident, nonlymphoid cells suppress proliferation of autoimmune T-helper lymphocytes."
}
] |
394
|
Excess gestational weight gain is associated with obesity-related pregnancy outcomes.
|
[
{
"docid": "11360768",
"text": "OBJECTIVE To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. DESIGN Systematic review and meta-analysis. DATA SOURCES Major databases from inception to January 2012 without language restrictions. STUDY SELECTION Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. DATA SYNTHESIS Results summarised as relative risks for dichotomous data and mean differences for continuous data. RESULTS We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference -50 g, -100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference -60 g, -120 to -10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. CONCLUSIONS Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.",
"title": "Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence"
}
] |
[
{
"docid": "70455704",
"text": "As women of childbearing age have become heavier, the trade-off between maternal and child health created by variation in gestational weight gain has become more difficult to reconcile. Weight Gain During Pregnancy responds to the need for a reexamination of the 1990 Institute of Medicine guidelines for weight gain during pregnancy. It builds on the conceptual framework that underscored the 1990 weight gain guidelines and addresses the need to update them through a comprehensive review of the literature and independent analyses of existing databases. The book explores relationships between weight gain during pregnancy and a variety of factors (e.g., the mother's weight and height before pregnancy) and places this in the context of the health of the infant and the mother, presenting specific, updated target ranges for weight gain during pregnancy and guidelines for proper measurement. New features of this book include a specific range of recommended gain for obese women. Weight Gain During Pregnancy is intended to assist practitioners who care for women of childbearing age, policy makers, educators, researchers, and the pregnant women themselves to understand the role of gestational weight gain and to provide them with the tools needed to promote optimal pregnancy outcomes.",
"title": "Weight gain during pregnancy: reexamining the guidelines."
},
{
"docid": "8842332",
"text": "OBJECTIVE To compare contemporary pregnancy outcomes in women with and without type 1 diabetes, and to examine the effects of obesity and glycaemic control on these outcomes. DESIGN AND SETTING Historical cohort study in a specialist diabetes and maternity network in Victoria. PARTICIPANTS All singleton births (at least 20 weeks' gestation), 2010-2013, were analysed: 107 pregnancies to women with type 1 diabetes and 27 075 pregnancies to women without diabetes. Women with type 2 diabetes or gestational diabetes were excluded. METHODS Data were extracted from the Birthing Outcomes System database; associations between type 1 diabetes and pregnancy outcomes were analysed by multivariable regression. MAIN OUTCOME MEASURES Mode of birth; maternal and neonatal outcomes. RESULTS The mean body mass index was higher for women with type 1 diabetes than for women without diabetes (mean, 27.3 kg/m(2) [SD, 5.0] v 25.7 kg/m(2) [SD, 5.9]; P = 0.01); the median gestation period for their babies was shorter (median, 37.3 weeks [IQR, 34.6-38.1] v 39.4 weeks [IQR, 38.4-40.4]; P < 0.001) and they were more likely to be large for gestational age (LGA) (adjusted odds ratio [aOR], 7.9; 95% CI, 5.3-11.8). Women with type 1 diabetes were more likely to have had labour induced (aOR, 3.0; 95% CI, 2.0-4.5), a caesarean delivery (aOR, 4.6; 95% CI, 3.1-7.0), or a pre-term birth (aOR, 6.7; 95% CI, 4.5-10.0); their babies were more likely to have shoulder dystocia (aOR, 8.2; 95% CI, 3.6-18.7), hypoglycaemia (aOR, 10.3; 95% CI, 6.8-15.6), jaundice (aOR, 5.1; 95% CI, 3.3-7.7), respiratory distress (aOR, 2.5; 95% CI, 1.4-4.4) or to suffer perinatal death (aOR, 4.3; 95% CI, 1.9-9.9). In women with type 1 diabetes, greater obesity was associated with increased odds for an LGA baby or congenital malformation, and increased HbA1c levels were associated with pre-term birth and perinatal death. CONCLUSION Women with type 1 diabetes, even when managed in a specialist setting, still experience adverse obstetric and neonatal outcomes. Poor glycaemic control is not wholly responsible for adverse outcomes, reinforcing the importance of other risk factors, such as obesity and weight gain.",
"title": "Contemporary type 1 diabetes pregnancy outcomes: impact of obesity and glycaemic control."
},
{
"docid": "2425364",
"text": "OBJECTIVE To assess the effect of 25-hydroxyvitamin D (25-OHD) levels on pregnancy outcomes and birth variables. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline (1966 to August 2012), PubMed (2008 to August 2012), Embase (1980 to August 2012), CINAHL (1981 to August 2012), the Cochrane database of systematic reviews, and the Cochrane database of registered clinical trials. STUDY SELECTION Studies reporting on the association between serum 25-OHD levels during pregnancy and the outcomes of interest (pre-eclampsia, gestational diabetes, bacterial vaginosis, caesarean section, small for gestational age infants, birth weight, birth length, and head circumference). DATA EXTRACTION Two authors independently extracted data from original research articles, including key indicators of study quality. We pooled the most adjusted odds ratios and weighted mean differences. Associations were tested in subgroups representing different patient characteristics and study quality. RESULTS 3357 studies were identified and reviewed for eligibility. 31 eligible studies were included in the final analysis. Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89), pre-eclampsia (1.79, 1.25 to 2.58), and small for gestational age infants (1.85, 1.52 to 2.26). Pregnant women with low serum 25-OHD levels had an increased risk of bacterial vaginosis and low birthweight infants but not delivery by caesarean section. CONCLUSION Vitamin D insufficiency is associated with an increased risk of gestational diabetes, pre-eclampsia, and small for gestational age infants. Pregnant women with low 25-OHD levels had an increased risk of bacterial vaginosis and lower birth weight infants, but not delivery by caesarean section.",
"title": "Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies."
},
{
"docid": "4550036",
"text": "The authors investigated the association between folic acid supplementation and gestational hypertension. The study population included women with nonmalformed infants in the United States and Canada who were participating in the Slone Epidemiology Center Birth Defects Study between 1993 and 2000. Women were interviewed within 6 months after delivery about sociodemographic and medical factors, the occurrence of hypertension with or without preeclampsia, and multivitamin use in pregnancy. Relative risks, adjusted for weight, parity, twin pregnancy, diabetes, smoking, education, and family income, were estimated using Cox regression models. Of 2,100 women, 204 (9.7%) reported gestational hypertension (onset after the 20th week of gestation). The multivariate-adjusted relative risk of developing gestational hypertension during the month after folic acid supplementation, compared with not using folic acid during that same month, was 0.55 (95% confidence interval: 0.39, 0.79). This finding suggests that folic acid-containing multivitamins may reduce the risk of gestational hypertension.",
"title": "Risk of gestational hypertension in relation to folic acid supplementation during pregnancy."
},
{
"docid": "37480103",
"text": "CONTEXT During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. OBJECTIVE To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. DESIGN AND SETTING Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. PARTICIPANTS Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. MAIN OUTCOME MEASURE Incidence of invasive breast cancer. RESULTS Of 314,019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (> or =4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). CONCLUSIONS Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk.",
"title": "Pregnancy characteristics and maternal risk of breast cancer."
},
{
"docid": "26611834",
"text": "CONTEXT Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). OBJECTIVE To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. DATA SOURCES AND STUDY SELECTION We searched for English-language and non-English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks' gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non-US-published studies met the selection criteria. DATA EXTRACTION Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. DATA SYNTHESIS Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. CONCLUSIONS Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.",
"title": "A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction."
},
{
"docid": "35714909",
"text": "OBJECTIVE In 1989 the St. Vincent declaration set a five-year target for approximating outcomes of pregnancies in women with diabetes to those of the background population. We investigated and quantified the risk of adverse pregnancy outcomes in pregnant women with type 1 diabetes (T1DM) to evaluate if the goals of the 1989 St. Vincent Declaration have been obtained concerning foetal and neonatal complications. METHODS Twelve population-based studies published within the last 10 years with in total 14,099 women with T1DM and 4,035,373 women from the background population were identified. The prevalence of four foetal and neonatal complications was compared. RESULTS In women with T1DM versus the background population, congenital malformations occurred in 5.0% (2.2-9.0) (weighted mean and range) versus 2.1% (1.5-2.9), relative risk (RR) = 2.4, perinatal mortality in 2.7% (2.0-6.6) versus 0.72% (0.48-0.9), RR = 3.7, preterm delivery in 25.2% (13.0-41.7) versus 6.0% (4.7-7.1), RR = 4.2 and delivery of large for gestational infants in 54.2% (45.1-62.5) versus 10.0%, RR = 4.5. Early pregnancy HbA1c was positively associated with adverse pregnancy outcomes. CONCLUSION The risk of adverse pregnancy outcomes was two to five times increased in women with T1DM compared with the general population. The goals of the St. Vincent declaration have not been achieved.",
"title": "Pregnancy in women with type 1 diabetes: have the goals of St. Vincent declaration been met concerning foetal and neonatal complications?"
},
{
"docid": "41310252",
"text": "The epidemiological evidence that a high-fat diet promotes the development of obesity is considered suggestive but not definitive. The purpose of this paper is to provide a review of various epidemiological methods that have been used to address this issue as well as an updated summary of the existing evidence. Ecological studies describing dietary fat intake and obesity at the population level provide mixed results and are likely to be biased by both confounding and unknown data quality factors that differ systematically across the populations studied. Cross-sectional studies are generally in agreement that the concentration of fat in the diet is positively associated with relative weight. Prospective studies of diet in relation to subsequent weight change give inconsistent results. This may be due to behavioural factors such as dieting in response to weight gain; in addition, this type of study rarely takes into account the possible interaction between genetic predisposition and dietary fat in promoting weight gain. Finally, intervention studies in free-living subjects are considered, providing evidence of a consistent but short-lived period of active weight loss on low-fat diets. The experimental evidence on this relationship is more conclusive than the epidemiological evidence, although biological mechanisms remain controversial. Some areas for future epidemiological research involve: longitudinal studies of dietary fat intake as a predictor of growth in children; observational studies relating total dietary fat and specific types of fat to overall as well as regional adiposity; and randomized intervention studies of the effect of low-fat diets with particular emphasis on and familial predisposition to obesity and other possible modifying factors.",
"title": "Dietary fat and obesity: evidence from epidemiology."
},
{
"docid": "1428830",
"text": "Atypical antipsychotics such as olanzapine often induce excessive weight gain and type 2 diabetes. However, the mechanisms underlying these drug-induced metabolic perturbations remain poorly understood. Here, we used an experimental model that reproduces olanzapine-induced hyperphagia and obesity in female C57BL/6 mice. We found that olanzapine treatment acutely increased food intake, impaired glucose tolerance, and altered physical activity and energy expenditure in mice. Furthermore, olanzapine-induced hyperphagia and weight gain were blunted in mice lacking the serotonin 2C receptor (HTR2C). Finally, we showed that treatment with the HTR2C-specific agonist lorcaserin suppressed olanzapine-induced hyperphagia and weight gain. Lorcaserin treatment also improved glucose tolerance in olanzapine-fed mice. Collectively, our studies suggest that olanzapine exerts some of its untoward metabolic effects via antagonism of HTR2C.",
"title": "The atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2C."
},
{
"docid": "9822397",
"text": "CONTEXT Sugar-sweetened beverages like soft drinks and fruit punches contain large amounts of readily absorbable sugars and may contribute to weight gain and an increased risk of type 2 diabetes, but these relationships have been minimally addressed in adults. OBJECTIVE To examine the association between consumption of sugar-sweetened beverages and weight change and risk of type 2 diabetes in women. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort analyses conducted from 1991 to 1999 among women in the Nurses' Health Study II. The diabetes analysis included 91,249 women free of diabetes and other major chronic diseases at baseline in 1991. The weight change analysis included 51,603 women for whom complete dietary information and body weight were ascertained in 1991, 1995, and 1999. We identified 741 incident cases of confirmed type 2 diabetes during 716,300 person-years of follow-up. MAIN OUTCOME MEASURES Weight gain and incidence of type 2 diabetes. RESULTS Those with stable consumption patterns had no difference in weight gain, but weight gain over a 4-year period was highest among women who increased their sugar-sweetened soft drink consumption from 1 or fewer drinks per week to 1 or more drinks per day (multivariate-adjusted means, 4.69 kg for 1991 to 1995 and 4.20 kg for 1995 to 1999) and was smallest among women who decreased their intake (1.34 and 0.15 kg for the 2 periods, respectively) after adjusting for lifestyle and dietary confounders. Increased consumption of fruit punch was also associated with greater weight gain compared with decreased consumption. After adjustment for potential confounders, women consuming 1 or more sugar-sweetened soft drinks per day had a relative risk [RR] of type 2 diabetes of 1.83 (95% confidence interval [CI], 1.42-2.36; P<.001 for trend) compared with those who consumed less than 1 of these beverages per month. Similarly, consumption of fruit punch was associated with increased diabetes risk (RR for > or =1 drink per day compared with <1 drink per month, 2.00; 95% CI, 1.33-3.03; P =.001). CONCLUSION Higher consumption of sugar-sweetened beverages is associated with a greater magnitude of weight gain and an increased risk for development of type 2 diabetes in women, possibly by providing excessive calories and large amounts of rapidly absorbable sugars.",
"title": "Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women."
},
{
"docid": "33740844",
"text": "Current understanding of biologic processes indicates that women's nutritional status before and during early pregnancy may play an important role in determining early developmental processes and ensuring successful pregnancy outcomes. We conducted a systematic review of the evidence for the impact of maternal nutrition before and during early pregnancy (<12 weeks gestation) on maternal, neonatal and child health outcomes and included 45 articles (nine intervention trials and 32 observational studies) that were identified through PubMed and EMBASE database searches and examining review articles. Intervention trials and observational studies show that periconceptional (<12 weeks gestation) folic acid supplementation significantly reduced the risk of neural tube defects. Observational studies suggest that preconceptional and periconceptional intake of vitamin and mineral supplements is associated with a reduced risk of delivering offspring who are low birthweight and/or small-for-gestational age (SGA) and preterm deliveries (PTD). Some studies report that indicators of maternal prepregnancy size, low stature, underweight and overweight are associated with increased risks of PTD and SGA. The available data indicate the importance of women's nutrition prior to and during the first trimester of pregnancy, but there is a need for well-designed prospective studies and controlled trials in developing country settings that examine relationships with low birthweight, SGA, PTD, stillbirth and maternal and neonatal mortality. The knowledge gaps that need to be addressed include the evaluation of periconceptional interventions such as food supplements, multivitamin-mineral supplements and/or specific micronutrients (iron, zinc, iodine, vitamin B-6 and B-12) as well as the relationship between measures of prepregnancy body size and composition and maternal, neonatal and child health outcomes.",
"title": "Effect of women's nutrition before and during early pregnancy on maternal and infant outcomes: a systematic review."
},
{
"docid": "1456068",
"text": "BACKGROUND Although cigarette smoking, excessive alcohol drinking, obesity, and several other well-studied unhealthy lifestyle-related factors each have been linked to the risk of multiple chronic diseases and premature death, little is known about the combined impact on mortality outcomes, in particular among Chinese and other non-Western populations. The objective of this study was to quantify the overall impact of lifestyle-related factors beyond that of active cigarette smoking and alcohol consumption on all-cause and cause-specific mortality in Chinese women. METHODS AND FINDINGS We used data from the Shanghai Women's Health Study, an ongoing population-based prospective cohort study in China. Participants included 71,243 women aged 40 to 70 years enrolled during 1996-2000 who never smoked or drank alcohol regularly. A healthy lifestyle score was created on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes (normal weight, lower waist-hip ratio, daily exercise, never exposed to spouse's smoking, higher daily fruit and vegetable intake). The score ranged from zero (least healthy) to five (most healthy) points. During an average follow-up of 9 years, 2,860 deaths occurred, including 775 from cardiovascular disease (CVD) and 1,351 from cancer. Adjusted hazard ratios for mortality decreased progressively with an increasing number of healthy lifestyle factors. Compared to women with a score of zero, hazard ratios (95% confidence intervals) for women with four to five factors were 0.57 (0.44-0.74) for total mortality, 0.29 (0.16-0.54) for CVD mortality, and 0.76 (0.54-1.06) for cancer mortality. The inverse association between the healthy lifestyle score and mortality was seen consistently regardless of chronic disease status at baseline. The population attributable risks for not having 4-5 healthy lifestyle factors were 33% for total deaths, 59% for CVD deaths, and 19% for cancer deaths. CONCLUSIONS In this first study, to our knowledge, to quantify the combined impact of lifestyle-related factors on mortality outcomes in Chinese women, a healthier lifestyle pattern-including being of normal weight, lower central adiposity, participation in physical activity, nonexposure to spousal smoking, and higher fruit and vegetable intake-was associated with reductions in total and cause-specific mortality among lifetime nonsmoking and nondrinking women, supporting the importance of overall lifestyle modification in disease prevention. Please see later in the article for the Editors' Summary.",
"title": "Combined Impact of Lifestyle-Related Factors on Total and Cause-Specific Mortality among Chinese Women: Prospective Cohort Study"
},
{
"docid": "25182647",
"text": "Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) are rare but major disorders of the third trimester of pregnancy. Over a 10-year period, 46 women (median age, 30 years; range, 17-41 years) developed hepatic dysfunction severe enough to require transfer to our Liver Failure Unit. Three quarters of the women were nulliparous, and 5 had twin pregnancies; the median gestational age was 35 weeks (range, 24-40 weeks). At admission, 32 patients (70%) were preeclamptic and 21 (46%) were encephalopathic and/or ventilated. Thirty-two patients (70%) had clinical features and laboratory values consistent with AFLP, and 7 (15%) had HELLP syndrome. One patient had preeclamptic liver rupture requiring liver transplantation. In 6 other patients, causes of severe liver dysfunction unrelated to pregnancy were found. Infectious complications occurred in 17 of the patients with AFLP (53%) and in 2 of those with HELLP syndrome (29%). Major intra-abdominal bleeding occurred in 12 women (10 with AFLP), 9 of whom required laparotomies for clot evacuation. Four patients with AFLP (12.5%) had a fatal outcome, with a corresponding perinatal mortality rate of 9%. There were no maternal or perinatal deaths associated with HELLP syndrome. In contrast to results of many previous studies, the results of this large series suggest a relatively favorable maternal and perinatal outcome in severe AFLP and HELLP syndrome. Further improvements in outcome are likely to be achieved through the prevention of the bleeding and infectious complications associated with these disorders.",
"title": "Maternal and perinatal outcome in severe pregnancy-related liver disease."
},
{
"docid": "1831916",
"text": "OBJECTIVE Impulsivity and inattention related to attention deficit hyperactivity disorder (ADHD) may increase food intake and, consequently, weight gain. However, findings on the association between obesity/overweight and ADHD are mixed. The authors conducted a meta-analysis to estimate this association. METHOD A broad range of databases was searched through Aug. 31, 2014. Unpublished studies were also obtained. Study quality was rated with the Newcastle-Ottawa Scale. Random-effects models were used. RESULTS Forty-two studies that included a total of 728,136 individuals (48,161 ADHD subjects; 679,975 comparison subjects) were retained. A significant association between obesity and ADHD was found for both children (odds ratio=1.20, 95% CI=1.05-1.37) and adults (odds ratio=1.55, 95% CI=1.32-1.81). The pooled prevalence of obesity was increased by about 70% in adults with ADHD (28.2%, 95% CI=22.8-34.4) compared with those without ADHD (16.4%, 95% CI=13.4-19.9), and by about 40% in children with ADHD (10.3%, 95% CI=7.9-13.3) compared with those without ADHD (7.4%, 95% CI=5.4-10.1). The significant association between ADHD and obesity remained when limited to studies 1) reporting odds ratios adjusted for possible confounding factors; 2) diagnosing ADHD by direct interview; and 3) using directly measured height and weight. Gender, study setting, study country, and study quality did not moderate the association between obesity and ADHD. ADHD was also significantly associated with overweight. Individuals medicated for ADHD were not at higher risk of obesity. CONCLUSIONS This study provides meta-analytic evidence for a significant association between ADHD and obesity/overweight. Further research should address possible underlying mechanisms and the long-term effects of ADHD treatments on weight in individuals with both ADHD and obesity.",
"title": "Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis."
},
{
"docid": "356218",
"text": "BACKGROUND Pregnant women with mild preexisting renal disease have relatively few complications of pregnancy, but the risks of maternal and obstetrical complications in women with moderate or severe renal insufficiency remain uncertain. METHODS We determined the frequency and types of maternal and obstetrical complications and the outcomes of pregnancy in 67 women with primary renal disease (82 pregnancies). All the women had initial serum creatinine concentrations of at least 1.4 mg per deciliter (124 mumol per liter) and gestations that continued beyond the first trimester. RESULTS The mean (+/- SD) serum creatinine concentration increased from 1.9 +/- 0.8 mg per deciliter (168 +/- 71 mumol per liter) in early pregnancy to 2.5 +/- 1.3 mg per deciliter (221 +/- 115 mumol per liter) in the third trimester. The frequency of hypertension rose from 28 percent at base line to 48 percent in the third trimester, and that of high-grade proteinuria (urinary protein excretion, > 3000 mg per liter) from 23 percent to 41 percent. For the 70 pregnancies (57 women) for which data were available during pregnancy and immediately post partum, pregnancy-related loss of maternal renal function occurred in 43 percent. Eight of these pregnancies (10 percent of the total) were associated with rapid acceleration of maternal renal insufficiency. Obstetrical complications included a high rate of preterm delivery (59 percent) and growth retardation (37 percent). The infant survival rate was 93 percent. CONCLUSIONS Among pregnant women with moderate or severe renal insufficiency, the rates of complications due to worsening renal function, hypertension, and obstetrical complications are increased, but fetal survival is high.",
"title": "Outcome of pregnancy in women with moderate or severe renal insufficiency."
},
{
"docid": "1365188",
"text": "Several data suggest that fermentable dietary fiber could play a role in the control of obesity and associated metabolic disorders. The aim of this study was to investigate the putative role of short chain fructo-oligosaccharide (OFS) - a non-digestible oligosaccharide - in mice fed a standard diet and in mice fed two distinct high fat diets inducing metabolic disorders associated to obesity. We confirmed, in mice, several effects previously shown in rats fed a standard diet enriched with OFS, namely an increase in total and empty caecum weight, a significant decrease in epididymal fat mass, and an increase in colonic and portal plasma glucagon-like peptide-1 (GLP-1), a phenomenon positively correlated with a higher colonic proglucagon mRNA level. Curiously, 4-week treatment with OFS added at the same dose induced different effects when added in the two different high fat diets. OFS decreased energy intake, body weight gain, glycemia, and epididymal fat mass only when added together with the high fat-carbohydrate free diet, in which OFS promoted colonic proglucagon expression and insulin secretion. Our results support an association between the increase in proglucagon expression in the proximal colon and OFS effects on glycemia, fat mass development, and/or body weight gain. In conclusion, dietary oligosaccharides would constitute an interesting class of dietary fibers promoting, in certain conditions, endogenous GLP-1 production, with beneficial physiological consequences. This remains to be proven in human studies.",
"title": "Relation between colonic proglucagon expression and metabolic response to oligofructose in high fat diet-fed mice."
},
{
"docid": "29387024",
"text": "BACKGROUND Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.",
"title": "Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial"
},
{
"docid": "43220289",
"text": "Extreme obesity is associated with severe psychiatric and somatic comorbidity and impairment of psychosocial functioning. Bariatric surgery is the most effective treatment not only with regard to weight loss but also with obesity-associated illnesses. Health-related psychological and psychosocial variables have been increasingly considered as important outcome variables of bariatric surgery. However, the long-term impact of bariatric surgery on psychological and psychosocial functioning is largely unclear. The aim of this study was to evaluate the relationship between the course of weight and psychological variables including depression, anxiety, health-related quality of life (HRQOL), and self-esteem up to 4 years after obesity surgery. By standardized questionnaires prior to (T1) and 1 year (T2), 2 years (T3), and 4 years (T4) after surgery, 148 patients (47 males (31.8 %), 101 females (68.2 %), mean age 38.8 ± 10.2 years) were assessed. On average, participants lost 24.6 % of their initial weight 1 year after surgery, 25.1 % after 2 years, and 22.3 % after 4 years. Statistical analysis revealed significant improvements in depressive symptoms, physical dimension of quality of life, and self-esteem with peak improvements 1 year after surgery. These improvements were largely maintained. Significant correlations between weight loss and improvements in depression, physical aspects of HRQOL (T2, T3, and T4), and self-esteem (T3) were observed. Corresponding to the considerable weight loss after bariatric surgery, important aspects of mental health improved significantly during the 4-year follow-up period. However, parallel to weight regain, psychological improvements showed a slow but not significant decline over time.",
"title": "Psychological Outcome 4 Years after Restrictive Bariatric Surgery"
},
{
"docid": "21547032",
"text": "Objective:In mice and in humans, treatment with the second-generation antipsychotic drug olanzapine (OLZ) produces excessive weight gain, adiposity and secondary metabolic complications, including loss of glucose and insulin homeostasis. In mice consuming a high-fat (HF) diet, a similar phenotype develops, which is inhibited by the analgesic acetaminophen (APAP) and by the antioxidant tetrahydroindenoindole (THII). Therefore, we examined the ability of APAP and THII to prevent metabolic changes in mice receiving OLZ.Design and Measurement:C57BL/6J mice received either a normal diet or a HF diet, and were administered daily dosages of OLZ (3 mg kg−1 body weight), alone or with APAP (30 mg kg−1 body weight) or THII (4.5 mg kg−1 body weight), for 10 weeks. Parameters of body composition and metabolism, including glucose and insulin homeostasis and oxidative stress, were examined. Results:OLZ treatment doubled the HF diet-induced increases in body weight and percent body fat. These increases were partially prevented by both APAP and THII, although food consumption was constant in all groups. The THII protection was associated with an increase in whole body and mitochondrial respiration. OLZ also exacerbated, and both APAP and THII prevented, HF diet-induced loss of glucose tolerance and insulin resistance. As increased body fat promotes insulin resistance by a pathway involving oxidative stress, we evaluated production of reactive oxygen and lipid peroxidation in white adipose tissue (WAT). HF diet caused an increase in lipid peroxidation, NADPH-dependent O2 uptake and H2O2 production, which were further exacerbated by OLZ. APAP, THII and the NADPH oxidase inhibitor, diphenyleneiodonium chloride, each abolished oxidative stress in WAT.Conclusions:We conclude that both APAP and THII intervene in the development of obesity and metabolic complications associated with OLZ treatment.",
"title": "Protection from olanzapine-induced metabolic toxicity in mice by acetaminophen and tetrahydroindenoindole"
},
{
"docid": "5824985",
"text": "BACKGROUND Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities. METHODS AND FINDINGS This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88-5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55-0.83); hypertension, 0.35 (95% CI 0.27-0.45); angina, 0.59 (95% CI 0.40-0.87);MI, 0.28 (95% CI 0.10-0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40-0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84-12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65-11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66-1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes. CONCLUSIONS Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.",
"title": "Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care."
},
{
"docid": "198309074",
"text": "Introduction: Among the inflammatory mediators involved in the pathogenesis of obesity, the cell adhesion molecules Pselectin, E-selectin, VCAM-1, ICAM-1 and the chemokine MCP-1 stand out. They play a crucial role in adherence of cells to endothelial surfaces, in the integrity of the vascular wall and can be modulated by body composition and dietary pattern. Objectives: To describe and discuss the relation of these cell adhesion molecules and chemokines to anthropometric, body composition, dietary and biochemical markers. Methods: Papers were located using scientific databases by topic searches with no restriction on year of publication. Results: All molecules were associated positively with anthropometric markers, but controversial results were found for ICAM-1 and VCAM-1. Not only obesity, but visceral fat is more strongly correlated with E-selectin and MCP-1 levels. Weight loss influences the reduction in the levels of these molecules, except VCAM-1. The distribution of macronutrients, excessive consumption of saturated and trans fat and a Western dietary pattern are associated with increased levels. The opposite could be observed with supplementation of w-3 fatty acid, healthy dietary pattern, high calcium diet and high dairy intake. Regarding the biochemical parameters, they have inverse relation to HDLC and positive relation to total cholesterol, triglycerides, blood glucose, fasting insulin and insulin resistance. Conclusion: Normal anthropometric indicators, body composition, biochemical parameters and eating pattern positively modulate the subclinical inflammation that results from obesity by reducing the cell adhesion molecules and chemokines.",
"title": "Adhesion molecules and chemokines: relation to anthropometric, body composition, biochemical and dietary variables"
},
{
"docid": "439670",
"text": "The objective of this study is to assess and quantify the risk for gestational diabetes mellitus (GDM) according to prepregnancy maternal body mass index (BMI). The design is a systematic review of observational studies published in the last 30 years. Four electronic databases were searched for publications (1977-2007). BMI was elected as the only measure of obesity, and all diagnostic criteria for GDM were accepted. Studies with selective screening for GDM were excluded. There were no language restrictions. The methodological quality of primary studies was assessed. Some 1745 citations were screened, and 70 studies (two unpublished) involving 671 945 women were included (59 cohorts and 11 case-controls). Most studies were of high or medium quality. Compared with women with a normal BMI, the unadjusted pooled odds ratio (OR) of an underweight woman developing GDM was 0.75 (95% confidence interval [CI] 0.69 to 0.82). The OR for overweight, moderately obese and morbidly obese women were 1.97 (95% CI 1.77 to 2.19), 3.01 (95% CI 2.34 to 3.87) and 5.55 (95% CI 4.27 to 7.21) respectively. For every 1 kg m(-2) increase in BMI, the prevalence of GDM increased by 0.92% (95% CI 0.73 to 1.10). The risk of GDM is positively associated with prepregnancy BMI. This information is important when counselling women planning a pregnancy.",
"title": "Prepregnancy BMI and the risk of gestational diabetes: a systematic review of the literature with meta-analysis."
},
{
"docid": "40949706",
"text": "Obesity affects 32% of adults in the USA. Surgery generates substantial weight loss, but 20–30% fails to achieve successful weight loss. Our objective was to identify preoperative psychosocial factors associated with weight loss following bariatric surgery. We performed a literature search of PubMed® and the Cochrane Database of Reviews of Effectiveness between 1988 and April 2010. Articles were screened for bariatric surgery and weight loss if they included a preoperative predictor of weight loss: body mass index (BMI), preoperative weight loss, eating disorders, or psychiatric disorder/substance abuse. One thousand seven titles were reviewed, 534 articles screened, and 115 included in the review. Factors that may be positively associated with weight loss after surgery include mandatory preoperative weight loss (7 of 14 studies with positive association). Factors that may be negatively associated with weight loss include preoperative BMI (37 out of 62 studies with negative association), super-obesity (24 out of 33 studies), and personality disorders (7 out of 14 studies). Meta-analysis revealed a decrease of 10.1% excess weight loss (EWL) for super-obese patients (95% confidence interval (CI) [3.7–16.5%]), though there was significant heterogeneity in the meta-analysis, and an increase of 5.9% EWL for patients with binge eating at 12 months after surgery (95% CI [1.9–9.8%]). Further studies are necessary to investigate whether preoperative factors can predict a clinically meaningful difference in weight loss after bariatric surgery. The identification of predictive factors may improve patient selection and help develop interventions targeting specific needs of patients.",
"title": "Preoperative Predictors of Weight Loss Following Bariatric Surgery: Systematic Review"
},
{
"docid": "14865329",
"text": "Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.",
"title": "Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders"
},
{
"docid": "6718824",
"text": "Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.",
"title": "Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat."
},
{
"docid": "52865789",
"text": "OBJECTIVE IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues. METHODS Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells. RESULTS Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues. CONCLUSIONS Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.",
"title": "Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues"
},
{
"docid": "5268462",
"text": "Accumulating evidence indicates that obesity is closely associated with an increased risk of metabolic diseases such as insulin resistance, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an imbalance between food intake and energy expenditure, which leads to an excessive accumulation of adipose tissue. Adipose tissue is now recognized not only as a main site of storage of excess energy derived from food intake but also as an endocrine organ. The expansion of adipose tissue produces a number of bioactive substances, known as adipocytokines or adipokines, which trigger chronic low-grade inflammation and interact with a range of processes in many different organs. Although the precise mechanisms are still unclear, dysregulated production or secretion of these adipokines caused by excess adipose tissue and adipose tissue dysfunction can contribute to the development of obesity-related metabolic diseases. In this review, we focus on the role of several adipokines associated with obesity and the potential impact on obesity-related metabolic diseases. Multiple lines evidence provides valuable insights into the roles of adipokines in the development of obesity and its metabolic complications. Further research is still required to fully understand the mechanisms underlying the metabolic actions of a few newly identified adipokines.",
"title": "Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease"
},
{
"docid": "8529693",
"text": "In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.",
"title": "Maternal and child undernutrition: consequences for adult health and human capital"
},
{
"docid": "597790",
"text": "Although mast cell functions have classically been related to allergic responses, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm and cancer. This study presents evidence that mast cells also contribute to diet-induced obesity and diabetes. For example, white adipose tissue (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Furthermore, in the context of mice on a Western diet, genetically induced deficiency of mast cells, or their pharmacological stabilization, reduces body weight gain and levels of inflammatory cytokines, chemokines and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer experiments of cytokine-deficient mast cells show that these cells, by producing interleukin-6 (IL-6) and interferon-gamma (IFN-gamma), contribute to mouse adipose tissue cysteine protease cathepsin expression, apoptosis and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance. Our results showing reduced obesity and diabetes in mice treated with clinically available mast cell-stabilizing agents suggest the potential of developing new therapies for these common human metabolic disorders.",
"title": "Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice"
},
{
"docid": "18997216",
"text": "Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.",
"title": "Sympathetic baroreflex gain in normotensive pregnant women."
}
] |
150200
|
Dolly Parton is incapable of being a songwriter.
|
[
{
"docid": "Dolly_Parton",
"text": "Dolly Rebecca Parton Dean ( born January 19 , 1946 ) , professionally known as Dolly Parton , is an American singer , songwriter , multi-instrumentalist , record producer , actress , author , businesswoman , and philanthropist , known primarily for her work in country music . After achieving success as a songwriter for others , Dolly Parton made her album debut in 1967 , with her album Hello , I 'm Dolly . With steady success during the remainder of the 1960s ( both as a solo artist and with a series of duet albums with Porter Wagoner ) , her sales and chart peak came during the 1970s and continuing into the 1980s ; Parton 's subsequent albums in the later part of the 1990s were lower in sales . However , in the new millennium , Parton achieved commercial success again and has released albums on independent labels since 2000 , including albums on her own label , Dolly Records . Parton is the most honored female country performer of all time . Achieving 25 Recording Industry Association of America ( RIAA ) certified Gold , Platinum , and Multi-Platinum awards , she has had 25 songs reach No. 1 on the Billboard country music charts , a record for a female artist ( tied with Reba McEntire ) . She has 41 career top 10 country albums , a record for any artist , and she has 110 career charted singles over the past 40 years . All-inclusive sales of singles , albums , hits collections , and digital downloads during her career have topped 100 million worldwide . She has garnered nine Grammy Awards , two Academy Award nominations , ten Country Music Association Awards , seven Academy of Country Music Awards , three American Music Awards , and is one of only seven female artists to win the Country Music Association 's Entertainer of the Year Award . Parton has received 47 Grammy nominations . In 1999 , Parton was inducted into the Country Music Hall of Fame . She has composed over 3,000 songs , notably `` I Will Always Love You '' ( a two-time U.S. country chart-topper for Parton , as well as an international pop hit for Whitney Houston ) , `` Jolene '' , `` Coat of Many Colors '' , and `` 9 to 5 '' . She is also one of the few to have received at least one nomination from the Academy Awards , Grammy Awards , Tony Awards , and Emmy Awards . As an actress , she starred in films such as 9 to 5 , The Best Little Whorehouse in Texas , Rhinestone , and Steel Magnolias .",
"title": ""
}
] |
[
{
"docid": "Pure_&_Simple_(Dolly_Parton_album)",
"text": "Pure & Simple is the 43rd solo studio album by American singer-songwriter Dolly Parton . It was released worldwide on August 19 , 2016 , by Dolly Records and RCA Nashville . It is Parton 's seventh No. 1 country album , her first in twenty-five years .",
"title": ""
},
{
"docid": "Stella_Parton",
"text": "Stella Mae Parton ( born May 4 , 1949 ) is an American country singer and songwriter . Parton is best known for a series of country singles that charted during the mid - to late-1970s , her biggest hit being 1975 's `` I Want to Hold You In My Dreams Tonight '' . She is the younger sister of country music entertainer Dolly Parton .",
"title": ""
},
{
"docid": "My_Favorite_Songwriter,_Porter_Wagoner",
"text": "My Favorite Songwriter , Porter Wagoner , released in 1972 , is the tenth solo studio album by Dolly Parton , performing the work of her duet partner Porter Wagoner . The album peaked on the U.S. country albums chart at # 33 , while its single , `` Washday Blues '' reached # 20 . `` When I Sing for Him '' is a gospel song that was released as a single but did not chart . `` Lonely Comin ' Down '' also appeared on 1974 's Jolene album and was later included ( as was `` When I Sing for Him '' ) on the 1975 compilation Best of Dolly Parton . The album 's liner notes are written by Dolly Parton herself ( who also wrote the liner notes that year to Skeeter Davis ' album of Parton originals , Skeeter Sings Dolly ) . This album was released on CD for the first time on August 17 , 2010 , along with 1970 's The Fairest of Them All .",
"title": ""
},
{
"docid": "The_Collection_(Dolly_Parton_album)",
"text": "The Collection is a 1999 album by singer-songwriter Dolly Parton .",
"title": ""
},
{
"docid": "Collector's_Series_(Dolly_Parton_album)",
"text": "Collectors Series '' is a 1985 album by singer-songwriter Dolly Parton .",
"title": ""
},
{
"docid": "List_of_recordings_by_Dolly_Parton",
"text": "The discography of country music singer Dolly Parton consists of 43 solo studio albums , four live albums , two holiday albums , three Dollywood Exclusive albums , and approximately 184 compilation albums worldwide . In addition to these solo albums , she has also released eighteen collaboration albums , of which thirteen were with country music singer Porter Wagoner . Parton has also appeared as a guest performer and provided harmony vocals on hundreds of recordings throughout her lengthy career . Dolly Parton made her album debut in 1967 ( she 'd previously achieved success as a songwriter for others ) , with her album Hello , I 'm Dolly . With steady success during the remainder of the 1960s ( both as a solo artist , and with a series of duet albums with Porter Wagoner ) , her sales and chart peak came during the 1970s and continuing into the 1980s ; Parton 's subsequent albums in the later part of the 1990s were lower in sales . At this time , country pop ruled the country albums and singles chart . However , in the new millennium , Parton achieved commercial success again . She has released albums on independent labels since 2000 , including albums on her own label , Dolly Records . In addition to the duet albums with Wagoner , Parton has released collaborative albums with Emmylou Harris and Linda Ronstadt ; Kenny Rogers ; and Tammy Wynette and Loretta Lynn .",
"title": ""
},
{
"docid": "The_Best_of_Dolly_Parton",
"text": "The Best of Dolly Parton is a compilation album by Dolly Parton , released in November 1970 . Featuring much of her early RCA material , the compilation album included the biggest hit she 'd had to that point , her cover of Jimmie Rodgers ' `` Mule Skinner Blues '' , which peaked at # 3 on the U.S. country charts in early 1970 . This recording was also released later by Time/Life Records - the other tracks were previously released on other albums . The Best of Dolly Parton was released just three years after Parton signed with the label and thus features several songs that were not single releases , `` Down From Dover '' , `` Gypsy Joe and Me '' , `` Just the Way I Am '' and the gospel standard `` How Great Thou Art '' . The album is occasionally confused with the 1975 RCA release Best of Dolly Parton . ( Sometimes the albums are differentiated by their being referred to as Best of ... Volume I and Best of ... Volume II ) and the 2007 compilation album The Very Best of Dolly Parton . `` Mule Skinner Blues '' earned Parton her first ever Grammy nomination for Best Female Country Vocal . The album was certified Gold by the Recording Industry Association of America .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Dolly_Parton",
"text": "Dolly Parton is an American singer-songwriter , multi-instrumentalist , actress , author , and philanthropist , best known for her work in country music .",
"title": ""
},
{
"docid": "Dolly_Parton_albums_discography",
"text": "The albums discography of country music singer Dolly Parton consists of 43 solo studio albums , four live albums , two holiday albums , three Dollywood Exclusive albums , and approximately 184 compilation albums worldwide . In addition to these solo albums , she has also released eighteen collaboration albums , of which thirteen were with country music singer Porter Wagoner . Dolly Parton made her album debut in 1967 ( she 'd previously achieved success as a songwriter for others ) , with her album Hello , Im Dolly . With steady success during the remainder of the 1960s ( both as a solo artist , and with a series of duet albums with Porter Wagoner ) , her sales and chart peak came during the 1970s and continuing into the 1980s ; Parton 's subsequent albums in the later part of the 1990s were lower in sales . At this time , country pop ruled the country albums and singles chart . However , in the new millennium , Parton achieved commercial success again . She has released albums on independent labels since 2000 , including albums on her own label , Dolly Records . In addition to the duet albums with Wagoner , Parton has released collaborative albums with Emmylou Harris and Linda Ronstadt ; Kenny Rogers ; and Tammy Wynette and Loretta Lynn .",
"title": ""
},
{
"docid": "Porter_Wayne_and_Dolly_Rebecca",
"text": "Porter Wayne and Dolly Rebecca is the fourth duet album by Porter Wagoner & Dolly Parton , released in March 1970 . It contains the singles `` Just Someone I Used to Know ' and `` Tomorrow Is Forever '' , both of which reached the top ten on the U.S. country charts , as well as one of their best remembered `` musical fights , '' `` Run That by Me One More Time . '' The album reached # 4 on the country albums charts . The album title comes from Wagoner and Parton 's first and middle names , Wagoner being Porter Wayne and Parton being Dolly Rebecca .",
"title": ""
},
{
"docid": "As_Long_as_I_Love",
"text": "As Long As I Love is a 1970 album by singer-songwriter Dolly Parton and the first compilation album of her career . This album consisted of previously unreleased tracks Parton had recorded while at Monument ( she left the label in 1967 after having released only one album , to sign with RCA Victor ) . Neither Parton nor Monument put much effort into promoting the album , and it did not chart , likely due to competition from Parton 's then current RCA release The Fairest of Them All , as well as her then current duet album with Porter Wagoner , Porter Wayne and Dolly Rebecca '' .",
"title": ""
},
{
"docid": "Great_Balls_of_Fire_(Dolly_Parton_album)",
"text": "Great Balls of Fire is a 1979 country music album recorded by Dolly Parton and released by RCA Records . It is Parton 's 21st solo studio album . The album 's first single , `` You 're the Only One '' , topped the U.S. country charts in mid 1979 ( # 59 pop ) , while the follow-up single , `` Sweet Summer Lovin ' '' , was a top ten country hit ( # 77 pop ) . The album included two covers : the title song , a remake of the Jerry Lee Lewis hit from 1957 ; and a bluegrass-inspired recording of The Beatles hit `` Help ! '' . In conjunction with Parton 's 2007 European tour , BMG Germany ( a division of Sony/BMG ) released the album for the first time on CD . It was paired with 1980s Dolly , Dolly , Dolly on a double CD . The album ended up being certified Gold by the Recording Industry Association of America .",
"title": ""
},
{
"docid": "Singer,_Songwriter_&_Legendary_Performer",
"text": "Singer , Songwriter & Legendary Performer is a 2007 album by Dolly Parton released exclusively through Britain 's Daily Mail and Dolly Records to support her European Tour 2007 .",
"title": ""
},
{
"docid": "Randy_Parton",
"text": "Randle Huston `` Randy '' Parton ( born December 15 , 1953 ) is an American singer-songwriter , actor and businessman , best known as the brother of Dolly Parton and Stella Parton . Born in Sevierville , Tennessee , Parton is the eighth of twelve children born to Avie Lee Caroline Owens and Robert Lee Parton Sr. . His sister Dolly Parton has stated in interviews that to her knowledge her father had strayed at least once or twice and fathered three illegitimate children . He is a distant cousin of adult-film actress Julia Parton . In 1984 he sang a song for the Rhinestone soundtrack ; his sister Dolly starred in the film . He also played bass for his sister . He is also known for the theater that once bore his name in Roanoke Rapids , North Carolina . In 2007 he signed a deal worth over $ 1.5 million yearly to manage and perform in a new theater bearing his name in the Carolina Crossroads entertainment and shopping complex . The relationship between Parton and the city soured as the theater struggled to attract customers and questions arose concerning Parton 's use of a nearly $ 3 million fund for personal travel and entertainment . Parton was also questioned by city leaders for unauthorized events held at the theater including a wedding reception for his daughter along with details about who would be marketing the theater . Throughout the controversy , Parton maintained that his actions were within the contract and that the theater would be successful given time . Parton 's contract with the city was terminated on January 8 , 2008 and the theater was renamed the Roanoke Rapids Theater . The city took over the theater and in July 2012 voted to allow electronic gambling to help pay expenses and possibly attract a buyer .",
"title": ""
},
{
"docid": "Mine_(Dolly_Parton_album)",
"text": "Mine is a 1973 compilation album by singer-songwriter Dolly Parton , issued by RCA 's budget compilation division , RCA Camden . As was the case with Parton 's 1972 RCA Camden compilation , Just the Way I Am , the album was an attempt by RCA to capitalize on Parton 's early 1970s chart success by reissuing some of her lesser known material ( in this case , tracks recorded between 1969 and 1970 ) as a budget release , for newer fans who might not have purchased her earlier albums . The majority of tracks on Mine had first appeared on Parton 's 1970 album , The Fairest of Them All . RCA Camden would release two additional Parton compilations : I Wish I Felt This Way at Home ( 1975 ) and Just Because I 'm a Woman '' ( not to be confused with Parton 's 1968 debut solo album for RCA of the same name ) ( 1976 ) ; all four RCA Camden reissues would later be rereleased on the Pickwick label during the late 1970s .",
"title": ""
},
{
"docid": "Two_of_a_Kind_(Porter_Wagoner_&_Dolly_Parton_album)",
"text": "Two of a Kind is the sixth duet album by Porter Wagoner and Dolly Parton , released on February 1971 . The album reached # 13 on the U.S. country albums chart . The album is unusual in that no single releases were issued of any of the songs . Although , the title track , `` Two of a Kind , '' would be issued as the B-side to `` Better Move It on Home '' from their 1971 greatest hits compilation The Best of Porter Wagoner & Dolly Parton ; and the track `` Oh , The Pain of Loving You '' was later released as the B-side of `` The Right Combination '' from their 1972 album The Right Combination • Burning the Midnight Oil , with the `` Oh '' being dropped from the title . `` Curse of the Wild Weed Flower '' is of note for being an anti-marijuana song , one of the few country songs of the period to discuss drugs . Parton later rerecorded `` Oh , The Pain of Loving You '' with Linda Ronstadt and Emmylou Harris , as part of their 1987 album Trio '' , once again with the `` Oh '' being dropped from the song 's title . Liner notes for the album are written by Don Howser , longtime announcer for The Porter Wagoner Show .",
"title": ""
},
{
"docid": "Playlist:_The_Very_Best_of_Dolly_Parton",
"text": "Playlist : The Very Best of Dolly Parton is a compilation album from Dolly Parton released as part of the Legacy Recordings Playlist series . The album features 14 tracks from her years at RCA Nashville ranging from her first # 1 country single , 1970 's `` Joshua '' to her 1983 # 1 country and pop smash `` Islands in the Stream '' with Kenny Rogers . Despite Columbia Records and RCA Nashville both being owned by Sony BMG , none of her Columbia Records material is represented here . The CD is packaged in eco-friendly recycled cardboard packaging and in lieu of an actual paper booklet , the disc includes a PDF file with song credits , photos , a bio on Parton , and wallpapers .",
"title": ""
},
{
"docid": "Home_for_Christmas_(Dolly_Parton_album)",
"text": "Home for Christmas is the second holiday album by singer/songwriter Dolly Parton . Unlike her 1984 duet holiday album Once Upon a Christmas with Kenny Rogers , which included a number of original songs , Home for Christmas relied heavily on classic holiday favorites . Its release was accompanied by an ABC television special . This album was certified Gold by the Recording Industry Association of America .",
"title": ""
},
{
"docid": "Dolly,_Dolly,_Dolly",
"text": "Dolly , Dolly , Dolly , released in 1980 , is the 22nd solo studio album by Dolly Parton . Coming at the height of her late 1970s-1980s quest for pop success , the album was her least traditional country-sounding album to that point , with a number of songs bordering on disco . Though the album 's two singles , `` Starting Over Again '' ( written by Donna Summer and Bruce Sudano ) and `` Old Flames Ca n't Hold a Candle to You '' topped the U.S. country charts ( `` Starting Over Again '' also hit # 36 on the pop charts ) , the album is generally regarded by critics , as well as Parton 's fans , as one of the least satisfying albums of her career ; it was almost universally panned at the time of its release ; of the major press , only People Magazine reviewed it favorably . The album was noteworthy for being one of the only Parton albums to that point not to include a single of her own compositions ; it was composed entirely of covers . In 2007 , the album was re-issused in the UK as a `` two-fer '' , along with 1979 's Great Balls of Fire , marking the first time it was available on CD . Sony released it as a solo CD in 2007 .",
"title": ""
},
{
"docid": "Best_of_Dolly_Parton,_Vol._3",
"text": "Best of Dolly Parton , Vol .3 is a 1987 compilation of Dolly Parton 's early - to mid-1980s hits that RCA Records issued after she left the label . This was the first Dolly Parton CD that featured the song `` Potential New Boyfriend '' .",
"title": ""
},
{
"docid": "Dolly!",
"text": "Dolly ! is an American variety show starring Dolly Parton that aired in first-run syndication during the 1976-77 season . In the mid-1970s , Parton was approached by Bill Graham , president of Show Biz , Inc. , the same company that produced The Porter Wagoner Show ( on which Parton had costarred for seven years ) , and soon afterward the syndicated variety show Dolly was born . The show boasted a budget of $ 85,000 per episode , an impressive sum at the time for a syndicated series . ( It was , in fact the most expensive show to be produced out of Nashville to that point . ) A variety of Nashville and Hollywood stars were scheduled to appear , including Karen Black , Tom T. Hall , Emmylou Harris , The Hues Corporation , Captain Kangaroo , Marilyn McCoo and Billy Davis , Jr. , Ronnie Milsap , Anne Murray , Kenny Rogers , Linda Ronstadt , KC & The Sunshine Band , and Anson Williams . According to her 1978 biography , Dolly by Alanna Nash , Parton spoke to Bob Dylan and he initially agreed to do the show , but eventually bowed out due to his discomfort with the television medium at the time . Despite the work that went into the show and the diverse collection of guests , Parton was said to have been less than pleased with the end product , as she found herself singing standards like `` My Funny Valentine '' ( which she felt did n't suit her voice or musical style ) , and interacting with guests with whom she had little in common . She told Nash during a 1977 interview for the biography Dolly `` I liked all of the people that were on ... but I would have had a totally different lineup of guests myself . It was really bad for me , that TV show . It was worse for me than good , because the people who did n't know me who liked the show thought that 's how I was . . . I mean , I still come through as myself , even with all the other stuff , but not really like I should . Not my real , natural way . And the people who did know me thought I was crazy . They knew that was n't me . Including me . I did n't know that woman on TV ! '' The show lasted only one season despite very high ratings , falling apart when Parton asked out of her contract for a variety of reasons , including the toll that eighteen-hour days were taking on her vocal cords . The show 's opening theme was `` Love Is Like A Butterfly '' and the show 's closing theme was `` I Will Always Love You '' , both # 1 hits for Parton in 1974 , both sung by Parton on the show . During the opening credits , Parton emerges from a swing and then comes out to sing an opening song ( either a cover of a then-current hit , or occasionally one of her own hits ) . At the closing of the show , Parton speaks the recitation from `` I Will Always Love You '' : `` And I hope life treats you kind , and I hope that you have all you ever dream of . I wish you joy and lots and lots of happiness , but above all this , I wish you love , I love you '' and then Dolly says `` Good Night '' and as the closing credits roll , Parton sings the rest of the song . Among the more well received installments , was one featuring the first televised performance of the `` Trio '' team : Parton , Emmylou Harris and Linda Ronstadt , a full decade before they released the first of their two critically acclaimed albums . The show also featured the first time Parton and Kenny Rogers had worked together ; the two would top the country and pop charts in 1983 with their mega hit `` Islands in the Stream '' . As Dolly 's career became more popular than ever , during the late 1970s and into the early 1980s , Dolly ! was seen widely in reruns . On February 27 , 2007 , Dolly ! has been released onto DVD under the title of Dolly Parton And Friends , and features six episodes of the show , among these being the Emmylou Harris and Linda Ronstadt episode , and the Kenny Rogers episode .",
"title": ""
},
{
"docid": "Old_Flames_Can't_Hold_a_Candle_to_You",
"text": "`` Old Flames Ca n't Hold a Candle to You '' is a country song written by singer-songwriter Patricia Rose Sebert and Hugh Moffatt . It was a number 14 U.S. country hit for Joe Sun in 1978 , and a number 86 hit for Brian Collins the same year . It was later covered by Dolly Parton , who took it to the top of the U.S. country singles charts in August 1980 . In the song , the narrator tells their lover not to feel threatened by past affairs for these `` old flames '' are in the past . Parton included her version on her 1980 Dolly , Dolly , Dolly album , and it was released as the album 's second single after the success of `` Starting Over Again '' . In 2013 , Sebert 's daughter , Kesha , released an acoustic cover of the song as part of her extended play Deconstructed .",
"title": ""
},
{
"docid": "The_Book_Lady",
"text": "The Book Lady is a documentary about country music legend and pop-culture icon Dolly Parton 's campaign for children 's literacy . Dolly Parton , Miley Ray Cyrus , Keith Urban , Canadian singer -- songwriters Sarah Harmer and Justin Rutledge , fiddler Natalie MacMaster and children 's author Robert Munsch are featured in the documentary , which chronicles the launch of Parton 's `` Imagination Library '' in Canada . The Book Lady was directed by Natasha Ryan , produced by Brad Horvath and executive-produced by filmmaker Thom Fitzgerald and Doug Pettigrew . It will air on CBC Television , Bravo ! and BookTelevision in Canada . It had its international premiere at the 28th Atlantic Film Festival in Halifax , Nova Scotia , on September 20 , 2008 .",
"title": ""
},
{
"docid": "Just_Because_I'm_a_Woman",
"text": "Just Because I 'm a Woman may refer to : Just Because I 'm a Woman ( 1968 album ) , by Dolly Parton Just Because I 'm a Woman ( 1976 album ) , a compilation album by Dolly Parton Just Because I 'm a Woman : Songs of Dolly Parton , a 2003 Dolly Parton tribute album",
"title": ""
},
{
"docid": "The_Seeker_(Dolly_Parton_song)",
"text": "`` The Seeker '' is a song by Dolly Parton , which served as one of the title songs to Parton 's 1975 album Dolly : The Seeker/We Used To , and was also a top ten single on the U.S. country charts . A spiritual , which Parton described as her `` talk with God '' , the song was released as a single in July 1975 , just missing the top spot on the U.S. country singles chart ; it peaked at # 2 . Two decades later , Parton rerecorded the song for her 1995 album Something Special . Nelly Furtado covered this song for the film The Year Dolly Parton Was My Mom . Merle Haggard who , in his 1981 autobiography , `` Sing Me Back Home '' , would confess his infatuation with Parton , also recorded the song .",
"title": ""
},
{
"docid": "Best_of_Dolly_Parton",
"text": "Best of Dolly Parton was a 1975 compilation album of Dolly Parton 's early 1970s work that has long been regarded by critics as the definitive representation of Parton 's most influential period . The album reached # 5 on the U.S. country albums chart , and contained the title tracks to the previous six Parton albums , as well as the tracks `` I Will Always Love You '' and `` Travelin ' Man '' .",
"title": ""
},
{
"docid": "The_Very_Best_of_Dolly_Parton",
"text": "The Very Best of Dolly Parton is a compilation album by Dolly Parton , released 7 March 2007 . It sold platinum in the UK .",
"title": ""
},
{
"docid": "Magnolia_Hill_Productions",
"text": "Magnolia Hill Productions , more commonly known as Magnolia Hill , is a film and television production company founded by Sam Haskell , former William Morris Worldwide Head of Television . Haskell hired Josh Hunter Rogers to run development . The company currently has an exclusive deal with WBTV . Established in 2013 , in a development deal with Warner Bros television and Sam Haskell , founder , Magnolia Hill was created to bring forth content that is lacking in today 's television climate . Magnolia Hill announced a development deal with NBCUniversal for four TV movies based on the songs , stories , and the life of Dolly Parton . The first picture , Coat of Many Colors , aired on December 10 drawing more than 13 million live viewers making it the most viewed film on broadcast TV in over five years . As of February , 2017 , Magnolia Hill Productions has six projects under development : Dolly Parton 's Jolene Dolly Parton 's The Seeker Untitled NBC Dolly Parton Project # 5 NBC Dolly Parton Music Special # 1 NBC Dolly Parton Music Special # 2 The Little Foxes ( film ) Television Remake",
"title": ""
},
{
"docid": "The_Year_Dolly_Parton_Was_My_Mom",
"text": "The Year Dolly Parton Was My Mom is a 2011 Canadian coming-of-age movie written and directed by Tara Johns . Dolly Parton provides a voice cameo .",
"title": ""
},
{
"docid": "Ultimate_Dolly_Parton",
"text": "Ultimate Dolly Parton is a compilation album by American country music artist Dolly Parton . It was released by RCA Records on June 3 , 2003 . The album peaked at number 20 on the Billboard Top Country Albums chart .",
"title": ""
}
] |
PLAIN-961
|
corn
|
[
{
"docid": "MED-3000",
"text": "An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.",
"title": "Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer."
},
{
"docid": "MED-2150",
"text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.",
"title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women"
},
{
"docid": "MED-4687",
"text": "Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.",
"title": "Vegetarian diets and public health: biomarker and redox connections."
},
{
"docid": "MED-2884",
"text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.",
"title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women."
},
{
"docid": "MED-1752",
"text": "The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals. Using degenerate polymerase chain reaction, we have identified a new murine TGF-beta family member, growth/differentiation factor-8 (GDF-8), which is expressed specifically in developing and adult skeletal muscle. During early stages of embryogenesis, GDF-8 expression is restricted to the myotome compartment of developing somites. At later stages and in adult animals, GDF-8 is expressed in many different muscles throughout the body. To determine the biological function of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null animals are significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass. Individual muscles of mutant animals weigh 2-3 times more than those of wild-type animals, and the increase in mass appears to result from a combination of muscle cell hyperplasia and hypertrophy. These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth.",
"title": "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member."
},
{
"docid": "MED-2152",
"text": "Walnuts contain bioactive molecules that may contribute to their beneficial effects, including alpha-linolenic acid (ALA) and phytosterols. In these studies, extracts of walnut, purified compounds, or postprandial serum were examined for effects on breast cancer cell proliferation and gene expression. Extracts derived from walnut oil decreased proliferation of MCF-7 cells, as did ALA and β-sitosterol. The gene expression response of ALA in the mouse breast cancer cell line TM2H indicates this molecule has multiple cellular targets with peroxisome proliferator-activated receptor (PPAR) target genes, liver X receptor (LXR), and farnesoid X receptor (FXR) target genes being affected. In transactivation assays, walnut oil extracts increased activity of FXR to a greater extent than the other tested nuclear receptors. When examined separately, walnut components ALA and β-sitosterol were the most efficacious activators of FXR. When serum from individuals fed walnut components were applied to MCF-7 cells, there was a correlation between body mass index and breast cancer cell proliferation in vitro. Taken together, these data support an effect of walnut and its bioactive constituents on mammary epithelial cells and that multiple molecular targets may be involved.",
"title": "Mechanistic examination of walnuts in prevention of breast cancer."
},
{
"docid": "MED-2891",
"text": "BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.",
"title": "Variations in product choices of frequently purchased herbs: caveat emptor."
},
{
"docid": "MED-2890",
"text": "Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.",
"title": "Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link?"
},
{
"docid": "MED-2886",
"text": "PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.",
"title": "Goji berry effects on macular characteristics and plasma antioxidant levels."
},
{
"docid": "MED-4154",
"text": "Daily diet may have implications for skin ageing. However, data on the relationship between diet and the parameters of skin conditions are scarce. The present study aimed to examine the associations of biophysical properties of the skin of women with intakes of fats and antioxidant micronutrients as well as food groups as sources of these nutrients. In a cross-sectional study, we measured the hydration, surface lipids and elasticity of the skin of 716 Japanese women using non-invasive techniques. The extent of facial wrinkles in the crow's-foot area was determined by observation using the Daniell scale. Each subject's usual diet was determined with the use of a validated FFQ. After controlling for covariates including age, smoking status, BMI and lifetime sun exposure, the results showed that higher intakes of total fat, saturated fat and monounsaturated fat were significantly associated with increased skin elasticity. A higher intake of green and yellow vegetables was significantly associated with a decreased Daniell wrinkling score. Intake of saturated fat was significantly inversely associated with the Daniell wrinkling score after additional adjustment for green and yellow vegetable intake. Further studies with more accurate measurement methods are needed to investigate the role of daily diet in skin ageing.",
"title": "Association of dietary fat, vegetables and antioxidant micronutrients with skin ageing in Japanese women."
},
{
"docid": "MED-2889",
"text": "Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Cataract is a self-defence reaction to protect the retina from oxidative damage."
},
{
"docid": "MED-5083",
"text": "A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.",
"title": "A systematic screening of total antioxidants in dietary plants."
},
{
"docid": "MED-2885",
"text": "OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.",
"title": "Ultraviolet phototoxicity to the retina."
},
{
"docid": "MED-1754",
"text": "Conspiracist ideation has been repeatedly implicated in the rejection of scientific propositions, although empirical evidence to date has been sparse. A recent study involving visitors to climate blogs found that conspiracist ideation was associated with the rejection of climate science and the rejection of other scientific propositions such as the link between lung cancer and smoking, and between HIV and AIDS (Lewandowsky et al., in press; LOG12 from here on). This article analyses the response of the climate blogosphere to the publication of LOG12. We identify and trace the hypotheses that emerged in response to LOG12 and that questioned the validity of the paper’s conclusions. Using established criteria to identify conspiracist ideation, we show that many of the hypotheses exhibited conspiratorial content and counterfactual thinking. For example, whereas hypotheses were initially narrowly focused on LOG12, some ultimately grew in scope to include actors beyond the authors of LOG12, such as university executives, a media organization, and the Australian government. The overall pattern of the blogosphere’s response to LOG12 illustrates the possible role of conspiracist ideation in the rejection of science, although alternative scholarly interpretations may be advanced in the future.",
"title": "Recursive Fury: Conspiracist Ideation in the Blogosphere in Response to Research on Conspiracist Ideation"
},
{
"docid": "MED-1749",
"text": "Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada."
},
{
"docid": "MED-1748",
"text": "Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly precise log-normal distribution in the plasma samples while non-plasma (cord blood) control sample was found to be free of plant DNA.",
"title": "Complete Genes May Pass from Food to Human Blood"
},
{
"docid": "MED-1884",
"text": "We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.",
"title": "Maintenance of the LDL cholesterol:HDL cholesterol ratio in an elderly population given a dietary cholesterol challenge."
},
{
"docid": "MED-1747",
"text": "Knowledge of the US Public Health Syphilis Study at Tuskegee is sometime cited as a principal reason for the relatively low participation rates seen among racial/ethnic minorities, particularly African Americans, in biomedical research. However, only a few studies have actually explored this possibility. We use data from a random digit dial telephone survey of 510 African-Americans and 253 Latinos, age 18 to 45 years, to investigate associations between knowledge of the USPHS Syphilis Study at Tuskegee and endorsement of HIV/AIDS conspiracy theories. All respondents were drawn from an area of low-income, predominantly race-segregated inner city households in Los Angeles. Results indicate that African Americans were significantly more likely than Latinos to endorse HIV/AIDS conspiracy theories. Further, African Americans were more aware of the USPHS Syphilis Study at Tuskegee (SST). Nevertheless, 72% of African Americans and 94% of Latinos reported that they have never heard of the Syphilis Study at Tuskegee. Further, while awareness of the Syphilis Study at Tuskegee was a significant predictor of endorsing HIV/AIDS conspiracy theories, results suggest that other factors may be more important in accounting for low biomedical and behavioral study participation rates.",
"title": "Is there a legacy of the U.S. Public Health Syphilis Study at Tuskegee in HIV/AIDS-related beliefs among heterosexual African-Americans and Latinos?"
},
{
"docid": "MED-2894",
"text": "AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.",
"title": "Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma."
},
{
"docid": "MED-2153",
"text": "Background: Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer. Methods: We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results: We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables. Conclusion: Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.",
"title": "Nut consumption and risk of pancreatic cancer in women"
},
{
"docid": "MED-2895",
"text": "PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight \"retinal responders\" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two \"retinal nonresponders\" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one \"serum and retinal nonresponder\" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.",
"title": "Dietary modification of human macular pigment density."
},
{
"docid": "MED-1750",
"text": "The discovery of myostatin and our introduction to the “Mighty Mouse” over a decade ago spurred both basic and applied research and impacted popular culture as well. The myostatin-null genotype produces “double muscling” in mice and livestock and was recently described in a child. The field’s rapid growth is by no means surprising considering the potential benefits of enhancing muscle growth in clinical and agricultural settings. Indeed, several recent studies suggest that blocking myostatin’s inhibitory effects could improve the clinical treatment of several muscle growth disorders, whereas comparative studies suggest that these actions are at least partly conserved. Thus, neutralizing myostatin’s effects could also have agricultural significance. Extrapolating between studies that use different vertebrate models, particularly fish and mammals, is somewhat confusing because whole genome duplication events have resulted in the production and retention of up to four unique myostatin genes in some fish species. Such comparisons, however, suggest that myostatin’s actions may not be limited to skeletal muscle per se, but may additionally influence other tissues including cardiac muscle, adipocytes, and the brain. Thus, therapeutic intervention in the clinic or on the farm must consider the potential of alternative side effects that could impact these or other tissues. In addition, the presence of multiple and actively diversifying myostatin genes in most fish species provides a unique opportunity to study adaptive molecular evolution. It may also provide insight into myostatin’s nonmuscle actions as results from these and other comparative studies gain visibility in biomedical fields.",
"title": "Clinical, Agricultural, and Evolutionary Biology of Myostatin: A Comparative Review"
},
{
"docid": "MED-4689",
"text": "Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.",
"title": "The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide"
},
{
"docid": "MED-3001",
"text": "Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease (\"complex research\") to studying the role of lifestyle factors (\"simple research\").",
"title": "Towards a new system of health: the challenge of Western disease."
},
{
"docid": "MED-2997",
"text": "If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.",
"title": "The Etiological Significance of Related Diseases"
},
{
"docid": "MED-1888",
"text": "BACKGROUND Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans. METHODS We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. We further examined the relationship between fasting plasma levels of TMAO and incident major adverse cardiovascular events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4007 patients undergoing elective coronary angiography. RESULTS Time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites, were detected after the phosphatidylcholine challenge. Plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event (hazard ratio for highest vs. lowest TMAO quartile, 2.54; 95% confidence interval, 1.96 to 3.28; P<0.001). An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors (P<0.001), as well as in lower-risk subgroups. CONCLUSIONS The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota. Increased TMAO levels are associated with an increased risk of incident major adverse cardiovascular events. (Funded by the National Institutes of Health and others.)",
"title": "Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk"
},
{
"docid": "MED-1753",
"text": "Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology. Copyright © 2012. Published by Elsevier Inc.",
"title": "The current state of GMO governance: are we ready for GM animals?"
},
{
"docid": "MED-1889",
"text": "Consumption of eggs for a long period was shown to result in hypercholesterolemia and is generally restricted for this reason. In the present study we analyzed the effect of eggs consumption for 3 weeks on lipoprotein atherogenicity. Consumption of 2 eggs per day with the meals, for 3 weeks resulted in a minor elevation in plasma glucose and urea concentrations. Plasma cholesterol concentration increased by 11% (p < 0.05) as a result of increased plasma low-density lipoprotein (LDL) cholesterol levels. Plasma triglycerides decreased by 13% (p < 0.01), but there were no significant alterations in plasma apolipoproteins A-I or B-100 concentrations. Plasma high-density lipoprotein (HDL) cholesterol decreased by 11% (p < 0.05). There was a 13% reduction, though not significant, in the cholesterol efflux from J-774 A.1 macrophages by HDL that was derived after eggs consumption in comparison to HDL that was obtained at baseline. The susceptibility of plasma [using 100 mM of 2,2' azobis 2-amidinopropane (AAPH)] as well as that of LDL (using 10 microM of copper ions) to lipid peroxidation was increased by 42% and 34%, respectively, as measured by the thiobarbituric acid reactive substance (TBARS) assay (p < 0.01). Kinetic analysis of LDL oxidation by copper ions revealed a 37% reduction in the lag time required for the initiation of LDL oxidation after 3 weeks of eggs consumption. The total plasma fatty acids concentration increased from 2.2 +/- 0.5 to 3.2 +/- 0.6 mg/ml. The plasma antioxidants, vitamin E and carotenoids were not significantly affected by eggs consumption. We conclude that eggs consumption, in addition to its hypercholesterolemic effect, increases plasma and LDL oxidizability, a phenomenon which was shown to enhance the progression of atherosclerosis. The atherogenic properties may contribute to the accelerated atherosclerosis prevalent in populations with high cholesterol intake.",
"title": "Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation."
},
{
"docid": "MED-4859",
"text": "Fresh blueberries were processed into sugar and sugar-free jams and stored for 6 months at 4 and 25 degrees C. The jams were analyzed immediately after processing and over 6 months of storage for polyphenolic content, percent polymeric color, and antioxidant capacity. Processing resulted in losses of anthocyanins, procyanidins, chlorogenic acid, and ORAC in both jam types, but flavonols were well retained. Marked losses of anthocyanins and procyanidins occurred over 6 months of storage and were accompanied by increased polymeric color values. Chlorogenic acid levels also declined during storage, but flavonols and ORAC changed little. Jams stored at 4 degrees C retained higher levels of anthocyanins, procyanidins, and ORAC and had lower polymeric color values than jams stored at 25 degrees C. Sugar-free jams retained higher levels of anthocyanins and had lower polymeric color values than sugar jams late during storage. Blueberry jams should be refrigerated to better retain polyphenolics and antioxidant capacity.",
"title": "Jam processing and storage effects on blueberry polyphenolics and antioxidant capacity."
},
{
"docid": "MED-5084",
"text": "We assessed the contribution of culinary and medicinal herbs to the total intake of dietary antioxidants. Our results demonstrate that there is more than a 1000-fold difference among antioxidant concentrations of various herbs. Of the dried culinary herbs tested, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix all contained very high concentrations of antioxidants (i.e., >75 mmol/100 g). In a normal diet, intake of herbs may therefore contribute significantly to the total intake of plant antioxidants, and be an even better source of dietary antioxidants than many other food groups such as fruits, berries, cereals and vegetables. In addition, the herbal drug, Stronger Neo-Minophagen C, a glycyrrhizin preparation used as an intravenous injection for the treatment of chronic hepatitis, boosts total antioxidant intake. It is tempting to speculate that several of the effects due to these herbs are mediated by their antioxidant activities.",
"title": "Several culinary and medicinal herbs are important sources of dietary antioxidants."
},
{
"docid": "MED-2489",
"text": "A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.",
"title": "Agricultural policies, food and public health"
},
{
"docid": "MED-2888",
"text": "Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.",
"title": "Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial."
},
{
"docid": "MED-1882",
"text": "BACKGROUND: Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction. METHODS AND RESULTS: This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles (-5%) while raising numbers of HDL particles (10%) and small HDL subclass particles (21%). Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant, independent predictors of new CHD events. For total LDL and HDL particles, odds ratios predicting CHD benefit were 1.28 (95% CI, 1.12 to 1.47) and 0.71 (95% CI, 0.61 to 0.81), respectively. Mean LDL and HDL particle sizes were not associated with CHD events. CONCLUSIONS: The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol.",
"title": "Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy i..."
},
{
"docid": "MED-1887",
"text": "Some practitioners use advanced lipoprotein analysis with the goal of better predicting risk and individualizing lifestyle and drug therapy for cardiovascular prevention. Unfortunately, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle number and size, other lipoprotein subfractionation, apolipoproteins B and A, and lipoprotein(a) have not yet met current standards for biomarker evaluation, and it remains to be determined whether these tests incrementally add to cardiovascular risk predicted by traditional risk factors. More importantly, it has yet to be determined whether treatment strategies guided by, or targeting, these measures improve cardiovascular outcomes. Drug therapies known to alter advanced lipoprotein analysis parameters, specifically niacin and fenofibrate, have not been shown to additionally reduce cardiovascular risk in recent randomized trials of high-risk patients treated with statin therapy. These findings suggest advanced lipoprotein analysis-guided strategies may not further reduce cardiovascular events and could lead to increased adverse effects and costs; this approach needs further research to establish its role in individualizing therapies for cardiovascular prevention. In contrast, a large body of evidence supports focusing on LDL cholesterol reduction and intensification of statin therapy to reduce cardiovascular risk. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
"title": "What is the role of advanced lipoprotein analysis in practice?"
},
{
"docid": "MED-2898",
"text": "PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.",
"title": "Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population."
},
{
"docid": "MED-2999",
"text": "Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.",
"title": "Western diseases and their emergence related to diet."
},
{
"docid": "MED-1890",
"text": "BACKGROUND: Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. OBJECTIVE: The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and Biological s searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. RESULTS: The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.",
"title": "Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis."
},
{
"docid": "MED-2765",
"text": "To prevent or delay the occurrence of chronic diseases, scientific bodies from the cardiologic and oncologic disciplines have made recommendations regarding the daily dietary intake of certain macro- and micronutrients. This study assessed the knowledge of a random population of 2,305 individuals comprising members of the public, health care workers, university graduate students, and health club attendees. Segments of this population might be expected to have a greater understanding and ability to implement these dietary recommendations. We found that over 90% of the participants were unaware of the recommendations for calcium, salt, vitamin A, and fiber, and the fiber content in a high fiber cereal. Approximately 80% of the participants were unaware of the recommendations regarding fat intake and could not calculate the fat content of a food product. Almost half of the study population took a vitamin pill daily. Of the subjects who were aware of the correct unit measurement for vitamin A (IU), almost 25% of gave a response that exceeded the recommended daily intake. A majority of this study population were unaware of the dietary recommendations regarding the prevention of cardiovascular events and cancer. Subgroups of this study population that might be expected to have more information regarding these recommendations (i.e., having higher education or being a health care professional) did not display a satisfactory level of knowledge. To further compound the problems of adhering to the recommended guidelines, the labeling of many food products is misleading. The recommendations on dietary intake and the information on food product content must be transmitted to the public in a form that allows for ready application when purchasing and consuming food.",
"title": "The value of current nutrition information."
},
{
"docid": "MED-2893",
"text": "Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.",
"title": "Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis."
},
{
"docid": "MED-1886",
"text": "Background Nuclear magnetic resonance (NMR) spectroscopy measures the number and size of lipoprotein particles, instead of their cholesterol or triglyceride content, but its clinical utility is uncertain. Methods and Results Baseline lipoproteins were measured by NMR in 27,673 initially healthy women followed for incident cardiovascular disease (CVD, N=1,015) over 11 years. Adjusting for non-lipid risk factors, hazard ratios (HRs) and 95% confidence intervals (CIs) for top vs bottom quintile of NMR-measured lipoprotein particle concentration (particles/L) were, for low-density lipoprotein (LDLNMR) 2.51 (1.91−3.30), high-density lipoprotein (HDLNMR) 0.91 (0.75−1.12), very-low-density lipoprotein (VLDLNMR) 1.71 (1.38−2.12), and LDLNMR/HDLNMR ratio 2.25 (1.80−2.81). Similarly-adjusted results for NMR-measured lipoprotein particle size (nanometers) were, for LDLNMR size 0.64 (0.52−0.79), HDLNMR size 0.65 (0.51−0.81), and VLDLNMR size 1.37 (1.10−1.70). Hazard ratios for NMR measures were comparable but not superior to standard lipids: total cholesterol 2.08 (1.63−2.67), LDL cholesterol 1.74 (1.40−2.16), HDL cholesterol 0.52 (0.42−0.64), triglycerides 2.58 (1.95−3.41), non-HDL cholesterol 2.52 (1.95−3.25), total/HDL cholesterol ratio 2.82 (2.23−3.58); and apolipoproteins: B100 2.57 (1.98−3.33), A-1 0.63 (0.52−0.77), B100/A-1 ratio 2.79 (2.21−3.54). There was essentially no reclassification improvement with adding LDLNMR particle concentration or apolipoprotein B100 to a model that already included the total/HDL cholesterol ratio and non-lipid risk factors (net reclassification index [NRI], 0% and 1.9%, respectively), nor did the addition of either variable result in a statistically significant improvement in the c-index. Conclusions In this prospective study of healthy women, CVD risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to standard lipids or apolipoproteins.",
"title": "Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared with Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women"
},
{
"docid": "MED-2899",
"text": "The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.",
"title": "Iris color and macular pigment optical density."
},
{
"docid": "MED-2488",
"text": "Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.",
"title": "Food prices and blood cholesterol."
},
{
"docid": "MED-2892",
"text": "PURPOSE: The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS). METHODS: This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment. RESULTS: There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments. CONCLUSION: The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.",
"title": "The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity."
},
{
"docid": "MED-1751",
"text": "There are many ways to categorise conspiracy theories. In the present study, we examined individual and demographic predictors of beliefs in commercial conspiracy theories among a British sample of over 300 women and men. Results showed many people were cynical and sceptical with regard to advertising tricks, as well as the tactics of organisations like banks and alcohol, drug and tobacco companies. Beliefs sorted into four identifiable clusters, labelled sneakiness, manipulative, change-the-rules and suppression/prevention. The high alpha for the overall scale suggested general beliefs in commercial conspiracy. Regressions suggested that those people who were less religious, more left-wing, more pessimistic, less (self-defined as) wealthy, less Neurotic and less Open-to-Experience believed there was more commercial conspiracy. Overall the individual difference variables explained relatively little of the variance in these beliefs. The implications of these findings for the literature on conspiracy theories are discussed. Limitations of the study are also discussed.",
"title": "Commercial conspiracy theories: a pilot study"
},
{
"docid": "MED-1885",
"text": "PURPOSE OF REVIEW: The perceived notion that dietary cholesterol is associated with increased risk for coronary heart disease (CHD) has led to dietary recommendations of no more than 300 mg/day for healthy populations in the USA. This study will review the recent evidence that challenges the current dietary restrictions regarding cholesterol while it presents some beneficial effects of eggs (an icon for dietary cholesterol) in healthy individuals. RECENT FINDINGS: The European countries, Australia, Canada, New Zealand, Korea and India among others do not have an upper limit for cholesterol intake in their dietary guidelines. Further, existing epidemiological data have clearly demonstrated that dietary cholesterol is not correlated with increased risk for CHD. Although numerous clinical studies have shown that dietary cholesterol challenges may increase plasma LDL cholesterol in certain individuals, who are more sensitive to dietary cholesterol (about one-quarter of the population), HDL cholesterol also rises resulting in the maintenance of the LDL/HDL cholesterol ratio, a key marker of CHD risk. SUMMARY: The lines of evidence coming from current epidemiological studies and from clinical interventions utilizing different types of cholesterol challenges support the notion that the recommendations limiting dietary cholesterol should be reconsidered.",
"title": "Rethinking dietary cholesterol."
},
{
"docid": "MED-2882",
"text": "Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.",
"title": "Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells."
},
{
"docid": "MED-4646",
"text": "Objective We examined the association between adolescent fiber intake and proliferative BBD, a marker of increased breast cancer risk, in the Nurses’ Health Study II. Methods Among 29,480 women who completed a high school diet questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed by centralized pathology review between 1991 and 2001. Multivariate-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD (multivariate HR (95% CI): 0.75 (0.59, 0.96), p-trend = 0.01) than women in the lowest quintile. High school intake of nuts and apples was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk (multivariate HR (95% CI): 0.64 (0.48, 0.85), p-trend < 0.01) than women consuming <1 serving/month. Results were essentially the same when the analysis was restricted to prospective cases (n = 142) diagnosed after return of the high school diet questionnaire. Conclusions These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influence subsequent risk of breast disease and may suggest a viable means for breast cancer prevention.",
"title": "Intake of Fiber and Nuts during Adolescence and Incidence of Proliferative Benign Breast Disease"
}
] |
[
{
"docid": "MED-5012",
"text": "This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.",
"title": "The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol."
},
{
"docid": "MED-5167",
"text": "OBJECTIVES: The phytoestrogen (plant estrogen) genistein, present in soy products, is of interest because in utero exposure to genistein can cause hypospadias in our mouse model and maternal consumption of soy is prevalent in human populations. Another compound of interest is the fungicide vinclozolin, which also causes hypospadias in the mouse and rat and can occur concurrently with genistein in the diet as a residue on exposed foods. A study in the United Kingdom found no relationship between a maternal organic vegetarian diet and hypospadias frequency, but women who consumed nonorganic vegetarian diets had a greater percentage of sons with hypospadias. Because nonorganic diets can include residues of pesticides such as vinclozolin, we sought to assess the interaction of realistic daily exposures to genistein and vinclozolin and their effects on the incidence of hypospadias. METHODS: Pregnant mice were fed a soy-free diet and orally gavaged from gestational days 13 to 17 with 0.17 mg/kg/day of genistein, 10 mg/kg/day of vinclozolin, or genistein and vinclozolin together at the same doses, all in 100 microL of corn oil. The controls received the corn oil vehicle. The male fetuses were examined at gestational day 19 for hypospadias, both macroscopically and histologically. RESULTS: We identified no hypospadias in the corn oil group. The incidence of hypospadias was 25% with genistein alone, 42% with vinclozolin alone, and 41% with genistein and vinclozolin together. CONCLUSIONS: These findings support the idea that exposure to these compounds during gestation could contribute to the development of hypospadias.",
"title": "Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin."
},
{
"docid": "MED-1710",
"text": "Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.",
"title": "Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People"
},
{
"docid": "MED-2054",
"text": "OBJECTIVE: To determine the prevalence of constipation in children <or=2 years, describe the symptoms of constipation, and review how often specific interventions were effective. STUDY DESIGN: Retrospective chart review. RESULTS: Of 4,157 children <2 years of age, 185 children had constipation. The prevalence rate for constipation in the first year of life was 2.9%, and in the second year of life, the rate was 10.1%. Functional constipation was the cause in 97% of the children. Boys and girls were affected with equal frequency. Constipation was caused by an underlying organic disease in 1.6% of cases, and 97% of the children had functional constipation. Dietary changes and corn syrup were the initial treatment suggestions for 116 children; 93% of these children underwent follow-up examinations, and the constipation resolved in 25% of the children. Of 100 children treated with milk of magnesia or polyethylene glycol 3350 without electrolytes, 93 children underwent follow-up examinations, and the constipation was resolved with treatment in 92% of the children. CONCLUSIONS: Dietary changes, corn syrup, or both resolved constipation in 25% of children, and laxatives resolved constipation in 92% of children. Both milk of magnesia and polyethylene glycol were efficient and safe in infants and toddlers.",
"title": "Prevalence, symptoms and outcome of constipation in infants and toddlers."
},
{
"docid": "MED-3143",
"text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.",
"title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial."
},
{
"docid": "MED-5056",
"text": "BACKGROUND: Oxidative damage is implicated in the etiology of cancer, cardiovascular disease, and other degenerative disorders. Recent nutritional research has focused on the antioxidant potential of foods, while current dietary recommendations are to increase the intake of antioxidant-rich foods rather than supplement specific nutrients. Many alternatives to refined sugar are available, including raw cane sugar, plant saps/syrups (eg, maple syrup, agave nectar), molasses, honey, and fruit sugars (eg, date sugar). Unrefined sweeteners were hypothesized to contain higher levels of antioxidants, similar to the contrast between whole and refined grain products. OBJECTIVE: To compare the total antioxidant content of natural sweeteners as alternatives to refined sugar. DESIGN: The ferric-reducing ability of plasma (FRAP) assay was used to estimate total antioxidant capacity. Major brands of 12 types of sweeteners as well as refined white sugar and corn syrup were sampled from retail outlets in the United States. RESULTS: Substantial differences in total antioxidant content of different sweeteners were found. Refined sugar, corn syrup, and agave nectar contained minimal antioxidant activity (<0.01 mmol FRAP/100 g); raw cane sugar had a higher FRAP (0.1 mmol/100 g). Dark and blackstrap molasses had the highest FRAP (4.6 to 4.9 mmol/100 g), while maple syrup, brown sugar, and honey showed intermediate antioxidant capacity (0.2 to 0.7 mmol FRAP/100 g). Based on an average intake of 130 g/day refined sugars and the antioxidant activity measured in typical diets, substituting alternative sweeteners could increase antioxidant intake an average of 2.6 mmol/day, similar to the amount found in a serving of berries or nuts. CONCLUSION: Many readily available alternatives to refined sugar offer the potential benefit of antioxidant activity.",
"title": "Total antioxidant content of alternatives to refined sugar."
},
{
"docid": "MED-717",
"text": "OBJECTIVE: Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. DESIGN: Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. SUBJECTS/SETTING: The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. INTERVENTION: Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. MAIN OUTCOME MEASURES: Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. STATISTICAL ANALYSES: Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. RESULTS: More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. CONCLUSIONS: Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with gastrointestinal dysfunction. Because breath hydrogen peaks occurred at 90 to 114 minutes and were highly correlated with 180-minute breath hydrogen AUC, the use of peak hydrogen measures may be considered to shorten the duration of the exam.",
"title": "Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults."
},
{
"docid": "MED-3382",
"text": "Artificial food colors (AFCs) have not been established as the main cause of attention-deficit hyperactivity disorder (ADHD), but accumulated evidence suggests that a subgroup shows significant symptom improvement when consuming an AFC-free diet and reacts with ADHD-type symptoms on challenge with AFCs. Of children with suspected sensitivities, 65% to 89% reacted when challenged with at least 100 mg of AFC. Oligoantigenic diet studies suggested that some children in addition to being sensitive to AFCs are also sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and orange. Some studies found \"cosensitivity\" to be more the rule than the exception. Recently, 2 large studies demonstrated behavioral sensitivity to AFCs and benzoate in children both with and without ADHD. A trial elimination diet is appropriate for children who have not responded satisfactorily to conventional treatment or whose parents wish to pursue a dietary investigation.",
"title": "Dietary sensitivities and ADHD symptoms: thirty-five years of research."
},
{
"docid": "MED-1672",
"text": "The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.",
"title": "Sugar, Uric Acid, and the Etiology of Diabetes and Obesity"
},
{
"docid": "MED-3494",
"text": "Americans are becoming more health conscious in their food choices and many are interested in reducing dietary fat intake. Fat replacers can affect meat flavor both by adding flavors of their own, by reducing the original aroma-generating substrate (fat) and by altering release of aroma compounds. When fat is removed from meat, water is generally added to replace it. Water-binding compounds can be added to prevent the added water from cooking out or evaporating and to prevent patty shrinkage. Fat replacers are generally classified by their composition: protein-based replacers including whey, soy and collagen, lipid-based substances such as soy lecithin which function as emulsifiers maintaining the fat that is retained distributed in the product, and carbohydrate-based substances including flours (wheat, soy, oat), starches (potato, modified corn starch, tapioca) and gums (carrageenan, xanthin). Duplication of the characteristics contributed by fat often requires a combination of replacers to address juiciness and texture (firmness) without negatively impacting flavor. Published by Elsevier Ltd.",
"title": "Reducing the fat content in ground beef without sacrificing quality: a review."
},
{
"docid": "MED-4446",
"text": "Twenty-four plant lignans were analyzed by high-performance liquid chromatography-tandem mass spectrometry in bran extracts of 16 cereal species, in four nut species, and in two oilseed species (sesame seeds and linseeds). Eighteen of these were lignans previously unidentified in these species, and of these, 16 were identified in the analyzed samples. Four different extraction methods were applied as follows: alkaline extraction, mild acid extraction, a combination of alkaline and mild acid extraction, or accelerated solvent extraction. The extraction method was of great importance for the lignan yield. 7-Hydroxymatairesinol, which has not previously been detected in cereals because of destructive extraction methods, was the dominant lignan in wheat, triticale, oat, barley, millet, corn bran, and amaranth whole grain. Syringaresinol was the other dominant cereal lignan. Wheat and rye bran had the highest lignan content of all cereals; however, linseeds and sesame seeds were by far the most lignan-rich of the studied species.",
"title": "Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts."
},
{
"docid": "MED-906",
"text": "Annatto dye is an orange-yellow food coloring extracted from the seeds of the tree Bixa orellana. It is commonly used in cheeses, snack foods, beverages, and cereals. Previously reported adverse reactions associated with annatto dye have included urticaria and angioedema. We present a patient who developed urticaria, angioedema, and severe hypotension within 20 minutes following ingestion of milk and Fiber One cereal, which contained annatto dye. Subsequent skin tests to milk, wheat, and corn were negative. The patient had a strong positive skin test to annatto dye, while controls had no response. The nondialyzable fraction of annatto dye on SDS-PAGE demonstrated two protein staining bands in the range of 50 kD. Immunoblotting demonstrated patient IgE-specific for one of these bands, while controls showed no binding. Annatto dye may contain contaminating or residual seed proteins to which our patient developed IgE hypersensitivity. Annatto dye is a potential rare cause of anaphylaxis.",
"title": "Anaphylaxis to annatto dye: a case report."
},
{
"docid": "MED-5263",
"text": "High postprandial serum lipid concentrations are associated with increased oxidative stress which, in turn, increases the risk of atherosclerosis. Epidemiological studies correlate lower incidence of cardiovascular disease with adherence to the Mediterranean diet. The aim of this study was to evaluate changes in inflammatory (TXB(2) and LTB(4)) and oxidative stress markers (urinary hydrogen peroxide levels and serum antioxidant capacity), in addition to classic lipid parameters, after a fat-rich meal administered to 12 normolipemic, healthy subjects. Following a Latin square design, subjects were divided into three groups, each one receiving a different kind of oil (extra virgin olive oil; EVOO, olive oil; OO or corn oil; CO, together with 150g of potatoes), with 2-week washout periods between treatments. Blood samples were drawn at baseline and after 1, 2, and 6h after the meal. A significant decrease in inflammatory markers, namely TXB(2) and LTB(4), after 2 and 6h after EVOO (but not OO or CO) consumption and a concomitant increase of serum antioxidant capacity were recorded. These data reinforce the notion that the Mediterranean diet reduces the incidence of coronary heart disease partially due to the protective role of its phenolic components, including those of extra virgin olive oil.",
"title": "Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil."
},
{
"docid": "MED-1837",
"text": "Because manganese (Mn) is potentially toxic, and because dietary fat type may affect Mn absorption, the objectives of the current study were to determine whether diets containing very low or very high amounts of Mn and enriched in either saturated or unsaturated fats affected measures of neuropsychological and basic metabolic function. Healthy young women were fed for 8 wk each, in a crossover design, diets that provided 0.8 or 20 mg of Mn/d. One half of the subjects received 15% of energy as cocoa butter, and one half received 15% of energy as corn oil. A meal containing (54)Mn was fed after 4 wk, and subjects underwent whole-body counting for the next 21 d. Blood draws and neuropsychological tests were administered at regular intervals during the dietary periods. When subjects consumed the diets low in Mn, compared with the high Mn diets, they absorbed a significantly higher percentage of (54)Mn, but had a significantly longer biological half-life of the absorbed (54)Mn. Manganese intake did not affect any neurological measures and only minimally affected psychologic variables. These data show that efficient mechanisms operate to maintain Mn homeostasis over the range of intakes that may be encountered in a mixed Western diet. Thus, dietary intakes of Mn from 0.8 to 20 mg for 8 wk likely do not result in Mn deficiency or toxicity signs in healthy adults.",
"title": "Dietary manganese intake and type of lipid do not affect clinical or neuropsychological measures in healthy young women."
},
{
"docid": "MED-3821",
"text": "Reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is important. Limited information about polyamine content of food is available, especially for diets in the United States. This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). Values for spermine, spermidine, and putrescine were calculated and reported per serving size (nmol/serving). Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine (36,988 nmol/serving). The polyamine database and FFQ were tested with a convenience sample (n=165). Average daily polyamine intakes from the sample were: 159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day spermine. Orange and grapefruit juices contributed the greatest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest amount of spermine (2,186 nmol/day). Development of this database linked to an FFQ provides a means of estimating polyamine intake and contributes to investigations relating polyamines to cancer.",
"title": "Development of a Polyamine Database for Assessing Dietary Intake"
},
{
"docid": "MED-5034",
"text": "The association between cured and broiled meat consumption by the mother during pregnancy and by the child was examined in relation to childhood cancer. Five meat groups (ham, bacon, or sausage; hot dogs; hamburgers; bologna, pastrami, corned beef, salami, or lunch meat; charcoal broiled foods) were assessed. Exposures among 234 cancer cases (including 56 acute lymphocytic leukemia [ALL], 45 brain tumor) and 206 controls selected by random-digit dialing in the Denver, Colorado (United States) standard metropolitan statistical area were compared, with adjustment for confounders. Maternal hot-dog consumption of one or more times per week was associated with childhood brain tumors (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.0-5.4). Among children, eating hamburgers one or more times per week was associated with risk of ALL (OR = 2.0, CI = 0.9-4.6) and eating hot dogs one or more times per week was associated with brain tumors (OR = 2.1, CI = 0.7-6.1). Among children, the combination of no vitamins and eating meats was associated more strongly with both ALL and brain cancer than either no vitamins or meat consumption alone, producing ORs of two to seven. The results linking hot dogs and brain tumors (replicating an earlier study) and the apparent synergism between no vitamins and meat consumption suggest a possible adverse effect of dietary nitrites and nitrosamines.",
"title": "Cured and broiled meat consumption in relation to childhood cancer: Denver, Colorado (United States)"
},
{
"docid": "MED-2490",
"text": "Background: Rice can be a major source of inorganic arsenic (Asi) for many sub-populations. Rice products are also used as ingredients in prepared foods, some of which may not be obviously rice based. Organic brown rice syrup (OBRS) is used as a sweetener in organic food products as an alternative to high-fructose corn syrup. We hypothesized that OBRS introduces As into these products. Objective: We determined the concentration and speciation of As in commercially available brown rice syrups and in products containing OBRS, including toddler formula, cereal/energy bars, and high-energy foods used by endurance athletes. Methods: We used inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography coupled to ICP-MS to determine total As (Astotal) concentrations and As speciation in products purchased via the Internet or in stores in the Hanover, New Hampshire, area. Discussion: We found that OBRS can contain high concentrations of Asi and dimethyl-arsenate (DMA). An “organic” toddler milk formula containing OBRS as the primary ingredient had Astotal concentrations up to six times the U.S. Environmental Protection Agency safe drinking water limit. Cereal bars and high-energy foods containing OBRS also had higher As concentrations than equivalent products that did not contain OBRS. Asi was the main As species in most food products tested in this study. Conclusions: There are currently no U.S. regulations applicable to As in food, but our findings suggest that the OBRS products we evaluated may introduce significant concentrations of Asi into an individual’s diet. Thus, we conclude that there is an urgent need for regulatory limits on As in food.",
"title": "Arsenic, Organic Foods, and Brown Rice Syrup"
},
{
"docid": "MED-3734",
"text": "Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.",
"title": "Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants."
},
{
"docid": "MED-5057",
"text": "High fructose corn syrup (HFCS) has become an increasingly common food ingredient in the last 40 years. However, there is concern that HFCS consumption increases the risk for obesity and other adverse health outcomes compared to other caloric sweeteners. The most commonly used types of HFCS (HFCS-42 and HFCS-55) are similar in composition to sucrose (table sugar), consisting of roughly equal amounts of fructose and glucose. The primary difference is that these monosaccharides exist free in solution in HFCS, but in disaccharide form in sucrose. The disaccharide sucrose is easily cleaved in the small intestine, so free fructose and glucose are absorbed from both sucrose and HFCS. The advantage to food manufacturers is that the free monosaccharides in HFCS provide better flavor enhancement, stability, freshness, texture, color, pourability, and consistency in foods in comparison to sucrose. Because the composition of HFCS and sucrose is so similar, particularly on absorption by the body, it appears unlikely that HFCS contributes more to obesity or other conditions than sucrose does. Nevertheless, few studies have evaluated the potentially differential effect of various sweeteners, particularly as they relate to health conditions such as obesity, which develop over relatively long periods of time. Improved nutrient databases are needed to analyze food consumption in epidemiologic studies, as are more strongly designed experimental studies, including those on the mechanism of action and relationship between fructose dose and response. At the present time, there is insufficient evidence to ban or otherwise restrict use of HFCS or other fructose-containing sweeteners in the food supply or to require the use of warning labels on products containing HFCS. Nevertheless, dietary advice to limit consumption of all added caloric sweeteners, including HFCS, is warranted.",
"title": "The effects of high fructose syrup."
},
{
"docid": "MED-5085",
"text": "In this study, the adhesion factors examined were time between frying and coating, surface oil content, chip temperature, oil composition, NaCl size, NaCl shape, and electrostatic coating. Three different surface oil content potato chips, high, low, and no, were produced. Oils used were soybean, olive, corn, peanut, and coconut. After frying, chips were coated immediately, after 1 d, and after 1 mo. NaCl crystals of 5 different particle sizes (24.7, 123, 259, 291, and 388 microm) were coated both electrostatically and nonelectrostatically. Adhesion of cubic, dendritic, and flake crystals was examined. Chips were coated at different temperatures. Chips with high surface oil had the highest adhesion of salt, making surface oil content the most important factor. Decreasing chip temperature decreased surface oil and adhesion. Increasing time between frying and coating reduced adhesion for low surface oil chips, but did not affect high and no surface oil chips. Changing oil composition did not affect adhesion. Increasing salt size decreased adhesion. Salt size had a greater effect on chips with lower surface oil content. When there were significant differences, cubic crystals gave the best adhesion followed by flake crystals then dendritic crystals. For high and low surface oil chips, electrostatic coating did not change adhesion of small size crystals but decreased adhesion of large salts. For no surface oil content chips, electrostatic coating improved adhesion for small salt sizes but did not affect adhesion of large crystals.",
"title": "Factors dominating adhesion of NaCl onto potato chips."
},
{
"docid": "MED-5164",
"text": "Exogenous dietary putrescine (1,4-diaminobutane) can increase growth rates of neonatal animals, including calves, chicks, and piglets, under nutritional stress. Turkey poults often have a high mortality rate and this may be due to poor initial feeding behavior and inadequate development of the intestinal tract. We conducted an experiment to determine the effect of dietary putrescine supplementation on growth performance and the role of dietary putrescine in prevention and recovery from a coccidial challenge. A total of 160 1-d-old turkey poults were fed a corn and soybean meal-based starter diet supplemented with 0.0 (control), 0.1, 0.2, and 0.3 g/100 g purified putrescine (8 birds/pen, 5 pens/diet). At 14 d of age, half the birds were infected with approximately 43,000 sporulated oocysts. The experiment lasted 24 d. Fecal samples were gathered from d 3 to d 5 postinfection by total collection. Ten control and 10 infected birds fed each diet were sampled on d 6 and d 10 postinfection. The induced infection produced significant depressions in growth and feed intake and detrimental morphological changes in the small intestine of poults in the absence of mortality. Weight gains, protein content of jejunum, and morphometric indices of duodenum, jejunum, and ileum were greater in challenged poults fed 0.3 g/100 g putrescine than in controls. We conclude that dietary putrescine supplementation may be beneficial to poult growth, mucosal development of the small intestine, and to recovery from subclinical coccidiosis.",
"title": "Dietary putrescine (1,4-diaminobutane) influences recovery of Turkey poults challenged with a mixed coccidial infection."
},
{
"docid": "MED-913",
"text": "In recent years, there has been a notable concern on the safety of genetically modified (GM) foods/plants, an important and complex area of research, which demands rigorous standards. Diverse groups including consumers and environmental Non Governmental Organizations (NGO) have suggested that all GM foods/plants should be subjected to long-term animal feeding studies before approval for human consumption. In 2000 and 2006, we reviewed the information published in international scientific journals, noting that the number of references concerning human and animal toxicological/health risks studies on GM foods/plants was very limited. The main goal of the present review was to assess the current state-of-the-art regarding the potential adverse effects/safety assessment of GM plants for human consumption. The number of citations found in databases (PubMed and Scopus) has dramatically increased since 2006. However, new information on products such as potatoes, cucumber, peas or tomatoes, among others was not available. Corn/maize, rice, and soybeans were included in the present review. An equilibrium in the number research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was currently observed. Nevertheless, it should be noted that most of these studies have been conducted by biotechnology companies responsible of commercializing these GM plants. These findings suggest a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. All this recent information is herein critically reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A literature review on the safety assessment of genetically modified plants."
},
{
"docid": "MED-1674",
"text": "What do the Atkins Diet and the traditional Japanese diet have in common? The Atkins Diet is low in carbohydrate and usually high in fat; the Japanese diet is high in carbohydrate and usually low in fat. Yet both work to promote weight loss. One commonality of both diets is that they both eliminate the monosaccharide fructose. Sucrose (table sugar) and its synthetic sister high fructose corn syrup consist of 2 molecules, glucose and fructose. Glucose is the molecule that when polymerized forms starch, which has a high glycemic index, generates an insulin response, and is not particularly sweet. Fructose is found in fruit, does not generate an insulin response, and is very sweet. Fructose consumption has increased worldwide, paralleling the obesity and chronic metabolic disease pandemic. Sugar (i.e., fructose-containing mixtures) has been vilified by nutritionists for ages as a source of “empty calories,” no different from any other empty calorie. However, fructose is unlike glucose. In the hypercaloric glycogen-replete state, intermediary metabolites from fructose metabolism overwhelm hepatic mitochondrial capacity, which promotes de novo lipogenesis and leads to hepatic insulin resistance, which drives chronic metabolic disease. Fructose also promotes reactive oxygen species formation, which leads to cellular dysfunction and aging, and promotes changes in the brain’s reward system, which drives excessive consumption. Thus, fructose can exert detrimental health effects beyond its calories and in ways that mimic those of ethanol, its metabolic cousin. Indeed, the only distinction is that because fructose is not metabolized in the central nervous system, it does not exert the acute neuronal depression experienced by those imbibing ethanol. These metabolic and hedonic analogies argue that fructose should be thought of as “alcohol without the buzz.”",
"title": "Fructose: It’s “Alcohol Without the Buzz”"
},
{
"docid": "MED-5032",
"text": "The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and orange juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR] = 9.5, 95 percent confidence interval [CI] = 1.6-57.6 for 12 or more hot dogs per month, trend P = 0.01), and fathers' intake of hot dogs (OR = 11.0, CI = 1.2-98.7 for highest intake category, trend P = 0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.",
"title": "Processed meats and risk of childhood leukemia (California, USA)."
},
{
"docid": "MED-3945",
"text": "The pomegranate fruit ( Punica granatum ) has become an international high-value crop for the production of commercial pomegranate juice (PJ). The perceived consumer value of PJ is due in large part to its potential health benefits based on a significant body of medical research conducted with authentic PJ. To establish criteria for authenticating PJ, a new International Multidimensional Authenticity Specifications (IMAS) algorithm was developed through consideration of existing databases and comprehensive chemical characterization of 45 commercial juice samples from 23 different manufacturers in the United States. In addition to analysis of commercial juice samples obtained in the United States, data from other analyses of pomegranate juice and fruits including samples from Iran, Turkey, Azerbaijan, Syria, India, and China were considered in developing this protocol. There is universal agreement that the presence of a highly constant group of six anthocyanins together with punicalagins characterizes polyphenols in PJ. At a total sugar concentration of 16 degrees Brix, PJ contains characteristic sugars including mannitol at >0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.",
"title": "International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration."
},
{
"docid": "MED-4188",
"text": "Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.",
"title": "Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot tr..."
},
{
"docid": "MED-5284",
"text": "Objective Habitual chocolate intake was recently found to be associated with lower body weight in three cross-sectional epidemiological studies. Our objective was to assess whether these cross-sectional results hold up in a more rigorous prospective analysis. Methods We used data from the Atherosclerosis Risk in Communities cohort. Usual dietary intake was assessed by questionnaire at baseline (1987–98), and after six years. Participants reported usual chocolate intake as the frequency of eating a 1-oz (∼28 g) serving. Body weight and height were measured at the two visits. Missing data were replaced by multiple imputation. Linear mixed-effects models were used to evaluate cross-sectional and prospective associations between chocolate intake and adiposity. Results Data were from 15,732 and 12,830 participants at the first and second visit, respectively. More frequent chocolate consumption was associated with a significantly greater prospective weight gain over time, in a dose-response manner. For instance, compared to participants who ate a chocolate serving less often than monthly, those who ate it 1–4 times a month and at least weekly experienced an increase in Body Mass Index (kg/m2) of 0.26 (95% CI 0.08, 0.44) and 0.39 (0.23, 0.55), respectively, during the six-year study period. In cross-sectional analyses the frequency of chocolate consumption was inversely associated with body weight. This inverse association was attenuated after excluding participants with preexisting obesity-related illness. Compared to participants without such illness, those with it had higher BMI and reported less frequent chocolate intake, lower caloric intake, and diets richer in fruits and vegetables. They tended to make these dietary changes after becoming ill. Conclusions Our prospective analysis found that a chocolate habit was associated with long-term weight gain, in a dose-response manner. Our cross-sectional finding that chocolate intake was associated with lower body weight did not apply to participants without preexisting serious illness.",
"title": "Habitual Chocolate Consumption May Increase Body Weight in a Dose-Response Manner"
},
{
"docid": "MED-3308",
"text": "An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.",
"title": "Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry."
},
{
"docid": "MED-4825",
"text": "Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.",
"title": "Pancreatic cancer: a review of the evidence on causation."
},
{
"docid": "MED-4178",
"text": "A method has been developed to identify pesticide residues and foodstuffs for inclusion in national monitoring programs with different priority levels. It combines two chronic dietary intake indicators: ATMDI based on maximum residue levels and agricultural uses, and EDI on food contamination data. The mean and 95th percentile of exposure were calculated for 490 substances using individual and national consumption data. The results show that mean ATMDI exceeds the acceptable daily intake (ADI) for 10% of the pesticides, and the mean upper-bound EDI is above the ADI for 1.8% of substances. A seven-level risk scale is presented for substances already analyzed in food in France and substances not currently sought. Of 336 substances analyzed, 70 pesticides of concern (levels 2-5) should be particularly monitored, 22 of which are priority pesticides (levels 4 and 5). Of 154 substances not sought, 36 pesticides of concern (levels 2-4) should be included in monitoring programs, including 8 priority pesticides (level 4). In order to refine exposure assessment, analytical improvements and developments are needed to lower the analytical limits for priority pesticide/commodity combinations. Developed nationally, this method could be applied at different geographic scales. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Chronic dietary risk characterization for pesticide residues: a ranking and scoring method integrating agricultural uses and food contamination data."
}
] |
PLAIN-3330
|
Fill in the Blank
|
[
{
"docid": "MED-2149",
"text": "BACKGROUND: Studies on the association between legume intake and metabolic syndrome (MetS) are sparse. The objective of this study is to evaluate the association between legume intake, MetS, and its components. METHODS: This study was conducted on 80 subjects (48% female) with MetS as cases and 160 age and gender-matched healthy controls. Anthropometric measures, blood pressure, fasting blood glucose, and lipid profiles were evaluated by standard methods. Dietary data were collected using a food frequency questionnaire (FFQ) and legume intake was determined. MetS was defined according to the definition of the Adult Treatment Panel III. RESULTS: The mean (SD) intake of legumes was 1.4 (0.9) servings/week for cases and 2.3 (1.1) servings/week for control subjects (P < 0.05). After adjustment for potential confounders, decreases in mean systolic blood pressure, fasting blood glucose, and increase in HDL cholesterol levels were observed across increasing quartile categories of legume intake. After adjustments for life style and food groups, subjects in the highest quartile of legume intake had lower odds of having MetS compared with those in the lowest quartile [odds ratio (OR): 0.25; 95% CI: 0.11 - 0.64, P < 0.05], an association that weakened after adjustment for body mass index (BMI), but remained significant (OR: 0.28; 95% CI: 0.12 - 0.81, P < 0.05). CONCLUSIONS: Legume intake is inversely associated with the risk of having MetS and some of its components.",
"title": "Legume intake is inversely associated with metabolic syndrome in adults."
},
{
"docid": "MED-2148",
"text": "Pulses are low in energy density, supporting their inclusion in the diet for the management of risk factors of the metabolic syndrome (MetSyn). The aim of the present study was to describe the effects of frequent consumption (five cups/week over 8 weeks) of pulses (yellow peas, chickpeas, navy beans and lentils), compared with counselling to reduce energy intake by 2093 kJ/d (500 kcal/d), on risk factors of the MetSyn in two groups (nineteen and twenty-one subjects, respectively) of overweight or obese (mean BMI 32·8 kg/m2) adults. Body weight, waist circumference, blood pressure, fasting blood parameters and 24 h food intakes were measured at weeks 1, 4 and 8. Blood glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and ghrelin were measured after a 75 g oral glucose load at weeks 1 and 8. At week 8, both groups reported reductions in energy intake, waist circumference, systolic blood pressure, glycosylated Hb (HbA1c) and glucose AUC and homeostasis model of insulin resistance (HOMA-IR) following the glucose load (P < 0·05). However, HDL, fasting C-peptide and insulin AUC responses were dependent on diet (P < 0·05). HDL and C-peptide increased by 4·5 and 12·3 %, respectively, in the pulse group, but decreased by 0·8 and 7·6 %, respectively, in the energy-restricted group. Insulin AUC decreased in both females and males on the energy-restricted diet by 24·2 and 4·8 %, respectively, but on the pulse diet it decreased by 13·9 % in females and increased by 27·3 % in males (P < 0·05). In conclusion, frequent consumption of pulses in an ad libitum diet reduced risk factors of the MetSyn and these effects were equivalent, and in some instances stronger, than counselling for dietary energy reduction.",
"title": "Regular consumption of pulses for 8 weeks reduces metabolic syndrome risk factors in overweight and obese adults."
},
{
"docid": "MED-2147",
"text": "Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.",
"title": "Phaseolus beans: impact on glycaemic response and chronic disease risk in human subjects."
},
{
"docid": "MED-2980",
"text": "Background Inoxitol hexakisphosphate (IP6) has been found to have an important role in biomineralization and a direct effect inhibiting mineralization of osteoblasts in vitro without impairing extracellular matrix production and expression of alkaline phosphatase. IP6 has been proposed to exhibit similar effects to those of bisphosphonates on bone resorption, however, its direct effect on osteoclasts (OCL) is presently unknown. Methodology/Principal Findings The aim of the present study was to investigate the effect of IP6 on the RAW 264.7 monocyte/macrophage mouse cell line and on human primary osteoclasts. On one hand, we show that IP6 decreases the osteoclastogenesis in RAW 264.7 cells induced by RANKL, without affecting cell proliferation or cell viability. The number of TRAP positive cells and mRNA levels of osteoclast markers such as TRAP, calcitonin receptor, cathepsin K and MMP-9 was decreased by IP6 on RANKL-treated cells. On the contrary, when giving IP6 to mature osteoclasts after RANKL treatment, a significant increase of bone resorption activity and TRAP mRNA levels was found. On the other hand, we show that 1 µM of IP6 inhibits osteoclastogenesis of human peripheral blood mononuclear cells (PBMNC) and their resorption activity both, when given to undifferentiated and to mature osteoclasts. Conclusions/Significance Our results demonstrate that IP6 inhibits osteoclastogenesis on human PBMNC and on the RAW264.7 cell line. Thus, IP6 may represent a novel type of selective inhibitor of osteoclasts and prove useful for the treatment of osteoporosis.",
"title": "Inositol Hexakisphosphate Inhibits Osteoclastogenesis on RAW 264.7 Cells and Human Primary Osteoclasts"
},
{
"docid": "MED-2990",
"text": "ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. INTRODUCTION: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. MATERIALS AND METHODS: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. RESULTS AND CONCLUSIONS: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1-10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined.",
"title": "Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research."
},
{
"docid": "MED-2146",
"text": "Over the last few decades, lifestyle changes have resulted in a drastic increase in the incidence of diabetes all over the world, especially in the developing countries. Oral hypoglycemic agents and insulin form the mainstay in controlling diabetes, but they have prominent side effects and fail to significantly alter the course of diabetic complications. Appropriate diet and exercise programs that form a part of lifestyle modifications have proven to be greatly effective in the management of this disease. Dietary therapy is showing a bright future in the prevention and treatment of diabetes. Legumes, owing to their high nutritive value, are increasingly being used in dietetic formulations in the treatment and prevention of diabetes on account of their antidiabetic potential. Given this background, this paper reviews the glucose- and lipid-lowering action possessed by various commonly consumed legumes through several animal and human studies. It is concluded that the various legumes not only have varying degrees of antidiabetic potential but are also beneficial in decreasing the risk factors for cardiovascular and renal disease.",
"title": "Antidiabetic potential of commonly consumed legumes: a review."
},
{
"docid": "MED-2010",
"text": "Legumes (including alfalfa, clover, lupins, green beans and peas, peanuts, soybeans, dry beans, broad beans, dry peas, chickpeas, and lentils) represent an important component of the human diet in several areas of the world, especially in the developing countries, where they complement the lack of proteins from cereals, roots, and tubers. In some regions of the world, legume seeds are the only protein supply in the diet. The health benefits of legume consumption have received rising interest from researchers, and their consumption and production extends worldwide. Among European countries, higher legume consumption is observed around the Mediterranean, with per capita daily consumption between 8 and 23 g, while in Northern Europe, the daily consumption is less than 5 g per capita. The physiological effects of different legumes vary significantly. These differences may result from the polysaccharides composition, in particular, the quantity and variety of dietary fibers and starch, protein make-up, and variability in phytochemical content. The majority of legumes contain phytochemicals: bioactive compounds, including enzyme inhibitors, phytohemagglutinins (lectins), phytoestrogens, oligosaccharides, saponins, and phenolic compounds, which play metabolic roles in humans who frequently consume these foods. Dietary intake of phytochemicals may provide health benefits, protecting against numerous diseases or disorders, such as coronary heart disease, diabetes, high blood pressure and inflammation. The synergistic or antagonistic effects of these phytochemical mixtures from food legumes, their interaction with other components of the diet, and the mechanism of their action have remained a challenge with regard to understanding the role of phytochemicals in health and diseases. Their mitigating effects and the mechanism of their action need to be further addressed if we are to understand the role of phytochemicals in health and diseases. This review provides an overview of the nutritional quality of legumes and their potential contribution in cardiometabolic risk prevention.",
"title": "Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review."
},
{
"docid": "MED-2143",
"text": "Many therapeutic agents had been used for the treatment of diabetes mellitus before insulin was discovered and several hundred plants have shown some extent of antidiabetic activity. This study tries to explore which agents were most widely used in Europe in the pre-insulin era. According to the scientific literature and the proprietary drug industry around 1900, more than 100 agents were considered to have hypoglycemic activity. Most of them seem to have been used only occasionally while some others were recommended and marketed to a large extent. Among the medicinal plants, Syzygium cumini (syn. S. jambolanum, Eugenia jambolana), Vaccinum myrtillus and Phaseolus sp. were most common, and other frequently used agents were opium, opium alkaloids, other alkaloids like quinine or Belladonna alkaloids, salicylates, alkaline substances like sodium (bi)carbonate and even strong poisons like arsenic or uranium salts. Syzygium jambolanum seed powder seems to be one of the most intensively studied antidiabetic agents of plant origin.",
"title": "Antidiabetic drugs used in Europe prior to the discovery of insulin."
},
{
"docid": "MED-2008",
"text": "Our purpose was to determine the effects of a pulse-based diet in individuals 50 years or older for reducing CVD risk factors. A total of 108 participants were randomised to receive pulse-based foods (two servings daily of beans, chickpeas, peas or lentils; about 150 g/d dry weight) or their regular diet for 2 months, followed by a washout of 1 month and a cross-over to the other diet for 2 months. Anthropometric measures, body composition and biochemical markers (i.e. serum LDL-cholesterol (LDL-C), as the primary outcome, and other lipids, glucose, insulin and C-reactive protein) were assessed before and after each diet phase. A total of eighty-seven participants (thirty males and fifty-seven females; 59·7 (sd 6·3) years, body mass 76 (sd 16) kg) completed the study. Compared with the regular diet, the pulse-based diet decreased total cholesterol by 8·3 % (pulse, 4·57 (sd 0·93) to 4·11 (sd 0·91) mmol/l; regular, 4·47 (sd 0·94) to 4·39 (sd 0·97) mmol/l; P < 0·001) and LDL-C by 7·9 % (pulse, 2·93 (sd 0·84) to 2·55 (sd 0·75) mmol/l; regular, 2·96 (sd 0·86) to 2·81 (sd 0·83) mmol/l; P = 0·01). In a sub-analysis of individuals with high lipid levels at baseline (twenty individuals with high cholesterol), the pulse-based diet reduced cholesterol by 6 % compared with the regular diet (pulse, 5·62 (sd 0·78) to 5·26 (sd 0·68) mmol/l; regular, 5·60 (sd 0·91) to 5·57 (sd 0·85) mmol/l; P = 0·05). A pulse-based diet is effective for reducing total cholesterol and LDL-C in older adults and therefore reduces the risk of CVD.",
"title": "A pulse-based diet is effective for reducing total and LDL-cholesterol in older adults."
},
{
"docid": "MED-3141",
"text": "OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.",
"title": "A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome."
},
{
"docid": "MED-3584",
"text": "Background: A high intake of white rice is associated with the metabolic syndrome and type 2 diabetes. Costa Ricans follow a staple dietary pattern that includes white rice and beans, yet the combined role of these foods on cardiometabolic risk factors has not been studied. Objective: We aimed to determine the association between intake of white rice and beans and the metabolic syndrome and its components in Costa Rican adults (n = 1879) without diabetes. Design: Multivariate-adjusted means were calculated for components of the metabolic syndrome by daily servings of white rice and beans (<1, 1, or >1) and by the ratio of beans to white rice. The OR for the metabolic syndrome was calculated by substituting one serving of beans for one serving of white rice. Results: An increase in daily servings of white rice was positively associated with systolic blood pressure (BP), triglycerides, and fasting glucose and inversely associated with HDL cholesterol (P-trend <0.01 for all). An increase in servings of beans was inversely associated with diastolic BP (P = 0.049). Significant trends for higher HDL cholesterol and lower BP and triglycerides were observed for 1:3, 1:2, 1:1, and 2:1 ratios of beans to white rice. Substituting one serving of beans for one serving of white rice was associated with a 35% (95% CI: 15%, 50%) lower risk of the metabolic syndrome. Conclusion: Increasing the ratio of beans to white rice, or limiting the intake of white rice by substituting beans, may lower cardiometabolic risk factors.",
"title": "A higher ratio of beans to white rice is associated with lower cardiometabolic risk factors in Costa Rican adults"
},
{
"docid": "MED-2009",
"text": "Chickpea (Cicer arietinum L.) is an important pulse crop grown and consumed all over the world, especially in the Afro-Asian countries. It is a good source of carbohydrates and protein, and protein quality is considered to be better than other pulses. Chickpea has significant amounts of all the essential amino acids except sulphur-containing amino acids, which can be complemented by adding cereals to the daily diet. Starch is the major storage carbohydrate followed by dietary fibre, oligosaccharides and simple sugars such as glucose and sucrose. Although lipids are present in low amounts, chickpea is rich in nutritionally important unsaturated fatty acids such as linoleic and oleic acids. β-Sitosterol, campesterol and stigmasterol are important sterols present in chickpea oil. Ca, Mg, P and, especially, K are also present in chickpea seeds. Chickpea is a good source of important vitamins such as riboflavin, niacin, thiamin, folate and the vitamin A precursor β-carotene. As with other pulses, chickpea seeds also contain anti-nutritional factors which can be reduced or eliminated by different cooking techniques. Chickpea has several potential health benefits, and, in combination with other pulses and cereals, it could have beneficial effects on some of the important human diseases such as CVD, type 2 diabetes, digestive diseases and some cancers. Overall, chickpea is an important pulse crop with a diverse array of potential nutritional and health benefits.",
"title": "Nutritional quality and health benefits of chickpea (Cicer arietinum L.): a review."
},
{
"docid": "MED-3143",
"text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.",
"title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial."
},
{
"docid": "MED-2011",
"text": "The relationship between diet diversity and hypertension was examined in a cross-sectional exploratory study of 82 randomly selected adult residents of Saba Island, Netherlands Antilles, in the eastern Caribbean Basin. Blood pressure measurements, taken over 4 years, and the appropriate use of antihypertensive medications, were used to identify chronic hypertensives. A 24-hour dietary recall, semi-quantitative food frequency interviews, and ethnographic confirmation techniques were used to calculate diet diversity, a measure of the overall dietary pattern. Results suggest hypertension is associated with lack of an overall balance of food groups in the daily diet beyond any imbalance of a particular dietary cation such as sodium, potassium, or calcium. Bivariate analyses found a significant association between a poorly diversified diet and hypertension (odds ratio [OR] = 4.25, 95 percent confidence intervals [CI] = 1.47,12.30). Dietary intake of sodium, potassium, and calcium was also examined and found not to be associated with the presence of hypertension in bivariate analyses. Including these cations individually in logistic regression models, which also included diet diversity, did not diminish the diet diversity-hypertension association. Multiple logistic regression models in which other potential confounding variables were individually entered as a control variable (body fat, skin color, age, sex, perceived stress, alcohol intake, aerobic activity, and socioeconomic status) did not alter this result. Analysis of the presence or absence of individual food groups indicate a lack of legumes in the daily diet is also associated with the diagnosis of hypertension (OR = 4.71, 95 percent CI = [1.71,13.01]).",
"title": "Exploratory study of the relationship between hypertension and diet diversity among Saba Islanders."
},
{
"docid": "MED-3139",
"text": "Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.",
"title": "Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women"
},
{
"docid": "MED-2144",
"text": "Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus. Historical knowledge is summarized and compared to recent study results. Reports dating from the first half of the 20(th) century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an alpha-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.",
"title": "Beans and diabetes: Phaseolus vulgaris preparations as antihyperglycemic agents."
},
{
"docid": "MED-2141",
"text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population."
},
{
"docid": "MED-3583",
"text": "Pulses are low-glycemic appetite-suppressing foods, but it is not known whether these properties persist after being consumed as part of a meal and after a second meal. The objective of this study was to determine the effects of a fixed-size pulse meal on appetite and blood glucose (BG) before and after an ad libitum test meal (pizza) and on food intake (FI) at the test meal. Males (n = 25; 21.3 ± 0.5 years; 21.6 ± 0.3 kg·m(-2)) randomly consumed 4 isocaloric meals: chickpea; lentil; yellow split pea; and macaroni and cheese (control). Commercially available canned pulses provided 250 kcal, and were consumed with macaroni and tomato sauce. FI was measured at a pizza meal 260 min after consumption of the isocaloric meal. BG and appetite were measured from 0 to 340 min. The lentil and yellow pea, but not chickpea, treatments led to lower appetite ratings during the 260 min prepizza meal period, and less FI at the pizza meal, compared with macaroni and cheese (p < 0.05). All pulse treatments lowered BG immediately following consumption (at 20 min) (p < 0.05), but there was no effect of treatment on prepizza meal BG AUC (p = 0.07). Immediately after the pizza meal, BG was lower following the chickpea and lentil treatments, but not the yellow pea treatment (p < 0.05). Postpizza meal BG AUC was lower following the chickpea and lentil treatments than in the yellow pea treatment (p < 0.05). The beneficial effects of consuming a pulse meal on appetite, FI at a later meal, and the BG response to a later meal are dependent on pulse type.",
"title": "First and second meal effects of pulses on blood glucose, appetite, and food intake at a later meal."
},
{
"docid": "MED-2985",
"text": "Several risk factors seem to play a role in the development of osteoporosis. Phytate is a naturally occurring compound that is ingested in significant amounts by those with diets rich in whole grains. The aim of this study was to evaluate phytate consumption as a risk factor in osteoporosis. In a first group of 1,473 volunteer subjects, bone mineral density was determined by means of dual radiological absorptiometry in the calcaneus. In a second group of 433 subjects (used for validation of results obtained for the first group), bone mineral density was determined in the lumbar column and the neck of the femur. Subjects were individually interviewed about selected osteoporosis risk factors. Dietary information related to phytate consumption was acquired by questionnaires conducted on two different occasions, the second between 2 and 3 months after performing the first one. One-way analysis of variance or Student's t test was used to determine statistical differences between groups. Bone mineral density increased with increasing phytate consumption. Multivariate linear regression analysis indicated that body weight and low phytate consumption were the risk factors with greatest influence on bone mineral density. Phytate consumption had a protective effect against osteoporosis, suggesting that low phytate consumption should be considered an osteoporosis risk factor.",
"title": "Phytate (myo-inositol hexaphosphate) and risk factors for osteoporosis."
},
{
"docid": "MED-3580",
"text": "The effects of the glycemic index (GI) of carbohydrate eaten the previous night on the glycemic response to a standard test meal eaten subsequently in the morning (breakfast) was studied. On separate evenings normal subjects ate low- or high-GI test meals of the same nutrient composition. The dinners consisted of single foods in two experiments and mixed meals containing several foods in the third. The differences between the observed glycemic responses to low- and high-GI dinners were predicted by their GIs. The glycemic responses to breakfast were significantly lower on mornings after low-GI dinners than after high-GI dinners. Eating, at dinner, foods with different fiber contents but the same GI had no effect on postbreakfast glycemia. We conclude that the GI predicts the difference between glycemic responses of mixed dinner meals; breakfast carbohydrate tolerance is improved when low-GI foods are eaten the previous evening.",
"title": "Second-meal effect: low-glycemic-index foods eaten at dinner improve subsequent breakfast glycemic response."
},
{
"docid": "MED-3136",
"text": "The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.",
"title": "Influence of frequent and long-term bean consumption on colonic function and fermentation."
},
{
"docid": "MED-2140",
"text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253",
"title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study"
},
{
"docid": "MED-3137",
"text": "A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.",
"title": "Americans Do Not Meet Federal Dietary Recommendations"
},
{
"docid": "MED-3138",
"text": "Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.",
"title": "Perceptions of flatulence from bean consumption among adults in 3 feeding studies"
},
{
"docid": "MED-3140",
"text": "To identify protective dietary predictors amongst long-lived elderly people (N= 785), the \"Food Habits in Later Life \"(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.",
"title": "Legumes: the most important dietary predictor of survival in older people of different ethnicities."
},
{
"docid": "MED-4319",
"text": "The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.",
"title": "Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis."
},
{
"docid": "MED-3582",
"text": "Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or \"lente\" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.",
"title": "Slow release dietary carbohydrate improves second meal tolerance."
},
{
"docid": "MED-2145",
"text": "AIMS/HYPOTHESIS: Dietary non-oil-seed pulses (chickpeas, beans, peas, lentils, etc.) are a good source of slowly digestible carbohydrate, fibre and vegetable protein and a valuable means of lowering the glycaemic-index (GI) of the diet. To assess the evidence that dietary pulses may benefit glycaemic control, we conducted a systematic review and meta-analysis of randomised controlled experimental trials investigating the effect of pulses, alone or as part of low-GI or high-fibre diets, on markers of glycaemic control in people with and without diabetes. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant controlled trials of >or=7 days. Two independent reviewers (A. Esfahani and J. M. W. Wong) extracted information on study design, participants, treatments and outcomes. Data were pooled using the generic inverse variance method and expressed as standardised mean differences (SMD) with 95% CIs. Heterogeneity was assessed by chi (2) and quantified by I (2). Meta-regression models identified independent predictors of effects. RESULTS: A total of 41 trials (39 reports) were included. Pulses alone (11 trials) lowered fasting blood glucose (FBG) (-0.82, 95% CI -1.36 to -0.27) and insulin (-0.49, 95% CI -0.93 to -0.04). Pulses in low-GI diets (19 trials) lowered glycosylated blood proteins (GP), measured as HbA(1c) or fructosamine (-0.28, 95% CI -0.42 to -0.14). Finally, pulses in high-fibre diets (11 trials) lowered FBG (-0.32, 95% CI -0.49 to -0.15) and GP (-0.27, 95% CI -0.45 to -0.09). Inter-study heterogeneity was high and unexplained for most outcomes, with benefits modified or predicted by diabetes status, pulse type, dose, physical form, duration of follow-up, study quality, macronutrient profile of background diets, feeding control and design. CONCLUSIONS/INTERPRETATION: Pooled analyses demonstrated that pulses, alone or in low-GI or high-fibre diets, improve markers of longer term glycaemic control in humans, with the extent of the improvements subject to significant inter-study heterogeneity. There is a need for further large, well-designed trials.",
"title": "Effect of non-oil-seed pulses on glycaemic control: a systematic review and meta-analysis of randomised controlled experimental trials in people wi..."
},
{
"docid": "MED-2987",
"text": "INTRODUCTION: The objective of this paper was to evaluate the relationship between urinary concentrations of InsP6, bone mass loss and risk fracture in postmenopausal women. MATERIALS AND METHODS: A total of 157 postmenopausal women were included in the study: 70 had low (≤0.76 μM), 42 intermediate (0.76-1.42 μM) and 45 high (≥1.42 μM) urinary phytate concentrations. Densitometry values for neck were measured at enrollment and after 12 months (lumbar spine and femoral neck), and 10-year risk fracture was calculated using the tool FRAX(®). RESULTS: Individuals with low InsP6 levels had significantly greater bone mass loss in the lumbar spine (3.08 ± 0.65 % vs. 0.43 ± 0.55 %) than did those with high phytate levels. Moreover, a significantly greater percentage of women with low than with high InsP6 levels showed more than 2 % of bone mass loss in the lumbar spine (55.6 vs. 20.7 %). The 10-year fracture probability was also significantly higher in the low-phytate group compared to the high-phytate group, both in hip (0.37 ± 0.06 % vs 0.18 ± 0.04 %) and major osteoporotic fracture (2.45 ± 0.24 % vs 1.83 ± 0.11 %). DISCUSSION: It can be concluded that high urinary phytate concentrations are correlated with reduced bone mass loss in lumbar spine over 12 months and with reduced 10-year probability of hip and major osteoporotic fracture, indicating that increased phytate consumption can prevent development of osteoporosis.",
"title": "Protective effect of myo-inositol hexaphosphate (phytate) on bone mass loss in postmenopausal women."
},
{
"docid": "MED-3581",
"text": "BACKGROUND: Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the \"second-meal effect\" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE: The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.",
"title": "Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect."
},
{
"docid": "MED-3142",
"text": "AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.",
"title": "Positive effects of soy isoflavone food on survival of breast cancer patients in China."
},
{
"docid": "MED-2986",
"text": "Zinc metabolism in male rats was studied by combining nutritional balance methods with an analysis of 65Zn kinetics. The rats, two groups of 84 each, were fed zinc-adequate diets (33 ppm Zn) with either 0 (basal) or 2% phytic acid added as sodium phytate. A fourth-order exponential function described the time-course of 65Zn in plasma, and compartmental models were developed accordingly. Plasma zinc exchanged more rapidly with zinc in liver and kidneys than it did with zinc in testes, skeletal muscle, or bone. Total body zinc content (2.6 mg/100 g live body weight) measured chemically was about 9 times higher than estimates of exchangeable zinc in the body. Whole-body retention of 65Zn was higher and endogenous fecal zinc excretion was lower in rats fed phytate than in those fed the basal diet; these responses to phytate may reflect a homeostatic adjustment to decreased absorption of zinc. Respective values for apparent absorption and true absorption of zinc were 13 and 32% of zinc intake in rats fed phytate, and 19 and 46% of zinc intake in rats fed the basal diet. When whole grains or mature seeds constitute a major portion of the diet, the phytate: zinc molar ratio may approach that (60:1) used in our study. Whether or not phytic acid occurring naturally in foods affects zinc metabolism to the same extent as sodium phytate can not be determined from our study.",
"title": "Effect of phytic acid on the absorption, distribution, and endogenous excretion of zinc in rats."
},
{
"docid": "MED-2988",
"text": "This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.",
"title": "The role of phytic acid in legumes: antinutrient or beneficial function?"
}
] |
[
{
"docid": "MED-872",
"text": "Dental amalgam is 50% metallic mercury (Hg) by weight and Hg vapour continuously evolves from in-place dental amalgam, causing increased Hg content with increasing amalgam load in urine, faeces, exhaled breath, saliva, blood, and various organs and tissues including the kidney, pituitary gland, liver, and brain. The Hg content also increases with maternal amalgam load in amniotic fluid, placenta, cord blood, meconium, various foetal tissues including liver, kidney and brain, in colostrum and breast milk. Based on 2001 to 2004 population statistics, 181.1 million Americans carry a grand total of 1.46 billion restored teeth. Children as young as 26 months were recorded as having restored teeth. Past dental practice and recently available data indicate that the majority of these restorations are composed of dental amalgam. Employing recent US population-based statistics on body weight and the frequency of dentally restored tooth surfaces, and recent research on the incremental increase in urinary Hg concentration per amalgam-filled tooth surface, estimates of Hg exposure from amalgam fillings were determined for 5 age groups of the US population. Three specific exposure scenarios were considered, each scenario incrementally reducing the number of tooth surfaces assumed to be restored with amalgam. Based on the least conservative of the scenarios evaluated, it was estimated that some 67.2 million Americans would exceed the Hg dose associated with the reference exposure level (REL) of 0.3 μg/m(3) established by the US Environmental Protection Agency; and 122.3 million Americans would exceed the dose associated with the REL of 0.03 μg/m(3) established by the California Environmental Protection Agency. Exposure estimates are consistent with previous estimates presented by Health Canada in 1995, and amount to 0.2 to 0.4 μg/day per amalgam-filled tooth surface, or 0.5 to 1 μg/day/amalgam-filled tooth, depending on age and other factors. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Mercury exposure and risks from dental amalgam in the US population, post-2000."
},
{
"docid": "MED-4125",
"text": "Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.",
"title": "Human gut microbiota does not ferment erythritol."
},
{
"docid": "MED-3847",
"text": "In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3-dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings.",
"title": "Lignans in man and in animal species."
},
{
"docid": "MED-4733",
"text": "OBJECTIVES: Mercury and most of its compounds are extremely toxic and should be handled with care. It can be inhaled and absorbed through the skin and mucous membranes. The most toxic forms of mercury are its organic compounds such as dimethylmercury and methylmercury. Fish have a natural tendency to accumulate mercury. Methylmercury is produced by microbial methylation of inorganic mercury in water sediment then it infiltrates the food chain and it consequently accumulates in fish. Fish are the main source of methylmercury in human food. Mercury is transferred into a hair; and this can be than used to monitor the long-term exposure to mercury. The content of mercury in hair depends on the frequency of fish consumption. The aim of our study was to compare mercury content in the hair of children that had various amounts of fish consumption (increased or reduced). DESIGN: Total mercury content in hair was determined by direct method of cold vapors using an AMA 245 analyzer. A total of 174 hair samples from the children (9-17 years old) were analyzed. In this study, the following localities were compared: Neratovice (n=42), Jeseníky (n=44), Prague (n=59) in Czech Republic and Olsztyn in Poland (n=29). Every sample was accompanied with questionnaire about age, gender, regions, amalgam fillings and fish consumption. RESULTS: We did not find a correlation between the content of mercury in hair with age, gender or amalgam fillings. We did find a correlation between fish consumption and the amount of mercury found in the hair samples. CONCLUSION: The amount of mercury in hair increases with more frequent consumption of freshwater and marine fish.",
"title": "Mercury in human hair as an indicator of the fish consumption."
},
{
"docid": "MED-3113",
"text": "Chronic diseases with a lifestyle-based aetiology currently make up a significant proportion of primary care consultations, but management often falls between the demands of public and clinical health. A modified clinical approach, based around the concept of \"lifestyle medicine\", helps fill the gap by adding behavioural, motivational and environmental skills to conventional medical practice. When used in a multidisciplinary setting, lifestyle medicine offers potential cost and effectiveness benefits, which are beginning to be realised.",
"title": "The emergence of \"lifestyle medicine\" as a structured approach for management of chronic disease."
},
{
"docid": "MED-1793",
"text": "Most research studies in the field of dietary polyphenols or phenolic compounds use a chemical approach focusing exclusively on polyphenols extracted from plant foods with organic solvents. However, an appreciable part of polyphenols are not extracted with organic solvents and thus are ignored in biological, nutritional, and epidemiological studies. Recent studies have shown that these nonextractable polyphenols (NEPP) are a major part of total dietary polyphenols and that they exhibit a significant biological activity. A physiological approach is proposed on the basis that the bioavailability and health-related properties of polyphenols depend on their solubility in intestinal fluids, which is different from their solubility in organic solvents. This paper tries to clarify the concept of NEPP, distinguishing between chemical and physiological approaches and pointing out the main qualitative and quantitative differences between them. It is stressed that the literature and databases refer to only extractable polyphenols. Greater attention to NEPP may fill the current gap in the field of dietary polyphenols.",
"title": "Concept and health-related properties of nonextractable polyphenols: the missing dietary polyphenols."
},
{
"docid": "MED-2571",
"text": "Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.",
"title": "Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study"
},
{
"docid": "MED-3153",
"text": "This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18-53 years, mean age: 36 ± 9, self-administered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP®) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon. Key points",
"title": "Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes"
},
{
"docid": "MED-1307",
"text": "Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States. While the American Association for the Study of Liver Diseases guidelines define NAFLD as hepatic steatosis detected either on histology or imaging without a secondary cause of abnormal hepatic fat accumulation, no imaging modality is recommended as standard of care for screening or diagnosis. Bedside ultrasound has been evaluated as a non-invasive method of diagnosing NAFLD with the presence of characteristic sonographic findings. Prior studies suggest characteristic sonographic findings for NAFLD include bright hepatic echoes, increased hepatorenal echogenicity, vascular blurring of portal or hepatic vein and subcutaneous tissue thickness. These sonographic characteristics have not been shown to aid bedside clinicians easily identify potential cases of NAFLD. While sonographic findings such as attenuation of image, diffuse echogenicity, uniform heterogeneous liver, thick subcutaneous depth, and enlarged liver filling of the entire field could be identified by clinicians from bedside ultrasound. The accessibility, ease of use, and low-side effect profile of ultrasound make bedside ultrasound an appealing imaging modality in the detection of hepatic steatosis. When used with appropriate clinical risk factors and steatosis involves greater than 33% of the liver, ultrasound can reliably diagnose NAFLD. Despite the ability of ultrasound in detecting moderate hepatic steatosis, it cannot replace liver biopsy in staging the degree of fibrosis. The purpose of this review is to examine the diagnostic accuracy, utility, and limitations of ultrasound in the diagnosis of NAFLD and its potential use by clinicians in routine practices.",
"title": "Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease"
},
{
"docid": "MED-2884",
"text": "Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.",
"title": "A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women."
},
{
"docid": "MED-981",
"text": "There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B₁₂ can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B₁₂ deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B₁₂ levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B₁₂ of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B₁₂ did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B₁₂, from which it can be concluded that the usual dietary source of vitamin B₁₂ is animal products and those who choose to omit or restrict these products are destined to become vitamin B₁₂ deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.",
"title": "Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis."
},
{
"docid": "MED-4033",
"text": "Saturated fatty acids (SFAs) produce an inflammatory response. Hyperinflammation is now recognized as one of the key underlying etiologic factors in periodontal disease. The longitudinal relationship between dietary SFAs and periodontal disease in 264 Japanese individuals, aged 75 years, for whom data were available for the years 2003-2004, was investigated. SFA intake was assessed with a brief self-administered diet history questionnaire. Participants were classified by quartiles of SFA intake. Full-mouth periodontal status, measured as the clinical attachment level (CAL), was recorded at baseline and follow-up examinations. The number of teeth with a loss of CAL≥3 mm at any site over a year was calculated as 'periodontal disease events'. Poisson regression analysis was conducted, with dietary SFAs as the primary predictor of interest, to estimate their influence on periodontal disease events. High dietary SFA intake was significantly associated with a greater number of periodontal disease events among non-smokers. The multivariate adjusted relative risk (95% confidence intervals) in the 1st, 2nd, 3rd, and 4th quartiles of dietary SFAs was 1.00, 1.19 (0.72-1.97), 1.55 (0.95-2.52), and 1.92 (1.19-3.11), respectively. These findings suggest an independent association of dietary SFA intake to the progression of periodontal disease in older Japanese non-smokers. ABBREVIATIONS: saturated fatty acid (SFA); clinical attachment level (CAL); Toll-like receptor (TLR); lipopolysaccharide (LPS); brief self-administered diet history questionnaire (BDHQ); decayed, missing, and filled teeth (DMFT); clinical attachment level (CAL); body mass index (BMI); relative risk (RR); confidence intervals (CI); nuclear factor-kappa B (NF-κB).",
"title": "Relationship between saturated fatty acids and periodontal disease."
},
{
"docid": "MED-4324",
"text": "BACKGROUND: Increasingly the potential harm from high cholesterol intake, and specifically from egg yolks, is considered insignificant. We therefore assessed total plaque area (TPA) in patients attending Canadian vascular prevention clinics to determine if the atherosclerosis burden, as a marker of arterial damage, was related to egg intake. To provide perspective on the magnitude of the effect, we also analysed the effect of smoking (pack-years). METHODS: Consecutive patients attending vascular prevention clinics at University Hospital had baseline measurement of TPA by duplex ultrasound, and filled out questionnaires regarding their lifestyle and medications, including pack-years of smoking, and the number of egg yolks consumed per week times the number of years consumed (egg-yolk years). RESULTS: Data were available in 1262 patients; mean (SD) age was 61.5 (14.8) years; 47% were women. Carotid plaque area increased linearly with age after age 40, but increased exponentially with pack-years of smoking and with egg-yolk years. Plaque area in patients consuming <2 eggs per week (n = 388) was 125 ± 129 mm(2), versus 132 ± 142 mm(2) in those consuming 3 or more eggs per week (n = 603); (p < 0.0001 after adjustment for age). In multiple regression, egg-yolk years remained significant after adjusting for coronary risk factors. INTERPRETATION: Our findings suggest that regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease. This hypothesis should be tested in a prospective study with more detailed information about diet, and other possible confounders such as exercise and waist circumference. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "Egg yolk consumption and carotid plaque."
},
{
"docid": "MED-5371",
"text": "We conducted a meta-analysis of randomized, placebo-controlled trials of omega-3 fatty acid treatment of major depressive disorder in order to determine efficacy and to examine sources of heterogeneity between trials. PubMED (1965-May 2010) was searched for randomized, placebo-controlled trials of omega-3 fatty acids for major depressive disorder. Our primary outcome measure was standardized mean difference in a clinical measure of depression severity. In stratified meta-analysis we examined the effects of trial duration, trial methodological quality, baseline depression severity, diagnostic indication, dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in omega-3 preparations, and whether omega-3 fatty acid was given as monotherapy or augmentation. In 13 randomized, placebo-controlled trials examining the efficacy of omega-3 fatty acids involving 731 participants, meta-analysis demonstrated no significant benefit of omega-3 fatty acid treatment compared to placebo (SMD=0.11, 95% CI: -0.04, 0.26). Meta-analysis demonstrated significant heterogeneity and publication bias. Nearly all evidence of omega-3 benefit was removed after adjusting for publication bias using the trim-and-fill method (SMD=0.01, 95% CI: -0.13, 0.15). Secondary analyses suggested a trend towards increased efficacy of omega-3 fatty acids in trials of lower methodological quality, trials of shorter duration, trials, which utilized completers rather than intention-to-treat analysis, and trials in which study participants had greater baseline depression severity, Current published trials suggest a small, non-significant benefit of omega-3 fatty acids for major depression. Nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias.",
"title": "Omega-3 Fatty Acids for the Treatment of Depression: Systematic Review and Meta-Analysis"
},
{
"docid": "MED-3800",
"text": "OBJECTIVE: To review the current management of women with breast pain. OPTIONS: The effect of various treatment modes and health practices, including medications, was considered for the management of both cyclical and noncyclical breast pain. OUTCOMES: Effective and timely management of the woman with breast pain and improved quality of life. EVIDENCE: A literature search was performed to identify reports published in English between 1975 and July 2003 using MEDLINE and Cochrane Database of Systematic Reviews. VALUES: Levels of evidence, as outlined, have been determined using the criteria outlined by the Canadian Task Force on the Periodic Health Examination. Participants were the principal authors: a clinical dietitian, a surgeon oncologist, and a nurse. BENEFITS, HARMS, AND COSTS: Utilizing the information will increase knowledge, enabling a consistent approach, which will reduce the number of ineffective interventions and ensure appropriate use medications. VALIDATION: Comparison has been made with management protocols in the literature, but no clinical guidelines have been located. No formal clinical testing has taken place. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada (SOGC). Work on these guidelines was initiated by team members to fill a need for practice guidelines at Winnipeg Regional Health Authority Breast Health Centre, Winnipeg, MB. RECOMMENDATIONS: 1. Education and reassurance is an integral part of the management of mastalgia and should be the first-line treatment. (II-1 A) 2. The use of a well-fitting bra that provides good support should be considered for the relief of cyclical and noncyclical mastalgia. (II-3 B) 3. A change in dose, formulation, or scheduling should be considered for women on HRT. HRT may be discontinued if appropriate. (III C) 4. Women with breast pain should not be advised to reduce caffeine intake. (1 E) 5. Vitamin E should not be considered for the treatment of mastalgia. (1 E) 6. There is presently insufficient evidence to recommend the use of evening primrose oil (EPO) in the treatment of breast pain. (II-2 C) 7. Flaxseed should be considered as a first-line treatment for cyclical mastalgia. (I A) 8. Topical non-steroidal anti-inflammatory gel, such as diclofenac 2% in pluronic lethicin organogel, should be considered for pain control for localized treatment of mastalgia. (I A) 9. Tamoxifen 10 mg daily or danazol 200 mg daily should be considered when first-line treatments are ineffective. (I A) 10. Mastectomy or partial mastectomy should not be considered an effective treatment for mastalgia. (III E).",
"title": "Mastalgia."
},
{
"docid": "MED-3983",
"text": "This study was aimed at determining the molecular epidemiology of rabies virus (RABV) circulating in Vietnam. Intra vitam samples (saliva and cerebrospinal fluid) were collected from 31 patients who were believed to have rabies and were admitted to hospitals in northern provinces of Vietnam. Brain samples were collected from 176 sick or furious rabid dogs from all over the country. The human and canine samples were subjected to reverse transcription-polymerase chain reaction analysis. The findings showed that 23 patients tested positive for RABV. Interestingly, 5 rabies patients did not have any history of dog or cat bites, but they had an experience of butchering dogs or cats, or consuming their meat. RABV was also detected in 2 of the 100 sick dogs from slaughterhouses. Molecular epidemiological analysis of 27 RABV strains showed that these viruses could be classified into two groups. The RABVs classified into Group 1 were distributed throughout Vietnam and had sequence similarity with the strains from China, Thailand, Malaysia, and the Philippines. However, the RABVs classified into Group 2 were only found in the northern provinces of Vietnam and showed high sequence similarity with the strain from southern China. This finding suggested the recent influx of Group 2 RABVs between Vietnam and China across the border. Although the incidence of rabies due to circulating RABVs in slaughterhouses is less common than that due to dog bite, the national program for rabies control and prevention in Vietnam should include monitoring of the health of dogs meant for human consumption and vaccination for workers at dog slaughterhouses. Further, monitoring of and research on the circulating RABVs in dog markets may help to determine the cause of rabies and control the spread of rabies in slaughterhouses in Vietnam.",
"title": "Molecular epidemiology of rabies virus in Vietnam (2006-2009)."
},
{
"docid": "MED-1956",
"text": "The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the \"chick edema factor\" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.",
"title": "Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine."
},
{
"docid": "MED-4411",
"text": "Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.",
"title": "Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial."
},
{
"docid": "MED-861",
"text": "OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.",
"title": "Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica."
},
{
"docid": "MED-2049",
"text": "Background In vitro and animal studies have demonstrated that Chlorella is a potent biological response modifier on immunity. However, there were no direct evidences for the effect of Chlorella supplementation on immune/inflammation response in healthy humans. Methods This study was designed for an 8-week randomized, double-blinded, placebo-controlled trial: 5g of Chlorella (n=23) or Placebo (n=28) as form of tablets. Mainly, cytotoxic activities of Natural killer (NK) cells and serum concentrations of interferon-γ, interleukin-1β and interleukin-12 were measured. Results After the 8-week, serum concentrations of interferon-γ (p<0.05) and interleukin-1β (p<0.001) significantly increased and that of interleukin-12 (p<0.1) tended to increase in the Chlorella group. The increments of these cytokines after the intervention were significantly bigger in the Chlorella group than those in the placebo group. In addition, NK cell activities (%) were significantly increased in Chlorella group, but not in Placebo group. The increments of NK cell activities (%) were also significantly bigger in the Chlorella group than the placebo group. Additionally, changed levels of NK cell activity were positively correlated with those of serum interleukin-1β (r=0.280, p=0.047) and interferon-γ (r=0.271, p<0.005). Signficantly positive correlations were also observed among the changed levels of serum cytokines; between interferon-γ and interleukin-1β (r=0.448, p<0.001), between interleukin-12 and interleukin-1β (r=0.416, p=0.003) and between interleukin-12 and interferon-γ (r=0.570, p<001). Conclusion These results may suggest a beneficial immunostimulatory effect of short-term Chlorella supplementation which enhances the NK cell activity and produces interferon-γ and interleukin-12 as well as interleukin-1β, the Th-1 cell-induced cytokines in healthy people.",
"title": "Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of Natural Killer cell activity and early inflammatory response (Randomized, double-blinded, placebo-controlled trial)"
},
{
"docid": "MED-3818",
"text": "BACKGROUND: Cellulite, which appears as orange peel-type or cottage cheese-like dimpling of the skin on the thighs and buttocks, is a complex, multifactorial, cosmetic disorder of the subcutaneous fat layer and the overlying superficial skin. Adiponectin is an adipocyte-derived hormone mainly produced by subcutaneous fat that shows important protective anti-inflammatory and vasodilatory effects. We hypothesized that adiponectin expressed in the subcutaneous adipose tissue (SAT) might play a role in the pathogenesis of cellulite. We reasoned that a reduction in the expression of adiponectin - a humoral vasodilator - in the SAT of cellulite areas might contribute to the altered microcirculation frequently found in these regions. METHODS: A total of 15 lean (body mass index [BMI] < 25 kg/m(2) ) women with cellulite and 15 age- and BMI-matched women without cellulite participated in this study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess adiponectin gene expression. Plasma adiponectin levels were measured using a commercial enzyme immunoassay kit. RESULTS: Adiponectin mRNA expression in the SAT of the gluteal region was significantly lower in areas with cellulite compared with those without (12.6 ± 3.1 AU versus 16.6 ± 4.1 AU; P=0.006). However, plasma adiponectin levels did not differ between women with (20.3 ± 7.3 μg/ml) and without (19.3 ± 6.1 μg/ml) cellulite (P=0.69). CONCLUSIONS: Adiponectin expression is significantly reduced in the SAT in areas affected by cellulite. Our findings provide novel insights into the nature of cellulite and may give clues to the treatment of this cosmetic issue. © 2011 The International Society of Dermatology.",
"title": "Adiponectin expression in subcutaneous adipose tissue is reduced in women with cellulite."
},
{
"docid": "MED-4643",
"text": "Breast cancer incidence was monitored in a cohort of 20,341 California Seventh-day Adventist women who completed a detailed lifestyle questionnaire in 1976, and who were followed for 6 years. There were 215 histologically confirmed primary breast cancer detected among some 115,000 person-years of follow-up. Mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. Established risk factors for breast cancer showed strong relationships to risk in these data. Age at first live birth, maternal history of breast cancer, age at menopause, educational attainment, and obesity were all significantly related to risk. However, increasing consumption of high fat animal products was not associated with increased risk of breast cancer in a consistent fashion. Nor were childhood and early teenage dietary habits (vegetarian versus nonvegetarian) related to subsequent, adult risk of developing breast cancer. Also, a derived index of percent of calories from animal fat in the adult years was not significantly related to risk. These results persisted after simultaneously controlling for other, potentially confounding variables, utilizing Cox proportional hazard regression models.",
"title": "Dietary habits and breast cancer incidence among Seventh-day Adventists."
},
{
"docid": "MED-4878",
"text": "Background Telomere length reflects biological aging and may be influenced by environmental factors, including those that affect inflammatory processes. Objective With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. Design Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (β ± SE: −0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming ≥1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. Conclusions Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.",
"title": "Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA)"
},
{
"docid": "MED-1988",
"text": "PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.",
"title": "Pediatrician's role in screening and treatment: bullying, prediabetes, oral health."
},
{
"docid": "MED-4374",
"text": "CONTEXT: Despite cancer patients' widespread and growing use of complementary and alternative medicine, minimal attention has been paid to the role of health food stores in the \"supply side\" of this phenomenon. OBJECTIVE: To gain a better understanding of health food store personnel's recommendations for breast cancer patient care. DESIGN: Researcher posing as the daughter of a breast cancer patient and surveying health food store personnel on their product recommendations for cancer care. SETTING: Oahu, Hawaii, summer 1998. PARTICIPANTS: All health food stores (N = 40) offering products for cancer patients. MAIN OUTCOME MEASURES: Recommended products and services, proposed mechanism of action, and costs. RESULTS: Store personnel readily provided information and product recommendations, with shark cartilage being the most frequent. Suggested mechanisms of action drew on traditional healing, scientific, and pseudoscientific rationales. Costs for recommended dosages varied multifold across stores and brands. CONCLUSIONS: Retailers supplying supplements can play an important role in the network of \"authorities\" for patients with breast and other cancers, as they readily provide advice and recommend products. The reasons why patients seek health food store remedies are useful in developing approaches to patient education. Physicians and other providers are in a key position to assist cancer patients in making informed choices when considering health store products.",
"title": "Health food store recommendations for breast cancer patients."
},
{
"docid": "MED-1711",
"text": "Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.",
"title": "Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer"
},
{
"docid": "MED-969",
"text": "The endothelium is a highly metabolically active organ that is involved in many physiological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion and trafficking, inflammation, and hemostasis. Endothelial cell phenotypes are differentially regulated in space and time. Endothelial cell heterogeneity has important implications for developing strategies in basic research, diagnostics and therapeutics. The goals of this review are to: (i) consider mechanisms of endothelial cell heterogeneity; (ii) discuss the bench-to-bedside gap in endothelial biomedicine; (iii) revisit definitions for endothelial cell activation and dysfunction; and (iv) propose new goals in diagnosis and therapy. Finally, these themes will be applied to an understanding of vascular bed-specific hemostasis.",
"title": "Spatial and temporal dynamics of the endothelium."
},
{
"docid": "MED-5283",
"text": "Chocolate/cocoa has been known for its good taste and proposed health effects for centuries. Earlier, chocolate used to be criticised for its fat content and its consumption was a sin rather than a remedy, associated with acne, caries, obesity, high blood pressure, coronary artery disease and diabetes. Therefore, many physicians tended to warn patients about the potential health hazards of consuming large amounts of chocolate. However, the recent discovery of biologically active phenolic compounds in cocoa has changed this perception and stimulated research on its effects in ageing, oxidative stress, blood pressure regulation, and atherosclerosis. Today, chocolate is lauded for its tremendous antioxidant potential. However, in many studies, contradictory results and concerns about methodological issues have made it hard for health professionals and the public to understand the available evidence on chocolate's effects on health. The purpose of this review is to interpret research done in the last decade on the benefits and risks of chocolate consumption.",
"title": "Chocolate/cocoa and human health: a review."
},
{
"docid": "MED-4529",
"text": "Context Lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be present due to the practice of rasa shastra (combining herbs with metals, minerals, and gems). Whether toxic metals are present in both US- and Indian-manufactured Ayurvedic medicines is unknown. Objectives To determine the prevalence of Ayurvedic medicines available via the Internet containing detectable lead, mercury, or arsenic and to compare the prevalence of toxic metals in US- vs Indian-manufactured medicines and between rasa shastra and non–rasa shastra medicines. Design A search using 5 Internet search engines and the search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda, indicated for oral use, and available for sale. From 673 identified products, 230 Ayurvedic medicines were randomly selected for purchase in August–October 2005. Country of manufacturer/Web site supplier, rasa shastra status, and claims of Good Manufacturing Practices were recorded. Metal concentrations were measured using x-ray fluorescence spectroscopy. Main Outcome Measures Prevalence of medicines with detectable toxic metals in the entire sample and stratified by country of manufacture and rasa shastra status. Results One hundred ninety-three of the 230 requested medicines were received and analyzed. The prevalence of metal-containing products was 20.7% (95% confidence interval [CI], 15.2%–27.1%). The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%–30.4%) compared with 19.5% (95% CI, 11.3%–30.1%) in Indian products (P=.86). Rasa shastra compared with non–rasa shastra medicines had a greater prevalence of metals (40.6% vs 17.1%; P=.007) and higher median concentrations of lead (11.5 μg/g vs 7.0 μg/g; P=.03) and mercury (20 800 μg/g vs 34.5 μg/g; P=.04). Among the metal-containing products, 95% were sold by US Web sites and 75% claimed Good Manufacturing Practices. All metal-containing products exceeded 1 or more standards for acceptable daily intake of toxic metals. Conclusion One-fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain detectable lead, mercury, or arsenic.",
"title": "Lead, Mercury, and Arsenic in US- and Indian-Manufactured Ayurvedic Medicines Sold via the Internet"
},
{
"docid": "MED-5252",
"text": "BACKGROUND: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, and risk factors are well established. Caffeine exposure has been associated with increased risk of AF, but heterogeneous data exist in the literature. OBJECTIVE: To evaluate the association between chronic exposure to caffeine and AF. DESIGN: Systematic review and meta-analysis of observational studies. DATA SOURCES: PubMed, CENTRAL, ISI Web of Knowledge and LILACS to December 2012. Reviews and references of retrieved articles were comprehensively searched. STUDY SELECTION: Two reviewers independently searched for studies and retrieved their characteristics and data estimates. DATA SYNTHESIS: Random-effects meta-analysis was performed, and pooled estimates were expressed as OR and 95% CI. Heterogeneity was assessed with the I(2) test. Subgroup analyses were conducted according to caffeine dose and source (coffee). RESULTS: Seven observational studies evaluating 115 993 individuals were included: six cohorts and one case-control study. Caffeine exposure was not associated with an increased risk of AF (OR 0.92, 95% CI 0.82 to 1.04, I(2)=72%). Pooled results from high-quality studies showed a 13% odds reduction in AF risk with lower heterogeneity (OR 0.87; 95% CI 0.80 to 0.94; I(2)=39%). Low-dose caffeine exposure showed OR 0.85 (95% CI 0.78 to 92, I(2)=0%) without significant differences in other dosage strata. Caffeine exposure based solely on coffee consumption also did not influence AF risk. CONCLUSIONS: Caffeine exposure is not associated with increased AF risk. Low-dose caffeine may have a protective effect.",
"title": "Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies."
}
] |
183791
|
A woman from Britain wrote Harry Potter.
|
[
{
"docid": "J._K._Rowling",
"text": "Joanne Rowling , ( -LSB- ˈrəʊlɪŋ -RSB- born 31 July 1965 ) , pen names J. K. Rowling and Robert Galbraith , is a British novelist , screenwriter and film producer best known as the author of the Harry Potter fantasy series . The books have gained worldwide attention , won multiple awards , and sold more than 400 million copies . They have become the best-selling book series in history and been the basis for a series of films over which Rowling had overall approval on the scripts and maintained creative control by serving as a producer on the final instalment . Born in Yate , Gloucestershire , England , Rowling was working as a researcher and bilingual secretary for Amnesty International when she conceived the idea for the Harry Potter series while on a delayed train from Manchester to London in 1990 . The seven-year period that followed saw the death of her mother , birth of her first child , divorce from her first husband and relative poverty until she finished the first novel in the series , Harry Potter and the Philosopher 's Stone , in 1997 . There were six sequels , the last , Harry Potter and the Deathly Hallows , in 2007 . Since then , Rowling has written four books for adult readers : The Casual Vacancy ( 2012 ) and -- under the pseudonym Robert Galbraith -- the crime fiction novels The Cuckoo 's Calling ( 2013 ) , The Silkworm ( 2014 ) and Career of Evil ( 2015 ) . Rowling has lived a `` rags to riches '' life story , in which she progressed from living on state benefits to multi-millionaire status within five years . She is the United Kingdom 's best-selling living author , with sales in excess of # 238M . The 2016 Sunday Times Rich List estimated Rowling 's fortune at # 600 million , ranking her as the joint 197th richest person in the UK . Time magazine named her as a runner-up for its 2007 Person of the Year , noting the social , moral , and political inspiration she has given her fans . In October 2010 , Rowling was named the `` Most Influential Woman in Britain '' by leading magazine editors . She has supported charities including Comic Relief , One Parent Families , Multiple Sclerosis Society of Great Britain and Lumos ( formerly the Children 's High Level Group ) .",
"title": ""
},
{
"docid": "Harry_Potter",
"text": "Harry Potter is a series of fantasy novels written by British author J. K. Rowling . The novels chronicle the life of a young wizard , Harry Potter , and his friends Hermione Granger and Ron Weasley , all of whom are students at Hogwarts School of Witchcraft and Wizardry . The main story arc concerns Harry 's struggle against Lord Voldemort , a dark wizard who intends to become immortal , overthrow the wizard governing body known as the Ministry of Magic , and subjugate all wizards and Muggles , a reference term that means non-magical people . Since the release of the first novel , Harry Potter and the Philosopher 's Stone , on 26 June 1997 , the books have found immense popularity , critical acclaim and commercial success worldwide . The series has now been translated into multiple languages including French , Irish , Spanish , German and Swedish to name a few . They have attracted a wide adult audience as well as younger readers , and are often considered cornerstones of modern young adult literature . The series has also had its share of criticism , including concern about the increasingly dark tone as the series progressed , as well as the often gruesome and graphic violence it depicts . , the books have sold more than 500 million copies worldwide , making them the best-selling book series in history , and have been translated into seventy-three languages . The last four books consecutively set records as the fastest-selling books in history , with the final instalment selling roughly eleven million copies in the United States within twenty-four hours of its release . The series was originally published in English by two major publishers , Bloomsbury in the United Kingdom and Scholastic Press in the United States . A play , Harry Potter and the Cursed Child , based on a story co-written by Rowling , premiered in London on 30 July 2016 at the Palace Theatre , and its script was published by Little , Brown as the eighth book in the series . The original seven books were adapted into an eight-part film series by Warner Bros. . Pictures , which has become the second highest-grossing film series of all time . In 2016 , the total value of the Harry Potter franchise was estimated at $ 25 billion , making Harry Potter one of the highest-grossing media franchises of all time . A series of many genres , including fantasy , drama , coming of age , friendship , and the British school story ( which includes elements of mystery , thriller , adventure , horror and romance ) , the world of Harry Potter explores numerous themes and includes many cultural meanings and references . According to Rowling , the main theme is death . Other major themes in the series include prejudice , corruption , and madness . The success of the books and films has ensured that the Harry Potter franchise continues to expand , with numerous derivative works , a travelling exhibition that premiered in Chicago in 2009 , a studio tour in London that opened in 2012 , a digital platform on which J.K. Rowling updates the series with new information and insight , and a pentalogy of spin-off films premiering in November 2016 , among many other developments . Most recently , themed attractions , collectively known as The Wizarding World of Harry Potter , have been built at several Universal Parks & Resorts amusement parks around the world .",
"title": ""
}
] |
[
{
"docid": "The_Magical_Worlds_of_Harry_Potter",
"text": "The Magical Worlds of Harry Potter : A Treasury of Myths , Legends , and Fascinating Facts is a guide to the fictional Harry Potter universe , written by David Colbert . It explores the references to history , legends , and literature in J.K. Rowling 's Harry Potter novels . Colbert conceived the idea for The Magical Worlds of Harry Potter while quizzing his nephew and nieces about the mythological references in the novels . He later wrote the book while teaching a seminar on self-publishing to graduate students at the University of North Carolina . The book was published in March 2001 , without approval from Rowling , and has since received positive reviews from critics . An updated version of The Magical Worlds of Harry Potter was published in 2004 by Berkley Books .",
"title": ""
},
{
"docid": "Michael_Goldenberg",
"text": "Michael Goldenberg ( born 1965 ) is an American playwright , Hollywood screenwriter , and film director . He graduated from the Carnegie Mellon College of Drama in 1986 with a B.F.A. Goldenberg was the screenwriter and director of Bed of Roses ( 1996 ) . He was the co-screenwriter for the film adaptation of Contact ( 1997 ) and co-adapted the live-action version of Peter Pan ( 2003 ) with director P. J. Hogan . He is also the screenwriter for the fifth Harry Potter film Harry Potter and the Order of the Phoenix ( 2007 ) . Goldenberg was selected to write the screenplay for Harry Potter and the Order of the Phoenix in November 2004 when Steve Kloves , who had adapted the previous four Harry Potter books , turned down the opportunity to do the fifth film due to exhaustion and an interest in pursuing other projects . The BBC reported Goldenberg was to write and direct a futuristic drama for Warner Bros. afterward . He was also one of the screenwriters for the superhero movie Green Lantern , having rewritten the script for director Martin Campbell . In August 2010 , Goldenberg was hired to write the screenplay for Green Lantern 2 . He also co-wrote ( with Geoff Johns ) the Green Lantern Prequel Special : SINESTRO # 1 for DC Comics ( featuring Sinestro from the Green Lantern film ) . It had a ` Movie Art ' cover ( using a still from the film ) and internal art by Fernando Dagnino Guerra . The comic was one of 5 different comic Prequel Specials . He has also written a screenplay for a Wonder Woman film . On July 29 , it was announced by Disney that he would be writing the screenplay for the upcoming Artemis Fowl movie .",
"title": ""
},
{
"docid": "Harry,_A_History",
"text": "Harry , A History : The True Story of a Boy Wizard , His Fans , and Life Inside the Harry Potter Phenomenon is a 2008 book by writer and webmistress of The Leaky Cauldron , Melissa Anelli . The book describes the Harry Potter phenomenon in detail . The book was published on November 4 , 2008 , by Pocket Books , and debuted at # 18 on The New York Times paperback bestseller list . Notably , the book features exclusive interview material and insights from Harry Potter author J.K. Rowling who also wrote the foreword .",
"title": ""
},
{
"docid": "Ministry_of_Magic",
"text": "The Ministry of Magic is the government of the Magical community of Britain in J. K. Rowling 's Harry Potter series . First mentioned in Harry Potter and the Philosopher 's Stone , the Ministry makes its first proper appearance in Harry Potter and the Order of the Phoenix . Throughout the books , it is generally depicted as either corrupt , incompetent , or both , with its high officials blind to actual events and dangers . It reaches a nadir of corruption before being effectively taken over by Lord Voldemort . At the end of the final book , following Voldemort 's death , Kingsley Shacklebolt takes over the ministry , changing it for the better . By the time of Harry Potter and the Cursed Child , Hermione Granger is the Minister for Magic .",
"title": ""
},
{
"docid": "Music_of_the_Harry_Potter_films",
"text": "The music of the Harry Potter film series was recorded and released in conjunction with the post-production and releases of each of the eight corresponding films . The scores were composed by John Williams , Patrick Doyle , Nicholas Hooper , and Alexandre Desplat . Musicians credited with writing source music include Jarvis Cocker , The Ordinary Boys and Nick Cave and the Bad Seeds . Jeremy Soule and James Hannigan wrote the music for the Harry Potter video games .",
"title": ""
},
{
"docid": "Hogwarts_Express_(disambiguation)",
"text": "Hogwarts Express may refer to the following , which are all related to the fictional Hogwarts Express from the Harry Potter series : Great Britain Warner Bros. . Studios , Leavesden , displaying GWR 4900 Class 5972 Olton Hall ( as 5972 Hogwarts Castle ) GWR 4900 Class 5972 Olton Hall hauling mainline steam trips run by West Coast Railways London King 's Cross station luggage trolley and Platform 9 3/4 sign United States Hogwarts Express ( Universal Orlando Resort ) , connecting both parks of The Wizarding World of Harry Potter at Universal Orlando Resort Static model of 5972 Hogwarts Castle within Islands of Adventure Australia Former repainted locomotive at Harry Potter Movie Magic Experience , Queensland Japan Static model of 5972 Hogwarts Castle within Universal Studios Japan",
"title": ""
},
{
"docid": "Mabel_Potter_Daggett",
"text": "Mabel Potter Daggett ( c. 1870 -- November 13 , 1927 ) was an American writer , journalist , editor and suffragist . Daggett reported from France during World War I , wrote a biography of Queen Marie of Romania , and was active in the woman 's movement in the USA .",
"title": ""
},
{
"docid": "Fantastic_Beasts_and_Where_to_Find_Them",
"text": "Fantastic Beasts and Where to Find Them is a 2001 book written by British author J. K. Rowling ( under the pen name of the fictitious author Newt Scamander ) about the magical creatures in the Harry Potter universe . The original version purports to be Harry Potter 's copy of the textbook of the same name mentioned in Harry Potter and the Philosopher 's Stone ( or Harry Potter and the Sorcerer 's Stone in the US ) , the first novel of the Harry Potter series . It includes several notes inside it supposedly handwritten by Harry , Ron Weasley , and Hermione Granger , detailing their own experiences with some of the beasts described , and including in-jokes relating to the original series . In a 2001 interview with publisher Scholastic , Rowling stated that she chose the subject of magical creatures because it was a fun topic for which she had already developed a lot of information in earlier books . Rowling 's name did not appear on the cover of the first edition , the work being credited under the pen name `` Newt Scamander '' , who , in the books , wrote this textbook as seen on Harry 's supply list for his first year . The book benefits the charity Comic Relief . Over 80 % of the cover price of each book sold goes directly to poor children in various places around the world . According to Comic Relief , sales from this book and its companion Quidditch Through the Ages have raised over # 17 million . On 12 September 2013 , Warner Bros. and Rowling announced they would be producing a film inspired by the book , being the first in a series of five such films . Rowling herself is the screenwriter . She came up with a plan for a movie after Warner Bros. suggested the idea . The story features Newt Scamander as a main character and is set in New York City , 70 years before Harry 's story started . The film was released on 18 November 2016 . On 14 March 2017 a new edition of the book was published with six new creatures and the foreword by Newt Scamander . It is assumed to be a new copy as it does not feature any handwritten notes . Proceeds from this edition are donated to Lumos as well as Comic Relief .",
"title": ""
},
{
"docid": "The_Wizarding_World_of_Harry_Potter_(Universal_Studios_Hollywood)",
"text": "The Wizarding World of Harry Potter is a themed area at Universal Studios Hollywood theme park near Los Angeles , California . The area is themed to the Harry Potter media franchise , adapting elements from the film series and novels by J.K. Rowling . The attraction -- the second Harry Potter-themed area to exist at a Universal resort -- was designed by Universal Creative from an exclusive license with Warner Bros. . Entertainment . After the successful debut of a similarly-themed area at Universal Orlando Resort , Universal Parks & Resorts announced the construction of a second Wizarding World of Harry Potter on December 6 , 2011 . The Wizarding World of Harry Potter officially began operation on April 7 , 2016 .",
"title": ""
},
{
"docid": "Adrian_Rawlins",
"text": "Adrian Justin Rawlins ( born 27 March 1958 ) is an English actor who is probably best known for playing Arthur Kidd in The Woman in Black ( 1989 ) and James Potter in the Harry Potter films .",
"title": ""
},
{
"docid": "Harry_Potter_(disambiguation)",
"text": "Harry Potter is a series of novels by J. K. Rowling . Harry Potter may also refer to : Harry Potter ( character ) , the main character in Harry Potter media Harry Potter ( film series ) , the film series based on the novels Harry Potter and the Cursed Child a theatrical play following up on the character Harry Potter ( journalist ) ( 1941 -- 2014 ) , Australian television journalist and crime reporter Harry Potter , the name of two characters in the 1986 film Troll",
"title": ""
},
{
"docid": "Lisa_Hammond",
"text": "Lisa Hammond ( b. 1956 ) is a British studio potter . She is a Fellow of the Craft Potters Association of Britain . She has specialised in vapour glazing since leaving college , first using salt and , since the early 1980s , soda glaze . She produces a range of functional ware for the preparation , cooking and serving of food . Alongside functional ware , she makes a range of work that she describes as `` individual and playful '' . Hammond worked in Greenwich , London , from 1979 and recently set up a studio at Okehampton , Devon . In 2003-2004 , she spent three months making and firing in the Mino , Gifu , area for several exhibitions in Japan . She taught ceramics at Goldsmith 's College , London , and has lectured and exhibited widely . Hammond has been described as one of the most committed and driven of modern studio potters , `` one of a small number who have clearly inherited the mantle of studio pioneers like Michael Cardew '' and `` the best woman potter working in Britain . '' Her work is represented in museums and collections in the UK and abroad . Hammond was awarded an MBE in the 2016 birthday honours list .",
"title": ""
},
{
"docid": "Harry_Potter_and_the_Methods_of_Rationality",
"text": "Harry Potter and the Methods of Rationality , often abbreviated HPMOR , is a Harry Potter fan fiction by Eliezer Yudkowsky . It adapts the story of Harry Potter by applying the scientific method to the fictional universe of author J. K. Rowling . It was published in chapters online from 2010 through 2015 . Unlike Rowling 's original books , where the orphaned Harry Potter is raised by the abusive Dursley family , the Harry Potter character in HPMOR is raised by an Oxford scientist , and is trained by his parents in science and rational thinking before learning about magic and traveling to the wizarding school Hogwarts . The book takes place during a single year , covering the same time period as the first volume of Rowling 's own series .",
"title": ""
},
{
"docid": "Legal_disputes_over_the_Harry_Potter_series",
"text": "Since first coming to wide notice in the late 1990s , the Harry Potter book series by J. K. Rowling has engendered a number of legal disputes . Rowling , her various publishers and Time Warner , the owner of the rights to the Harry Potter films , have taken numerous legal actions to protect their copyrights , and also have fielded accusations of copyright theft themselves . The worldwide popularity of the Harry Potter series has led to the appearance of a number of locally produced , unauthorised sequels and other derivative works , sparking efforts to ban or contain them . While these legal proceedings have countered a number of cases of outright piracy , other attempts have targeted not-for-profit endeavours and have been criticised . Another area of legal dispute involves a series of injunctions obtained by Rowling and her publishers to prohibit anyone from distributing or reading her books before their official release dates . The sweeping powers of these injunctions have occasionally drawn fire from civil liberties and free speech campaigners and sparked debates over the `` right to read '' . One of these injunctions was used in an unrelated trespassing case as precedent supporting the issuance of an injunction against a John Doe . Outside these controversies , a number of particular incidents related to Harry Potter have also led , or almost led , to legal action . In 2005 , a man was sentenced to four years in prison after firing a replica gun at a journalist during a staged deal for stolen copies of an unreleased Harry Potter novel , and attempting to blackmail the publisher with threats of releasing secrets from the book . Then in 2007 Bloomsbury Publishing contemplated legal action against the supermarket chain Asda for libel after the company accused them of overpricing the final Harry Potter novel , Harry Potter and the Deathly Hallows . A comprehensive list of intellectual property and speech lawsuits involving Harry Potter , Harry Potter Lawsuits and Where to Find Them , was compiled by attorney David Kluft in 2015 for the Trademark and Copyright Law Blog .",
"title": ""
},
{
"docid": "Chamber_of_Secrets_(disambiguation)",
"text": "Chamber of Secrets may refer to : Great Pyramid of Giza , the Chamber of Secrets inside The Great Pyramid of Giza in Egypt , approx . 2500 BCE newscientist.com/first-images-from-great-pyramids-chamber-of-secrets Solomon 's Temple , Chamber of Secrets in Solomon 's Temple , built 953 BCE Chamber of Secrets may also refer to the location at Hogwarts , a fictional school in the Harry Potter series by J.K. Rowling Harry Potter and the Chamber of Secrets , the second novel in the Harry Potter series Harry Potter and the Chamber of Secrets ( film ) , a film adaptation of the novel directed by Chris Columbus Harry Potter and the Chamber of Secrets ( soundtrack ) , the soundtrack to the film composed by John Williams Harry Potter and the Chamber of Secrets ( video game ) , the game based on the film",
"title": ""
},
{
"docid": "Lego_Harry_Potter:_Years_1–4",
"text": "Lego Harry Potter : Years 1 -- 4 is a Lego-themed action-adventure video game developed by Traveller 's Tales and published by Warner Bros. . The game is based on the Lego Harry Potter line and its storyline covers the first four films in the Harry Potter series : Harry Potter and the Sorcerer 's Stone , Harry Potter and the Chamber of Secrets , Harry Potter and the Prisoner of Azkaban , and Harry Potter and the Goblet of Fire . The game is available on the Wii , Xbox 360 , PlayStation 3 , Nintendo DS , PlayStation Portable , Microsoft Windows , OS X , iOS and Android . The OS X version of the game was released on 22 February 2011 by Feral Interactive . The game was released for the PlayStation 4 on October 21 , 2016 , as part of the Lego Harry Potter Collection , which bundles the game with its sequel , Lego Harry Potter : Years 5 -- 7 .",
"title": ""
},
{
"docid": "Harry_Potter_and_the_Prisoner_of_Azkaban_(film)",
"text": "Harry Potter and the Prisoner of Azkaban is a 2004 British-American fantasy film directed by Alfonso Cuarón and distributed by Warner Bros. . Pictures . It is based on the novel of the same name by J. K. Rowling . The film , which is the third instalment in the Harry Potter film series , was written by Steve Kloves and produced by Chris Columbus ( director of the first two instalments ) , David Heyman , and Mark Radcliffe . The story follows Harry Potter 's third year at Hogwarts as he is informed that a prisoner named Sirius Black has escaped from Azkaban intending to kill him . The film stars Daniel Radcliffe as Harry Potter , alongside Rupert Grint and Emma Watson as Harry 's best friends Ron Weasley and Hermione Granger . It also features well-known actors in supporting roles , including Gary Oldman , David Thewlis , Michael Gambon ( in his debut in the role of Albus Dumbledore ) , Emma Thompson and Timothy Spall . It is the sequel to Harry Potter and the Chamber of Secrets and is followed by Harry Potter and the Goblet of Fire . The film was released on 31 May 2004 in the United Kingdom and on 4 June 2004 in North America , as the first Harry Potter film released into IMAX theatres and to be using IMAX Technology . It is also the last Harry Potter film to be released on VHS . The film was nominated for two Academy Awards , Best Original Music Score and Best Visual Effects at the 77th Academy Awards in 2005 . Prisoner of Azkaban grossed a total of $ 796.7 million worldwide , making it the second highest grossing film of 2004 and received widespread critical acclaim , with particular praise to Cuarón 's directing and the performances of the leads . It marked a notable change in the film series ' tone and direction and is widely considered to be the best Harry Potter film by many critics and fans .",
"title": ""
},
{
"docid": "Harry_Potter_and_the_Forbidden_Journey",
"text": "Harry Potter and the Forbidden Journey is a motion-based dark ride located in The Wizarding World of Harry Potter themed areas of Islands of Adventure in Orlando , Florida , Universal Studios Hollywood in Universal City , California , and Universal Studios Japan in Osaka , Japan . The ride takes guests through scenes and environments in and around Hogwarts Castle from the Harry Potter series of books and films . Mark Woodbury , president of Universal Creative , described the ride as an in-depth look at the world of Harry Potter , which utilizes never-before-seen technology which transforms `` the theme park experience as you know it '' . The ride first opened at Islands of Adventure with The Wizarding World of Harry Potter on June 18 , 2010 , at Universal Studios Japan on July 15 , 2014 , and at Universal Studios Hollywood on April 7 , 2016 .",
"title": ""
},
{
"docid": "Harry_and_the_Potters",
"text": "Harry and the Potters are an American rock band known for spawning the genre of wizard rock . Founded in Norwood , Massachusetts in 2002 , the group is primarily composed of brothers Joe and Paul DeGeorge , who both perform under the persona of the title character from the Harry Potter book series . Harry and the Potters are known for their elaborate live performances , and have developed a cult following within the Harry Potter fandom . The band is often backed up by musicians like Ernie Kim , Andrew MacLeay , Brad Mehlenbacher , John Clardy , Mike Gintz , Jacob Nathan , Ben Macri , Phillip Dickey , Jason Anderson and Zach Burba . Most of them played drums . The band 's most recent songs feature drummer Mike Harpring and bassist Paul Baribeau . Since 2002 , Harry and the Potters have released three studio albums , five extended plays , and a single . The duo founded the independent record label Eskimo Laboratories , and appeared in the documentary films We Are Wizards and Wizard Rockumentary . They also co-founded charity organisation The Harry Potter Alliance , and formed the Wizard Rock EP of the Month Club , an extended play syndicate .",
"title": ""
},
{
"docid": "PotterCast",
"text": "PotterCast is the official podcast of the Harry Potter fansite The Leaky Cauldron . Its episodes are posted once per month and are typically about an hour long . In every episode , the hosts discuss particular passages , themes , and questions from the Harry Potter books and films , and they go over the Potter-related news stories reported during the previous week by The Leaky Cauldron . The podcast often includes input from everyday Potter fans , but it has also featured numerous interviews with professionals involved in making the Potter books , films , and video games . PotterCast frequently hosts contests , and it has presented a variety of themed shows , including a special wizard rock video edition and an episode for Banned Books Week 2005 , in which staff interviewed representatives from the American Library Association . It also covers breaking news , such as the press conference hosted by Warner Brothers before the release of Harry Potter and the Goblet of Fire . PotterCast was launched on August 22 , 2005 , and with episode 130 it became the first podcast to interview Harry Potter author J.K. Rowling .",
"title": ""
},
{
"docid": "Harry_Potter_in_Calcutta",
"text": "Harry Potter in Calcutta is a work by Uttam Ghosh in which Harry Potter meets figures from Bengali literature . J. K. Rowling and her lawyers sued for the novel to be removed from the market , citing intellectual property concerns , and subsequently they were removed from sales .",
"title": ""
},
{
"docid": "Controversy_over_the_Harry_Potter_series",
"text": "The Harry Potter book series by JK Rowling has resulted in numerous controversies over its publication and content , primarily in the realms of law and religion . For further information see : Religious debates over the Harry Potter series Legal disputes over the Harry Potter series Politics of Harry Potter Harry Potter influences and analogues",
"title": ""
},
{
"docid": "Lego_Harry_Potter:_Years_5–7",
"text": "Lego Harry Potter : Years 5 -- 7 is a Lego-themed action-adventure video game developed by Traveller 's Tales and published by Warner Bros. . Interactive Entertainment . Released on 11 November 2011 in North America and 18 November in Europe , the game is based on the Lego Harry Potter line and is based on the final three books and four films in the Harry Potter series : Harry Potter and the Order of the Phoenix , Harry Potter and the Half-Blood Prince , Harry Potter and the Deathly Hallows -- Part 1 , and Harry Potter and the Deathly Hallows -- Part 2 . The game was released for the PlayStation 3 , Xbox 360 , PlayStation Portable , PlayStation Vita , Wii , Nintendo DS , Nintendo 3DS , Microsoft Windows , iOS and Android . The first trailer of three trailers was released 6 October 2011 , and the demo was released on 1 November . The game was released on Steam on 5 January 2012 . The OS X version of the game was released by Feral Interactive on 7 March 2012 . The game was released for the PlayStation 4 on October 21 , 2016 , as part of the Lego Harry Potter Collection , which bundles the game with its predecessor , Lego Harry Potter : Years 1 -- 4 .",
"title": ""
},
{
"docid": "Lego_Creator:_Harry_Potter",
"text": "Lego Creator : Harry Potter is a construction and management simulation video game based on the Harry Potter story series and the Lego brand of building blocks . It was developed by Superscape and published by Lego Software . In the game , the player can build Harry Potter-themed worlds and complete challenges . Lego Creator was first introduced in 1998 , then came Lego Creator : Knights ' Kingdom in 2000 , and then Lego Creator : Harry Potter in 2001 . This game was considered to be related to the film version of Harry Potter and the Philosopher 's Stone and allowed the player to play as the different characters and go into four general areas , plus 5 extra areas . The area of Inside Hogwarts school has four place-able extra rooms to reach other areas , including Professor Snape 's Potions Class and the Forbidden Corridor . The game includes many features that give the player a lot of creative ability . Features include taking control of minifigures and animals , driving the Hogwarts Express , changing the weather from rain to snow to night to day , casting spells and flying on broomsticks , and creating your own minifigures and models with classical and Harry Potter style Lego faces , bodies , cloaks and even wands ; while the workshop contains castle pieces , to extras , to standard pieces .",
"title": ""
},
{
"docid": "Harry_Potter_and_the_Philosopher's_Stone_(film)",
"text": "Harry Potter and the Philosopher 's Stone ( released in some countries as Harry Potter and the Sorcerer 's Stone ) is a 2001 British-American fantasy film directed by Chris Columbus and distributed by Warner Bros. . Pictures . It is based on the novel of the same name by J. K. Rowling . The film was the first instalment in the long-running Harry Potter film series , and was written by Steve Kloves and produced by David Heyman . Its story follows Harry Potter 's first year at Hogwarts School of Witchcraft and Wizardry as he discovers that he is a famous wizard and begins his education . The film stars Daniel Radcliffe as Harry Potter , with Rupert Grint as Ron Weasley , and Emma Watson as Hermione Granger . Warner Bros. bought the film rights to the book in 1999 for a reported # 1 million . Production began in the United Kingdom in 2000 , with Chris Columbus being chosen to create the film from a short list of directors that included Steven Spielberg and Rob Reiner . Rowling insisted that the entire cast be British or Irish , and the film was shot at Leavesden Film Studios and historic buildings around the United Kingdom . The film was released in theatres in the United Kingdom and the United States on 16 November 2001 . It received a very positive critical reception , earned more than $ 970 million at the box office worldwide , and was nominated for many awards including the Academy Award for Best Original Score , Best Art Direction and Best Costume Design . It was followed by seven sequels , beginning with Harry Potter and the Chamber of Secrets in 2002 and ending with Harry Potter and the Deathly Hallows -- Part 2 in 2011 , nearly ten years after the first film 's release . , it is the 31st-highest-grossing film of all time and the second-highest-grossing film in the series behind Harry Potter and the Deathly Hallows -- Part 2 .",
"title": ""
},
{
"docid": "Harry_Potter_Movie_Magic_Experience",
"text": "The Harry Potter Movie Magic Experience at Warner Bros. . Movie World was a walk-through attraction which featured several recreations of sets from the Harry Potter movies . The original attraction opened on 26 December 2001 , themed to the first movie while a second version opened one year later to coincide with the second movie . The Harry Potter Movie Magic Experience closed in 2003 and was replaced by The Official Matrix Exhibit .",
"title": ""
},
{
"docid": "Harry_Potter:_Quidditch_World_Cup",
"text": "Harry Potter : Quidditch World Cup is a 2003 sports action video game that features the fictional sport of Quidditch from Rowling 's Harry Potter franchise , using the likeness from the films . The user plays in the Hogwarts Quidditch Cup competition .",
"title": ""
},
{
"docid": "Harry_Potter_and_the_Goblet_of_Fire_(disambiguation)",
"text": "Harry Potter and the Goblet of Fire is a novel by J. K. Rowling . Harry Potter and the Goblet of Fire may also refer to : Harry Potter and the Goblet of Fire ( film ) , the novel 's film adaptation , directed by Mike Newell Harry Potter and the Goblet of Fire ( soundtrack ) , the soundtrack based on the film , composed by Patrick Doyle Harry Potter and the Goblet of Fire ( video game ) , a video game based on the film",
"title": ""
},
{
"docid": "Harry_Potter_The_Exhibition",
"text": "Harry Potter : The Exhibition is an international traveling exhibition , created by Global Experience Specialists , featuring hundreds of authentic props , costumes , artifacts and set dressings from the Harry Potter feature films .",
"title": ""
},
{
"docid": "Deathly_Hallows_(disambiguation)",
"text": "Deathly Hallows or Harry Potter and the Deathly Hallows is a novel by J. K. Rowling . Deathly Hallows may also refer to : Harry Potter and the Deathly Hallows -- Part 1 , a 2010 film Harry Potter and the Deathly Hallows -- Part 1 ( soundtrack ) , the soundtrack to the film Harry Potter and the Deathly Hallows -- Part 1 ( video game ) , a game based on the film Harry Potter and the Deathly Hallows -- Part 2 , a 2011 film Harry Potter and the Deathly Hallows -- Part 2 ( soundtrack ) , the soundtrack to the film Harry Potter and the Deathly Hallows -- Part 2 ( video game ) , a game based on the film Deathly Hallows ( objects ) , fictional magical objects in the novel",
"title": ""
}
] |
777
|
Mice defective for deoxyribonucleic acid (DNA) polymerase m (polm) reveal increased sensitivity to ionizing radiation (IR).
|
[
{
"docid": "32275758",
"text": "DNA polymerases mu (pol mu), lambda (pol lambda), and terminal deoxynucleotidyltransferase (TdT) are enzymes of the pol X family that share homology in sequence and functional domain organization. We showed previously that pol mu participates in light chain but surprisingly not heavy chain gene rearrangement. We show here that immunoglobulin heavy chain junctions from pol lambda-deficient animals have shorter length with normal N-additions, thus indicating that pol lambda is recruited during heavy chain rearrangement at a step that precedes the action of TdT. In contrast to previous in vitro studies, analysis of animals with combined inactivation of these enzymes revealed no overlapping or compensatory activities for V(D)J recombination between pol mu, pol lambda, and TdT. This complex usage of polymerases with distinct catalytic specificities may correspond to the specific function that the third hypervariable region assumes for each immunoglobulin chain, with pol lambda maintaining a large heavy chain junctional heterogeneity and pol mu ensuring a restricted light chain junctional variability.",
"title": "Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo."
}
] |
[
{
"docid": "11569583",
"text": "DNA polymerase β (Pol β) is an error-prone enzyme which has been found to be overexpressed in several human tumors. By using a couple of recombinant CHO cells differing only from the exogenous expression of Pol β, we showed here that cells overexpressing Pol β are much more sensitive to IR treatments by increasing apoptosis. We also found that the surviving cells displayed an hypermutator phenotype which could be explained by different pathways involving Pol β, such as (i) an increased capacity to incorporate into DNA the mutagenic dGTP analog, 8-oxo-dGTP, one of the most abundant purine-derived nucleotides exposed to γ-irradiation, (ii) the induction of IR-induced DNA breaks and (iii) accumulation of chromosome aberrations induced by radiation. Alteration of Pol β expression in irradiated cells thus appears to strengthen both cell death and genetic changes associated with a malignant phenotype. These data provide new insights into the cellular response to radiations and the associated carcinogenic consequences.",
"title": "Deregulated DNA polymerase β strengthens ionizing radiation-induced nucleotidic and chromosomal instabilities"
},
{
"docid": "27635177",
"text": "Mammalian DNA polymerase mu (pol mu) is related to terminal deoxynucleotidyl transferase, but its biological role is not yet clear. We show here that after exposure of cells to ionizing radiation (IR), levels of pol mu protein increase. pol mu also forms discrete nuclear foci after IR, and these foci are largely coincident with IR-induced foci of gammaH2AX, a previously characterized marker of sites of DNA double-strand breaks. pol mu is thus part of the cellular response to DNA double-strand breaks. pol mu also associates in cell extracts with the nonhomologous end-joining repair factor Ku and requires both Ku and another end-joining factor, XRCC4-ligase IV, to form a stable complex on DNA in vitro. pol mu in turn facilitates both stable recruitment of XRCC4-ligase IV to Ku-bound DNA and ligase IV-dependent end joining. In contrast, the related mammalian DNA polymerase beta does not form a complex with Ku and XRCC4-ligase IV and is less effective than pol mu in facilitating joining mediated by these factors. Our data thus support an important role for pol mu in the end-joining pathway for repair of double-strand breaks.",
"title": "Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair."
},
{
"docid": "31293581",
"text": "Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with lifelong delayed repair and regeneration of irradiated tissues. We hypothesized that IR-induced senescence markers could persist long-term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here, we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analyzed) DNA damage foci and increased p16(INK4a) expression, two hallmarks of cellular senescence and aging. BrdU-labeling experiments revealed that IR-induced damaged cells are preferentially eliminated, at least partially, in a tissue-dependent manner. Unexpectedly, the accumulation of damaged cells was found to occur independent from the DNA damage response modulator p53, and from an intact immune system, as their levels were similar in wild-type and Rag2(-/-) gammaC(-/-) mice, the latter being deficient in T, B, and NK cells. Together, our results provide compelling evidence that exposure to IR induces long-term expression of senescence markers in vivo, an effect that may contribute to the reduced tissue functionality observed in cancer survivors.",
"title": "Ionizing radiation-induced long-term expression of senescence markers in mice is independent of p53 and immune status."
},
{
"docid": "12552297",
"text": "DNA polymerase lambda (polλ) is a recently identified DNA polymerase whose cellular function remains elusive. Here we show, that polλ participates at the molecular level in a chromosomal context, in the repair of DNA double strand breaks (DSB) via non-homologous end joining (NHEJ) in mammalian cells. The expression of a catalytically inactive form of polλ (polλDN) decreases the frequency of NHEJ events in response to I-Sce-I-induced DSB whereas inactivated forms of its homologues polβ and polμ do not. Only events requiring DNA end processing before ligation are affected; this defect is associated with large deletions arising in the vicinity of the induced DSB. Furthermore, polλDN-expressing cells exhibit increased sensitization and genomic instability in response to ionizing radiation similar to that of NHEJ-defective cells. Our data support a requirement for polλ in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway.",
"title": "The DNA polymerase λ is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells"
},
{
"docid": "3173489",
"text": "DNA replication stress promotes genome instability in cancer. However, the contribution of the replication stress response to the development of malignancies remains unresolved. The DNA replication stress response protein SMARCAL1 stabilizes DNA replication forks and prevents replication fork collapse, a cause of DNA breaks and apoptosis. While the fork regression/remodeling functions of SMARCAL1 have been investigated, its in vivo functions in replication stress and cancer are unclear. Using a gamma radiation (IR)-induced replication stress T-cell lymphoma mouse model, we observed a significant inhibition of lymphomagenesis in mice lacking one or both alleles of Smarcal1. Notably, a quarter of the Smarcal1-deficient mice did not develop tumors. Moreover, hematopoietic stem/progenitor cells (HSPCs) and developing thymocytes in Smarcal1-deficient mice showed increased DNA damage and apoptosis during the proliferation burst following IR and an impaired ability to repopulate the thymus after IR. Additionally, mice lacking Smarcal1 showed significant HSPC defects when challenged to respond to other replication stress stimuli. Thus, our data reveal the critical function of the DNA replication stress response and, specifically, Smarcal1 in hematopoietic cell survival and tumor development. Our results also provide important insight into the immunodeficiency observed in individuals with mutations in SMARCAL1 by suggesting that it is an HSPC defect.",
"title": "Defective replication stress response inhibits lymphomagenesis and impairs lymphocyte reconstitution"
},
{
"docid": "23599024",
"text": "Background/Aims: Radiotherapy is applied to patients with inoperable cancer types including advanced stage non-small cell lung cancer (NSCLC) and radioresistance functions as a critical obstacle in radiotherapy. This study was aimed to investigate the mechanism of radioresistance regulated by surfactant protein B (SP-B). Methods: To investigate the role of SP-B in radioresistance, ΔSFTPB A549 cell line was established and SP-B expression was analyzed. In response to ionizing radiation (IR), the change of SP-B expression was analyzed in A549 and NCI-H441 cell lines. Conditioned media (CM) from NSCLC cells were utilized to evaluate the downstream signaling pathway. The in vivo effects of SP-B were assessed through mouse xenograft model with intratumoral injection of CM. Results: In response to IR, NSCLC cell lines showed decreased SP-B regulated by the TGF-β signaling and decreased SP-B stimulated cell survival and epithelial-mesenchymal transition. Treatment with CM from irradiated cells activated sPLA2, enhanced protein kinase Cδ-MAPKs signaling pathway, and increased arachidonic acid production. We confirmed the in vivo roles of SP-B through mouse xenograft model. Conclusion: Our results revealed that down-regulation of SP-B was involved in the radiation-induced metastatic conversion of NSCLC and provided evidence that SP-B acted as a suppressor of NSCLC progression.",
"title": "Surfactant Protein B Suppresses Lung Cancer Progression by Inhibiting Secretory Phospholipase A2 Activity and Arachidonic Acid Production"
},
{
"docid": "18987782",
"text": "The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA. Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in Emu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc-overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a new mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective messenger RNAs. We show that an aberrant increase in cap-dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site (IRES)-dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic-specific expression of the endogenous IRES-dependent form of Cdk11 (also known as Cdc2l and PITSLRE), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in Emu-Myc/+ mice. When accurate translational control is re-established in Emu-Myc/+ mice, genome instability is suppressed. Our findings demonstrate how perturbations in translational control provide a highly specific outcome for gene expression, genome stability and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post-genomic level.",
"title": "Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency"
},
{
"docid": "16630060",
"text": "Somatic stem cell depletion due to the accumulation of DNA damage has been implicated in the appearance of aging-related phenotypes. Hair graying, a typical sign of aging in mammals, is caused by the incomplete maintenance of melanocyte stem cells (MSCs) with age. Here, we report that irreparable DNA damage, as caused by ionizing radiation, abrogates renewal of MSCs in mice. Surprisingly, the DNA-damage response triggers MSC differentiation into mature melanocytes in the niche, rather than inducing their apoptosis or senescence. The resulting MSC depletion leads to irreversible hair graying. Furthermore, deficiency of Ataxia-telangiectasia mutated (ATM), a central transducer kinase of the DNA-damage response, sensitizes MSCs to ectopic differentiation, demonstrating that the kinase protects MSCs from their premature differentiation by functioning as a \"stemness checkpoint\" to maintain the stem cell quality and quantity.",
"title": "Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation"
},
{
"docid": "6536598",
"text": "Chromatin structure is modulated during deoxyribonucleic acid excision repair, but how this is achieved is unclear. Loss of the yeast Ino80 chromatin-remodeling complex (Ino80-C) moderately sensitizes cells to ultraviolet (UV) light. In this paper, we show that INO80 acts in the same genetic pathway as nucleotide excision repair (NER) and that the Ino80-C contributes to efficient UV photoproduct removal in a region of high nucleosome occupancy. Moreover, Ino80 interacts with the early NER damage recognition complex Rad4-Rad23 and is recruited to chromatin by Rad4 in a UV damage-dependent manner. Using a modified chromatin immunoprecipitation assay, we find that chromatin disruption during UV lesion repair is normal, whereas the restoration of nucleosome structure is defective in ino80 mutant cells. Collectively, our work suggests that Ino80 is recruited to sites of UV lesion repair through interactions with the NER apparatus and is required for the restoration of chromatin structure after repair.",
"title": "The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair"
},
{
"docid": "43014661",
"text": "Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer. Consistent with the ability of Pol eta to efficiently bypass UV light-induced cyclobutane pyrimidine dimers, XPV cells lacking Pol eta have diminished capacity to replicate UV-damaged DNA and are sensitive to UV light-induced killing and mutagenesis. To better understand these and other Pol eta functions, we generated Pol eta-deficient mice. Mice homozygous for a null mutation in pol eta are viable, fertile, and do not show any obvious spontaneous defects during the first year of life. However, fibroblasts derived from these mutant mice are sensitive to killing by exposure to UV light, and all Pol eta-deficient mice develop skin tumors after UV irradiation, in contrast to the wild-type littermate controls that did not develop such tumors. These results and biochemical studies of translesion synthesis by mouse Pol eta indicate that Pol eta-dependent bypass of cyclobutane pyrimidine dimers suppresses UV light-induced skin cancer in mice. Moreover, 37.5% of pol eta heterozygous mice also developed skin cancer during 5 months after a 5-month exposure to UV light, suggesting that humans who are heterozygous for mutations in pol eta may also have an increased risk of skin cancer.",
"title": "Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice."
},
{
"docid": "2679511",
"text": "Werner's syndrome (WS) and Bloom's syndrome (BS) are cancer predisposition disorders caused by loss of function of the RecQ helicases WRN or BLM, respectively. BS and WS are characterized by replication defects, hyperrecombination events and chromosomal aberrations, which are hallmarks of cancer. Inefficient replication of the G-rich telomeric strand contributes to chromosome aberrations in WS cells, demonstrating a link between WRN, telomeres and genomic stability. Herein, we provide evidence that BLM also contributes to chromosome-end maintenance. Telomere defects (TDs) are observed in BLM-deficient cells at an elevated frequency, which is similar to cells lacking a functional WRN helicase. Loss of both helicases exacerbates TDs and chromosome aberrations, indicating that BLM and WRN function independently in telomere maintenance. BLM localization, particularly its recruitment to telomeres, changes in response to replication dysfunction, such as in WRN-deficient cells or after aphidicolin treatment. Exposure to replication challenge causes an increase in decatenated deoxyribonucleic acid (DNA) structures and late-replicating intermediates (LRIs), which are visible as BLM-covered ultra-fine bridges (UFBs) in anaphase. A subset of UFBs originates from telomeric DNA and their frequency correlates with telomere replication defects. We propose that the BLM complex contributes to telomere maintenance through its activity in resolving LRIs.",
"title": "The BLM helicase contributes to telomere maintenance through processing of late-replicating intermediate structures"
},
{
"docid": "9291596",
"text": "Following introduction of DNA interstrand cross-links (ICLs), mammalian cells display chromosome breakage or cell cycle delay with a 4N DNA content. To further understand the nature of the delay, previously described as a G(2)/M arrest, we developed a protocol to generate ICLs during specific intervals of the cell cycle. Synchronous populations of G(1), S, and G(2) cells were treated with photoactivated 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) and scored for normal passage into mitosis. In contrast to what was found for ionizing radiation, ICLs introduced during G(2) did not result in a G(2)/M arrest, mitotic arrest, or chromosome breakage. Rather, subsequent passage through S phase was required to trigger both chromosome breakage and arrest in the next cell cycle. Similarly, ICLs introduced during G(1) did not cause a G(1)/S arrest. We conclude that DNA replication is required to elicit the cellular responses of cell cycle arrest and genomic instability after psoralen-induced ICLs. In primary human fibroblasts, the 4N DNA content cell cycle arrest triggered by ICLs was long lasting but reversible. Kinetic analysis suggested that these cells could remove up to approximately 2,500 ICLs/genome at an average rate of 11 ICLs/genome/h.",
"title": "DNA replication is required To elicit cellular responses to psoralen-induced DNA interstrand cross-links."
},
{
"docid": "5273056",
"text": "Eukaryotes have numerous checkpoint pathways to protect genome fidelity during normal cell division and in response to DNA damage. Through a screen for G2/M checkpoint regulators in zebrafish, we identified ticrr (for TopBP1-interacting, checkpoint, and replication regulator), a previously uncharacterized gene that is required to prevent mitotic entry after treatment with ionizing radiation. Ticrr deficiency is embryonic-lethal in the absence of exogenous DNA damage because it is essential for normal cell cycle progression. Specifically, the loss of ticrr impairs DNA replication and disrupts the S/M checkpoint, leading to premature mitotic entry and mitotic catastrophe. We show that the human TICRR ortholog associates with TopBP1, a known checkpoint protein and a core component of the DNA replication preinitiation complex (pre-IC), and that the TICRR-TopBP1 interaction is stable without chromatin and requires BRCT motifs essential for TopBP1's replication and checkpoint functions. Most importantly, we find that ticrr deficiency disrupts chromatin binding of pre-IC, but not prereplication complex, components. Taken together, our data show that TICRR acts in association with TopBP1 and plays an essential role in pre-IC formation. It remains to be determined whether Ticrr represents the vertebrate ortholog of the yeast pre-IC component Sld3, or a hitherto unknown metazoan replication and checkpoint regulator.",
"title": "A vertebrate gene, ticrr, is an essential checkpoint and replication regulator."
},
{
"docid": "40901687",
"text": "The DNA damage response (DDR) is a complex regulatory network that is critical for maintaining genome integrity. Posttranslational modifications are widely used to ensure strict spatiotemporal control of signal flow, but how the DDR responds to environmental cues, such as changes in ambient oxygen tension, remains poorly understood. We found that an essential component of the ATR/CHK1 signaling pathway, the human homolog of the Caenorhabditis elegans biological clock protein CLK-2 (HCLK2), associated with and was hydroxylated by prolyl hydroxylase domain protein 3 (PHD3). HCLK2 hydroxylation was necessary for its interaction with ATR and the subsequent activation of ATR/CHK1/p53. Inhibiting PHD3, either with the pan-hydroxylase inhibitor dimethyloxaloylglycine (DMOG) or through hypoxia, prevented activation of the ATR/CHK1/p53 pathway and decreased apoptosis induced by DNA damage. Consistent with these observations, we found that mice lacking PHD3 were resistant to the effects of ionizing radiation and had decreased thymic apoptosis, a biomarker of genomic integrity. Our identification of HCLK2 as a substrate of PHD3 reveals the mechanism through which hypoxia inhibits the DDR, suggesting hydroxylation of HCLK2 is a potential therapeutic target for regulating the ATR/CHK1/p53 pathway.",
"title": "PHD3-dependent hydroxylation of HCLK2 promotes the DNA damage response."
},
{
"docid": "7151961",
"text": "Double-strand breaks (DSBs) occur frequently during DNA replication. They are also caused by ionizing radiation, chemical damage or as part of the series of programmed events that occur during meiosis. In yeast, DSB repair requires RAD52, a protein that plays a critical role in homologous recombination. Here we describe the actions of human RAD52 protein in a model system for single-strand annealing (SSA) using tailed (i.e. exonuclease resected) duplex DNA molecules. Purified human RAD52 protein binds resected DSBs and promotes associations between complementary DNA termini. Heteroduplex intermediates of these recombination reactions have been visualized by electron microscopy, revealing the specific binding of multiple rings of RAD52 to the resected termini and the formation of large protein complexes at heteroduplex joints formed by RAD52-mediated annealing.",
"title": "Visualization of recombination intermediates produced by RAD52-mediated single-strand annealing."
},
{
"docid": "13025574",
"text": "High doses of ionizing radiation clearly produce deleterious consequences in humans, including, but not exclusively, cancer induction. At very low radiation doses the situation is much less clear, but the risks of low-dose radiation are of societal importance in relation to issues as varied as screening tests for cancer, the future of nuclear power, occupational radiation exposure, frequent-flyer risks, manned space exploration, and radiological terrorism. We review the difficulties involved in quantifying the risks of low-dose radiation and address two specific questions. First, what is the lowest dose of x- or gamma-radiation for which good evidence exists of increased cancer risks in humans? The epidemiological data suggest that it is approximately 10-50 mSv for an acute exposure and approximately 50-100 mSv for a protracted exposure. Second, what is the most appropriate way to extrapolate such cancer risk estimates to still lower doses? Given that it is supported by experimentally grounded, quantifiable, biophysical arguments, a linear extrapolation of cancer risks from intermediate to very low doses currently appears to be the most appropriate methodology. This linearity assumption is not necessarily the most conservative approach, and it is likely that it will result in an underestimate of some radiation-induced cancer risks and an overestimate of others.",
"title": "Cancer risks attributable to low doses of ionizing radiation: assessing what we really know."
},
{
"docid": "44172171",
"text": "The RNA-guided DNA endonuclease Cas9 is a powerful tool for genome editing. Little is known about the kinetics and fidelity of the double-strand break (DSB) repair process that follows a Cas9 cutting event in living cells. Here, we developed a strategy to measure the kinetics of DSB repair for single loci in human cells. Quantitative modeling of repaired DNA in time series after Cas9 activation reveals variable and often slow repair rates, with half-life times up to ∼10 hr. Furthermore, repair of the DSBs tends to be error prone. Both classical and microhomology-mediated end joining pathways contribute to the erroneous repair. Estimation of their individual rate constants indicates that the balance between these two pathways changes over time and can be altered by additional ionizing radiation. Our approach provides quantitative insights into DSB repair kinetics and fidelity in single loci and indicates that Cas9-induced DSBs are repaired in an unusual manner.",
"title": "Kinetics and Fidelity of the Repair of Cas9-Induced Double-Strand DNA Breaks"
},
{
"docid": "15305881",
"text": "Deinococcus spp. are renowned for their amazing ability to recover rapidly from severe genomic fragmentation as a result of exposure to extreme levels of ionizing radiation or desiccation. Despite having been originally characterized over 50 years ago, the mechanism underlying this remarkable repair process is still poorly understood. Here, we report the 2.8 A structure of DdrB, a single-stranded DNA (ssDNA) binding protein unique to Deinococcus spp. that is crucial for recovery following DNA damage. DdrB forms a pentameric ring capable of binding single-stranded but not double-stranded DNA. Unexpectedly, the crystal structure reveals that DdrB comprises a novel fold that is structurally and topologically distinct from all other single-stranded binding (SSB) proteins characterized to date. The need for a unique ssDNA binding function in response to severe damage, suggests a distinct role for DdrB which may encompass not only standard SSB protein function in protection of ssDNA, but also more specialized roles in protein recruitment or DNA architecture maintenance. Possible mechanisms of DdrB action in damage recovery are discussed.",
"title": "The structure of DdrB from Deinococcus: a new fold for single-stranded DNA binding proteins"
},
{
"docid": "17695748",
"text": "Transglutaminase 2 (TGase 2) is a Ca+2-dependent enzyme that catalyzes both intracellular and extracellular cross-linking reactions by transamidation of specific glutamine residues. TGase 2 is known to be involved in the membrane-mediated events required for glucose-stimulated insulin release from the pancreatic beta cells. Here we show that targeted disruption of TGase 2 impairs glucose-stimulated insulin secretion. TGase 2-/- mice show glucose intolerance after intraperitoneal glucose loading. TGase 2-/- mice manifest a tendency to develop hypoglycemia after administration of exogenous insulin as a consequence of enhanced insulin receptor substrate 2 (IRS-2) phosphorylation. We suggest that the increased peripheral sensitivity to insulin partially compensates for the defective secretion in this animal model. TGase 2-/- mouse phenotype resembles that of the maturity-onset diabetes of young (MODY) patients. In the course of screening for human TGase 2 gene in Italian subjects with the clinical features of MODY, we detected a missense mutation (N333S) in the active site of the enzyme. Collectively, these results identify TGase 2 as a potential candidate gene in type 2 diabetes.",
"title": "in"
},
{
"docid": "43880096",
"text": "Activation of p53 can occur in response to a number of cellular stresses, including DNA damage, hypoxia and nucleotide deprivation. Several forms of DNA damage have been shown to activate p53, including those generated by ionising radiation (IR), radio-mimetic drugs, ultraviolet light (UV) and chemicals such as methyl methane sulfonate (MMS). Under normal conditions, p53 levels are maintained at a low state by virtue of the extremely short-half life of the polypeptide. In addition to this, p53 normally exists in an largely inactive state that is relatively inefficient at binding to DNA and activating transcription. Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair. Recent work has suggested that this regulation is brought about largely through DNA damage triggering a series of phosphorylation, de-phosphorylation and acetylation events on the p53 polypeptide. Here, we discuss the nature of these modifications, the enzymes that bring them about, and how changes in p53 modification lead to p53 activation.",
"title": "Regulation of p53 in response to DNA damage"
},
{
"docid": "32408470",
"text": "Cigarette smoking promotes body weight reduction in humans while paradoxically also promoting insulin resistance (IR) and hyperinsulinemia. However, the mechanisms behind these effects are unclear. Here we show that nicotine, a major constituent of cigarette smoke, selectively activates AMP-activated protein kinase α2 (AMPKα2) in adipocytes, which in turn phosphorylates MAP kinase phosphatase-1 (MKP1) at serine 334, initiating its proteasome-dependent degradation. The nicotine-dependent reduction of MKP1 induces the aberrant activation of both p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, leading to increased phosphorylation of insulin receptor substrate 1 (IRS1) at serine 307. Phosphorylation of IRS1 leads to its degradation, protein kinase B inhibition, and the loss of insulin-mediated inhibition of lipolysis. Consequently, nicotine increases lipolysis, which results in body weight reduction, but this increase also elevates the levels of circulating free fatty acids and thus causes IR in insulin-sensitive tissues. These results establish AMPKα2 as an essential mediator of nicotine-induced whole-body IR in spite of reductions in adiposity.",
"title": "Activation of AMPKα2 in adipocytes is essential for nicotine-induced insulin resistance in vivo"
},
{
"docid": "2701077",
"text": "Most adult stem cells, including hematopoietic stem cells (HSCs), are maintained in a quiescent or resting state in vivo. Quiescence is widely considered to be an essential protective mechanism for stem cells that minimizes endogenous stress caused by cellular respiration and DNA replication. We demonstrate that HSC quiescence can also have detrimental effects. We found that HSCs have unique cell-intrinsic mechanisms ensuring their survival in response to ionizing irradiation (IR), which include enhanced prosurvival gene expression and strong activation of p53-mediated DNA damage response. We show that quiescent and proliferating HSCs are equally radioprotected but use different types of DNA repair mechanisms. We describe how nonhomologous end joining (NHEJ)-mediated DNA repair in quiescent HSCs is associated with acquisition of genomic rearrangements, which can persist in vivo and contribute to hematopoietic abnormalities. Our results demonstrate that quiescence is a double-edged sword that renders HSCs intrinsically vulnerable to mutagenesis following DNA damage.",
"title": "Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis."
},
{
"docid": "23698769",
"text": "DNA polymerase μ (Pol μ) is the only template-dependent human DNA polymerase capable of repairing double-strand DNA breaks (DSBs) with unpaired 3′ ends in nonhomologous end joining (NHEJ). To probe this function, we structurally characterized Pol μ's catalytic cycle for single-nucleotide incorporation. These structures indicate that, unlike other template-dependent DNA polymerases, Pol μ shows no large-scale conformational changes in protein subdomains, amino acid side chains or DNA upon dNTP binding or catalysis. Instead, the only major conformational change is seen earlier in the catalytic cycle, when the flexible loop 1 region repositions upon DNA binding. Pol μ variants with changes in loop 1 have altered catalytic properties and are partially defective in NHEJ. The results indicate that specific loop 1 residues contribute to Pol μ's unique ability to catalyze template-dependent NHEJ of DSBs with unpaired 3′ ends.",
"title": "Sustained active site rigidity during synthesis by human DNA polymerase μ"
},
{
"docid": "2481032",
"text": "Sirt1 is a NAD(+)-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. To assess this idea, we generated Sirt1 neuron-specific knockout (SINKO) mice. On both standard chow and HFD, SINKO mice were more insulin sensitive than Sirt1(f/f) mice. Thus, SINKO mice had lower fasting insulin levels, improved glucose tolerance and insulin tolerance, and enhanced systemic insulin sensitivity during hyperinsulinemic euglycemic clamp studies. Hypothalamic insulin sensitivity of SINKO mice was also increased over controls, as assessed by hypothalamic activation of PI3K, phosphorylation of Akt and FoxO1 following systemic insulin injection. Intracerebroventricular injection of insulin led to a greater systemic effect to improve glucose tolerance and insulin sensitivity in SINKO mice compared with controls. In line with the in vivo results, insulin-induced AKT and FoxO1 phosphorylation were potentiated by inhibition of Sirt1 in a cultured hypothalamic cell line. Mechanistically, this effect was traced to a reduced effect of Sirt1 to directly deacetylate and repress IRS-1 function. The enhanced central insulin signaling in SINKO mice was accompanied by increased insulin receptor signal transduction in liver, muscle, and adipose tissue. In summary, we conclude that neuronal Sirt1 negatively regulates hypothalamic insulin signaling, leading to systemic insulin resistance. Interventions that reduce neuronal Sirt1 activity have the potential to improve systemic insulin action and limit weight gain on an obesigenic diet.",
"title": "Neuronal Sirt1 deficiency increases insulin sensitivity in both brain and peripheral tissues."
},
{
"docid": "7986878",
"text": "We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation therapy and intetumumab in human cancer xenograft models in nude rats to assess effects on both tumor cells and the tumor microenvironment. Nude rats bearing human head and neck cancer and non-small cell lung cancer (NSCLC) xenografts were treated with intetumumab and fractionated local tumor radiotherapy. Effects on tumor growth and metastasis, blood perfusion, oxygenation, and gastrointestinal toxicity were studied. Intetumumab alone had a moderate effect on tumor growth. When combined with fractionated radiation therapy, intetumumab significantly inhibited tumor growth and produced a tumor response rate that was significantly better than with radiation therapy alone. Treatment with intetumumab also significantly reduced lung metastasis in the A549 NSCLC xenograft model. The oxygenation and blood perfusion in xenograft tumors measured by microbubble-enhanced ultrasound imaging were substantially increased after treatment with intetumumab. The combined use of intetumumab and radiation therapy reduced the microvessel density and increased apoptosis in tumor cells and the tumor microenvironment. Toxicity studies showed that treatment with intetumumab did not cause the histopathologic changes in the lungs and did not sensitize the sensitive gastrointestinal epithelium to the effect of radiation therapy. Intetumumab can potentiate the efficacy of fractionated radiation therapy in human cancer xenograft tumors in nude rats without increased toxicity.",
"title": "Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats."
},
{
"docid": "28441310",
"text": "Mutation frequency and specificity were determined as a function of age in nuclear DNA from liver, bladder, and brain of Big Blue lacI transgenic mice aged 1.5-25 months. Mutations accumulated with age in liver and accumulated more rapidly in bladder. In the brain a small initial increase in mutation frequency was observed in young animals; however, no further increase was observed in adult mice. To investigate the origin of mutations, the mutational spectra for each tissue and age were determined. DNA sequence analysis of mutant lacI transgenes revealed no significant changes in mutational specificity in any tissue at any age. The spectra of mutations found in aging animals were identical to those in younger animals, suggesting that they originated from a common set of DNA lesions manifested during DNA replication. The data also indicated that there were no significant age-related mutational changes due to oxidative damage, or errors resulting from either changes in the fidelity of DNA polymerase or the efficiency of DNA repair. Hence, no evidence was found to support hypotheses that predict that oxidative damage or accumulation of errors in nuclear DNA contributes significantly to the aging process, at least in these three somatic tissues.",
"title": "Mutation frequency and specificity with age in liver, bladder and brain of lacI transgenic mice."
},
{
"docid": "15535511",
"text": "Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis. To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)). IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia. While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Moreover, these mice exhibited an altered response to cocaine under food-restricted conditions. Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.",
"title": "Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis."
},
{
"docid": "19356271",
"text": "Prim-pol is a recently identified DNA primase-polymerase belonging to the archaeao-eukaryotic primase (AEP) superfamily. Here, we characterize a previously unrecognized prim-pol in human cells, which we designate hPrimpol1 (human primase-polymerase 1). hPrimpol1 possesses primase and DNA polymerase activities in vitro, interacts directly with RPA1 and is recruited to sites of DNA damage and stalled replication forks in an RPA1-dependent manner. Cells depleted of hPrimpol1 display increased spontaneous DNA damage and defects in the restart of stalled replication forks. Both RPA1 binding and the primase activity of hPrimpol1 are required for its cellular function during DNA replication. Our results indicate that hPrimpol1 is a novel factor involved in the response to DNA replication stress.",
"title": "hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the maintenance of genome integrity."
},
{
"docid": "712320",
"text": "We have developed a mass microscope (mass spectrometry imager with spatial resolution higher than the naked eye) equipped with an atmospheric pressure ion-source chamber for laser desorption/ionization (AP-LDI) and a quadrupole ion trap time-of-flight (QIT-TOF) analyzer. The optical microscope combined with the mass spectrometer permitted us to precisely determine the relevant tissue region prior to performing imaging mass spectrometry (IMS). An ultraviolet laser tightly focused with a triplet lens was used to achieve high spatial resolution. An atmospheric pressure ion-source chamber enables us to analyze fresh samples with minimal loss of intrinsic water or volatile compounds. Mass-microscopic AP-LDI imaging of freshly cut ginger rhizome sections revealed that 6-gingerol ([M + K](+)at m/z 333.15, positive mode; [M - H](-) at m/z 293.17, negative mode) and the monoterpene ([M + K](+) at m/z 191.09), which are the compounds related to pungency and flavor, respectively, were localized in oil drop-containing organelles. AP-LDI-tandem MS/MS analyses were applied to compare authentic signals from freshly cut ginger directly with the standard reagent. Thus, our atmosphere-imaging mass spectrometer enabled us to monitor a quality of plants at the organelle level.",
"title": "Visualization of volatile substances in different organelles with an atmospheric-pressure mass microscope."
},
{
"docid": "37641175",
"text": "A DNA fraction is spontaneously released from living, but not dead or dying, human, other mammalian, avian, amphibian, plant, and prokaryote cells. The spontaneously released DNA fraction has been shown to be (a) present in both actively dividing and nondividing, differentiated cell populations; (b) labile; (c) associated with DNA-dependent RNA or DNA polymerase; (d) associated with an RNA fraction; and to have (e) a lower molecular weight than the typical genetic DNA fraction; and (f) Alu repeat sequences in increased proportions compared to a unique gene in plasma/serum. On the other hand, early autoradiographic and biochemical and quantitative cytochemical and cytophysical studies on DNA permitted the identification of a DNA fraction which was (1) present in both actively dividing and nondividing, differentiated cell populations; (2) labile; and (3) had a lower molecular weight than the typical genetic DNA fraction. This DNA fraction was termed metabolic DNA (m-DNA) and was proposed as possibly forming extra gene copies for the rapid production of m-RNA, to be destroyed subsequently. Therefore, we suggest that the metabolic DNA fraction might represent the precursor to the formation of the spontaneously released DNA fraction.",
"title": "Metabolic DNA as the origin of spontaneously released DNA?"
}
] |
10893
|
Renters Liability in Case of Liability Claims for Property Damage or Fire
|
[
{
"docid": "153285",
"text": "\"According to US News, renter's insurance does cover liability as well as your own belongings. They list this as one of four \"\"myths\"\" often promulgated about renter's insurance. This is backed up by esurance.com, which explicitly mentions \"\"Property damage to others\"\" as covered. Nationwide Insurance says that renter's insurance covers \"\"Personal liability insurance for renters\"\" and \"\"Personal umbrella liability insurance\"\". Those were the first three working links for \"\"what does renters insurance cover\"\" on Google. In short, while it is possible that you currently have a different kind of coverage, this is not a limitation of renter's insurance per se. It could be a limitation in your current coverage. You may be able to simply change your coverage with your current provider. Or switch providers. Or you may already be covered. Note that renter's insurance does not cover the building against general damage, e.g. tornado or a fire spreading from an adjacent building. It is specific to covering things that you caused. This may be the cause of the confusion, as some sources say that it doesn't cover anything in the building. That's generally not true. It usually covers all your liability except for specific exceptions (e.g. waterbed insurance is often extra).\"",
"title": ""
},
{
"docid": "215066",
"text": "\"The truth is anyone can sue anyone for anything. So yes you could be sued, but the more important part to measure is the probability of success. While this is probably more of a legal stack exchange question, in order for a successful suit there has to be proven at least some negligence on your part in the situation you cite. The very fact that the landlord is not willing to turn on the heat is probably enough to absolve you from any liability. Once you go down to a local store and purchase a UL certified heater then a suit would have a very low probability of success. Perhaps a case could be made if you made your own heater and it burned down the house. But that would require finding a jury that is sympathetic to landlords that will not provide heat for their tenants (highly unlikely). Could the landlord sue the heater company? Yes and would likely receive an out of court settlement. Even in the case that liability can be proven on your part, it is very unlikely you would be targeted. These type of suits target \"\"deep pockets\"\" or those with wealth. Unless something is specifically known about you having a high level of net worth a civil suit will not be brought against a \"\"room renter\"\" because of the lack of funds. People in your demographic tend not to have a lot of money. (No offense intended, I was there myself once.) In the case that you do have a high net worth, then get renters insurance and possibly an umbrella policy. It is a small price to pay to protect a significant amount of assets. If I was in your shoes here is what I would do:\"",
"title": ""
}
] |
[
{
"docid": "349705",
"text": "Renters' Insurance should also have some level of liability coverage. I.e.: if you caused a flooding because you went on and broke the pipe, or a fire because you smoked in the bed - there should be some level of coverage for that. However, most of the damage the tenant can do is probably not accidental. If you broke the pipe - you probably did something wrong. If you caused fire by smoking in bed - you obviously did something wrong. While seemingly accidental, you're deeply at fault. Insurance companies are not in business for rewarding risky behavior. Accidents where the tenant has nothing to do with what happened (earthquakes, fires because of, say, wiring, flooding because it rained too much, or bird flying into a window and shattering it) - are covered by the homeowner's insurance. In any case, talk to your insurance agent about your specific policy and concerns.",
"title": ""
},
{
"docid": "215289",
"text": "The basis of homeowner's insurance pricing is the AOI, or Amount of Insurance. This pertains to the cost to rebuild the dwelling in the event of a total loss. The standard coverages (e.g., contents, loss of use, medical payments, liability) are calculated relative to this amount. Consequently, the AOI is selected by appraising the value of the dwelling. This is why it is important that if parts of the dwelling are upgraded, that the cost of those upgrades are taken into account. The question is not one of denying claims should a loss occur, unless the nature of the upgrade is such that policy should not have been underwritten in the first place. (This can happen if, for example, the homeowner builds an extension onto the house that damages the structural integrity of the dwelling.) In the end, the AOI is still just an estimate, but the takeaway is that, like scheduled personal property, jewelry, rare collectibles, or other endorsements, every home (and homeowner) has slightly different insurance needs, and it is in your interest to tailor your coverage to be as accurate as possible in reflecting your needs. Insurance is not a one-size-fits-all product; consequently, the selection of sufficient coverage for your mix of risks is only prudent. Now, if after you get a quote back and you find that the premium is too high, you can typically select a deductible that can reduce it, but you have to consider what amount of exposure you are willing to retain. You should shop around, too: different insurers use different methods and criteria to price their products, so even if the coverage is substantially similar, the premiums may vary: for example, some insurers ask whether you own a dog (exposure to liability claims), but others do not. Some insurers put more weight on your dwelling's geographic location (exposure to fire, theft, wind/hail) than others.",
"title": ""
},
{
"docid": "215267",
"text": "It's still an asset because you're keeping it on your books in an interest bearing account. And it's still also a liability because as you note, the money is not technically yours and you owe it to the renter until you settle at the end of the lease/term. Thus, I'd recommend setting the security deposit up in two accounts - an asset account and a liability account. The two will cancel each other out so it won't add to your net worth or equity. If the money is in a bank account that's shared for other purposes, you can create a sub account for the security deposit: Assets->Savings->Bank->Security Deposit: $1500 and the liability can simply be: Liabilities->Security Deposit: $1500 You of course can modify these to best fit your account structure (e.g. organize by property, etc). Finally, instead of transferring the money from an 'Income' account to your savings account, you transfer it directly from the liability account in one go:",
"title": ""
},
{
"docid": "393934",
"text": "\"In terms of how to make your decision, here are some considerations. Comprehensive insurance often covers other perils besides collision, including fire, theft, hail or other weather damage, additional liability coverage etc. It may be worth looking at your specific policy to see what is covered. No matter what you do, make sure you have some form of personal liability coverage in case you are sued (doesn't necessarily need to be through the auto policy). While it can make financial sense to drop comprehensive coverage once you can afford to self-insure against collision, this will only be the case if you are certain that you can set aside dedicated savings that you would only need to dip in to in the case of a collision or other major loss. For example, if you only have $5-$10,000 in the bank, and you happen to lose your job, and then the next month you happen to be hit in an accident and the car is totaled, could you afford to replace the car out of pocket? I would recommend looking at dropping comprehensive insurance as similar to a \"\"DNR\"\" (do not resuscitate) order for your car, i.e. under no circumstances would you choose repair the car were it totaled or damaged. For example, if your car's exterior were badly damaged in a hail storm (but still ran fine), would you pay $500 or more to repair it, or would you simply get a new car? Ultimately, this is going to be a judgement call based on how much financial risk you want to take on. Personally, I would continue to pay the extra $300 per year for now in order to insure a $6-8,000 asset (5% of the asset value) However, in the next few years the resale value of your car will continue to decline. If in a few years the car were worth $1,500, I would probably not pay the same $300 a year (or 20% of the asset's value). When you should make that choice depends on how many more years of service you expect to get from the car, which is a very localized question. Hope that helps!\"",
"title": ""
},
{
"docid": "311252",
"text": "Your basic point is correct; the savvy move is to use insurance only to cover losses that would be painful or catastrophic for you. Otherwise, self-insure. In the specific example of car insurance, you may be missing that it doesn't only cover replacement of the car, it also covers liability, which is a hundreds-of-thousands-of-dollars risk. The liability coverage may well be legally required; it may also be required as a base layer if you want to get a separate umbrella policy up to millions in liability. So you have to be very rich before this insurance stops making sense. In the US at least you can certainly buy car insurance that doesn't cover loss of the car, or that has a high deductible. And in fact, if you can afford to self-insure up to a high deductible, on average as you say that should be a good idea. Same is true of most kinds of insurance, a high deductible is best as long as you can afford it, unless you know you'll probably file a claim. (Health insurance in particular is weird in many ways, and one is that you often can estimate whether you'll have claims.) On our auto policy, the liability and uninsured motorist coverage is about 60% of the cost while damage to the car coverage is 40%. I'm sure this varies a lot depending on the value of your cars and how much you drive and driving record, etc. On an aging car the coverage for the car itself should get cheaper and cheaper since the car is worth less, while liability coverage would not necessarily get cheaper.",
"title": ""
},
{
"docid": "509936",
"text": "To your secondary question: Appropriately consider all estimated numbers involved with keeping the house compared to your closest estimate of what the home could sell for. Weigh out the pros and cons yourself as a stranger will not be able to 100% appreciate what you value and dislike. Remember to include insurances, taxes, HOA(s), and the actual mortgage payment. Depending on how you also plan to rent out the property, include whichever utilities you intend to cover (if any). There will also be costs for property management and upkeep as things will break overtime and tenants will not hesitate to get you (or your management) to fix them, either way that means you are paying. I would also keep in mind while homes typically appreciate in value there is a higher risk with tenants for the value to depreciate to damages and poor upkeep. There are increased legal risks to renting, so be sure you have properly vetted whichever management you are going with. In extreme circumstances you also could be required to retain an attorney to defend yourself again litigation because whichever management team you hire will most likely defend themselves and not include you in that umbrella. My family lives in the LA area as well and a judge refused to throw out an obvious frivolous suit when my parents attempted to rent out a house. The possible renters after signing the main paperwork never showed to finish a second set of documents for renting. Parents immediately declined to rent to these people as they missed something so important without any explanation and they sued claiming racism, emotional damages, and some other really crazy things despite my parents never having met them (first meeting was between property management and renters only). Personally and professionally, I would only suggest renting our the place and not selling if you can turn a profit after all the above mentioned costs. If renters are only paying to keep the property in the black you have yourself a non-earning asset which WILL be damaged over time and require repairs which will come out of your pocket. Also, while the property is unoccupied you also must remember it is not earning at that time. Much of this may sound obvious, overcautious, etc... I simply wish to provide my family's experience to help you in making your decisions. Best of luck with your endeavor. Edit: Also, you will be required to report all earned rental income on your taxes. They will fall under the Schedule E and possibly K-1 area. I would strongly recommend consulting with an actual accountant about the impacts to you.",
"title": ""
},
{
"docid": "11122",
"text": "\"Disclaimer: I am neither a lawyer nor a tax-expert This page on the HMRC site lists several pages that appear to be relevant, starting with CG78401 - Foreign currency: delayed remittances and on to CG78408 - Foreign currency: example which seems pertinent to your case [paraphrased]: A property bought in 1983 is sold for a [taxable] gain in one tax-year (1986/87) but the proceeds cannot be released/remitted to the UK until later (1991/92), by which time currency fluctuations have created a second [taxable] gain. The size of the first gain (selling the property) is determined by the exchange rate in effect at the time of the sale but because of local restrictions, this can be deferred. The size of the second gain (currency movement) is determined by the change in exchange-rate between the time of the sale and the time of conversion. In your case, the first \"\"gain\"\" was actually a loss, so I believe you should be able to use this to offset any tax due second gain. This page states that losses can be claimed up to four years after the end of the tax-year in which they were incurred, so you are probably still OK. (The example makes application under TCGA92/S279 to defer the gain made on the original sale [because of the inability to transfer funds], but as I understand it, this is primarily to avoid a tax liability in that year. Since you made a loss on the sale, there wouldn't have been a tax liability, so there would be no need to defer it).\"",
"title": ""
},
{
"docid": "476859",
"text": "\"What drives the stock of bankrupt companies? Such stock is typically considered \"\"distressed assets\"\". Technically, what drives it is what drives every stock - supply and demand. A more interesting question is of course, why would there be demand? First, who exerts the buying pressure on the stock? Typically, three types of entities: The largest ones are financial institutions specializing in distressed assets (frequently, alternatives specialists - hedge funds, private equity firms etc...). Usually, they invest in distressed debt or distressed preferred equity; but sometimes distressed equity as well. Why? We will discuss their motivations separately in this answer. Second one are existing equity holders. Why? Short answer, behavioral psychology and behavioral economics. Many investors - especially non-professionals - insist on holding distressed stocks due to variety of investment fallacies (sunk cost etc...); usually constructing elaborate theories of why and how the company and the stock will recover Sometimes, people who buy into penny stock scams, pump and dump schemes etc... Why? \"\"There's a sucker born every minute.\"\" - P.T. Barnum Let's find out why an investment professional would invest in distressed equity? First, the general process is always the same. Company's assets are used to pay off its liabilities; in accordance with applicable law. There are two ways this can be done - either through selling the company; OR through bankruptcy process. The liabilities are paid according to seniority. The seniority priorities rules are covered by 11 U.S. Code § 507 - Priorities A company in bankruptcy can have one of 2 outcomes: Buyout. Some buyer might decide that the company's assets are worth something to them as a whole; and buy the whole enterprise; rather than risk it being destroyed piecemeal in bankruptcy proceedings. In that case, the proceeds from the sale will be used to fund the liabilities as discussed above. This option is one of the possible reasons people might consider investing in distressed equity. For example, if the company is in bankruptcy because it can't get enough financing right now, but is likely to have good profits in the future. The chances are, some buyer will buy it for a premium that includes those future profits; and that sale amount might possibly exceed the liabilities. Bankruptcy. The assets are sold and liabilities are covered according to priorities. In that case, the investors in distressed equity might be hoping that there are un-obvious assets whose value would also put the total assets above claimed liabilities. Additional possible beneficial factor is that unsecured debtors must file with the court in order to be paid; and the claim must be validated. Some might fail on either count; so total amount of liabilities might lessen once the bankruptcy process goes through. Assets Now, here's where things get interesting. Of course, companies have usual assets. Real estate, inventory, plants, cash, etc... These are all able to be sold to cover liabilities, and at first glance are possibly not enough to cover liabilities, leaving equity holders with nothing (and even that's not a certainty - bankruptcy is simply inability to service debt payments; and while it correlates to assetsliquid assets, not full asset valuation). But some assets are less sure, and are thus rarely included in such calculations. These may include: Chances of winning appeals if specific existing liabilities are results of litigation, e.g. tax appeals, court judgement appeals etc... Clawbacks and lawsuits against former executives, especially in cases where the company's financial distress resulted from executive malfeasance. I was personally involved in one such case as an equity holder, where the company assets were valued at $X; had liabilities of $X*2; but had a real possibility of winning about $X*3 in a lawsuit against former CEO accused of various malfeasance including fraud and insider trading. As such, the best case scenario was literally 100% profit on holding that distressed equity.\"",
"title": ""
},
{
"docid": "495874",
"text": "\"The two questions inherent in any decision to purchase an insurance plan is, \"\"how likely am I to need it?\"\", and \"\"what's the worst case scenario if I don't have it?\"\". The actuary that works for the insurance company is asking these same questions from the other end (with the second question thus being \"\"what would we be expected to have to pay out for a claim\"\"), using a lot of data about you and people like you to arrive at an answer. It really boils down to little more than a bet between you and the insurance company, and like any casino, the insurer has a house edge. The question is whether you think you'll beat that edge; if you're more likely than the insurer thinks you are to have to file a claim, then additional insurance is a good bet. So, the reasons you might decide against getting umbrella insurance include: Your everyday liability is low - Most people don't live in an environment where the \"\"normal\"\" insurance they carry won't pay for their occasional mistakes or acts of God. The scariest one for most is a car accident, but when you think of all the mistakes that have to be made by both sides in order for you to burn through the average policy's liability limits and still be ruined for life, you start feeling better. For instance, in Texas, minimum insurance coverage levels are 50/100/50; assuming neither party is hurt but the car is a total loss, your insurer will pay the fair market value of the car up to $50,000. That's a really nice car, to have a curbside value of 50 grand; remember that most cars take an initial hit of up to 25% of their sticker value and a first year depreciation of up to 50%. That 50 grand would cover an $80k Porsche 911 or top-end Lexus ES, and the owner of that car, in the U.S. at least, cannot sue to recover replacement value; his damages are only the fair market value of the car (plus medical, lost wages, etc, which are covered under your two personal injury liability buckets). If that's a problem, it's the other guy's job to buy his own supplemental insurance, such as gap insurance which covers the remaining payoff balance of a loan or lease above total loss value. Beyond that level, up into the supercars like the Bentleys, Ferraris, A-Ms, Rollses, Bugattis etc, the drivers of these cars know full well that they will never get the blue book value of the car from you or your insurer, and take steps to protect their investment. The guys who sell these cars also know this, and so they don't sell these cars outright; they require buyers to sign \"\"ownership contracts\"\", and one of the stipulations of such a contract is that the buyer must maintain a gold-plated insurance policy on the car. That's usually not the only stipulation; The total yearly cost to own a Bugatti Veyron, according to some estimates, is around $300,000, of which insurance is only 10%; the other 90% is obligatory routine maintenance including a $50,000 tire replacement every 10,000 miles, obligatory yearly detailing at $10k, fuel costs (that's a 16.4-liter engine under that hood; the car requires high-octane and only gets 3 mpg city, 8 highway), and secure parking and storage (the moguls in Lower Manhattan who own one of these could expect to pay almost as much just for the parking space as for the car, with a monthly service contract payment to boot). You don't have a lot to lose - You can't get blood from a turnip. Bankruptcy laws typically prevent creditors from taking things you need to live or do your job, including your home, your car, wardrobe, etc. For someone just starting out, that may be all you have. It could still be bad for you, but comparing that to, say, a small business owner with a net worth in the millions who's found liable for a slip and fall in his store, there's a lot more to be lost in the latter case, and in a hurry. For the same reason, litigious people and their legal representation look for deep pockets who can pay big sums quickly instead of $100 a month for the rest of their life, and so very few lawyers will target you as an individual unless you're the only one to blame (rare) or their client insists on making it personal. Most of your liability is already covered, one way or the other - When something happens to someone else in your home, your homeowner's policy includes a personal liability rider. The first two \"\"buckets\"\" of state-mandated auto liability insurance are for personal injury liability; the third is for property (car/house/signpost/mailbox). Health insurance covers your own emergency care, no matter who sent you to the ER, and life and AD&D insurance covers your own death or permanent disability no matter who caused it (depending on who's offering it; sometimes the AD&D rider is for your employer's benefit and only applies on the job). 99 times out of 100, people just want to be made whole when it's another Average Joe on the other side who caused them harm, and that's what \"\"normal\"\" insurance is designed to cover. It's fashionable to go after big business for big money when they do wrong (and big business knows this and spends a lot of money insuring against it), but when it's another little guy on the short end of the stick, rabidly pursuing them for everything they're worth is frowned on by society, and the lawyer virtually always walks away with the lion's share, so this strategy is self-defeating for those who choose it; no money and no friends. Now, if you are the deep pockets that people look for when they get out of the hospital, then a PLP or other supplemental liability insurance is definitely in order. You now think (as you should) that you're more likely to be sued for more than your normal insurance will cover, and even if the insurance company thinks the same as you and will only offer a rather expensive policy, it becomes a rather easy decision of \"\"lose a little every month\"\" or \"\"lose it all at once\"\".\"",
"title": ""
},
{
"docid": "336043",
"text": "I don't see this article being about the merit of the customers claim but rather the condition of sale: > You agree not to file any complaint, chargeback, claim, dispute, or make any public forum post, review, Better Business Bureau complaint, social media post, or any public statement regarding the order, our website, or any issue regarding your order, for any reason, within this 90 day period, or to threaten to do so within the 90 day period, or it is a breach of the terms of sale, creating liability for damages in the amount of $250, plus any additional fees, damages - both consequential and incidental, calculated on an ongoing basis. I'm happy to rally my pitchfork against any company that includes these conditions.",
"title": ""
},
{
"docid": "100655",
"text": "\"If your meaning of \"\"asset protection\"\" is buying gold and canned food in the name of a Nevada LLC because some radio guy said so, bad idea. For a person, if you have assets, buy appropriate liability limits with your homeowner/renter insurance policy or purchase an \"\"umbrella\"\" liability policy. This type of insurance is cheap. If you don't have assets, it may not be worth the cost of insuring yourself beyond the default limits on your renter's or homeowner's policy. If you have a business, you need to talk to your insurance agent about what coverage is appropriate for the business as a whole vs. you personally. You also need to talk to your attorney about how to conduct yourself so that your business interests are separated from your personal interests.\"",
"title": ""
},
{
"docid": "7428",
"text": "> How do I guarantee that people are held liable for damages and/or trying to steal the stuff? Would a credit card number be sufficient? This might belong more in /r/entrepreneur or /r/business, however... you could do a few things: 1. The renter's agreement can (and imo should) include language that obligates the renter to pay for damaged goods and/or stipulates a fixed charge for non-return. 2. As part of the terms to rent, you can demand a credit card hold as part of the renter's agreement. 3. You can insure your rented goods, either in addition to the above or as an alternative (note: because the goods will be changing hands multiple times throughout its life, there is a higher chance of insurance claims. This fact will likely mean higher insurance payments).",
"title": ""
},
{
"docid": "415514",
"text": "\"You need one \"\"company file\"\" for each company that you want to track through QuickBooks. Looks like, in your case, that is at least the PM and the PH (as you labeled them in your question). The companies that just hold property and pay utilities might be simple enough that you don't need the full power of QB, in which case you might just track their finances on a spread sheet. Subsidiary companies will probably appear as \"\"assets\"\" of some sort on the books of the parent company. This set-up probably does limit liability at some level, but it's going to create a lot of overhead for your that incurs some expense either in your time or in actual fees paid. You should really consider whether the limitations on liability balance against those costs. (Think ahead to what you're going to do when you have to file taxes on this network of companies, whether you need separate insurance policies for each instead of getting one policy covering multiple properties, etc.)\"",
"title": ""
},
{
"docid": "350151",
"text": "\"There is an economic, a social and a psychological side to the decision whether to buy insurance or not, and if yes, which one. Economically, as you say already in your question, an insurance is on average a net loss for the insured. The key word here is \"\"average\"\". If you know that there are many cancer cases in your family buy health insurance by all means; it's a sound investment. If you are a reckless driver make sure you have extensive coverage on your liability insurance. But absent such extra risks: Independently of somebody's wealth insurance should be limited to covering catastrophic events. What is often overlooked is that the insurance by all means should really cover those catastrophic events. For example the car liability minimums in many states are not sufficient. The typical upper middle class person could probably pay the 15k/30k/10k required in Arizona with a loan on their house; but a really catastrophic accident is simply not covered and would totally ruin that person and their family. Insuring petty damage is a common mistake: economically speaking, all insurances should have deductibles which are as high as one could afford to pay without feeling too much pain. That \"\"pain\"\" qualification has an economical and a social aspect. Of course any risk which materialized is an economical damage of some kind; perhaps now I can't buy the PS4, or the diamond ring, or the car, or the house, or the island which had caught my eye. I could probably do all these things, just perhaps without some extras, even if I had paid for insurance; so if I don't want to live with the risk to lose that possibility I better buy insurance. Another economical aspect is that the money may not be available without selling assets, possibly on short notice and hence not for the best price. Then an insurance fee takes the role of paying for a permanent backup credit line (and should not be more expensive than that). The social aspect is that even events which wouldn't strictly ruin a person might still force them to, say, sell their Manhattan penthouse (no more parties!) or cancel their country club membership. That is a social pain which is probably to be avoided. Another socioeconomic aspect is that you may have a relationship to the person selling you the insurance. Perhaps he buys his car at your dealership? Perhaps he is your golf buddy? Then the insurance may be a good investment. It is only borderline bad to begin with; any benefits move the line into the profit zone. The psychological aspect is that an insurance buys peace of mind, and that often seems to be the most important benefit. A dart hits the flat screen? Hey, it was insured. Junior totals the Ferrari? Hey, it was insured. Even if the house burns down having fire insurance will be a consolation.\"",
"title": ""
},
{
"docid": "50357",
"text": ">“If you were to disallow deductions for settlements, then that would create an incentive for companies to litigate the case all the way to a trial verdict,” Victor Fleischer, a tax law professor at the University of Colorado, said. “If the company had to pay a claim in that instance, it would be deductible. That’s not wise public policy either.” Huh? First of all, if the deduction were disallowed why would the payment of a claim at the end of a trial be deductible? Second, part of the problem, which is unaddressed in the article, is that the companies paying these fines typically sign agreements that admit liability for the fine but deny all aspects of wrongdoing. Thus, there is no precedent set and there are no guidelines to follow in the future. As such, the result of a trial would actually be instructional to future participants in these markets. Similarly, it might actually result in personal liability for the worst offenders in the organizations.",
"title": ""
},
{
"docid": "516845",
"text": "This is easier than you think: 1) At the end of the year, AirBnb will send you a 1099 form. You will need to report the amount on this form as your rental income - they will report it to the IRS so it has to match. As a bonus, turning your condo into a rental property can become advantageous in that you can deduct repairs and improvements against any rental income. 2) As a host, you will have the option of charging a cleaning fee. Take a look at competitor listings to determine the average cleaning fee in your area. You do not have to clean before and after each guest, only before. 3) As a host, you also have the option of charging a security deposit to cover any damages. Don't get confused by AirBnb's host protection plan - this plan protects you against liability for damages incurred by your guests. Now take a look at competitor listings to determine your rental price. (You may want to lower your price initially to get positive reviews going). Deduct your cleaning fee plus any reasonable wear and tear not covered by the security deposit above. This is your rental income. If your rental income is a positive number - and as long as you charge a realistic cleaning fee/security deposit, it will be - you should rent it out. The worst that can happen is low occupancy i.e. you can't rent your place out as often as you expect. In which case you will be no worse off than you are today. Good luck!",
"title": ""
},
{
"docid": "372744",
"text": "If you want to prove the actual tax liability you have in the US - you have to file a tax return. If the Romanian government believes you that the withholding is your actual tax - fine, but that would be a lie. Withholding is not a tax. The American payers must withhold from foreigners enough to have transferred more than the actual tax the foreigners would have paid. The standard withholding is 30%, but the actual tax on dividends varies. In case the tax treaty limits the tax on dividends - the withholding is usually up to the maximum of the tax allowed by the treaty. But allowed doesn't mean that would be the actual tax. In many cases it is not. So if you want to claim the US tax paid as a credit towards your Romanian tax - you'll need to file a tax return in the US, calculate the actual tax liability and that would be the amount of credit you can claim. The difference between that amount and the amount withheld by the payer will be refunded to you by the IRS. You don't have to file a US tax return, that is true. But the withholding is not the tax, the actual tax liability may have been less, and the Romanian tax authority may deny your credit, in whole or in part, based on the fact that you haven't filed a US tax return and as such have no proof of your actual tax paid. You had some experience with the UK tax treaty, and you think all the treaties are the same. That may be a reasonable line of thought, but it is incorrect. Treaties are not the same. More importantly, even if the treaty is the same - the tax law is not. While in the UK the tax on dividends may be flat and from the first pound - in the US it is neither flat nor from the first dollar. Thus, while in the UK you may have been used to paying tax at source and that's it - in the US it doesn't work that way at all.",
"title": ""
},
{
"docid": "138849",
"text": "I assume having real estate in a good popular city is much more secure way of keeping money than having it in a bank account Not at all! Many things can go wrong with rental property. Renters can be late on rent, they can cause damage to property, you can have unexpected repairs. I'm not saying that you should just let it sit, but rental property is not risk-free my any means. Are you prepared to be a landlord as a part time job (for 500/mo?). Rental property is not passive income - it takes work to maintain. You can outsource this to a property manager, but that eats into the 500/mo that you are estimating). I want to stay flexible and have a possibility to change my location whenever I want. That's a perfectly reasonable reason not to buy a home, but what will you do with the rental when you move? It will still need maintenance, you'll still need to interact with renters, etc. I'm not saying you shouldn't do this, but I get the feeling that you are not fully aware of the risks involved in rental properties.",
"title": ""
},
{
"docid": "298970",
"text": "\"Directors can be held responsible for the liabilities of the corporation - see this Wikipedia article - and especially if it was clear that was the reason for the arrangement, you might well find this happening. That said, I know a Canadian who sold his house to a corporation he already owned (he was doing consulting work through it) at the (in his opinion ridiculously high) amount it had been assessed for property tax purposes. The company paid and claimed any and all expenses including paying for the lawn to be mowed and the house to be painted. He lived in it at a reduced rent (this rent was then income to the company) in exchange for looking after it. He was very happy with the arrangement. He was losing the \"\"no income tax when you sell your primary residence\"\" benefit we have here, but since he expected to never be able to sell it for more than the amount the company had paid, he wasn't worried. If the company exists for no reason other than to shelter income, hide you from liability, and reduce your taxes, then I would expect it would get you some unwanted attention and possibly some rulings you didn't like. If the company exists for a real purpose, and has income and expenses that outweigh whatever games you're playing with cars and homes, you might be able to achieve this. You need to work out what the benefits (other than ducking liabilities) would be and whether they are worth the hassle.\"",
"title": ""
},
{
"docid": "74709",
"text": "\"The decision as to what counts as income is up to the bank. You'll need to ask them whether or not rental income can be included in the total. I can offer some anecdotal evidence: when I applied for a mortgage to buy my home, I already had a rental property with a buy-to-let mortgage on it. Initially the bank regarded that property as a liability, not an asset, because it was mortgaged! However, once I was able to show that there was a good history of receiving enough rent, they chose to ignore the property altogether -- i.e. it wasn't regarded as a liability, but it wasn't regarded as a source of income either. More generally, as AakashM says, residential mortgages are computed based on affordability, which is more than just a multiple of your salary. To answer your specific questions: Covered above; it's up to the bank. If you're married, and you don't have a written tenancy agreement, and you're not declaring the \"\"rent\"\" on your tax return, then it seems unlikely that this would be regarded as income at all. Conversely, if your partner is earning, why not put their name on the mortgage application too? Buy-to-let mortgages are treated differently. While it used to be the case that they were assessed on rental income only, nowadays lenders may ask for proof of the landlord's income from other sources. Note that a BTL cannot be used for a property you intend to live in, and a residential mortgage cannot be used for a property you intend to let to tenants -- at least, not without the bank's permission.\"",
"title": ""
},
{
"docid": "315168",
"text": "Your house is not an asset, it is a liability. Assets feed you. Liabilites eat you. Robert Kiyosaki From a cash flow perspective your primary residence (ie your house) is an investment but it is not an asset. If you add up all the income your primary residence generates and subtract all the expenses it incurs, you will see why investment gurus claim this. Perform the same calculations for a rental property and you're more likely to find it has a positive cash flow. If it has a negative cash flow, it's not an asset either; it's a liability. A rental property with a negative cash flow is still an investment, but cash flow gurus will tell you it's a bad investment. While it is possible that your house may increase in value and you may be able to sell it for more than you paid, will you be able to sell it for more than all of the expenses incurred while living there? If so, you have an asset. Some people will purchase a home in need of repair, live in it and upgrade it, sell it for profit exceeding all expenses, and repeat. These people are flipping houses and generating capital gains based on their own hard work. In this instance a person's primary residence can be an asset. How much of an asset is calculated when the renovated house is sold.",
"title": ""
},
{
"docid": "569720",
"text": "\"When trying to understand accounting, it's always helpful to reference the balance sheet identity, thus , and debits and credits must balance. In this case, one would So that \"\"Cash\"\" is subtracted (credited) from assets, and \"\"Loans to family members\"\" is added (debited) to assets. The income identity is treated differently as So, unless if the \"\"Cash\"\" and \"\"Loans to family members\"\" did not start imbalanced, there was no revenue or expense. A revenue will be any interest paid. The expenses will be any costs related to loaning the money such as drafting a contract or any amount defaulted. Assets are not liabilities A liability on the balance sheet is a liability owed by the entity measured, such as a person or a company. The family members in this case are the borrowers, so they are the ones who must increase their liability accounts like so: The lender to family members would not increase liabilities in this case because the lender is not borrowing from the borrower. Debits, credits, and the balance sheet Debits & credits must be equal, or an identity is violated. Debits add to assets and subtract from liabilities (and equity) while credits subtract from assets and add to liabilities (and equity). If a lender were to try to simultaneously subtract cash from assets and add loans to liabilities to book a loan, the operation would look like this This would cause an immediate imbalance because there are no offsetting debits, but more importantly, crediting Loans to family members as a liability would actually mean that the lender owes Loans to family members.\"",
"title": ""
},
{
"docid": "274050",
"text": "Keep in mind that if you choose a loan for the boat, you may be required by the lender to maintain a minimum coverage of insurance during the term of the loan. Further, some states require you to carry some level of liability insurance on your boat, and some entities require liability insurance when using certain bodies of water within their jurisdiction. If neither apply to you, and if you could suffer the loss of the boat itself, could you similarly suffer the damages caused by your boat if you lose control? Let's say you hit a much larger, more expensive boat, or your boat breaks free from it's dock and damages the dock well beyond the cost of your boat. Are you also able to withstand these costs? If not, you may want to invest in minimum liability insurance. If, at this point, you are still convinced that you are not at financial risk due to the boat, I'd strongly suggest a plan of self insurance. Take the money you would normally spend on insurance, and invest it in low risk investments that can be liquidated in a matter of months. If you do have a problem with the boat, your risk is mitigated by the self-insurance. If you don't, then you have not only saved that money, but increased its value.",
"title": ""
},
{
"docid": "399418",
"text": "\"Do not give them any money until you have a signed contract that releases your liability completely. It's imperative that this contract be drafted correctly. The contract needs proper consideration (money in exchange for release of liability), among other things. In other words, talk to a lawyer if you want to go this route. If you just cut them a check, there's nothing stopping them from taking your money and making an insurance claim anyway, or taking your money and then suing for \"\"whiplash\"\" or some other fake injury. The best way is just to go through insurance. It might cost a bit more, but you're covered in case they sue.\"",
"title": ""
},
{
"docid": "25440",
"text": "Property taxes cover more items than have already been mentioned. As an example, my property tax bill lists the following items: county general purpose, community college, police, police, headquarters, fire prevention, environmental bonds, sewage, town general purpose, highway department, building & zoning, town lighting, park district, garbage disposal, water district, library district, and of course, schools which are now about 60% of the total. In my area, a $500K home could easily have over $10K in total property taxes. Many of these services are for things that you need or might even want such as parks and libraries. In any case, they must be funded and property taxes are the most prevalent way of doing that. I was once told that you never actually own property because if you don't pay the property taxes, they will take the property away. By the way, property taxes are not the only expenses that you may have overlooked. You need to have insurance on your house to cover fire, theft, storm damage, and injuries to persons visiting you. In some areas, flood insurance may also be required. You should also budget for repairs and maintenance. Eventually you will need to replace major items like roofs, appliances and heating/cooling equipment. Don't underestimate the cost of maintaining a lawn if you have one. Basically owning a home is an expensive undertaking and you should have a good understanding of all the expenses involved or you will find yourself in financial trouble.",
"title": ""
},
{
"docid": "404656",
"text": "It's always hard to know the exact policy terms, but as a general rule there are two main contributions to insurance payouts. The first part covers expenses aimed at restoring the situation to its previous state pre-incident. This may include repair work and materials etcetera. The second part kicks in when it's not reasonably possible to repair the damage, or at least not in a financially efficient way. In this case, the insurer can decide to pay out the decrease in value. This is in fact very common in car accidents, where the car is a total loss. In your case, it's quite possible that your roof, even with the two partial repairs is in a worse condition than it was before the storm. For instance, the new shingles may not match the old ones exactly. Thus the value of your home has decreased despite the reasonable repair attempt. And as mhoran_psprep points out, there can be hidden damage as well, which is a lurking liability. If you've accepted the cash payment in lieu of a full repair, you also accept the roof in its new condition.",
"title": ""
},
{
"docid": "42329",
"text": "\"The perceived risk depends on the entire situation, but often it is considered more risk, especially if you want to occupy yourself. Things you need to consider: It can be very difficult to show a property with tenants occupying it. There are many reasons for this and most homes show / sell better empty. I have found many tenants make it difficult on the seller. Leaving their areas a mess, being unaccommodating and especially in markets that are flooded with options, a lot of buyers just won't bother with the difficulty of scheduling a showing in occupied properties. I've tried to purchase many properties where the renter insists on being there during a showing, but won't open the door and there's no recourse for the landlord because his lease or laws in the area don't allow you to enter without permission. Also, it can be difficult to look past a lot of clutter and other people's decorating and aroma \"\"preferences\"\" to be kind. :) Is the property currently under lease and what is the period of that lease? It could be that the lease is month to month, or it could be years remaining on the lease period. It is likely a legal requirement in most areas that you honor the existing lease. I would never buy a property that has multiple years remaining. While some amateur landlords will allow 2 or even 5 year leases, this is a very bad idea for many reasons! What are laws like in your area for evicting tenants? You should know this regardless of whether or not you intend to occupy or keep it a rental. It can be a very difficult process evicting tenants and this process is vastly different from country to country and state to state here in the USA. Look into the security deposit - assuming there is one. How much is the deposit? Will it cover damage that may not exist yet? Don't think that just because you plan on evicting them soon, it isn't important. People can trash a place on the way out and an expensive lawsuit could be your only recourse. It is far easier to take a deposit than sue. I would absolutely demand that the deposit transfer to you upon sale. View the current renters with a fresh eye. Especially if you are considering leave it a rental, look into all of the typical requirements: Their monthly income, their credit history, their criminal record, their payment history, their references. Are they likely to be good or terrible renters? If you're interested in the property, consider an offer which requires the current landlord to evict within the time-frame of the buy/sell agreement. This isn't an uncommon requirement. I think the first thing to do is go look at the property and see if you can determine for yourself why it hasn't sold yet. Properties all have different reasons for not selling in a reasonable time to the local market. Having renters alone in most markets shouldn't be that big of a factor. I would suspect bad smells, nasty renters, or an unfavorable lease agreement exists.\"",
"title": ""
},
{
"docid": "297465",
"text": "\"Is there any way for me to get my money bank? It would be a long drawn process. You would have to file a fraud complaint, they should be able to catch the imposter and / or get a freeze on the account you did wire transfer on [even courts would be involved in process] ... could take lot of time and money. Depending on the amount it may or may not be worth it. If so, should I talk to my bank Your Bank will not take any liability. From their point of view, you deposited a check, they sent it get cleared and reversed the transaction moment they realized it was fraud. the \"\"vendor's\"\" bank You could talk to Vendor Bank. However as you have no relationship with them, they may or may not co-operate. If its a large institution they may do their own internal investigations. If you act sooner, they maybe able to place a hold on the account. Often this is a parking account and the funds are moved elsewhere. They will not be able to refund the funds unless the legal system / process is involved. bank that the fraudulent check came from Depending on how the check was made ... the Bank can easily claim that someone printed something with their Bank's name on it and they are not responsible for it. If there are large cases, the Bank may to contain reputational damage may lodge a complaint with Police and put out some advertisement.\"",
"title": ""
},
{
"docid": "82157",
"text": "For each liability, you should insure to the risk. A $150k home should be insured for that amount plus contents. Same for your car, if you want to insure for damages, fine, but liability is mandatory. It's not about what you want to spend but how to not take on more risk than nescesary and not over insure which is just wasteful.",
"title": ""
},
{
"docid": "360621",
"text": "\"QUICK ANSWER When it comes to fixed income assets, whether rental real estate or government bonds, it's unusual for highly-leveraged assets to yield less than the same asset unleveraged or lowly-leveraged. This is especially so in countries where interest costs are tax deductible. If we exclude capital losses (i.e. the property sells in future at a price less than it was purchased) or net rental income that doesn't keep up with maintenance, regulatory, taxation, inflation and / or other costs, there is one primary scenario where higher leverage results in lower yields compared to lower leverage, even if rental income keeps up with non-funding costs. This occurs when variable rate financing is used and rates substantially increase. EXPLANATION Borrowers and lenders in different countries have different mortgage rate customs. Some are more likely to have long-term fixed rates; some prefer variable rates; and others are a hybrid, i.e. fixed for a few years and then become variable. If variable rates are used for a mortgage and the reference rates increase substantially, as they did in the US during the 1970s, the borrower can easily become \"\"upside-down,\"\" i.e. owe more on the mortgage than the property is then worth, and have mortgage service costs that exceed the net rental income. Some of those costs aren't easy to pass along to renters, even when there are periodic lease renewals or base rent increases referencing inflation rates. Central banks set policies for what would be the lowest short-term rates in a country that has such a bank. Private sector rates are established broadly by supply and demand for credit and can thus diverge markedly from central bank rates. Over time, the higher finance-carrying-cost-to-net-rental-income ratio should abate as (1) rental market prices change to reflect the costs and (2) the landlord can reinvest his net rental income at a higher rate. In the short-term though, this can result in the landlord having to \"\"eat\"\" the costs making his yield on his leveraged fixed income asset less than what he would have without leverage, even if the property was later sold at same price regardless of financing method. ========== Interestingly, and on the flip side, this is one of the quirks in finance where an accounting liability can become, at least in part, an economic asset. If a landlord borrows at a high loan-to-value ratio for a fixed interest rate for the life of the mortgage and rates, variable and fixed, were to increase substantially, the difference between his original rate and the present rates accrues to him. If he's able to sell the property with the loan attached (which is not uncommon for commercial, industrial and sometimes municipal real estate), the buyer will be assuming a liability with a lower carrying cost than his present alternatives and will hence pay a higher price for the property than if it were unleveraged. With long-term rates in many economically advanced countries at historic lows, if a borrower today were to take a long-term fixed rate loan and rates shortly after increased substantially, he may have an instant profit in this scenario even if his property hasn't increased in value.\"",
"title": ""
}
] |
PLAIN-2533
|
PCBs in Children’s Fish Oil Supplements
|
[
{
"docid": "MED-2644",
"text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.",
"title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene."
},
{
"docid": "MED-2652",
"text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.",
"title": "Xeno-estrogenic compounds in precipitation."
},
{
"docid": "MED-2754",
"text": "BACKGROUND: Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD. METHODS: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials. RESULTS: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment. CONCLUSION: Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease.",
"title": "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: ..."
},
{
"docid": "MED-2655",
"text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.",
"title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"
},
{
"docid": "MED-5072",
"text": "Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.",
"title": "Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept."
},
{
"docid": "MED-2758",
"text": "Context Though multivitamins aim to prevent vitamin and mineral deficiency, there is a perception that multivitamins may prevent cardiovascular disease (CVD). Observational studies examining regular multivitamin use have been inconsistently associated with CVD, with no long-term clinical trials of multivitamin use. Objective To determine whether long-term multivitamin supplementation decreases the risk of major cardiovascular events among men. Design The Physicians' Health Study II is a randomized, double-blind, placebo-controlled trial of a common daily multivitamin, that began in 1997 with continued treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 754 men with a history of CVD at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures The primary cardiovascular outcome was a composite endpoint of major cardiovascular events, including nonfatal myocardial infarction (MI), nonfatal stroke, and fatal CVD. Secondary outcomes included MI and stroke individually. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 1,732 confirmed major cardiovascular events. Compared with placebo, there was no significant effect of a daily multivitamin on major cardiovascular events (active and placebo multivitamin groups, 11.0 and 10.8 events per 1,000 person-years; hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.91–1.10; P=0.91). Further, a daily multivitamin had no effect on total MI (active and placebo multivitamin groups, 3.9 and 4.2 events per 1,000 person-years; HR, 0.93; 95% CI, 0.80–1.09; P=0.39), total stroke (active and placebo multivitamin groups, 4.1 and 3.9 events per 1,000 person-years; HR, 1.06; 95% CI, 0.91–1.23; P=0.48), or cardiovascular mortality (active and placebo multivitamin groups, 5.0 and 5.1 events per 1,000 person-years; HR, 0.95; 95% CI, 0.83–1.09; P=0.47). A daily multivitamin was also not significantly associated with total mortality (HR, 0.94; 95% CI, 0.88–1.02; P=0.13). The effect of a daily multivitamin on major cardiovascular events did not differ between men with or without a baseline history of CVD (P, interaction = 0.62). Conclusions A daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up.",
"title": "Multivitamins in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial"
},
{
"docid": "MED-2452",
"text": "A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.",
"title": "A prospective study of diet and adult-onset asthma."
},
{
"docid": "MED-3034",
"text": "In the 1970s several states in the Great Lakes region became concerned about mercury contamination in lakes and rivers and were the first to issue local fish consumption advisories. In 2001, the Food and Drug Administration (FDA) advised pregnant women, nursing mothers, young children, and women who may become pregnant not to consume shark, swordfish, king mackerel, and tilefish and recommended that these women not exceed 12 ounces of other fish per week. In 2004, FDA reissued this advice jointly with the U.S. Environmental Protection Agency (EPA) and modified it slightly to provide information about consumption of canned tuna and more details about consumption of recreationally caught fish. Though several studies have examined consumers' awareness of the joint FDA and EPA advisory as well as different state advisories, few used representative data. We examined the changes in awareness and knowledge of mercury as a problem in fish using the pooled nationally representative 2001 and 2006 Food Safety Surveys (FSS) with sample sizes of 4482 in 2001 and 2275 in 2006. Our results indicated an increase in consumers' awareness of mercury as a problem in fish (69% in 2001 to 80% in 2006, p<.001). In our regression models, we found that in both years, parents having children less than 5 years of age were more aware of mercury in fish and knowledgeable about the information contained in the national advisories about mercury in fish (p<.01) than other adults. In both 2001 and 2006, women of childbearing age (aged 18-45) were less aware and knowledgeable about this information than other women. However, women of all age groups had larger gains in awareness and knowledge than their male counterparts during this time. Participants' race, education, income, region, fish preparation experiences, having a foodborne illness in the past year, and risk perceptions about the safety of food were significant predictors of their awareness and knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Awareness and knowledge of methylmercury in fish in the United States."
},
{
"docid": "MED-2444",
"text": "This is a review of the side-effects of cyclosporin A (CyA) in patients with severe psoriasis; renal dysfunction and hypertension are discussed elsewhere. In particular, paraesthesia, hypertrichosis, gingival hyperplasia and gastrointestinal disorders may occur, but are generally transient, mild-to-moderate in severity and only rarely require discontinuation of CyA. Infections are not a problem. As expected with an immunosuppressive drug, there is the possible risk of tumour development, particularly squamous cell carcinomas. However, these skin malignancies developed almost exclusively in patients previously treated with PUVA and/or methotrexate. The few lymphoproliferative disorders regressed spontaneously on discontinuation of the drug. Whether the isolated cases of solid tumours were CyA-related is not known. Apart from a raised serum creatinine, an important indicator of renal dysfunction, the laboratory abnormalities included hypomagnesaemia, hyperkalaemia, increased uric acid, changes in liver function tests, and fluctuations in the serum cholesterol and triglyceride levels. Although most of these changes were not clinically relevant, laboratory monitoring of patients with psoriasis treated with CyA is essential.",
"title": "Side-effect profile of cyclosporin A in patients treated for psoriasis."
},
{
"docid": "MED-3021",
"text": "The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.",
"title": "Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans."
},
{
"docid": "MED-3026",
"text": "Background Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Methods Inputs to the model consist of dose–response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point–to–end point variability. Results We find a central estimate of −0.18 IQ points (95% confidence interval, −0.378 to −0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from −0.13 to −0.25. Conclusions IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose–response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.",
"title": "Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data"
},
{
"docid": "MED-2657",
"text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel",
"title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis."
},
{
"docid": "MED-2479",
"text": "BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.",
"title": "The intestinal microflora in allergic Estonian and Swedish 2-year-old children."
},
{
"docid": "MED-1831",
"text": "In children, omega-3 polyunsaturated fatty acids (PUFAs) may elicit a suite of health benefits including enhancement of cognitive development. Subsequently, dietary supplements containing omega-3 PUFAs have become increasingly popular. Often, the largest source of beneficial PUFAs in these supplements is fish oil, which may contain significant levels of contaminants such as polychlorinated biphenyls (PCBs). The objectives of this study were to evaluate congener-specific PCB concentrations in 13 over-the-counter children's dietary supplements containing fish oils/powders and assess potential PCB exposures through ingestion of these products on a daily basis. Every supplement analysed contained PCBs, with a mean concentration of 9 ± 8 ng PCBs/g supplement. When following serving size suggestions, mean daily exposure values ranged from 2.5 to 50.3 ng PCBs/day. Daily exposures for children's supplements were significantly lower than those previously reported for adult supplements and may be explained, in part, by the variability in the amount of fish oil (and PUFA content) in a serving size. Based on this study, factors such as fish oil purification methods (e.g., molecular distillation) and the trophic level of the fish species used to make the fish oil cannot be used as indicators of PCB levels within children's supplements. Fish supplements may decrease or increase daily PCB exposure compared with ingestion of fresh fish. However, eating fish high in omega-3 PUFAs and low in PCBs may reduce PCB exposure compared with daily supplementation with fish oils for some products studied.",
"title": "Children's daily exposure to polychlorinated biphenyls from dietary supplements containing fish oils."
},
{
"docid": "MED-2464",
"text": "BACKGROUND: In recent decades, children's diet quality has changed and asthma prevalence has increased, although it remains unclear if these events are associated. OBJECTIVE: To examine children's total and component diet quality and asthma and airway hyperresponsiveness (AHR), a proxy for asthma severity. METHODS: Food frequency questionnaires adapted from the Nurses' Health Study and supplemented with foods whose nutrients which have garnered interest of late in relation to asthma were administered. From these data, diet quality scores (total and component), based on the Youth Healthy Eating Index (YHEI adapted) were developed. Asthma assessments were performed by pediatric allergists and classified by atopic status: Allergic asthma (≥1 positive skin prick test to common allergens >3 mm compared to negative control) versus non-allergic asthma (negative skin prick test). AHR was assessed via the Cockcroft technique. Participants included 270 boys (30% with asthma) and 206 girls (33% with asthma) involved in the 1995 Manitoba Prospective Cohort Study nested case-control study. Logistic regression was used to examine associations between diet quality and asthma, and multinomial logistic regression was used to examine associations between diet quality and AHR. RESULTS: Four hundred seventy six children (56.7% boys) were seen at 12.6 ± 0.5 years. Asthma and AHR prevalence were 26.2 and 53.8%, respectively. In fully adjusted models, high vegetable intake was protective against allergic asthma (OR 0.49; 95% CI 0.29-0.84; P < 0.009) and moderate/severe AHR (OR 0.58; 0.37-0.91; P < 0.019). CONCLUSIONS: Vegetable intake is inversely associated with allergic asthma and moderate/severe AHR. Copyright © 2012 Wiley Periodicals, Inc.",
"title": "Low vegetable intake is associated with allergic asthma and moderate-to-severe airway hyperresponsiveness."
},
{
"docid": "MED-2456",
"text": "Several studies have suggested that the increasing prevalence of symptoms of asthma, rhinitis and eczema, could be associated with dietary factors. In the present paper, a global analysis of prevalence rates of wheeze, allergic rhinoconjunctivitis and atopic eczema was performed in relation to diet, as defined by national food intake data. Analyses were based on the International Study of Asthma and Allergies in Childhood (ISAAC) data for 6-7 and 13-14 yr old children. Symptoms of wheeze, allergic rhinoconjunctivitis and atopic eczema symptom prevalence were regressed against per capita food intake, and adjusted for gross national product to account for economic development. Dietary data were based on 1995 Food and Agriculture Organisation of the United Nations data for 53 of the 56 countries that took part in ISAAC phase I (1994/1995). The 13-14 year age group showed a consistent pattern of decreases in symptoms of wheeze (current and severe), allergic rhinoconjunctivitis and atopic eczema, associated with increased per capita consumption of calories from cereal and rice, protein from cereals and nuts, starch, as well as vegetables and vegetable nutrients. The video questionnaire data for 13-14 yr olds and the ISAAC data for 6-7 yr olds showed similar patterns for these foods. A consistent inverse relationship was seen between prevalence rates of the three conditions and the intake of starch, cereals, and vegetables. If these findings could be generalised, and if the average daily consumption of these foods increased, it is speculated that an important decrease in symptom prevalence may be achieved.",
"title": "Diet and asthma, allergic rhinoconjunctivitis and atopic eczema symptom prevalence: an ecological analysis of the International Study of Asthma and..."
},
{
"docid": "MED-4365",
"text": "A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Adverse effects of concentrated green tea extracts."
},
{
"docid": "MED-3013",
"text": "A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.",
"title": "Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008."
},
{
"docid": "MED-1833",
"text": "BACKGROUND: Cod liver oil is an important source of vitamin D, but also contains other fat-soluble components such as vitamin A. Before 1999, the cod liver oil formula in Norway contained a high concentration of vitamin A (1000 µg per 5 ml). High vitamin A status is associated with increased risks of several chronic diseases. OBJECTIVE: To investigate the association between cod liver oil intake and asthma development. METHODS: In the Nord-Trøndelag Health Study, a total of 25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006-2008. Current analysis based on 17 528 subjects who were free of asthma and had complete information on cod liver oil intake at baseline. Cod liver oil intake was defined as daily intake ≥ 1 month during the year prior to baseline. Incident asthma was reported as new-onset asthma during the 11-year follow-up. RESULTS: Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for ≥ 1 month over the past year. Cod liver oil intake was significantly associated with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment for age, sex, daily smoking, physical activity, education, socio-economic status, family history of asthma, and body mass index (BMI). The positive association was consistent across age (< 40/≥ 40 years), sex (men/women), family history of asthma (yes/no) and BMI subgroups (< 25/≥ 25 kg/m(2)). CONCLUSIONS: Intake of cod liver oil with high vitamin A content was significantly associated with increased incidence of adult-onset asthma.",
"title": "Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study."
},
{
"docid": "MED-3687",
"text": "This study was aimed at determining the probiotic potential of a large number of autochthonous lactic acid bacteria isolated from fruit and vegetables. Survival under simulated gastric and intestinal conditions showed that 35% of the strains, mainly belonging to the species Lactobacillus plantarum maintained high cell densities. Selected strains did not affect the immune-mediation by Caco-2 cells. All strains stimulated all 27 immune-mediators by peripheral blood mononuclear cells (PBMC). A significant (P<0.05; P<0.01) increase of the major part of cytokines and growth factors was found. A few chemokines were stimulated. Immune-mediators with pro-inflammatory activity (IL-17, EOTAXIN and IFNγ) were significantly (P<0.01) stimulated by all strains, followed by IL-1b>IP-10>IL-6>MIP1α. Stimulation of IL-12, IL-2 and IL-7 was strain dependent. Only a few strains increased the synthesis of cytokines with anti-inflammatory activity. Six L. plantarum strains were further selected. Four were defined as the strongly adhesive strains (more than 40 bacteria adhering to one Caco-2 cell), and 2 as the adhesive strains (5-40 bacteria adhering to one Caco-2 cell). Five strains grew and acidified chemically defined medium with fructo-oligosaccharides (FOS) as the only carbon source. End-products of FOS fermentation were found. All strains inhibited enterohemorragic Escherichia coli K12 and Bacillus megaterium F6 isolated from human sources. The results of this study showed that some autochthonous lactic acid bacteria from raw fruit and vegetables have functional features to be considered as novel probiotic candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Novel probiotic candidates for humans isolated from raw fruits and vegetables."
},
{
"docid": "MED-2755",
"text": "A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI.",
"title": "Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART)."
},
{
"docid": "MED-3019",
"text": "Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited. Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide. Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon). Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent. Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.",
"title": "Evidence on the Human Health Effects of Low-Level Methylmercury Exposure"
},
{
"docid": "MED-2662",
"text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.",
"title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)."
},
{
"docid": "MED-3028",
"text": "OBJECTIVE The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09–1.26), 0.98 (0.70–1.37), and 0.90 (0.82–0.98). CONCLUSIONS Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged.",
"title": "Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes"
},
{
"docid": "MED-5092",
"text": "BACKGROUND: While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy, longterm visual and cognitive outcome data from randomized trials are scarce. AIM: To evaluate docosahexaenoic acid (DHA) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age. METHODS: Fifty-two of 79 healthy term infants who were enrolled in a single-center, double-blind, randomized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age. In addition, 32 breast-fed infants served as a \"gold standard\". Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence--Revised. RESULTS: At 4 years, the control formula group had poorer visual acuity than the breast-fed group; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group. The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group. CONCLUSION: DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants.",
"title": "Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented in..."
},
{
"docid": "MED-3023",
"text": "Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. Mothers and their newborns are divided in two groups according to their hair mercury levels; examined group with high body levels of mercury (≥ 1 μg/g) and control group with low body levels of mercury (<1 μg/g). Neurosonographic examination was conducted to all newborns. Two dimensions of cerebellum in the sagital-medial plane have been measured: maximum height and width starting from the roof of the fourth chamber. Majority of mothers had hair mercury levels lower than 1 μg/g (N = 107). Mean value was 0.88 μg/g (SD 1.24), ranging from 0.02 to 8.71 μg/g. There was no significant difference between the two groups when it comes to the width of cerebellum (Mann-Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 μg/g (Mann-Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn's cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Relationship between the prenatal exposure to low-level of mercury and the size of a newborn's cerebellum."
},
{
"docid": "MED-2643",
"text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.",
"title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action"
},
{
"docid": "MED-3035",
"text": "Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986–1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.",
"title": "Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity"
},
{
"docid": "MED-2441",
"text": "Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.",
"title": "Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocy..."
},
{
"docid": "MED-2750",
"text": "OBJECTIVE: To see whether mortality among men with angina can be reduced by dietary advice. DESIGN: A randomized controlled factorial trial. SETTING: Male patients of general practitioners in south Wales. SUBJECTS: A total of 3114 men under 70 y of age with angina. INTERVENTIONS: Subjects were randomly allocated to four groups: (1) advised to eat two portions of oily fish each week, or to take three fish oil capsules daily; (2) advised to eat more fruit, vegetables and oats; (3) given both the above types of advice; and (4) given no specific dietary advice. Mortality was ascertained after 3-9 y. RESULTS: Compliance was better with the fish advice than with the fruit advice. All-cause mortality was not reduced by either form of advice, and no other effects were attributable to fruit advice. Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised; the adjusted hazard ratio was 1.26 (95% confidence interval 1.00, 1.58; P=0.047), and even greater for sudden cardiac death (1.54; 95% CI 1.06, 2.23; P=0.025). The excess risk was largely located among the subgroup given fish oil capsules. There was no evidence that it was due to interactions with medication. CONCLUSIONS: Advice to eat more fruit was poorly complied with and had no detectable effect on mortality. Men advised to eat oily fish, and particularly those supplied with fish oil capsules, had a higher risk of cardiac death. This result is unexplained; it may arise from risk compensation or some other effect on patients' or doctors' behaviour.",
"title": "Lack of benefit of dietary advice to men with angina: results of a controlled trial."
},
{
"docid": "MED-2448",
"text": "A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.",
"title": "Clinical efficacy of apple polyphenol for treating cedar pollinosis."
},
{
"docid": "MED-2649",
"text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.",
"title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"
},
{
"docid": "MED-2661",
"text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.",
"title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)."
},
{
"docid": "MED-2646",
"text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.",
"title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..."
},
{
"docid": "MED-2762",
"text": "BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of s of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.",
"title": "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. ..."
},
{
"docid": "MED-2450",
"text": "Background Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods A cross‐sectional survey was performed in 690 children aged 7–18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58‐item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes—the main local products in Crete—had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.",
"title": "Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete"
},
{
"docid": "MED-2757",
"text": "BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.",
"title": "Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-2455",
"text": "BACKGROUND: It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. METHODS: The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. RESULTS: Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. CONCLUSIONS: This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.",
"title": "Bronchial reactivity and dietary antioxidants"
},
{
"docid": "MED-2756",
"text": "BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by β-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis."
},
{
"docid": "MED-2461",
"text": "This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.",
"title": "The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."
},
{
"docid": "MED-2753",
"text": "The Diet and Reinfarction Trial (DART) involved 2033 men (mean age 56.5 years) recovering from myocardial infarction. They were randomly allocated to receive advice or to receive no advice on each of three dietary factors: an increase in fatty fish intake; a reduction in fat intake with an increase in polyunsaturated fat:saturated fat; an increased intake of cereal fibre. Compliance was satisfactory with the fish and fibre advice, but less so with the fat advice. The men given fish advice had 29% lower 2-year all-cause mortality; the other forms of advice did not have any significant effects. The Diet and Angina Randomized Trial (DART-2) involved 3114 men (mean age 61.1 years) with stable angina, who were followed up for 3-9 years. Advice to eat oily fish or take fish oil did not affect all-cause mortality, but it was associated with a significant increase in sudden cardiac death (P=0.018), and this effect was largely confined to the subgroup given fish oil capsules. Advice to eat more fruit and vegetables had no effect, probably because of poor compliance. The outcome of DART-2 appears to conflict with that of DART and some other studies; various possible explanations are considered. Nutritional interventions are not equally acceptable and should be tailored to the individuals for whom they are intended. Various distinct groups have a raised risk of CHD, and it cannot be assumed that the same nutritional interventions are appropriate to them all. Nutritional supplements do not necessarily have the same effects as the foods from which they are derived.",
"title": "Secondary prevention of CHD in UK men: the Diet and Reinfarction Trial and its sequel."
},
{
"docid": "MED-2469",
"text": "The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.",
"title": "An anthroposophic lifestyle and intestinal microflora in infancy."
},
{
"docid": "MED-2459",
"text": "BACKGROUND: Free radical-mediated oxidative damage to lipids is thought to be an important process in the pathogenesis of atherosclerosis. Although previous studies have demonstrated a beneficial impact of antioxidant vitamin supplements on lipid peroxidation, the effect of dietary patterns on lipid peroxidation is unknown. METHODS AND RESULTS: During the 3-week run-in period of a randomized trial, 123 healthy individuals were fed a control diet, low in fruits, vegetables, and dairy products, with 37% of calories from fat. Participants were then randomized to consume for 8 weeks: (1) the control diet, (2) a diet rich in fruits and vegetables but otherwise similar to the control diet, and (3) a combination diet rich in fruits, vegetables, and low-fat dairy products and reduced in fat. Serum oxygen radical-absorbing capacity, malondialdehyde (an in vitro measure of lipid peroxidation), and breath ethane (an in vivo measure of lipid peroxidation) were measured at the end of run-in and intervention periods. Between run-in and intervention, mean (95% CI) change in oxygen radical-absorbing capacity (U/mL) was -35 (-93, 13) in the control diet, 26 (-15, 67) in the fruits and vegetables diet (P=0.06 compared with control), and 19 (-22, 54) in the combination diet (P=0.10 compared with control). Median (interquartile range) change in ethane was 0.84 (0.10, 1.59) in the control diet, 0.02 (-0.61, 0.83) in the fruits and vegetables diet (P=0.04 compared with control), and -1.00 (-1.97, 0.25) in the combination diet (P=0.005 compared with control). Change in malondialdehyde did not differ between diets. CONCLUSIONS: This study demonstrates that modification of diet can favorably affect serum antioxidant capacity and protect against lipid peroxidation.",
"title": "Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial."
},
{
"docid": "MED-3030",
"text": "Consumption of marine fish provides both benefits (lean protein, omega-3 fatty acids and essential nutrients) and risks (main source of mercury (Hg) exposure for humans). Mercury is a potent neurotoxin and the source of more fish advisories nationwide than any other toxicant. Despite the widespread nature of Hg, it is unknown whether local Hg contamination reflects national and regional levels often used as bases to inform consumers of potential fish consumption risk. Thus, the objectives of our study were to examine Hg levels of six commonly consumed marine species harvested locally off the North Carolina coast and to compare our results to published regional (Monterey Bay Aquarium's Seafood Watch List) and national (Environmental Protection Agency, EPA, and Food and Drug Administration, FDA) Hg averages, action levels, and guidelines. We found significant differences in Hg concentrations among collected species, and we identified correlations between Hg concentration and fish length and trophic levels. Collected mahi mahi and triggerfish were below the EPA fish tissue action level (0.3ppm). Wahoo and grouper exceeded the EPA action level but were below the FDA action level (1.0ppm). King mackerel had the highest Hg concentration among targeted species, exceeding both EPA and FDA action levels. Further, our local results were not always consistent with calculated averages from EPA and FDA databases for the same species, and although many of our findings were consistent with Monterey Bay Aquarium's Seafood Watch List (southeast region), recommendations based on Hg levels would conflict with recommendations they provide based on sustainability. We find regional and national averages are not always reflective of local Hg contamination and suggest local data may be needed to accurately assess consumer risk.",
"title": "Do national advisories serve local consumers: an assessment of mercury in economically important North Carolina fish."
},
{
"docid": "MED-2759",
"text": "A commercial weight loss program with a client base composed of >95% women experienced sporadic complaints of nausea and vomiting after changing its multivitamin supplier. This retrospective and observational study was designed to determine if related adverse event reports were significant, and to investigate potential mechanism for their occurrence in this group of subjects, many of whom were concurrently receiving oral contraceptives or hormone replacement therapy. Incidence of nausea, vomiting, rash, and total complaints in the 3 months following the change of the multivitamin formulation was compared with the same complaints in the 3 months before the change. In the 3 months following the multivitamin change, there were 166 complaints of nausea and vomiting, 9 complaints of rash and 194 total complaints from a group of 88,468 patients. In the 3 months before the change in the multivitamin, there had been 2 complaints of nausea and vomiting, no complaints of rash, and 11 total complaints from 88,252 patients. The difference detected by a chi-squared test was significant for all events studied; nausea and vomiting (P < 0.0001), rash (P < 0.02), and total complaints (P < 0.0001). The altered multivitamins contained added citrus bioflavanoids not included in the original formula. Citrus bioflavanoids decrease the clearance of exogenous estrogens by inhibiting cytochrome P450 enzyme systems. Elevated estrogen levels could account for the increased incidence of nausea and vomiting. This experience demonstrates that adding dietary herbal supplements to multivitamins may be associated with adverse interactions with prescription drugs.",
"title": "Vomiting from multivitamins: a potential drug interaction."
},
{
"docid": "MED-2751",
"text": "Recent data on fishmeal and fish-oil supply are presented identifying key producer countries and raw material sources and distinguishing between whole fish and by-products. The conversion of these raw materials into marine ingredients is discussed and global volumes presented. This is followed by a summary of the main countries using these marine ingredients over recent years. Uses of fishmeal and fish-oil by market segment are then presented. From this, a global mass balance of inputs and outputs is derived which allows the calculation of the input-to-output ratios (fish in:fish out; FIFO) for the main aquaculture production types to be made. Current areas of focus by the industry include the need to demonstrate sustainable practice, more strategic use of marine ingredients, greater use of fishery and land-animal by-products as well as vegetable substitutes, and novel sources of essential omega-3 fats, notably the long-chain polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Implications are drawn for future supply prospects of fishmeal and fish-oil and their future role in aquaculture, agriculture and human health. © 2013 The Fisheries Society of the British Isles.",
"title": "Global fishmeal and fish-oil supply: inputs, outputs and markets."
},
{
"docid": "MED-3027",
"text": "Background Some persistent environmental chemicals are suspected of causing an increased risk of type 2 diabetes mellitus, a disease particularly common after age 70. This concern was examined in a cross-sectional study of elderly subjects in a population with elevated contaminant exposures from seafood species high in the food chain. Methods Clinical examinations of 713 Faroese residents aged 70-74 years (64% of eligible population) included fasting plasma concentrations of glucose and insulin, and glycosylated hemoglobin. Lifetime exposure to persistent environmental chemicals from pilot whale and other traditional food was estimated from a dietary questionnaire and by analysis of blood samples for polychlorinated biphenyls (PCBs) and related food contaminants. Results Septuagenarians with type 2 diabetes or impaired fasting glycemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. In non-diabetic subjects, the fasting insulin concentration decreased by 7% (95% CI= −12% to −2%) for each doubling of the PCB concentration after adjustment for sex and body mass index at age 20. Conversely, the fasting glucose concentration increased by 6% (−1% to 13%) for each doubling in PCB. Similar associations were seen in subjects without impaired fasting glycemia, while further adjustment for current body mass index and lipid metabolism parameters attenuated some of the associations. Conclusions Impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants.",
"title": "Marine Food Pollutants as a Risk Factor for Hypoinsulinemia and Type 2 Diabetes"
},
{
"docid": "MED-1832",
"text": "The need for a dietary supply of docosahexaenoic acid (DHA) and arachidonic aid (AA) in term infants was evaluated in a double-masked randomized clinical trial of the effects of supplementation of term infant formula with DHA (0.35% of total fatty acids) or with DHA (0.36%) and AA (0.72%) on visual acuity development. One hundred and eight healthy term infants were enrolled in the study; 79 were exclusively formula-fed from birth (randomized group) and 29 were exclusively breast-fed (gold standard group). Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition, growth, sweep visual evoked potential (VEP) acuity, and forced choice preferential looking acuity. Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell (RBC) lipid composition. Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6, 17, and 52 wk of age but not at 26 wk of age, when acuity development reaches a plateau. The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants, whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants. Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol. Infants in all diet groups had similar rates of growth and tolerated all diets well. Thus, early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant.",
"title": "Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants."
},
{
"docid": "MED-3032",
"text": "Fish consumption during gestation can provide the fetus with long chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Ω-3 and Ω-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Ω-3 LCPUFA and negatively associated with the ratio of Ω-6/Ω-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Ω-6/Ω-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30 month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II Mental Developmental Index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Ω-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.",
"title": "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study"
},
{
"docid": "MED-2468",
"text": "BACKGROUND AND METHODS: We estimated the prevalence of self-reported asthma in adult Indians and examined several risk factors influencing disease prevalence. Analysis is based on 99 574 women and 56 742 men aged 20–49 years included in India’s third National Family Health Survey, 2005–2006. Multiple logistic regression analysis was used to estimate the prevalence odds ratios for asthma, adjusting for various risk factors. RESULTS: The prevalence of self-reported asthma was 1.8% (95%CI 1.6–2.0) among men and 1.9% (95%CI 1.8–2.0) among women, with higher rates in rural than in urban areas and marked geographic differences. After adjustment for known asthma risk factors, women were 1.2 times more likely to have asthma than men. Daily/weekly consumption of milk/milk products, green leafy vegetables and fruits were associated with a lower asthma risk, whereas consumption of chicken/meat, a lower body mass index (BMI; <16 kg/m2, OR 2.08, 95%CI 1.73–2.50) as well as a higher BMI (>30 kg/m2, OR 1.67, 95%CI 1.36–2.06), current tobacco smoking (OR 1.30, 95%CI 1.12–1.50) and ever use of alcohol (OR 1.21, 95%CI 1.05–1.39) were associated with an increased asthma risk. CONCLUSIONS: There are wide regional variations in the prevalence of asthma in India. With the exception of the findings for BMI, however, most of the associations of asthma with the risk factors are relatively weak and account for only a small proportion of cases. RÉSUMÉ CONTEXTE ET MÉTHODES: Nous avons estimé la prévalence auto-rapportée de l’asthme chez les Indiens adultes et examiné plusieurs facteurs de risque influençant la prévalence de la maladie. L’analyse repose sur 99 574 femmes et 56 742 hommes âgés de 20 à 49 ans et inclus dans la troisième Enquête Nationale des Familles en Inde, 2005–2006. On a utilisé l’analyse de régression logistique multiple pour estimer les odds ratio de prévalence pour l’asthme, après ajustement pour divers facteurs de risque. RÉSULTATS: La prévalence auto-rapportée de l’asthme est de 1,8% (IC95% 1,6–2,0) parmi les hommes et de 1,9% (IC95% 1,8–2,0) parmi les femmes, les taux étant plus élevés dans les zones rurales que dans les zones urbaines, et les différences géographiques étant marquées. Après ajustement pour les facteurs de risque d’asthme connus, les femmes sont 1,2 fois plus susceptibles de souffrir de l’asthme que les hommes. La consommation quotidienne ou hebdomadaire de lait/produits laitiers, de légumes à feuilles vertes et de fruits est en association avec un risque plus faible d’asthme alors que la consommation de poulet ou de viande, un index de masse corporelle (BMI) plus bas (<16 kg/m2, OR 2,08 ; IC95% 1,73–2,50) ainsi qu’un BMI plus élevé (>30 kg/m2, OR 1,67 ; IC95% 1,36–2,06), le fait de fumer du tabac actuellement (OR 1,30 ; IC95% 1,12–1,50) et l’utilisation de l’alcool à un moment quelconque (OR 1,21 ; IC95% 1,05–1,39) sont en association avec un risque accru d’asthme. La prévalence de l’asthme en Inde varie largement selon les régions. Toutefois, à l’exception des observations sur le BMI, l’association de l’asthme avec les facteurs de risque est relativement faible et ne rend compte que d’une petite proportion des cas seulement. RESUMEN MARCO DE REFERENCIA Y MÉTODOS: Se calculó la prevalencia de asma autorreferida en los adultos en la India y se evaluaron varios factores de riesgo que influyen sobre la prevalencia de la enfermedad. El estudio se basó en las 99 574 mujeres y los 56 742 hombres de 20 a 49 años de edad que participaron en la tercera Encuesta Nacional sobre la Salud de la Familia en la India entre el 2005 y el 2006. Mediante un análisis de regresión logística multifactorial se calculó la prevalencia de asma y el cociente de posibilidades de padecerla, al corregir diversos factores de riesgo. RESULTADOS: La prevalencia de asma autorreferida fue 1,8% en los hombres (intervalo de confianza [IC] del 95% 1,6 a 2,0) y 1,9% en las mujeres (IC95% 1,8 a 2,0); se observaron tasas más altas en las zonas rurales que en las zonas urbanas y se presentaron diferencias geográficas considerables. Tras corregir en función de algunos factores de riesgo de padecer asma conocidos, las mujeres presentaron una probabilidad 1,2 veces superior a los hombres de sufrir la enfermedad. El consumo diario o semanal de leche o productos lácteos, hortalizas de hojas verdes y frutas se asoció con un menor riesgo de asma y el consumo de carne de pollo o de res, un bajo índice de masa corporal (<16 kg/m2; OR 2,08; IC95% 1,73 a 2,50) igual que un alto índice de masa corporal (>30 kg/m2; OR 1,67; IC95% 1,36 a 2,06), el tabaquismo actual (OR 1,30; IC95% 1,12 a 1,50) y el consumo de alcohol en algún momento de la vida (OR 1,21; IC95% 1,05 a 1,39) se asociaron con un mayor riesgo de padecer la enfermedad. CONCLUSIÓN: Existen amplias variaciones geográficas en la prevalencia de asma en la India. Sin embargo, con la excepción del índice de masa corporal, la mayor parte de las asociaciones del asma con los factores de riesgo fueron débiles y explican solo una pequeña proporción de los casos.",
"title": "Prevalence and risk factors for self-reported asthma in an adult Indian population: a cross-sectional survey"
},
{
"docid": "MED-2472",
"text": "Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.",
"title": "Vegan regimen with reduced medication in the treatment of bronchial asthma."
},
{
"docid": "MED-1834",
"text": "Observations of increasing allergy prevalence with decreasing distance from the Equator and positive associations with ambient ultraviolet radiation have contributed to a growing interest in the possible role of vitamin D in the etiology of allergy. The aims of this study were to describe any latitudinal variation in the prevalence of childhood allergy in Australia and to evaluate, in parallel, the individual associations between ultraviolet radiation (UVR)- and vitamin D-related measures and hayfever asthma and both conditions. Participants were population-based controls who took part in a multicenter case-control study, aged 18-61 yr and resident in one of four study regions ranging in latitude from 27°S to 43°S. Data were derived from a self-administered questionnaire, interview and examination by a research officer and biologic sampling. Latitude and longitude coordinates were geocoded from participants' residential locations and climatic data were linked to postcodes of current residence. Stored serum was analyzed for 25-hydroxyvitamin D concentrations and silicone rubber casts of the skin were used as an objective measure of cumulative actinic damage. There was an inverse latitude gradient for asthma (a 9% decrease per increasing degree of latitude); however, this pattern did not persist after adjusting for average daily temperature. There was no association between any of the UVR- or vitamin D-related measures and childhood asthma, but greater time in the sun in winter between the ages 6-15 yr was associated with an increase in the odds of having hayfever [adjusted odds ratios (OR) 1.29; 95% CI 1.01-1.63]. Oral supplementation with cod liver oil in childhood increased the odds of a history of having both asthma and hayfever (2.87; 1.00-8.32). Further investigation of the possible role of early vitamin D supplementation in the development of allergy is warranted. Our results also suggest that solar exposure during childhood may be important in allergic sensitization. Plausible explanations, including biologic mechanisms, exist for both observations. © 2010 John Wiley & Sons A/S.",
"title": "The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study."
},
{
"docid": "MED-3012",
"text": "The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment."
},
{
"docid": "MED-2760",
"text": "Context Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Limited observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality. Objective To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men. Design The Physicians’ Health Study II is a randomized, double-blind, placebo-controlled trial of a common multivitamin that began in 1997 with treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 1,312 men with a history of cancer at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures A primary outcome was total cancer (excluding non-melanoma skin cancer), with prostate, colorectal, and other site-specific cancers among secondary endpoints included in this report. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 2,669 men with confirmed cancer, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (active and placebo multivitamin groups, 17.0 and 18.3 events, respectively, per 1,000 person-years; hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86–0.998; P=0.044). There was no significant effect of a daily multivitamin on prostate cancer (HR, 0.98; 95% CI, 0.88–1.09; P=0.76), colorectal cancer (HR, 0.89; 95% CI, 0.68–1.17; P=0.39), or other site-specific cancers There was a lower risk of cancer mortality that did not reach statistical significance (HR, 0.88; 95% CI, 0.77–1.01; P=0.07). Daily multivitamin use was associated with a reduction in total cancer among 1,312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56–0.96; P=0.022), but this did not differ significantly from that among 13,329 men initially free of cancer (HR, 0.94; 95% CI, 0.87–1.02; P=0.15) (P, interaction = 0.07). Conclusions In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.",
"title": "Multivitamins in the Prevention of Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial"
},
{
"docid": "MED-2442",
"text": "A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.",
"title": "Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis."
},
{
"docid": "MED-2656",
"text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.",
"title": "Effects of intestinal microflora and the environment on the development of asthma and allergy."
},
{
"docid": "MED-3022",
"text": "Methylmercury (MM) is a very potent neurotoxic agent. Its role in polluting the environment is well documented. A vast amount of study over the past several decades has finally provided insight into many aspects of its effect. Exposure to MM may be through ingestion of poisoned fish or inadvertent misuse of grain treated with the poison as a fungicide. Major epidemics have occurred in Japan (Fetal Minamata disease), Iraq, Pakistan, Guatemala, and Ghana. Sporadic incidences have occurred in the United States and Canada. There is no effective antidote to counteract the effect of MM on the central nervous system, although the information documented should provide hope for more effective therapy in acute cases.",
"title": "The many faces of methylmercury poisoning."
},
{
"docid": "MED-2482",
"text": "Previous studies have suggested that probiotic administration may have therapeutic and/or preventive effects on atopic dermatitis in infants; however, its role in allergic airway diseases remains controversial. To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis (AR). We conducted a randomized, double-blind, placebo-controlled study on school children (age, 6-12 years) with asthma and AR. The eligible study subjects received either L. gasseri A5 (n = 49) or a placebo (n = 56) daily for 2 months. Pulmonary function tests were performed, and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period. Diary cards with records of the day- and nighttime peak expiratory flow rates (PEFR), symptoms of asthma, and AR scores of the patients were used for measuring the outcome of the treatment. Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells (PBMCs) were determined before and after the probiotic treatments. Our results showed the pulmonary function and PEFR increased significantly, and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls. Further, there was a significant reduction in the TNF-α, IFN-γ, IL-12, and IL-13 production by the PBMCs following the probiotic treatment. In conclusion, probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR.",
"title": "Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis."
},
{
"docid": "MED-2474",
"text": "This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.",
"title": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis."
},
{
"docid": "MED-2449",
"text": "BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.",
"title": "An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis."
},
{
"docid": "MED-2446",
"text": "BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.",
"title": "Dietary antioxidant intake, allergic sensitization and allergic diseases in young children."
},
{
"docid": "MED-2659",
"text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.",
"title": "European bans on surfactant trigger transatlantic debate."
},
{
"docid": "MED-4366",
"text": "BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail (\"junk mail\"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.",
"title": "The marketing of dietary supplements in North America: the emperor is (almost) naked."
},
{
"docid": "MED-2453",
"text": "BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross- sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = - 0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.",
"title": "Effect of fresh fruit consumption on lung function and wheeze in children"
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-2475",
"text": "Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.",
"title": "The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study."
},
{
"docid": "MED-3025",
"text": "Detailed clinical and neuropathological studies have been made in two fullterm newborn human infants who were exposed to methylmercury in utero as a result of maternal ingestion of methylmercury-contaminated bread in early phases of pregnancy. High levels of mercury were detected in various regions of the brain at autopsy. Study of the brains revealed a disturbance in the development in both cases, consisting essentially of an incomplete or abnormal migration of neurons to the cerebellar and cerebral cortices, and deranged cortical organization of the cerebrum. There were numerous heterotopic neurons, both isolated and in groups, in the white matter of cerebrum and cerebellum and the laminar cortical pattern of the laminar cortical pattern of the cerebrum was disturbed in many regions as was shown by the irregular groupings and the deranged alignment of cortical. Prominent in the white matter of the cerebrum and the cerebellum was diffuse gemistocytic astrocytosis accompanied by an accumulation of mercury grains in their cytoplasm. These findings indicate a high degree of vulnerability of human fetal brain to maternal intoxication by methylmercury. A major effect appears to be related to faulty development and not to destructive focal neuronal damage as has been observed in mercury intoxicaiton in adults and children exposed postnatally.",
"title": "Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: a major effect of..."
},
{
"docid": "MED-2761",
"text": "PURPOSE: The aim of this study was to examine the prevalence of self-reported multivitamin use in the Physicians' Health Study (PHS) cohort and its association with various lifestyle, clinical, and dietary factors to improve our understanding of who tends to use multivitamins. METHODS: Among 18,040 middle-aged and older men, information on lifestyle and clinical factors was collected from a baseline enrollment questionnaire, and supplement use and dietary factors were assessed through a food-frequency questionnaire. Four categories of multivitamin use were considered: (1) no supplement use, (2) use of multivitamins only, (3) use of multivitamins with other individual vitamin/mineral supplements, and (4) use of other supplements only. We used logistic regression to calculate multivariate odds ratios and 95% confidence intervals of taking multivitamin supplements for various lifestyle, clinical and dietary factors. RESULTS: Overall, 36% of men reported current multivitamin use. Men who were older, current smokers, and currently using aspirin were 143, 43, and 74% more likely to use multivitamins only. Men having a history of hypercholesterolemia were 16% more likely to use multivitamins only. A 14, 24, and 26% greater likelihood of using multivitamins was also observed among men consuming more fruits and vegetables, whole grains, and tea, respectively. Similar associations were observed for the likelihood of using multivitamins with other supplements; however, men with higher physical activity, history of cancer, hypertension, higher consumption of nuts, and lower consumption of red meat and coffee were also more likely to use multivitamins with other supplements (all P < 0.05). CONCLUSION: Self-reported multivitamin use associated with lifestyle, clinical and dietary factors may be an indicator of healthy behaviors. These results provide important information for the interpretation of the recent findings from the PHS II trial and consideration of results from observational studies of multivitamin use and chronic disease.",
"title": "Who uses multivitamins? A cross-sectional study in the Physicians' Health Study."
},
{
"docid": "MED-2445",
"text": "Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.",
"title": "Dietary polyphenols in the prevention and treatment of allergic diseases."
},
{
"docid": "MED-2460",
"text": "BACKGROUND: Elevated oxidative stress and impaired antioxidant defences are increasingly recognised features of asthma. Carotenoids are potent dietary antioxidants that may protect against asthma by reducing oxidative damage. OBJECTIVES: This study aimed firstly, to characterise circulating and airway levels of carotenoids in asthma compared to healthy controls, in relation to dietary intake. Secondly, the study aimed to test whether airway lycopene defences can be improved using oral supplements. METHODS: Induced sputum and peripheral blood samples were collected from subjects with asthma (n = 15) and healthy controls (n = 16). Dietary carotenoid intakes were estimated using the 24-hour recall method and analysed using a modified version of the Foodworks 210 Nutrient Calculation Software. Another group of healthy controls (n = 9) were supplemented with 20 mg/day lycopene for 4 weeks. Carotenoids (beta-carotene, lycopene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin) were measured by HPLC. RESULTS: Despite similar dietary intake, whole blood levels of total carotenoids, lycopene, lutein, beta-cryptoxanthin, alpha-carotene and beta-carotene were significantly lower in asthma than controls. However, there were no differences in plasma or sputum carotenoid levels. Induced sputum carotenoid levels were significantly lower than plasma and whole blood levels, but correlated strongly with plasma levels (r = 0.798, p < 0.001). Although there were no overall increases in either plasma or sputum lycopene levels following supplementation, changes in airway lycopene levels correlated with changes in plasma levels (r = 0.908, p < 0.002). CONCLUSIONS: Whole blood, but not plasma or sputum, carotenoid levels are deficient in asthma. Plasma carotenoid levels reflect airway carotenoid levels and when plasma levels are improved using oral supplements this is reflected in the airways.",
"title": "Airway and circulating levels of carotenoids in asthma and healthy controls."
},
{
"docid": "MED-3024",
"text": "This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Dietary lipids modulate methylmercury toxicity in Atlantic salmon."
},
{
"docid": "MED-2451",
"text": "BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function. METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV1) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. RESULTS—Good lung function, indicated by high maximum FEV1 given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.",
"title": "Diet, lung function, and lung function decline in a cohort of 2512 middle aged men"
},
{
"docid": "MED-3029",
"text": "Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts of fish consumption. In addition, policy and fishery management inter-ventions will be necessary to ensure long-term availability of fish as an important source of human nutrition.",
"title": "Which Fish Should I Eat? Perspectives Influencing Fish Consumption Choices"
},
{
"docid": "MED-3033",
"text": "Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.",
"title": "Smoking and lung cancer risk in American and Japanese men: an international case-control study."
},
{
"docid": "MED-2471",
"text": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.",
"title": "Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One"
},
{
"docid": "MED-2484",
"text": "Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.",
"title": "The burden of childhood asthma"
},
{
"docid": "MED-2645",
"text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.",
"title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."
},
{
"docid": "MED-2752",
"text": "CONTEXT: Considerable controversy exists regarding the association of omega-3 polyunsaturated fatty acids (PUFAs) and major cardiovascular end points. OBJECTIVE: To assess the role of omega-3 supplementation on major cardiovascular outcomes. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012. STUDY SELECTION: Randomized clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke. DATA EXTRACTION: Descriptive and quantitative information was extracted; absolute and relative risk (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I2. Subgroup analyses were performed for the presence of blinding, the prevention settings, and patients with implantable cardioverter-defibrillators, and meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of .0063 was assumed after adjustment for multiple comparisons. DATA SYNTHESIS: Of the 3635 citations retrieved, 20 studies of 68,680 patients were included, reporting 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No statistically significant association was observed with all-cause mortality (RR, 0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] -0.004, 95% CI, -0.01 to 0.02), cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, -0.01; 95% CI, -0.02 to 0.00), sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, -0.003; 95% CI, -0.012 to 0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, -0.002; 95% CI, -0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95% CI, -0.002 to 0.004) when all supplement studies were considered. CONCLUSION: Overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.",
"title": "Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis."
},
{
"docid": "MED-2458",
"text": "BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.",
"title": "Manipulating antioxidant intake in asthma: a randomized controlled trial."
},
{
"docid": "MED-4551",
"text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S",
"title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."
}
] |
[
{
"docid": "MED-4943",
"text": "Fish and seal oil dietary supplements, marketed to be rich in omega-3 fatty acids, are frequently consumed by Canadians. Samples of these supplements (n = 30) were collected in Vancouver, Canada, between 2005 and 2007. All oil supplements were analyzed for polychlorinated biphenyls (PCBs) and organochlorine insecticides (OCs) and each sample was found to contain detectable residues. The highest SigmaPCB and SigmaDDT (1,1,1-trichloro-di-(4-chlorophenyl)ethane) concentrations (10400 ng/g and 3310 ng/g, respectively) were found in a shark oil sample while lowest levels were found in supplements prepared using mixed fish oils (anchovy, mackerel, and sardine) (0.711 ng SigmaPCB/g and 0.189 ng SigmaDDT/g). Mean SigmaPCB concentrations in oil supplements were 34.5, 24.2, 25.1, 95.3, 12.0, 5260, 321, and 519 ng/g in unidentified fish, mixed fish containing no salmon, mixed fish with salmon, salmon, vegetable with mixed fish, shark, menhaden (n = 1), and seal (n = 1), respectively. Maximum concentrations of the other OCs were generally observed in the seal oil. The hexachlorinated PCB congeners were the dominant contributors to SigmaPCB levels, while SigmaDDT was the greatest contributor to organochlorine levels. Intake estimates were made using maximum dosages on manufacturers' labels and results varied widely due to the large difference in residue concentrations obtained. Average SigmaPCB and SigmaDDT intakes were calculated to be 736 +/- 2840 ng/d and 304 +/- 948 ng/d, respectively.",
"title": "Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides."
},
{
"docid": "MED-4730",
"text": "We successfully optimized an analytical method using gel permeation chromatography followed by direct sample introduction comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry to quantify multiple groups of targeted persistent organic pollutants and halogenated natural products (HNPs) simultaneously in fish oil samples. This new method has a wider analytical scope than the traditional approach to use multiple methods to cover each class of compounds. Our analysis revealed that the relatively more volatile and lighter organic compounds, such as polychlorinated biphenyls (PCBs), organochlorine pesticides, and other smaller organohalogen compounds, were still present in two brands of \"PCB-free\" cod liver oils, albeit at much lower levels than in an untreated commercial sample. Moreover, the less volatile organic compounds, such as polybrominated diphenyl ethers and brominated HNPs, were detected at similar levels in all three cod liver oils. This suggests that the commercial molecular distillation treatment used for removal of organic/inorganic toxic contaminants is only effective for the lighter organic contaminants.",
"title": "Simultaneous quantitation of multiple classes of organohalogen compounds in fish oils with direct sample introduction comprehensive two-dimensional..."
},
{
"docid": "MED-4731",
"text": "BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.",
"title": "No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-..."
},
{
"docid": "MED-2412",
"text": "OBJECTIVE: To determine the effects of fish oil supplementation on lipid levels and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A comprehensive search of Medline, Embase, Lilacs, the Cochrane Clinical Trials Registry bibliographies of relevant papers, and expert input updated through September 1998 was undertaken. All randomized placebo-controlled trials were included in which fish oil supplementation was the only intervention in subjects with type 2 diabetes. Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. Eighteen trials including 823 subjects followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day The outcomes studied were glycemic control and lipid levels. RESULTS: Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil on lowering triglycerides (-0.56 mmol/l [95% CI -0.71 to -0.41]) and raising LDL cholesterol (0.21 mmol/l [0.02 to 0.41]). No statistically significant effect was observed for fasting glucose. HbA1c total cholesterol, or HDL cholesterol. The triglyceride-lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited hypertriglyceridemic subjects and used higher doses of fish oil. Heterogeneity was observed and explained by the recruitment of subjects with baseline hypertriglyceridemia in some studies. CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, raises LDL cholesterol, and has no statistically significant effect on glycemic control. Trials with hard clinical end points are needed.",
"title": "Fish oil supplementation in type 2 diabetes: a quantitative systematic review."
},
{
"docid": "MED-839",
"text": "Long-chain EPA/DHA omega-3 fatty acid supplementation can be co-preventative and co-therapeutic. Current research suggests increasing accumulated long chain omega-3s for health benefits and as natural medicine in several major diseases. But many believe plant omega-3 sources are nutritionally and therapeutically equivalent to the EPA/DHA omega-3 in fish oil. Although healthy, precursor ALA bio-conversion to EPA is inefficient and production of DHA is nearly absent, limiting the protective value of ALA supplementation from flax-oil, for example. Along with pollutants certain fish acquire high levels of EPA/DHA as predatory species. However, the origin of EPA/DHA in aquatic ecosystems is algae. Certain microalgae produce high levels of EPA or DHA. Now, organically produced DHA-rich microalgae oil is available. Clinical trials with DHA-rich oil indicate comparable efficacies to fish oil for protection from cardiovascular risk factors by lowering plasma triglycerides and oxidative stress. This review discusses 1) omega-3 fatty acids in nutrition and medicine; 2) omega-3s in physiology and gene regulation; 3) possible protective mechanisms of EPA/DHA in major diseases such as coronary heart disease, atherosclerosis, cancer and type 2 diabetes; 4) EPA and DHA requirements considering fish oil safety; and 5) microalgae EPA and DHA-rich oils and recent clinical results.",
"title": "Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA."
},
{
"docid": "MED-4114",
"text": "Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..."
},
{
"docid": "MED-5100",
"text": "Historically, concerns with fish consumption have addressed risks from contaminants (e.g., methylmercury (MeHg), and PCBs). More recently public health concerns have widened in appreciation of the specific benefits of fish consumption such as those arising from polyunsaturated fatty acids (PUFAs) in fish oil. Fish contains varying levels of PUFAs and MeHg. Since both address the same health outcomes (in opposite directions) and occur together in fish, great care must be exercised in providing public health guidance. Mozaffarian and Rimm in a recent article (JAMA. 2006, 296:1885–99) have made a strong case for the beneficial effects of PUFAs in reducing the risk of coronary heart disease, but at the same time, have also broadly discounted the increased risks of coronary heart disease posed by MeHg in fish, stating that \"... among adults... the benefits of fish intake exceed the potential risks.\" This conclusion appears to be based on an inaccurate and insufficiently critical analysis of the literature. This literature is re-examined in light of their conclusions, and the available and appropriate public health options are considered.",
"title": "Public health guidance on cardiovascular benefits and risks related to fish consumption"
},
{
"docid": "MED-4631",
"text": "BACKGROUND: Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA. METHODS: Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period. RESULTS: Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs 217%) and lower formation of leukotriene B(4) (34% vs 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6-8 of the experiment. CONCLUSION: A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.",
"title": "Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis."
},
{
"docid": "MED-2391",
"text": "Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.",
"title": "Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA"
},
{
"docid": "MED-928",
"text": "Background Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared. Methods In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed. Results The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC0-72 h: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC0-72 h: 59.78 ± 36.75%*h) and EE (mean AUC0-72 h: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA. Conclusion Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.",
"title": "Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations - a comparative bioavailability study of fish oil vs. krill oil"
},
{
"docid": "MED-5105",
"text": "Food, especially dairy products, meat, and fish, is the primary source of environmental exposure to dioxins in the general population. Little data exists on dioxin levels in the popular and widely consumed \"fast foods\". Data presented in a previously published pilot study was limited to measuring only the levels of dioxins and dibenzofurans in three types of U.S. fast food. This study adds to the previous paper by presenting data, in addition to dioxins and dibenzofurans, on the closely related dioxin-like polychlorinated biphenyls (PCBs), and the persistent metabolite of DDT, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (DDE), in four types of popular U.S. fast food. These include McDonald's Big Mac Hamburger, Pizza Hut's Personal Pan Pizza Supreme, Kentucky Fried Chicken (KFC) three piece original recipe mixed dark and white meat luncheon package, and Häagen-Daz chocolate-chocolate chip ice cream. Dioxin plus dibenzofuran dioxin toxic equivalents (TEQ) ranged from 0.03 to 0.28 TEQ pg/g wet or whole weight for the Big Mac, from 0.03 to 0.29 for the Pizza, from 0.01 to 0.31 for the KFC, and from 0.03 to 0.49 TEQ pg/g for the ice cream. Daily TEQ consumption per kilogram body weight (kg/BW), assuming an average 65 kg adult and a 20 kg child, from one serving of each of these fast food ranged between 0.046 and 1.556 pg/kg in adults whereas in children the values were between 0.15 and 5.05 pg/kg. Total measured PCDD/Fs in the Big Mac, Personal Pan Pizza, KFC, and the Häagen-Daz ice cream varied from 0.58 to 9.31 pg/g. Measured DDE levels in the fast foods ranged from 180 to 3170 pg/g. Total mono-ortho PCB levels ranged up to 500 pg/g or 1.28 TEQ pg/g for the KFC and for di-ortho PCBs up to 740 pg/g or 0.014 TEQ pg/g for the pizza sample. Total PCB values in the four samples ranged up to 1170 pg/g or 1.29 TEQ pg/g for the chicken sample.",
"title": "Dioxins, dibenzofurans, dioxin-like PCBs, and DDE in U.S. fast food, 1995."
},
{
"docid": "MED-1098",
"text": "The first U.S. nationwide food sampling with measurement of dioxins, dibenzofurans, and coplanar, mono-ortho and di-ortho polychlorinated biphenyls (PCBs) is reported in this study. Twelve separate analyses were conducted on 110 food samples divided into pooled lots by category. The samples were purchased in 1995 in supermarkets in Atlanta, GA, Binghamton, NY, Chicago, IL, Louisville, KY, and San Diego, CA. Human milk also was collected to estimate nursing infants' consumption. The food category with highest World Health Organization (WHO) dioxin toxic equivalent (TEQ) concentration was farm-grown freshwater fish fillet with 1.7 pg/g, or parts per trillion (ppt), wet, or whole, weight. The category with the lowest TEQ level was a simulated vegandiet, with 0.09 ppt. TEQ concentrations in ocean fish, beef, chicken, pork, sandwich meat, eggs, cheese, and ice cream, as well as human milk, were in the range O.33 to 0.51 ppt, wet weight. In whole dairy milk TEQ was 0.16 ppt, and in butter 1.1 ppt. Mean daily intake of TEQ for U.S. breast-fed infants during the first year of life was estimated at 42 pg/kg body weight. For children aged 1-11 yr the estimated daily TEQ intake was 6.2 pg/kg body weight. For males and females aged 12-19 yr, the estimated TEQ intake was 3.5 and 2.7 pg/kg body weight, respectively. For adult men and women aged 20-79 yr, estimated mean daily TEQ intakes were 2.4 and 2.2 pg/kg body weight, respectively. Estimated mean daily intake of TEQ declined with age to a low of 1.9 pg/kg body weight at age 80 yr and older. For all ages except 80 yr and over, estimates were higher for males than females. For adults, dioxins, dibenzofurans, and PCBs contributed 42%, 30%, and 28% of dietary TEQ intake, respectively. DDE was also analyzed in the pooled food samples.",
"title": "Intake of dioxins and related compounds from food in the U.S. population."
},
{
"docid": "MED-2397",
"text": "Background Studies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs). Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking. Objectives This study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers. Methods The cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status. Results DDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status. Conclusions This study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.",
"title": "Organochlorine Exposure and Incidence of Diabetes in a Cohort of Great Lakes Sport Fish Consumers"
},
{
"docid": "MED-4180",
"text": "The aim was to determine half-life of six most abundant PCB congeners in the body of early adolescents. In 304 environmentally exposed children, PCB serum concentration was determined at the age of 8 and 12years. Half-life was determined for each child assuming exponential decrease or for the whole cohort using multiple regression. Results obtained by both approaches were in agreement. PCB reuptakes corrupting half-life estimates for each child and each congener were evaluated. If one of the serum PCB concentration values fell below the level of detection (LOD) the pair was excluded and if PCB half-life value exceeded the arbitrary value of 30years. The following median half-lives in years 4.46, 10.59, 9.7, 4.7, 9.1 and 9.8 were obtained for PCB congeners 118, 138(+163), 153, 156(+171), 170 and 180, respectively. The elimination half-life values were not systematically related to PCB serum concentration at any examination age. Between half-life values, percentage of children with significant reuptakes and PCB congener abundance in serum were found significant associations. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Half-lives of serum PCB congener concentrations in environmentally exposed early adolescents."
},
{
"docid": "MED-2496",
"text": "Persistent organic pollutants (POPs) exert harmful effects on cognitive, endocrine and immune functions and bioaccumulate in the environment and human tissues. The aim of this study was to investigate the body burden of several POPs in the adult population (n=246) and their association to diet and other lifestyle factors in a Swedish national survey. Serum concentrations of several polychlorinated biphenyls (PCBs), and the pesticides hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), chlordane compounds and dichlorodiphenyldichloroethylene (DDE) were determined by liquid-liquid extraction, silica column cleanup and gas chromatography high resolution mass spectrometry. Diet was assessed using 4-day food records and complementary dietary and lifestyle factors by questionnaire. Fish intake was additionally assessed by plasma fatty acid composition. Clustering of the compounds revealed that PCBs were separated into two clusters, one including low-chlorinated PCB 28 and 52, and the other high-chlorinated mono- and di-ortho PCBs, suggesting similarities and dissimilarities in exposure sources and possibly also toxicokinetics. Men had 24% and 32% higher levels of PCB 138-180 and chlordane compounds, respectively, compared with women. This may partly be explained by elimination of the POPs among women reporting a history of breastfeeding. The proportion of very long-chain n-3 fatty acids in plasma were positively correlated with the pollutants: r=0.24 (PCB 28), r=0.33 (PCB 118), r=0.35 (PCB 138-180), r=0.29 (HCB), r=0.18 (β-HCH), r=0.34 (chlordane compounds), r=0.34 (p,p'-DDE), p≤0.005. Individuals consuming fatty Baltic fish≥1 time per months had 45% higher serum levels of PCB 118 compared with non-consumers. Levels of PCB 28 were associated with the age of the residential building. To conclude, the population-distributed approach of surveying dietary habits, lifestyle factors and POP body burdens, made it possible to identify personal characteristics associated with the POP body burdens in Sweden. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Fish intake and breastfeeding time are associated with serum concentrations of organochlorines in a Swedish population."
},
{
"docid": "MED-4170",
"text": "Researchers have long debated the adverse effects of exposure to polychlorinated biphenyls (PCBs) on children versus the benefits of breastfeeding. In this article, the authors provide an overview of the known health effects of PCBs in children and examine the level of evidence regarding the risk of postnatal exposure via breastfeeding. The major source of PCBs is environmental, with over 90% of human exposure through the food chain. PCB exposure in infants is predominantly via breast milk, but limited evidence exists of significant toxicity associated with this mode of transmission. Breastfeeding should, therefore, continue to be encouraged on the basis of evidence of the benefits derived from human milk coupled with inconclusive proof that lactational PCB exposure has major detrimental effects on the overall health and development of infants.",
"title": "To breastfeed or not to breastfeed: a review of the impact of lactational exposure to polychlorinated biphenyls (PCBs) on infants."
},
{
"docid": "MED-4936",
"text": "Food and nutrition professionals question whether supplement-sourced nutrients appear to be equivalent to those derived from natural food sources. We compared the nutritional availability of docosahexaenoic acid (DHA) from algal-oil capsules to that from assayed cooked salmon in 32 healthy men and women, ages 20 to 65 years, in a randomized, open-label, parallel-group study. In this 2-week study comparing 600 mg DHA/day from algal-oil capsules to that from assayed portions of cooked salmon, mean change from baseline in plasma phospholipids and erythrocyte DHA levels was analyzed and DHA levels were compared by Student's t tests. In post-hoc analyses to determine bioequivalence, least-squares mean ratios of percent change from baseline in plasma phospholipid and erythrocyte DHA levels were compared. DHA levels increased by approximately 80% in plasma phospholipids and by approximately 25% in erythrocytes in both groups. Changes in DHA levels in plasma phospholipids and erythrocytes were similar between groups. As measured by delivery of DHA to both plasma and erythrocytes, fish and algal-oil capsules were equivalent. Both regimens were generally well-tolerated. These results indicate that algal-oil DHA capsules and cooked salmon appear to be bioequivalent in providing DHA to plasma and red blood cells and, accordingly, that algal-oil DHA capsules represent a safe and convenient source of non-fish-derived DHA.",
"title": "Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid."
},
{
"docid": "MED-4934",
"text": "Concentrations of polybrominated diphenyl ethers (PBDEs), pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons were measured in 136 fish from 14 remote lakes in 8 western US National Parks/Preserves between 2003 and 2005 and compared to human and wildlife contaminant health thresholds. A sensitive (median detection limit −18 pg/g wet weight), efficient (61% recovery at 8 ng/g), reproducible (4.1 %RSD), and accurate (7 % deviation from SRM) analytical method was developed and validated for these analyses. Concentrations of PCBs, hexachlorobenzene, hexachlorocyclohexanes, DDTs and chlordanes in western US fish were comparable to or lower than mountain fish recently collected from Europe, Canada, and Asia. Dieldrin and PBDE concentrations were higher than recent measurements in mountain fish and Pacific Ocean salmon. Concentrations of most contaminants in western US fish were 1–6 orders of magnitude below calculated recreational fishing contaminant health thresholds. However, contaminant concentrations exceeded subsistence fishing cancer screening values in 8 of 14 lakes. Average contaminant concentrations in fish exceeded wildlife contaminant health thresholds for piscivorous mammals in 5 lakes, and piscivorous birds in all 14 lakes. These results indicate that atmospherically deposited organic contaminants can accumulate in high elevation fish, reaching concentrations relevant to human and wildlife health.",
"title": "Atmospherically Deposited PBDEs, Pesticides, PCBs, and PAHs in Western US National Park Fish: Concentrations and Consumption Guidelines"
},
{
"docid": "MED-2917",
"text": "The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted.",
"title": "Nutrients and contaminants in human milk from mothers on macrobiotic and omnivorous diets."
},
{
"docid": "MED-1171",
"text": "A number of chemicals have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. This article aims at evaluating the impact of exposure to several chemicals including: organophosphate, organochlorine pesticides, polychlorinated biphenyls (PCBs), mercury and lead on the neurodevelopment of children by reviewing the most recent published literature, and answer the question whether any progress has been made in the epidemiology of the neurodevelopment of children induced by exposure to those chemicals. The result of the presented studies show that exposure to the above-mentioned chemicals may impair the neurodevelopment of children. Neonates exposed to organophosphate pesticides demonstrated a higher proportion of abnormal reflexes, and young children had more attention problems. Exposure to organochlorine pesticides in children was associated with alertness, quality of alert responsiveness, cost of attention and other potential attention associated measures. The majority of studies indicate the negative impact of lead exposure at the level <10 µg/dl or even <5 µg/dl on the neurodevelopment of children. The results of studies on exposure to PCBs, mercury, and their effect on neurodevelopment are inconsistent. Some suggest that prenatal exposure to PCBs and mercury is related to performance impairments, attention and concentration problems, while other do not present any statistically significant association. The studies were mostly well designed, using prospective cohorts with the exposure assessment based on the biomarker of exposure. Concerning the covariates and confounders affecting the endpoints in most of the presented studies, confounders were included in data analysis. In order to recognize the early cognitive, motor and language outcomes of chemical exposures, well standardized tools were used for evaluating the neurodevelopmental effects and offer an early and fairly comprehensive measure of child development. Because the neurotoxicants may cross the placenta and the fetal brain, exposure consideration regarding the reduction of exposure to those chemicals should be implemented.",
"title": "Chemical exposure early in life and the neurodevelopment of children--an overview of current epidemiological evidence."
},
{
"docid": "MED-4735",
"text": "BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.",
"title": "Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption."
},
{
"docid": "MED-3554",
"text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.",
"title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."
},
{
"docid": "MED-3241",
"text": "The diagnosis of cancer can motivate survivors to alter their lifestyle habits. Healthcare providers need to be aware of what changes patients are likely to make in order to derive more pertinent recommendations; however, few studies have reported pre- and post-diagnostic lifestyle behaviours. Semi-quantitative food frequency questionnaires (FFQs) completed approximately 1 year after diagnosis were used to evaluate dietary intake and supplement use before and after diagnosis in a cohort of 1,560 breast cancer patients participating in the UK, prospective DietCompLyf study. Intake of fruit and vegetables, wholegrains and lean sources of protein increased significantly post-diagnosis (P < 0.05, each). Conversely, after diagnosis consumption of high-fat, high-sugar products, red meat, coffee, some alcoholic drinks and refined grains significantly decreased (P < 0.05, each). Post-diagnostic changes in diet were accompanied by changes in the intake of macronutrients and a number of vitamins and minerals. Supplement use was highly prevalent (56.1%) pre-diagnosis, increasing to 62.8% after diagnosis (P = 0.001). Fish oils, multivitamin and minerals, and evening primrose oil were most often used and the proportion of users significantly increased (P < 0.05, each) after diagnosis. The percentage of women using oestrogenic botanical supplements (OBSs) was small but more than doubled to 8.4% after diagnosis (P < 0.05). British women participating in the DietCompLyf study reported significant changes in dietary intake and supplement use after their breast cancer diagnosis. These findings contribute to our understanding of female cancer survivors' dietary behaviours which is crucial for developing and implementing recommendations.",
"title": "Significant changes in dietary intake and supplement use after breast cancer diagnosis in a UK multicentre study."
},
{
"docid": "MED-2913",
"text": "The elimination kinetics of polychlorinated biphenyls (PCBs) in humans is difficult to assess in observational studies, because PCB exposure is never completely abolished. In a community with high dietary PCB exposures from whale blubber, we examined two groups of children with increased body burdens from breast-feeding. Follow-up was from ages 4.5 years to 7.5 years (99 subjects) and 7 to 14 years (101 subjects). The calculations were performed by the use of structural equation models, with adjustment for body weight and dietary blubber intake as the main source of postnatal exposure. As a likely result of background exposures, apparent elimination half-lives were unexpectedly long when based on results from all cohort members. Subjects with exposures above the median and in the highest quartile showed half-lives of about 3-4 years for CB-138, and 4.5-5.5 years for CB-105 and CB-118; 6.5-7.5 years for CB-156, CB-170, and CB-187; and 7-9 years for CB-153 and CB-180. The longest half-lives correspond to elimination of the parent PCB solely with a daily fat excretion rate of 1-2 g, while shorter half-lives assume metabolic break-down.",
"title": "Elimination Half-lives of Polychlorinated Biphenyl Congeners in Children"
},
{
"docid": "MED-5095",
"text": "Docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for eye and brain development and ongoing visual, cognitive, and cardiovascular health. Unlike fish-sourced oils, the bioavailability of DHA from vegetarian-sourced (algal) oils has not been formally assessed. We assessed bioequivalence of DHA oils in capsules from two different algal strains versus bioavailability from an algal-DHA-fortified food. Our 28-day randomized, placebo-controlled, parallel group study compared bioavailability of (a) two different algal DHA oils in capsules (\"DHASCO-T\" and \"DHASCO-S\") at doses of 200, 600, and 1,000 mg DHA per day (n = 12 per group) and of (b) an algal-DHA-fortified food (n = 12). Bioequivalence was based on changes in plasma phospholipid and erythrocyte DHA levels. Effects on arachidonic acid (ARA), docosapentaenoic acid-n-6 (DPAn-6), and eicosapentaenoic acid (EPA) were also determined. Both DHASCO-T and DHASCO-S capsules produced equivalent DHA levels in plasma phospholipids and erythrocytes. DHA response was dose-dependent and linear over the dose range, plasma phospholipid DHA increased by 1.17, 2.28 and 3.03 g per 100 g fatty acid at 200, 600, and 1,000 mg dose, respectively. Snack bars fortified with DHASCO-S oil also delivered equivalent amounts of DHA on a DHA dose basis. Adverse event monitoring revealed an excellent safety and tolerability profile. Two different algal oil capsule supplements and an algal oil-fortified food represent bioequivalent and safe sources of DHA.",
"title": "Bioequivalence of Docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food."
},
{
"docid": "MED-4951",
"text": "OBJECTIVE: To evaluate the role of the environmental estrogens polychlorinated biphenyls (PCBs) and phthalate esters (PEs) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology. DESIGN: Randomized controlled study. SETTING: Tertiary care referral infertility clinic and academic research center. PATIENT(S): Twenty-one infertile men with sperm counts <20 million/mL and/or rapid progressive motility <25% and/or <30% normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception. Semen and blood samples were obtained as part of the treatment protocol. MAIN OUTCOME MEASURE(S): Evaluation of semen parameters such as ejaculate volume, sperm count, motility, morphology, vitality, osmoregulatory capacity, sperm chromatin stability, and sperm nuclear DNA integrity. RESULT(S): PCBs were detected in the seminal plasma of infertile men but not in controls, and the concentration of PEs was significantly higher in infertile men compared with controls. Ejaculate volume, sperm count, progressive motility, normal morphology, and fertilizing capacity were significantly lower in infertile men compared with controls. The highest average PCB and PE concentrations were found in urban fish eaters, followed by rural fish eaters, urban vegetarians, and rural vegetarians. The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls. CONCLUSION(S): PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology.",
"title": "Role of environmental estrogens in the deterioration of male factor fertility."
},
{
"docid": "MED-2497",
"text": "The birth cohort BraMat (n = 205; a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health) was established to study whether prenatal exposure to toxicants from the maternal diet affects immunological health outcomes in children. We here report on the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide generated in food during heat treatment. The frequency of common infections, eczema or itchiness, and periods of more than 10 days of dry cough, chest tightness or wheeze (called wheeze) in the children during the first year of life was assessed by questionnaire data (n = 195). Prenatal dietary exposure to the toxicants was estimated using a validated food frequency questionnaire from MoBa. Prenatal exposure to PCBs and dioxins was found to be associated with increased risk of wheeze and exanthema subitum, and also with increased frequency of upper respiratory tract infections. We found no associations between prenatal exposure to acrylamide and the health outcomes investigated. Our results suggest that prenatal dietary exposure to dioxins and PCBs may increase the risk of wheeze and infectious diseases during the first year of life. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants."
},
{
"docid": "MED-4937",
"text": "In the late 1960s the first scientific studies on contamination in Antarctica demonstrated the presence of pollutants in Antarctic ecosystems. Many Persistent Organic Pollutants (POPs) are transported globally from the areas in which they are produced and released into the environment in remote areas, including Antarctica. Here we report results obtained concerning the accumulation of polybrominated diphenyl ethers (PBDEs), mono- and non-ortho-polychlorobiphenyls (PCBs), polychlorodibenzodioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in the tissues of two species of Antarctic fish (Chionodraco hamatus and Trematomus bernacchii). The 2,3,7,8-TCDD toxic equivalents (TEQs) were also calculated to evaluate the potential risk of these compounds for the two species. In general, POP levels were higher in the tissues of T. bernacchii than in C. hamatus and the highest concentrations were found in the liver of both species. The PBDE levels varied from 160.5 pg g(-1) wet wt in C. hamatus muscle to 789.9 pg g(-1) wet wt in T. bernacchii liver and were lower than the levels of PCBs. PCBs were the main organochlorine compounds detected and their concentrations ranged from 0.3 ng g(-1) wet wt in C. hamatus muscle to 15.1 ng g(-1) wet wt in T. bernacchii liver. TEQ concentrations resulted higher in C. hamatus than in T. bernacchii and were due mainly to PCDDs. The presence of PBDEs and organochlorine pollutants in the tissues of Antarctic organisms confirms their global transport and distribution.",
"title": "Levels of polybrominated diphenyl ethers (PBDEs) and organochlorine pollutants in two species of Antarctic fish (Chionodraco hamatus and Trematomus..."
},
{
"docid": "MED-2495",
"text": "We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood. Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n=162, 2-3years; n=180), and blood parameters were examined at three years of age (n=114). The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa. Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections. Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine. No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles. Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist int..."
},
{
"docid": "MED-927",
"text": "OBJECTIVE: To assess the effects of krill oil on blood lipids, specifically total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). METHODS: A multi-center, three-month, prospective, randomized study followed by a three-month, controlled follow-up of patients treated with 1 g and 1.5 g krill oil daily. Patients with hyperlipidemia able to maintain a healthy diet and with blood cholesterol levels between 194 and 348 mg per dL were eligible for enrollment in the trial. A sample size of 120 patients (30 patients per group) was randomly assigned to one of four groups. Group A received krill oil at a body mass index (BMI)-dependent daily dosage of 2-3 g daily. Patients in Group B were given 1-1.5 g krill oil daily, and Group C was given fish oil containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) per gram of oil at a dose of 3 g daily. Group D was given a placebo containing microcrystalline cellulose. The krill oil used in this study was Neptune Krill Oil, provided by Neptune Technologies and Bioresources, Laval, Quebec, Canada. OUTCOME MEASURES: Primary parameters tested (baseline and 90-day visit) were total blood cholesterol, triglycerides, LDL, HDL, and glucose. RESULTS: Krill oil 1-3 g per day (BMI-dependent) was found to be effective for the reduction of glucose, total cholesterol, triglycerides, LDL, and HDL, compared to both fish oil and placebo. CONCLUSIONS: The results of the present study demonstrate within high levels of confidence that krill oil is effective for the management of hyperlipidemia by significantly reducing total cholesterol, LDL, and triglycerides, and increasing HDL levels. At lower and equal doses, krill oil was significantly more effective than fish oil for the reduction of glucose, triglycerides, and LDL levels.",
"title": "Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia."
}
] |
PLAIN-1976
|
rabies
|
[
{
"docid": "MED-2112",
"text": "Medical students in the United States are taught little about nutrition and dietetics. Worse yet, their training biases them against the studies that show the power of dietary approaches to managing disease. The current approach to evidence-based medicine encourages physicians to ignore any information that does not come from a double-blind, randomized controlled trial. Yet human beings cannot be blinded to a dietary intervention. As a result, physicians are biased toward drug treatments and against dietary interventions for the management of chronic disease. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "How evidence-based medicine biases physicians against nutrition."
},
{
"docid": "MED-4255",
"text": "The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations. (c)2001 CHF, Inc.",
"title": "Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition."
},
{
"docid": "MED-2111",
"text": "Coronary artery disease is essentially nonexistent in cultures whose nutrition assures cholesterol levels <150 mg/dl. Patients with advanced coronary artery disease may abolish disease progression through a plant-based diet and cholesterol-lowering medication to achieve and maintain a total cholesterol <150 mg/dl.",
"title": "Updating a 12-year experience with arrest and reversal therapy for coronary heart disease (an overdue requiem for palliative cardiology)."
},
{
"docid": "MED-2109",
"text": "Thirty-nine newborn infants with severe persistent pulmonary hypertension and respiratory failure who met criteria for 85% likelihood of dying were enrolled in a randomized trial in which extracorporeal membrane oxygenation (ECMO) therapy was compared with conventional medical therapy (CMT). In phase I, 4 of 10 babies in the CMT group died and 9 of 9 babies in the ECMO group survived. Randomization was halted after the fourth CMT death, as planned before initiating the study, and the next 20 babies were treated with ECMO (phase II). Of the 20, 19 survived. All three treatment groups (CMT and ECMO in phase I and ECMO, phase II) were comparable in severity of illness and mechanical ventilator support. The overall survival of ECMO-treated infants was 97% (28 of 29) compared with 60% (6 of 10) in the CMT group (P less than .05).",
"title": "Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospecti..."
},
{
"docid": "MED-3984",
"text": "In recent years, the number of human rabies cases in the People’s Republic of China has increased during severe epidemics in 3 southern provinces (Guizhou, Guangxi, and Hunan). To analyze the causes of the high incidence of human rabies in this region, during 2005–2007, we collected 2,887 brain specimens from apparently healthy domestic dogs used for meat consumption in restaurants, 4 specimens from suspected rabid dogs, and 3 from humans with rabies in the 3 provinces. Partial nucleoprotein gene sequences were obtained from rabies-positive specimens. Phylogenetic relationships and distribution of viruses were determined. We infer that the spread of rabies viruses from high-incidence regions, particularly by long-distance movement or transprovincial translocation of dogs caused by human-related activities, may be 1 cause of the recent massive human rabies epidemics in southern China.",
"title": "Molecular Epidemiology of Rabies in Southern People’s Republic of China"
},
{
"docid": "MED-3983",
"text": "This study was aimed at determining the molecular epidemiology of rabies virus (RABV) circulating in Vietnam. Intra vitam samples (saliva and cerebrospinal fluid) were collected from 31 patients who were believed to have rabies and were admitted to hospitals in northern provinces of Vietnam. Brain samples were collected from 176 sick or furious rabid dogs from all over the country. The human and canine samples were subjected to reverse transcription-polymerase chain reaction analysis. The findings showed that 23 patients tested positive for RABV. Interestingly, 5 rabies patients did not have any history of dog or cat bites, but they had an experience of butchering dogs or cats, or consuming their meat. RABV was also detected in 2 of the 100 sick dogs from slaughterhouses. Molecular epidemiological analysis of 27 RABV strains showed that these viruses could be classified into two groups. The RABVs classified into Group 1 were distributed throughout Vietnam and had sequence similarity with the strains from China, Thailand, Malaysia, and the Philippines. However, the RABVs classified into Group 2 were only found in the northern provinces of Vietnam and showed high sequence similarity with the strain from southern China. This finding suggested the recent influx of Group 2 RABVs between Vietnam and China across the border. Although the incidence of rabies due to circulating RABVs in slaughterhouses is less common than that due to dog bite, the national program for rabies control and prevention in Vietnam should include monitoring of the health of dogs meant for human consumption and vaccination for workers at dog slaughterhouses. Further, monitoring of and research on the circulating RABVs in dog markets may help to determine the cause of rabies and control the spread of rabies in slaughterhouses in Vietnam.",
"title": "Molecular epidemiology of rabies virus in Vietnam (2006-2009)."
},
{
"docid": "MED-2110",
"text": "Almost all types of newborn respiratory failure are reversible. However, supportive treatment (oxygen and positive airway pressure) can damage the lung, and newborn respiratory failure remains a major cause of morbidity and death in infants. Prolonged extracorporeal membrane oxygenation (ECMO) provides life support while allowing the lung to \"rest.\" We have used ECMO in 45 moribund newborn infants; 25 survived. Neonatologists referred patients who were unresponsive to maximal therapy. The right atrium and aortic arch were cannulated via the jugular vein and carotid artery. Heparin was infused continuously to main activated clotting time at 200 to 300 seconds. Airway oxygenation and pressure were reduced to low levels. Primary diagnoses were hyaline membrane disease, 14 (6 survived, 8 died); meconium aspiration, 22 (15 survived, 7 died); persistent fetal circulation including diaphragmatic hernia, 5 (3 survived, 2 died); and sepsis, 4 (1 survived, 3 died). Growth, development, and brain and lung function are normal in 20 of 25 survivors. ECMO decreased newborn respiratory failure mortality and morbidity rates in this phase I trial. A controlled randomized study is underway. The results suggest that ECMO may be effective in older patients if used before irreversible lung damage occurs.",
"title": "Extracorporeal membrane oxygenation for newborn respiratory failure: forty-five cases."
},
{
"docid": "MED-3982",
"text": "OBJECTIVE: To test the claim that pet ownership reduces cardiovascular risk. DESIGN: Community survey. PARTICIPANTS: 2528 adults aged 40-44 years and 2551 aged 60-64 years who lived in the Australian Capital Territory and Queanbeyan, New South Wales, and were drawn randomly from the Australian electoral roll in 2000 and 2001. MAIN OUTCOME MEASURES: Sociodemographic measures, including pet ownership, and measures of physical health (including body mass index [BMI], alcohol and cigarette consumption, and levels of physical activity). Two readings of diastolic and systolic blood pressure were also taken. RESULTS: While pet owners and non-pet owners had similar levels of systolic blood pressure, those with pets had significantly higher diastolic blood pressure. Pet owners also had higher BMI and were more likely to smoke. While those with pets undertook more mild physical activity, they continued to have significantly higher diastolic blood pressure after controlling for hypertensive risk factors. CONCLUSIONS: In this study, we found no evidence that pet ownership per se is associated with cardiovascular health benefits. Rather, pet owners had higher diastolic blood pressure than those without pets. It is likely that this increased health risk is linked to other hypertensive risk factors that are only indirectly associated with pet ownership.",
"title": "Pet ownership and risk factors for cardiovascular disease: another look."
}
] |
[
{
"docid": "MED-3601",
"text": "Experimentation involving children is not a new phenomenon. Children have been used as research subjects in a diverse set of experiments, including the trials of new vaccines and sera, in efforts to understand normal pediatric anatomy and physiology and in the development of new drugs and procedures. Concern about child participants in research is also not a new development. For more than a century, critics of medical research have called attention to the fact that children and other vulnerable populations--pregnant women, prisoners, the mentally ill--have too often served as the unwitting and unwilling subjects of medical experiments. This paper looks at several early cases in which children participated, including the first trial of cowpox vaccine, the first human trial of rabies vaccine, and the first treatment of Listerian wound antisepsis. The history of concern for children, especially institutionalized children, in medical research is considered along with the development of regulations or guidelines, including the Declaration of Helsinki (1964).",
"title": "Children as guinea pigs: historical perspective."
},
{
"docid": "MED-2453",
"text": "BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross- sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = - 0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.",
"title": "Effect of fresh fruit consumption on lung function and wheeze in children"
},
{
"docid": "MED-1682",
"text": "Background The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products. Methods We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair. Results Plasma vitamin C increased after supplementation as did resistance towards H2O2-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation. Conclusion Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.",
"title": "Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection"
},
{
"docid": "MED-1431",
"text": "Objective: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. Methods: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of >1.0 SD on each test) was analyzed with logistic regression. Results: Older adults with high pentosidine level had worse baseline DSST score (p=0.05) but not different 3MS score (p=0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall <0.001; DSST 5.9, 7.4, and 4.5 point decline, p=0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio=1.55; 95% confidence interval 1.07–2.26; DSST: 31% vs 22%, odds ratio=1.62; 95% confidence interval 1.13–2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. Conclusion: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes.",
"title": "Advanced glycation end product level, diabetes, and accelerated cognitive aging"
},
{
"docid": "MED-3866",
"text": "Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.",
"title": "Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design"
},
{
"docid": "MED-4322",
"text": "The marked age-related decline in serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) has suggested that a deficiency of these steroids may be causally related to the development of a series of diseases that are generally associated with aging. Postulated consequences of low DHEA levels include insulin resistance, obesity, cardiovascular disease, cancer, reduction of the immune defence system as well as psychosocial problems such as depression and a general deterioration in the sensation of well-being and cognitive function. Clinically, the spectrum of women that would benefit from DHEA therapy is not clearly defined and nor is the dosage of hormone treatment. Whether DHEA therapy could be prescribed as a general anti-aging therapy or could be an alternative treatment for women suffering from androgen deficiency syndrome remains uncertain across studies. The lack of definitive evidence for biological mechanisms and the presence of only a few studies that address these emerging issues of DHEA therapy in postmenopausal women might encourage a new critical analysis of the available literature, evidencing current limits and incongruities.",
"title": "DHEA therapy in postmenopausal women: the need to move forward beyond the lack of evidence."
},
{
"docid": "MED-4116",
"text": "The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.",
"title": "The flip side of immune surveillance: immune dependency."
},
{
"docid": "MED-3535",
"text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.",
"title": "Cherries and health: a review."
},
{
"docid": "MED-4315",
"text": "In a group of patients dying suddenly from ischemic heart disease, the uninfarcted heart muscle contained significantly lower concentrations of magnesium, iron, and potassium and a significantly higher concentration of calcium than the heart muscle from a group of normal controls and a group of patients dying more than three months after a coronary thrombosis. The late death group had significantly lower concentrations of manganese and copper than the normal group, and a slight decrease in magnesium concentration which was probably significant. There was no significant difference in the sodium concentration between the three groups. The results are discussed in relation to the increased death rate from ischemic heart disease in areas with soft drinking water, and possible dietary deficiencies in mineral salts.",
"title": "Differences in metal content of the heart muscle in death from ischemic heart disease."
},
{
"docid": "MED-1592",
"text": "The presence of natural estrogen hormones as trace concentrations in the environment has been reported by many researchers and is of growing concern due to its possible adverse effects on the ecosystem. In this study, municipal biosolids, poultry manure (PM) and cow manure (CM), and spent mushroom compost (SMC) were analyzed for the presence of seven estrogen hormones. 17α-estradiol, 17β-estradiol, 17α-dihydroequilin, and estrone were detected in the sampled biosolids and manures at concentrations ranging from 6 to 462 ng/g of dry solids. 17α-estradiol, 17β-estradiol, and estrone were also detected in SMC at concentrations ranging from 4 to 28 ng/g of dry solids. Desorption experiments were simulated in the laboratory using deionized water (milli-Q), and the aqueous phase was examined for the presence of estrogen hormones to determine their desorption potential. Very low desorption of 0.4% and 0.2% estrogen hormones was observed from municipal biosolids and SMC, respectively. An estimate of total estrogen contribution from different solid waste sources is reported. Animal manures (PM and CM) contribute to a significant load of estrogen hormones in the natural environment.",
"title": "Occurrence of estrogen hormones in biosolids, animal manure and mushroom compost."
},
{
"docid": "MED-2296",
"text": "This study aimed to investigate health belief as a major motive for diet and lifestyle behaviors of 100 vegans in the United States; and to determine congruence with selected health and nutrition outcomes. Response data from an administered questionnaire was analyzed. Statistical analyses determined the most common factors influencing diet choice; the number of vegans practicing particular lifestyle behaviors; body mass index; and prevalence of self-reported chronic disease diagnoses. Nutrient intakes were analyzed and assessed against Dietary Reference Intakes. Health was the most reported reason for diet choice (47%). In the health belief, animal welfare, and religious/other motive categories, low percentages of chronic disease diagnoses were reported: 27%, 11%, and 15%, respectively. There were no significant differences in health behaviors and indices among vegan motive categories, except for product fat content choices. Within the entire study population, health-related vegan motive coincided with regular exercise; 71% normal BMI (mean=22.6); minimal alcohol and smoking practices; frequently consumed vegetables, nuts, and grains; healthy choices in meal types, cooking methods, and low-fat product consumption; and adequate intakes for most protective nutrients when compared to reference values. But incongruence was found with 0% intake adequacy for vitamin D; and observation of excessive sodium use. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Vegan lifestyle behaviors: an exploration of congruence with health-related beliefs and assessed health indices."
},
{
"docid": "MED-3641",
"text": "Cranberry juice is known to inhibit bacterial adhesion. We examined the inhibitory effect of cranberry juice on the adhesion of oral streptococci strains labeled with [3H]-thymidine to saliva-coated hydroxyapatite beads (s-HA). When the bacterial cells were momentarily exposed to cranberry juice, their adherence to s-HA decreased significantly compared with the control (P < 0.01). Their hydrophobicity also decreased dependently with the concentration of cranberry juice. We also evaluated the inhibitory effect of cranberry juice on biofilm formation. By using a microplate system, we found that the high molecular mass constituents of cranberry juice inhibited the biofilm formation of the tested streptococci. The inhibitory activity was related to the reduction of the hydrophobicity. The present findings suggest that cranberry juice component(s) can inhibit colonization by oral streptococci to the tooth surface and can thus slow development of dental plaque. Copyright Blackwell Munksgaard, 2004.",
"title": "Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation."
},
{
"docid": "MED-3974",
"text": "BACKGROUND: Viral respiratory tract infection (VRTI) is the most common illness in humans. Despite the high incidence, the economic impact of non-influenza-related VRTI has not been rigorously explored. Our objectives were to obtain an updated incidence of non-influenza-related VRTI in the United States and to quantify the health care resource use (direct costs) and productivity losses (indirect costs) associated with these infections. METHODS: A nationwide telephone survey of US households (N = 4051) was conducted between November 3, 2000, and February 12, 2001 to obtain a representative estimate of the self-reported incidence of non-influenza-related VRTI and related treatment patterns. Direct treatment costs measured included outpatient clinician encounters, use of over-the-counter and prescription drugs, and associated infectious complications of non-influenza-related VRTI. Absenteeism estimates for infected individuals and parents of infected children were extrapolated from National Health Interview Survey data. RESULTS: Of survey respondents, 72% reported a non-influenza-related VRTI within the past year. Respondents who experienced a self-reported non-influenza-related VRTI averaged 2.5 episodes annually. When these rates are extrapolated to the entire US population, approximately 500 million non-influenza-related VRTI episodes occur per year. Similarly, if the treatment patterns reported by the respondents are extended to the population, the total economic impact of non-influenza-related VRTI approaches $40 billion annually (direct costs, $17 billion per year; and indirect costs, $22.5 billion per year). CONCLUSIONS: Largely because of the high attack rate, non-influenza-related VRTI imposes a greater economic burden than many other clinical conditions. The pending availability of effective antiviral therapies warrants increased attention be paid to this common and expensive illness.",
"title": "The economic burden of non-influenza-related viral respiratory tract infection in the United States."
},
{
"docid": "MED-4089",
"text": "Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.",
"title": "Antiproliferative effects of apple peel extract against cancer cells."
},
{
"docid": "MED-2326",
"text": "The radioactivity from 3H-methyl methionine was rapidly incorporated into the surface lipids of Mycobacterium avium. The transmethylation reaction was efficiently inhibited by DL-ethionine, D-norleucine and DL-norleucine. The structure of the outerlayer of the M. avium envelope was profoundly altered in the bacteria treated with DL-norleucine.",
"title": "Methionine as methyl-group donor in the synthesis of Mycobacterium avium envelope lipids, and its inhibition by DL-ethionine, D-norleucine and DL-n..."
},
{
"docid": "MED-2141",
"text": "We investigated the association between dietary patterns and insulin resistance in the 3871 healthy Korean adults from the 2007 to 2008 Korea National Health and Nutrition Examination Survey. The whole grains and beans pattern was associated with lower prevalence of insulin resistance (OR for highest quintile=0.80, 95% CI=0.61-1.03, P for trend=0.013). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.",
"title": "High intake of whole grains and beans pattern is inversely associated with insulin resistance in healthy Korean adult population."
},
{
"docid": "MED-993",
"text": "The main objective of this study was to assess the association between dietary fiber intake and the folate status of Canadian female adolescents. We also assessed dietary folate intakes and evaluated the prevalence of biochemical folate deficiency in these subjects. Female adolescents aged 14-19 y (n = 224) were recruited and fasting blood samples were collected. Dietary intakes (3-d food record) were recorded and participants were classified as lactoovovegetarians, semivegetarians, or omnivores on the basis of food-consumption patterns assessed with food-frequency questionnaires. Fourteen percent, 17%, and 26% of lactoovovegetarians, semivegetarians, and omnivores, respectively, had dietary folate intakes below their predicted requirements; 1%, 4%, and 23%, respectively, had serum folate concentrations indicative of deficiency. Despite low dietary folate intakes and serum folate concentrations, few subjects had homocysteine concentrations indicative of deficiency, suggesting that the degree of folate depletion had not yet produced functional consequences. Most important, results suggest that the consumption of nonstarch polysaccharide is significantly associated with serum folate concentrations (P < 0.001). For each 1-g increase in nonstarch polysaccharide intake, a 1.8% increase in serum folate concentration is expected. In summary, we propose that an increase in nonstarch polysaccharide intake may promote the intestinal biosynthesis of folate, providing a complementary strategy to enhance the folate nutriture of humans.",
"title": "Association between dietary fiber intake and the folate status of a group of female adolescents."
},
{
"docid": "MED-759",
"text": "Smoking has been positively and fruit and vegetable intake has been negatively associated with cervical cancer, the second most common cancer among women worldwide. However, a lower consumption of fruits and reduced serum carotenoids have been observed among smokers. It is not known whether the smoking effect on the risk of cervical neoplasia is modified by a low intake of fruits and vegetables. The present study examined the combined effects of tobacco smoking and diet using a validated FFQ and serum carotenoid and tocopherol levels on cervical intraepithelial neoplasia grade 3 (CIN3) risk in a hospital-based case-control study conducted in São Paulo, Brazil, between 2003 and 2005. The sample comprised 231 incident, histologically confirmed cases of CIN3 and 453 controls. A low intake ( ≤ 39 g) of dark-green and deep-yellow vegetables and fruits without tobacco smoking had a lesser effect on CIN3 (OR 1·14; 95 % CI 0·49, 2·65) than among smokers with higher intake ( ≥ 40 g; OR 1·83; 95 % CI 0·73, 4·62) after adjusting for confounders. The OR for the joint exposure of tobacco smoking and low intake of vegetables and fruits was greater (3·86; 95 % CI 1·74, 8·57; P for trend < 0·001) compared with non-smokers with higher intake after adjusting for confounding variables and human papillomavirus status. Similar results were observed for total fruit, serum total carotene (including β-, α- and γ-carotene) and tocopherols. These findings suggest that the effect of nutritional factors on CIN3 is modified by smoking.",
"title": "Associations of dietary dark-green and deep-yellow vegetables and fruits with cervical intraepithelial neoplasia: modification by smoking."
},
{
"docid": "MED-2985",
"text": "Several risk factors seem to play a role in the development of osteoporosis. Phytate is a naturally occurring compound that is ingested in significant amounts by those with diets rich in whole grains. The aim of this study was to evaluate phytate consumption as a risk factor in osteoporosis. In a first group of 1,473 volunteer subjects, bone mineral density was determined by means of dual radiological absorptiometry in the calcaneus. In a second group of 433 subjects (used for validation of results obtained for the first group), bone mineral density was determined in the lumbar column and the neck of the femur. Subjects were individually interviewed about selected osteoporosis risk factors. Dietary information related to phytate consumption was acquired by questionnaires conducted on two different occasions, the second between 2 and 3 months after performing the first one. One-way analysis of variance or Student's t test was used to determine statistical differences between groups. Bone mineral density increased with increasing phytate consumption. Multivariate linear regression analysis indicated that body weight and low phytate consumption were the risk factors with greatest influence on bone mineral density. Phytate consumption had a protective effect against osteoporosis, suggesting that low phytate consumption should be considered an osteoporosis risk factor.",
"title": "Phytate (myo-inositol hexaphosphate) and risk factors for osteoporosis."
},
{
"docid": "MED-3580",
"text": "The effects of the glycemic index (GI) of carbohydrate eaten the previous night on the glycemic response to a standard test meal eaten subsequently in the morning (breakfast) was studied. On separate evenings normal subjects ate low- or high-GI test meals of the same nutrient composition. The dinners consisted of single foods in two experiments and mixed meals containing several foods in the third. The differences between the observed glycemic responses to low- and high-GI dinners were predicted by their GIs. The glycemic responses to breakfast were significantly lower on mornings after low-GI dinners than after high-GI dinners. Eating, at dinner, foods with different fiber contents but the same GI had no effect on postbreakfast glycemia. We conclude that the GI predicts the difference between glycemic responses of mixed dinner meals; breakfast carbohydrate tolerance is improved when low-GI foods are eaten the previous evening.",
"title": "Second-meal effect: low-glycemic-index foods eaten at dinner improve subsequent breakfast glycemic response."
},
{
"docid": "MED-4751",
"text": "The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that \"man has been drinking cows' milk for around 2000 years without apparent harm.\" However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.",
"title": "The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers."
},
{
"docid": "MED-1457",
"text": "Obesity and type 2 diabetes have been associated with a high-fat diet (HFD) and reduced mitochondrial mass and function. We hypothesized a HFD may affect expression of genes involved in mitochondrial function and biogenesis. To test this hypothesis, we fed 10 insulin-sensitive males an isoenergetic HFD for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarray analysis revealed 297 genes were differentially regulated by the HFD (Bonferonni adjusted P < 0.001). Six genes involved in oxidative phosphorylation (OXPHOS) decreased. Four were members of mitochondrial complex I: NDUFB3, NDUFB5, NDUFS1, and NDUFV1; one was SDHB in complex II and a mitochondrial carrier protein SLC25A12. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1) alpha and PGC1beta mRNA were decreased by -20%, P < 0.01, and -25%, P < 0.01, respectively. In a separate experiment, we fed C57Bl/6J mice a HFD for 3 weeks and found that the same OXPHOS and PGC1 mRNAs were downregulated by approximately 90%, cytochrome C and PGC1alpha protein by approximately 40%. Combined, these results suggest a mechanism whereby HFD downregulates genes necessary for OXPHOS and mitochondrial biogenesis. These changes mimic those observed in diabetes and insulin resistance and, if sustained, may result in mitochondrial dysfunction in the prediabetic/insulin-resistant state.",
"title": "A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle."
},
{
"docid": "MED-4767",
"text": "We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.",
"title": "Association of adenovirus infection with human obesity."
},
{
"docid": "MED-4972",
"text": "Heterocyclic amines (HCAs), compounds formed when meat is cooked at high temperatures particularly through pan frying, grilling, or barbequing, pose a potential carcinogenic risk to the public. It is unclear whether there is any level at which consumption of HCAs can be considered safe. Efforts to measure these compounds mainly include cooking studies under laboratory conditions and some measurement of home-cooked foods, but analysis of commercially cooked foods has been minimal. Attempts to estimate exposure of the public to these compounds must take into consideration dining outside the home, which could result in significant exposure for some individuals. We surveyed at least 9 locations each of 7 popular chain restaurants (McDonald's, Burger King, Chick-fil-A, Chili's, TGI Friday's, Outback Steakhouse, and Applebee's) in California, collecting one or two entrees from each location. Entrees were analyzed for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using high-performance liquid chromatography tandem mass spectrometry. All 100 samples contained PhIP. Concentrations were variable within and between entrees and ranged from 0.08 to 43.2 ng/g. When factoring in the weight of the entrees, absolute levels of PhIP reached over 1,000 ng for some entrees. Potential strategies for reducing exposure include the avoidance of meats cooked using methods that are known to form PhIP.",
"title": "Detection of PhIP in grilled chicken entrées at popular chain restaurants throughout California."
},
{
"docid": "MED-4570",
"text": "BACKGROUND: Studies indicate that intake of vitamin D in the range from 1,100 to 4,000 IU/d and a serum 25-hydroxyvitamin D concentration [25(OH)D] from 60-80 ng/ml may be needed to reduce cancer risk. Few community-based studies allow estimation of the dose-response relationship between oral intake of vitamin D and corresponding serum 25(OH)D in the range above 1,000 IU/d. MATERIALS AND METHODS: A descriptive study of serum 25(OH)D concentration and self-reported vitamin D intake in a community-based cohort (n = 3,667, mean age 51.3 ± 13.4 y). RESULTS: Serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion, with no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml). Unsupplemented all-source input was estimated at 3,300 IU/d. The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d. CONCLUSION: Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.",
"title": "Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention."
},
{
"docid": "MED-2386",
"text": "OBJECTIVE Emerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively determine associations of mercury exposure, as assessed by biomarker measurement, with incident diabetes. RESEARCH DESIGN AND METHODS We used neutron activation analysis to measure toenail mercury, an objective biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline in two separate U.S. prospective cohorts. Incident diabetes was identified from biennial questionnaires and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Associations of mercury exposure with incident diabetes were assessed using Cox proportional hazards. RESULTS During mean ± SD follow-up of 19.7 ± 7.0 years, 1,010 new cases of diabetes were diagnosed. The 95th percentile of toenail mercury was 1.32 μg/g in men and 0.76 μg/g in women, corresponding to exposures ∼3.5-fold and 2-fold higher than the U.S. Environmental Protection Agency reference dose. In multivariable analyses, toenail mercury concentrations were not associated with higher incidence of diabetes in women, men, or both cohorts combined. Comparing the highest to lowest quintile of exposure, the hazard ratio (95% CI) for incident diabetes was 0.86 (0.66–1.11) in women, 0.69 (0.42–1.15) in men, and 0.77 (0.61–0.98) in the combined cohorts. Findings were similar when more extreme categories (deciles) of mercury were compared, and in analyses stratified by fish or omega-3 consumption, BMI, and age. CONCLUSIONS These findings from two separate large prospective cohorts do not support adverse effects of methylmercury on development of diabetes in men or women at usual levels of exposure seen in these populations.",
"title": "Methylmercury Exposure and Incident Diabetes in U.S. Men and Women in Two Prospective Cohorts"
},
{
"docid": "MED-4617",
"text": "The need for consistent and current data describing the true incidence of SCA and/or SCD was highlighted during the most recent Sudden Cardiac Arrest Thought Leadership Alliance’s (SCATLA) Think Tank meeting of national experts with broad representation of key stakeholders including thought leaders and representatives from the American College of Cardiology, American Heart Association, and the Heart Rhythm Society. As such, to evaluate the true magnitude of this public health problem, we performed a systematic literature search in MEDLINE using the MeSH headings, “death, sudden” OR the terms “sudden cardiac death” OR “sudden cardiac arrest” OR “cardiac arrest” OR “cardiac death” OR “sudden death” OR “arrhythmic death.” Study selection criteria included peer-reviewed publications of primary data used to estimate SCD incidence in the U.S. We used Web of Science®’s Cited Reference Search to evaluate the impact of each primary estimate on the medical literature by determining the number of times each “primary source” has been cited. The estimated U.S. annual incidence of SCD varied widely from 180,000 to > 450,000 among 6 included studies. These different estimates were in part due to different data sources (with data age ranging from 1980 to 2007), definitions of SCD, case ascertainment criteria, methods of estimation/extrapolation, and sources of case ascertainment. The true incidence of SCA and/or SCD in the U.S. remains unclear with a wide range in the available estimates, which are badly dated. As reliable estimates of SCD incidence are important for improving risk stratification and prevention, future efforts are clearly needed to establish uniform definitions of SCA and SCD and then to prospectively and precisely capture cases of SCA and SCD in the overall U.S. population.",
"title": "Systematic Review of the Incidence of Sudden Cardiac Death in the United States"
},
{
"docid": "MED-1750",
"text": "The discovery of myostatin and our introduction to the “Mighty Mouse” over a decade ago spurred both basic and applied research and impacted popular culture as well. The myostatin-null genotype produces “double muscling” in mice and livestock and was recently described in a child. The field’s rapid growth is by no means surprising considering the potential benefits of enhancing muscle growth in clinical and agricultural settings. Indeed, several recent studies suggest that blocking myostatin’s inhibitory effects could improve the clinical treatment of several muscle growth disorders, whereas comparative studies suggest that these actions are at least partly conserved. Thus, neutralizing myostatin’s effects could also have agricultural significance. Extrapolating between studies that use different vertebrate models, particularly fish and mammals, is somewhat confusing because whole genome duplication events have resulted in the production and retention of up to four unique myostatin genes in some fish species. Such comparisons, however, suggest that myostatin’s actions may not be limited to skeletal muscle per se, but may additionally influence other tissues including cardiac muscle, adipocytes, and the brain. Thus, therapeutic intervention in the clinic or on the farm must consider the potential of alternative side effects that could impact these or other tissues. In addition, the presence of multiple and actively diversifying myostatin genes in most fish species provides a unique opportunity to study adaptive molecular evolution. It may also provide insight into myostatin’s nonmuscle actions as results from these and other comparative studies gain visibility in biomedical fields.",
"title": "Clinical, Agricultural, and Evolutionary Biology of Myostatin: A Comparative Review"
},
{
"docid": "MED-2172",
"text": "Co-mutagenic beta-carbolines, such as norharman and harman, were quantified in mainstream and sidestream smoke condensates of six Japanese brands of cigarettes, and also in 13 kinds of cooked foods, using a combination of blue cotton treatment and HPLC. Norharman and harman were detected in all the cigarette smoke condensate samples. Their levels in the mainstream smoke case were 900-4240 ng per cigarette for norharman, and 360-2240 ng for harman, and in sidestream smoke, 4130-8990 ng for norharman and 2100-3000 ng for harman. These beta-carbolines were also found to be present in all the cooked food samples, at levels of 2.39-795 ng for norharman and 0.62-377 ng for harman per gram of cooked food. The observed concentrations are much higher than those found for mutagenic and carcinogenic heterocyclic amines (HCAs), suggesting that humans are exposed to norharman and harman in daily life to a larger extent than to HCAs.",
"title": "Quantification of the co-mutagenic beta-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods."
},
{
"docid": "MED-3793",
"text": "OBJECTIVES: To determine cross-cultural and other effects on women's experiences of premenstrual symptoms and their impact on activities of daily life (ADL). STUDY DESIGN: Cross-sectional survey. Sample A total of 7226 women aged 15-49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables, ADL and women's knowledge of premenstrual terms. RESULTS: The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains. Severity of symptoms was directly proportional to duration (number of affected cycles) (R = 0.78). A linear model found that symptom prevalence (duration × severity) was associated with age (linear and quadratic effects), parity, current smoking and country. Premenstrual physical and mental symptom domains had similar negative effects on ADL. Impact on ADL was affected by education and exercise participation. Women's knowledge of the terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age, education and country. CONCLUSIONS: Four of the five most prevalent premenstrual symptoms were physical. There was a great deal of similarities of women's experiences of these symptoms across countries and regions. Women's knowledge of PMS terms is highly dependent on the country in which they live.",
"title": "Global study of women's experiences of premenstrual symptoms and their effects on daily life."
}
] |
126
|
Approximately 250,000 people are infected with human T-cell lymphotropic virus type 1 in the United Kingdom.
|
[
{
"docid": "24512064",
"text": "Apart from HIV two exogenous retroviruses (human T cell leukaemia viruses type I (HTLV-I) and type II (HTLV-II)) infect humans. HTLV-I infection is endemic in Japan, the Caribbean, Africa, and Melanesia and is found among immigrants from these regions in Europe. HTLV-I infection is associated with a 1-5% lifetime risk of adult T cell leukaemia/lymphoma, 1 a 0.25% lifetime risk of HTLV-I associated myelopathy, 2 and other inflammatory conditions (uveitis, alveolitis, and arthritis).1 HTLV-II infection is endemic in some native American and African peoples and among injecting drug users and has been associated with neurological disease.1 Between 1986 and 1992, 100 cases of HTLV-I associated myelopathy and 44 cases of adult T cell leukaemia/lymphoma were diagnosed in the United Kingdom.3 Adult T cell leukaemia/lymphoma was first described in 1977 and patients with it have a mean life expectancy of only six months, so most of the 44 cases were probably incident cases. …",
"title": "HTLV-I/II associated disease in England and Wales, 1993-7: retrospective review of serology requests."
}
] |
[
{
"docid": "27063470",
"text": "OBJECTIVE To identify changes in the occurrence of Creutzfeldt-Jakob disease that might be related to the epidemic of bovine spongiform encephalopathy. DESIGN Epidemiological surveillance of the United Kingdom population for Creutzfeldt-Jakob disease based on (a) referral of suspected cases by neurologists, neuropathologists, and neurophysiologists and (b) death certificates. SETTING England and Wales during 1970-84, and whole of the United Kingdom during 1985-96. SUBJECTS All 662 patients identified as sporadic cases of Creutzfeldt-Jakob disease. MAIN OUTCOME MEASURES Age distribution of patients, age specific time trends of disease, occupational exposure to cattle, potential exposure to causative agent of bovine spongiform encephalopathy. RESULTS During 1970-96 there was an increase in the number of sporadic cases of Creutzfeldt-Jakob disease recorded yearly in England and Wales. The greatest increase was among people aged over 70. There was a statistically significant excess of cases among dairy farm workers and their spouses and among people at increased risk of contact with live cattle infected with bovine spongiform encephalopathy. During 1994-6 there were six deaths from sporadic Creutzfeldt-Jakob disease in the United Kingdom in patients aged under 30. CONCLUSIONS The increase in the incidence of sporadic Creutzfeldt-Jakob disease and the high incidence in dairy farmers in the United Kingdom may be unrelated to bovine spongiform encephalopathy. The most striking change in the pattern of Creutzfeldt-Jakob disease in the United Kingdom after the epidemic of bovine spongiform encephalopathy is provided by the incidence in a group of exceptionally young patients with a consistent and unusual neuropathological profile. The outcome of mouse transmission studies and the future incidence of the disease in the United Kingdom and elsewhere, will be important in judging whether the agent causing bovine spongiform encephalopathy has infected humans.",
"title": "Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970-96."
},
{
"docid": "5476778",
"text": "One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS). There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5,6,7). HAM/TSP patients develop antibodies to neurons. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.",
"title": "Autoimmunity due to molecular mimicry as a cause of neurological disease"
},
{
"docid": "28738741",
"text": "Adult T-cell leukemia/lymphoma (ATLL) is uncommon in the United Kingdom and has so far been restricted to people of Afro-Caribbean extraction. Between 1981 and 1995, 21 cases presented to 2 inner London teaching hospitals where 17% of the population are of Afro-Caribbean origin. Clinical presentations were similar to those of the disease in HTLV-I-endemic areas. Major responses (CR + PR) were obtained in 10/16 assessable patients (63%) treated with combination chemotherapy. However, median survival was only 5.5 months. Disease progression and opportunistic infection were the major causes of treatment failure and death. Three patients (14%) relapsed in the central nervous system (CNS). Our cases confirm the profound immunosuppression in ATLL. The poor prognosis of acute and lymphoma types of ATLL highlight the need for new approaches to treatment such as zidovudine and alpha-interferon, incorporating prophylaxis against CNS disease and opportunistic infections.",
"title": "Adult T-cell leukemia/lymphoma in London: clinical experience of 21 cases."
},
{
"docid": "23985464",
"text": "Wild-type p53 has recently been shown to repress transcription from several cellular and viral promoters. Since p53 mutations are the most frequently reported genetic defects in human cancers, it becomes important to study the effects of mutations of p53 on promoter functions. We, therefore, have studied the effects of wild-type and mutant human p53 on the human proliferating-cell nuclear antigen (PCNA) promoter and on several viral promoters, including the herpes simplex virus type 1 UL9 promoter, the human cytomegalovirus major immediate-early promoter-enhancer, and the long terminal repeat promoters of Rous sarcoma virus and human T-cell lymphotropic virus type I. HeLa cells were cotransfected with a wild-type or mutant p53 expression vector and a plasmid containing a chloramphenicol acetyltransferase reporter gene under viral (or cellular) promoter control. As expected, expression of the wild-type p53 inhibited promoter function. Expression of a p53 with a mutation at any one of the four amino acid positions 175, 248, 273, or 281, however, correlated with a significant increase of the PCNA promoter activity (2- to 11-fold). The viral promoters were also activated, although to a somewhat lesser extent. We also showed that activation by a mutant p53 requires a minimal promoter containing a lone TATA box. A more significant increase (25-fold) in activation occurs when the promoter contains a binding site for the activating transcription factor or cyclic AMP response element-binding protein. Using Saos-2 cells that do not express p53, we showed that activation by a mutant p53 was a direct enhancement. The mutant forms of p53 used in this study are found in various cancer cells. The activation of PCNA by mutant p53s may indicate a way to increase cell proliferation by the mutant p53s. Thus, our data indicate a possible functional role for the mutants of p53 found in cancer cells in activating several important loci, including PCNA.",
"title": "Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells."
},
{
"docid": "5867846",
"text": "The question of whether retroviruses, including human immunodeficiency virus type 1 (HIV-1), interact with the cellular RNA interference machinery has been controversial. Here, we present data showing that neither HIV-1 nor human T-cell leukemia virus type 1 (HTLV-1) expresses significant levels of either small interfering RNAs or microRNAs in persistently infected T cells. We also demonstrate that the retroviral nuclear transcription factors HIV-1 Tat and HTLV-1 Tax, as well as the Tas transactivator encoded by primate foamy virus, fail to inhibit RNA interference in human cells. Moreover, the stable expression of physiological levels of HIV-1 Tat did not globally inhibit microRNA production or expression in infected human cells. Together, these data argue that HIV-1 and HTLV-1 neither induce the production of viral small interfering RNAs or microRNAs nor repress the cellular RNA interference machinery in infected cells.",
"title": "Analysis of the interaction of primate retroviruses with the human RNA interference machinery."
},
{
"docid": "20996244",
"text": "Productive infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile, reverse transcripts. We have previously identified G1b as the cell cycle stage required for the optimal completion of the reverse transcription process in T lymphocytes. However, the mechanism(s) involved in the blockage of reverse transcription remains undefined. In this study we investigated whether nucleotide levels influence viral reverse transcription in G0 cells. For this purpose the role of the enzyme ribonucleotide reductase was bypassed, by adding exogenous deoxyribonucleosides to highly purified T cells in the G0 or the G1a phase of the cell cycle. Our data showed a significant increase in the efficiency of the reverse transcription process following the addition of the deoxyribonucleosides. To define the stability and functionality of these full reverse transcripts, we used an HIV-1 reporter virus that expresses the murine heat-stable antigen on the surfaces of infected cells. Following activation of infected quiescent cells treated with exogenous nucleosides, no increased rescue of productive infection was seen. Thus, in addition to failure to complete reverse transcription, there was an additional nonreversible blockage of productive infection in quiescent T cells. These experiments have important relevance in the gene therapy arena, in terms of improving the ability of lentivirus vectors to enter metabolically inactive cells, such as hematopoietic stem cells.",
"title": "Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes."
},
{
"docid": "46202852",
"text": "Several recent reports indicate that cholesterol might play an important role in human immunodeficiency virus type 1 (HIV-1) replication. We investigated the effects of HIV-1 infection on cholesterol biosynthesis and uptake using microarrays. HIV-1 increased gene expression of cholesterol genes in both transformed T-cell lines and primary CD4(+) T cells. Consistent with our microarray data, (14)C-labeled mevalonate and acetate incorporation was increased in HIV-1-infected cells. Our data also demonstrate that changes in cholesterol biosynthesis and uptake are only observed in the presence of functional Nef, suggesting that increased cholesterol synthesis may contribute to Nef-mediated enhancement of virion infectivity and viral replication.",
"title": "Nef induces multiple genes involved in cholesterol synthesis and uptake in human immunodeficiency virus type 1-infected T cells."
},
{
"docid": "12885341",
"text": "West Nile virus (WNV) is the most common arthropod-borne flavivirus in the United States; however, the vector ligand(s) that participate in infection are not known. We now show that an Aedes aegypti C-type lectin, mosGCTL-1, is induced by WNV, interacts with WNV in a calcium-dependent manner, and facilitates infection in vivo and in vitro. A mosquito homolog of human CD45 in A. aegypti, designated mosPTP-1, recruits mosGCTL-1 to enable viral attachment to cells and to enhance viral entry. In vivo experiments show that mosGCTL-1 and mosPTP-1 function as part of the same pathway and are critical for WNV infection of mosquitoes. A similar phenomenon was also observed in Culex quinquefasciatus, a natural vector of WNV, further demonstrating that these genes participate in WNV infection. During the mosquito blood-feeding process, WNV infection was blocked in vivo with mosGCTL-1 antibodies. A molecular understanding of flaviviral-arthropod interactions may lead to strategies to control viral dissemination in nature.",
"title": "A C-Type Lectin Collaborates with a CD45 Phosphatase Homolog to Facilitate West Nile Virus Infection of Mosquitoes"
},
{
"docid": "20471181",
"text": "Despite widespread use of antiretroviral therapies to control replication of the human immunodeficiency virus (HIV), dysfunctions of cognition that are collectively termed HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of those infected by the virus. Currently there is not a biomarker that can identify HIV-infected people who are at risk for the development of HAND. Previous studies have identified particular sphingolipid species that are dysregulated in HAND, but the neurocognitive correlates of these biochemical findings are not currently understood. To address this question, we compared cerebrospinal fluid (CSF) levels of sphingomyelin, ceramide, and sterol species with performance on standard neurological tests designed to assess the function of multiple cognitive and motor domains in HIV-infected subjects. We found that sphingomyelin:ceramide ratios for acyl chain lengths of C16∶0, C18∶0, C22∶0, and C24∶0 were associated with worse performance on several indices of memory. The most striking finding was for the acyl chain of C18∶0 that consistently associatedwith performance onmultiple tests of memory. These findings suggest that the sphingomyelin:ceramide ratio for C18∶0 may be a reasonable surrogate marker for memory dysfunction in HIV-infected subjects.",
"title": "Disturbance in cerebral spinal fluid sphingolipid content is associated with memory impairment in subjects infected with the human immunodeficiency virus"
},
{
"docid": "39443128",
"text": "Adult T-cell leukaemia lymphoma (ATLL) is an aggressive disease caused by the human T-lymphotropic virus 1 (HTLV-I) with a short survival. Responses to interferon alpha (IFN-alpha) and zidovudine (AZT) have been documented but not with long-term follow-up. We treated 15 ATLL patients with IFN and AZT. Eleven patients had acute ATLL, two had lymphoma and two smouldering ATLL, with progression. The main features were: organomegaly (14), skin lesions (10), high white blood cell (WBC) count (11) and hypercalcaemia (9). Eleven patients had previously received chemotherapy and one had received an autograft. At the time of the study, seven patients had progressive disease and eight were in partial or complete clinical remission. Responses (PR) lasting 2+ to 44+ months were seen in 67%; 26% did not respond (NR) and one patient was not evaluable. Hypercalcaemia predicted a poor outcome but differences were not significant. Eight of the 15 patients have died 3-41 months from diagnosis. Median survival for the 15 patients was 18 months. Survival of the NR ranged from 4 to 20 months; six PR patients are alive 8-82 months from diagnosis. The differences in survival between NR (median: 6 months) and PR (55% of patients alive at 4 years) were statistically significant (P = 0.002). In conclusion, IFN and AZT improves the outcome of ATLL patients and helps maintain responses.",
"title": "Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: response and outcome in 15 patients."
},
{
"docid": "26124606",
"text": "Liver disease secondary to hepatitis C virus (HCV) infection is a rising cause of morbidity and mortality among individuals who have been infected parenterally with human immunodeficiency virus (HIV) such as injection drug users, hemophiliacs, and transfused patients. We analyzed both the efficacy of interferon (IFN) alpha therapy in these patients and the predictors of response to this agent. A total of 119 patients with chronic hepatitis C (90 of whom were infected with HIV and 29 of whom were not) were included in a multicenter, prospective, open, nonrandomized observational study. IFN-alpha was given subcutaneously in a dosage of 5 million units three times a week during a 3-month period; those patients who responded received a dose of 3 million units given subcutaneously three times a week for an additional 9 months. One hundred seven patients completed the study; the level of aminotransferases returned to normal and sera became negative (complete response) for HCV RNA in 26 (32.5%) of 80 HIV-infected patients and 10 (37.0%) of 27 non-HIV-infected patients (P = .666) after completion of the treatment. Two variables were independently associated with a response in HIV-infected patients: a CD4+ T lymphocyte count of > 500 x 10(6)/L and a baseline HCV viremia level of < 10(7) copies/mL. In the 12 months following treatment, relapses occurred in 30.8% of the HIV-infected patients and 12.5% of non-HIV-infected patients (P = .403).",
"title": "Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group."
},
{
"docid": "8038329",
"text": "Although the role of CD28-B7 interaction in the activation of naive T cells is well established, its importance in the generation and maintenance of T cell memory is not well understood. In this study, we examined the requirement for CD28-B7 interactions in primary T cell activation and immune memory. Ag-specific CD8 T cell responses were compared between wild-type (+/+) and CD28-deficient (CD28(-/-)) mice following an acute infection with lymphocytic choriomeningitis virus (LCMV). During the primary response, there was a substantial activation and expansion of LCMV-specific CD8 T cells in both +/+ and CD28(-/-) mice. However, the magnitude of the primary CD8 T cell response to both dominant and subdominant LCMV CTL epitopes was approximately 2- to 3-fold lower in CD28(-/-) mice compared with +/+ mice; the lack of CD28-mediated costimulation did not lead to preferential suppression of CD8 T cell responses to the weaker subdominant epitopes. As seen in CD28(-/-) mice, blockade of B7-mediated costimulation by CTLA4-Ig treatment of +/+ mice also resulted in a 2-fold reduction in the anti-LCMV CD8 T cell responses. Loss of CD28/B7 interactions did not significantly affect the generation and maintenance of CD8 T cell memory; the magnitude of CD8 T cell memory was approximately 2-fold lower in CD28(-/-) mice as compared with +/+ mice. Further, in CD28(-/-) mice, LCMV-specific memory CD8 T cells showed normal homeostatic proliferation in vivo and also conferred protective immunity. Therefore, CD28 signaling is not necessary for the proliferative renewal and maintenance of memory CD8 T cells.",
"title": "Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory."
},
{
"docid": "3662510",
"text": "OBJECTIVE To estimate the lost investment of domestically educated doctors migrating from sub-Saharan African countries to Australia, Canada, the United Kingdom, and the United States. DESIGN Human capital cost analysis using publicly accessible data. SETTINGS Sub-Saharan African countries. PARTICIPANTS Nine sub-Saharan African countries with an HIV prevalence of 5% or greater or with more than one million people with HIV/AIDS and with at least one medical school (Ethiopia, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe), and data available on the number of doctors practising in destination countries. MAIN OUTCOME MEASURES The financial cost of educating a doctor (through primary, secondary, and medical school), assuming that migration occurred after graduation, using current country specific interest rates for savings converted to US dollars; cost according to the number of source country doctors currently working in the destination countries; and savings to destination countries of receiving trained doctors. RESULTS In the nine source countries the estimated government subsidised cost of a doctor's education ranged from $21,000 (£13,000; €15,000) in Uganda to $58,700 in South Africa. The overall estimated loss of returns from investment for all doctors currently working in the destination countries was $2.17bn (95% confidence interval 2.13bn to 2.21bn), with costs for each country ranging from $2.16m (1.55m to 2.78m) for Malawi to $1.41bn (1.38bn to 1.44bn) for South Africa. The ratio of the estimated compounded lost investment over gross domestic product showed that Zimbabwe and South Africa had the largest losses. The benefit to destination countries of recruiting trained doctors was largest for the United Kingdom ($2.7bn) and United States ($846m). CONCLUSIONS Among sub-Saharan African countries most affected by HIV/AIDS, lost investment from the emigration of doctors is considerable. Destination countries should consider investing in measurable training for source countries and strengthening of their health systems.",
"title": "The financial cost of doctors emigrating from sub-Saharan Africa: human capital analysis"
},
{
"docid": "8300657",
"text": "Human and simian immunodeficiency virus (HIV and SIV) replicate optimally in activated memory CD4(+) T cells, a cell type that is abundant in the intestine. SIV infection of rhesus monkeys resulted in profound and selective depletion of CD4+ T cells in the intestine within days of infection, before any such changes in peripheral lymphoid tissues. The loss of CD4+ T cells in the intestine occurred coincident with productive infection of large numbers of mononuclear cells at this site. The intestine appears to be a major target for SIV replication and the major site of CD4+ T cell loss in early SIV infection.",
"title": "Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection."
},
{
"docid": "6182947",
"text": "BACKGROUND Influenza A virus (IAV) infection primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. Recent studies have shown the importance of lung antioxidant defense systems against injury by IAV. Nuclear factor-erythroid 2 related factor 2 (Nrf2) activates the majority of antioxidant genes. METHODS Alveolar type II (ATII) cells and alveolar macrophages (AM) were isolated from human lungs not suitable for transplantation and donated for medical research. In some studies ATII cells were transdifferentiated to alveolar type I-like (ATI-like) cells. Alveolar epithelial cells were infected with A/PR/8/34 (PR8) virus. We analyzed PR8 virus production, influenza A nucleoprotein levels, ROS generation and expression of antiviral genes. Immunocytofluorescence was used to determine Nrf2 translocation and western blotting to detect Nrf2, HO-1 and caspase 1 and 3 cleavage. We also analyzed ingestion of PR8 virus infected apoptotic ATII cells by AM, cytokine levels by ELISA, glutathione levels, necrosis and apoptosis by TUNEL assay. Moreover, we determined the critical importance of Nrf2 using adenovirus Nrf2 (AdNrf2) or Nrf2 siRNA to overexpress or knockdown Nrf2, respectively. RESULTS We found that IAV induced oxidative stress, cytotoxicity and apoptosis in ATI-like and ATII cells. We also found that AM can ingest PR8 virus-induced apoptotic ATII cells (efferocytosis) but not viable cells, whereas ATII cells did not ingest these apoptotic cells. PR8 virus increased ROS production, Nrf2, HO-1, Mx1 and OAS1 expression and Nrf2 translocation to the nucleus. Nrf2 knockdown with siRNA sensitized ATI-like cells and ATII cells to injury induced by IAV and overexpression of Nrf2 with AdNrf2 protected these cells. Furthermore, Nrf2 overexpression followed by infection with PR8 virus decreased virus replication, influenza A nucleoprotein expression, antiviral response and oxidative stress. However, AdNrf2 did not increase IFN-λ1 (IL-29) levels. CONCLUSIONS Our results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies.",
"title": "Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus"
},
{
"docid": "6144969",
"text": "Virally induced inflammatory responses, beta cell destruction and release of beta cell autoantigens may lead to autoimmune reactions culminating in type 1 diabetes. Therefore, viral capability to induce beta cell death and the nature of virus-induced immune responses are among key determinants of diabetogenic viruses. We hypothesised that enterovirus infection induces a specific gene expression pattern that results in islet destruction and that such a host response pattern is not shared among all enterovirus infections but varies between virus strains. The changes in global gene expression and secreted cytokine profiles induced by lytic or benign enterovirus infections were studied in primary human pancreatic islet using DNA microarrays and viral strains either isolated at the clinical onset of type 1 diabetes or capable of causing a diabetes-like condition in mice. The expression of pro-inflammatory cytokine genes (IL-1-α, IL-1-β and TNF-α) that also mediate cytokine-induced beta cell dysfunction correlated with the lytic potential of a virus. Temporally increasing gene expression levels of double-stranded RNA recognition receptors, antiviral molecules, cytokines and chemokines were detected for all studied virus strains. Lytic coxsackievirus B5 (CBV-5)-DS infection also downregulated genes involved in glycolysis and insulin secretion. The results suggest a distinct, virus-strain-specific, gene expression pattern leading to pancreatic islet destruction and pro-inflammatory effects after enterovirus infection. However, neither viral replication nor cytotoxic cytokine production alone are sufficient to induce necrotic cell death. More likely the combined effect of these and possibly cellular energy depletion lie behind the enterovirus-induced necrosis of islets.",
"title": "Enterovirus-induced gene expression profile is critical for human pancreatic islet destruction"
},
{
"docid": "8665891",
"text": "Dengue virus and its four serotypes (DENV 1-4) infect approximately 390 million people worldwide each year, with most cases in tropical and subtropical regions. Because of repeated introduction of DENV from epidemic regions and suitable weather conditions, many regions have shifted from hypo-endemicity to hyper-endemicity over recent decades. Since the first dengue outbreak in 1978, it is crucial to understand the current situation in China over nearly 40 years. The purpose of the study was to examine whether dengue in China was endemic or not, which is essential for relevant dengue control and prevention strategy implementation in China. The study, combining epidemiological characteristics of dengue from the disease notification system, phylogenetic and phylogeographic analyses, showed that all four serotypes had been detected in Guangzhou, China, which was dominated by DENV 1-2. The Maximum Likelihood tree analytic results showed that the virus detected in Guangzhou localized in different clades, except of virus of 2002 and 2003 clustered together. There existed the mutual introductions between Guangzhou and Southeast Asia. Most of the viruses were imported from Southeast Asia and the sources of outbreaks in Guangzhou mainly originated from Thailand, Indonesia, and the Philippines. The study indicates that dengue in China still remains as an imported disease, with the possibility of localization.",
"title": "Dengue is still an imported disease in China: a case study in Guangzhou."
},
{
"docid": "42065070",
"text": "Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four mandrills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected mandrill. Two noninfected control animals were monitored in parallel. Blood and lymph nodes were collected at three time points before infection, twice a week during the first month, and at days 60, 180, and 360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 x 10(6) to 2 x 10(8) RNA equivalents/ml). Viremia then decreased 10- to 1,000-fold, reaching the viral set point between days 30 to 60 p.i. The levels during the chronic phase of infection were similar to that in the naturally infected donor mandrill (2 x 10(5) RNA equivalents/ml). The CD4(+) cell numbers and percentages in blood and lymph nodes decreased slightly (<10%) during primary infection, and CD8(+) cell numbers increased transiently. All values returned to preinfection infection levels by day 30 p.i. CD8(+) cell numbers or percentages, in peripheral blood and lymph nodes, did not increase during the 1 year of follow-up. In conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in mandrills. Despite high levels of viremia, CD4(+) and CD8(+) cell numbers remained stable in the post-acute phase of infection, raising questions regarding the susceptibility of mandrill T cells to activation and/or cell death in response to SIVmnd-1 infection in vivo.",
"title": "High levels of viral replication contrast with only transient changes in CD4(+) and CD8(+) cell numbers during the early phase of experimental infection with simian immunodeficiency virus SIVmnd-1 in Mandrillus sphinx."
},
{
"docid": "11784947",
"text": "Short interfering RNAs (siRNAs) have been used to inhibit HIV-1 replication. The durable inhibition of HIV-1 replication by RNA interference has been impeded, however, by a high mutation rate when viral sequences are targeted and by cytotoxicity when cellular genes are knocked down. To identify cellular proteins that contribute to HIV-1 replication that can be chronically silenced without significant cytotoxicity, we employed a shRNA library that targets 54,509 human transcripts. We used this library to select a comprehensive population of Jurkat T-cell clones, each expressing a single discrete shRNA. The Jurkat clones were then infected with HIV-1. Clones that survived viral infection represent moieties silenced for a human mRNA needed for virus replication, but whose chronic knockdown did not cause cytotoxicity. Overall, 252 individual Jurkat mRNAs were identified. Twenty-two of these mRNAs were secondarily verified for their contributions to HIV-1 replication. Five mRNAs, NRF1, STXBP2, NCOA3, PRDM2, and EXOSC5, were studied for their effect on steps of the HIV-1 life cycle. We discuss the similarities and differences between our shRNA findings for HIV-1 using a spreading infection assay in human Jurkat T-cells and results from other investigators who used siRNA-based screenings in HeLa or 293T cells.",
"title": "A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication."
},
{
"docid": "37444589",
"text": "Although 13 years have passed since identification of human immunodeficiency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its primary target, the T cell that carries the CD4 antigen. We and others have shown an increase in the percentage of apoptotic cells among circulating CD4+ (and CD8+) T cells of HIV-seropositive individuals and an increase in frequency of apoptosis with disease progression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apoptosis occurs predominantly in bystander cells and not in the productively infected cells themselves. These data have implications for pathogenesis and therapy, namely, arguing that rational drug therapy may involve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells.",
"title": "Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes"
},
{
"docid": "27602752",
"text": "Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.",
"title": "CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS."
},
{
"docid": "10559501",
"text": "Studies with mice lacking the common plasma membrane receptor for type I interferon (IFN-αβR(-)(/)(-)) have revealed that IFN signaling restricts tropism, dissemination, and lethality after infection with West Nile virus (WNV) or several other pathogenic viruses. However, the specific functions of individual IFN subtypes remain uncertain. Here, using IFN-β(-)(/)(-) mice, we defined the antiviral and immunomodulatory function of this IFN subtype in restricting viral infection. IFN-β(-)(/)(-) mice were more vulnerable to WNV infection than wild-type mice, succumbing more quickly and with greater overall mortality, although the phenotype was less severe than that of IFN-αβR(-)(/)(-) mice. The increased susceptibility of IFN-β(-)(/)(-) mice was accompanied by enhanced viral replication in different tissues. Consistent with a direct role for IFN-β in control of WNV replication, viral titers in ex vivo cultures of macrophages, dendritic cells, fibroblasts, and cerebellar granule cell neurons, but not cortical neurons, from IFN-β(-)(/)(-) mice were greater than in wild-type cells. Although detailed immunological analysis revealed no major deficits in the quality or quantity of WNV-specific antibodies or CD8(+) T cells, we observed an altered CD4(+) CD25(+) FoxP3(+) regulatory T cell response, with greater numbers after infection. Collectively, these results suggest that IFN-β controls WNV pathogenesis by restricting infection in key cell types and by modulating T cell regulatory networks.",
"title": "Beta interferon controls West Nile virus infection and pathogenesis in mice."
},
{
"docid": "12584053",
"text": "OBJECTIVE To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years. DESIGN Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level. SETTING 207 general practices in 13 primary care sites in the United Kingdom. PARTICIPANTS 731 of the 824 participants included in the original trial were eligible for follow-up. Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants. INTERVENTION A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care. MAIN OUTCOME MEASURES The primary outcome was glycated haemoglobin (HbA(1c)) levels. The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years. RESULTS HbA(1c) levels at three years had decreased in both groups. After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17). The groups did not differ for the other biomedical and lifestyle outcomes and drug use. The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01). Depression scores and quality of life did not differ at three years. CONCLUSION A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs. TRIAL REGISTRATION Current Controlled Trials ISRCTN17844016.",
"title": "Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care"
},
{
"docid": "10450300",
"text": "Human cytomegalovirus (HCMV) is a widely prevalent human herpesvirus, which, after primary infection, persists in the host for life. In healthy individuals, the virus is well controlled by the HCMV-specific T cell response. A key feature of this persistence, in the face of a normally robust host immune response, is the establishment of viral latency. In contrast to lytic infection, which is characterised by extensive viral gene expression and virus production, long-term latency in cells of the myeloid lineage is characterised by highly restricted expression of viral genes, including UL138 and LUNA. Here we report that both UL138 and LUNA-specific T cells were detectable directly ex vivo in healthy HCMV seropositive subjects and that this response is principally CD4⁺ T cell mediated. These UL138-specific CD4⁺ T cells are able to mediate MHC class II restricted cytotoxicity and, importantly, show IFNγ effector function in the context of both lytic and latent infection. Furthermore, in contrast to CDCD4⁺ T cells specific to antigens expressed solely during lytic infection, both the UL138 and LUNA-specific CD4⁺ T cell responses included CD4⁺ T cells that secreted the immunosuppressive cytokine cIL-10. We also show that cIL-10 expressing CD4⁺ T-cells are directed against latently expressed US28 and UL111A. Taken together, our data show that latency-associated gene products of HCMV generate CD4⁺ T cell responses in vivo, which are able to elicit effector function in response to both lytic and latently infected cells. Importantly and in contrast to CD4⁺ T cell populations, which recognise antigens solely expressed during lytic infection, include a subset of cells that secrete the immunosuppressive cytokine cIL-10. This suggests that HCMV skews the T cell responses to latency-associated antigens to one that is overall suppressive in order to sustain latent carriage in vivo.",
"title": "Human Cytomegalovirus Latency-Associated Proteins Elicit Immune-Suppressive IL-10 Producing CD4+ T Cells"
},
{
"docid": "5398179",
"text": "HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection.",
"title": "Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication."
},
{
"docid": "7224723",
"text": "HIV causes a chronic infection characterized by depletion of CD4(+) T lymphocytes and the development of opportunistic infections. Despite drugs that inhibit viral spread, HIV infection has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy (HAART) and the immune response. Here we used CD34(+) cells from infected people as well as in vitro studies of wild-type HIV to show infection and killing of CD34(+) multipotent hematopoietic progenitor cells (HPCs). In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. A unique reporter HIV that directly detects latently infected cells in vitro confirmed the presence of distinct populations of active and latently infected HPCs. These findings have major implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.",
"title": "HIV–1 Infects Multipotent Progenitor Cells Causing Cell Death and Establishing Latent Cellular Reservoirs"
},
{
"docid": "5824985",
"text": "BACKGROUND Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities. METHODS AND FINDINGS This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88-5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55-0.83); hypertension, 0.35 (95% CI 0.27-0.45); angina, 0.59 (95% CI 0.40-0.87);MI, 0.28 (95% CI 0.10-0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40-0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84-12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65-11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66-1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes. CONCLUSIONS Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.",
"title": "Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care."
},
{
"docid": "40473317",
"text": "In this report, we demonstrate that CD28(-/-) mice are severely impaired in the initial expansion of D(b)/NP366-374-specific CD8 T cells in response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)(-/-) mice show no defect in primary T cell expansion to influenza virus. In contrast, 4-1BBL(-/-) mice show a decrease in D(b)/NP366-374-specific T cells late in the primary response. Upon secondary challenge with influenza virus, 4-1BBL(-/-) mice show a decrease in the number of D(b)/NP366-374-specific T cells compared to wild-type mice such that the level of the CD8 T cell expansion during the in vivo secondary response is reduced to the level of a primary response, with concomitant reduction of CTL effector function. In contrast, Ab responses, as well as secondary CD4 T cell responses, to influenza are unaffected by 4-1BBL deficiency. Thus, CD28 is critical for initial T cell expansion, whereas 4-1BB/4-1BBL signaling affects T cell numbers much later in the response and is essential for the survival and/or responsiveness of the memory CD8 T cell pool.",
"title": "Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection."
},
{
"docid": "31460499",
"text": "Overusing antibiotics is not the only cause and reducing use is not the only solution W arning signs of antimicrobial resistance, chinks in the antimicrobial armour, began to appear in the middle of the last century, and by the 1990s various reports had signalled the dangers of excessive or inappropriate use of antibiotics in clinical medicine and of the use of antibiotics in animal feed as growth promoters.1–3 Overuse of antimicrobials emerged as the main culprit, and reducing their use was seen as the answer. But it may not be that simple. The idea that reducing antibiotic use would redress the problem formed part of a positive response on the part of the United Kingdom government to the House of Lords report,1 including a public information campaign, surveillance of resistance along the food chain, targets with respect to hospital acquired infections, and setting up of an overarching advisory body on all aspects of antibiotic use. However, the concept of overuse has proved too simplistic, for, although the evidence of overprescribing as the …",
"title": "Resistance to antimicrobials in humans and animals."
},
{
"docid": "696006",
"text": "Patients with asthma, a major public health problem, are at high risk for serious disease from influenza virus infection, but the pathogenic mechanisms by which influenza A causes airway disease and asthma are not fully known. We show here in a mouse model that influenza infection acutely induced airway hyper-reactivity (AHR), a cardinal feature of asthma, independently of T helper type 2 (TH2) cells and adaptive immunity. Instead, influenza infection induced AHR through a previously unknown pathway that required the interleukin 13 (IL-13)–IL-33 axis and cells of the non-T cell, non-B cell innate lymphoid type called 'natural helper cells'. Infection with influenza A virus, which activates the NLRP3 inflammasome, resulted in much more production of IL-33 by alveolar macrophages, which in turn activated natural helper cells producing substantial IL-13.",
"title": "Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity"
}
] |
PLAIN-3057
|
A Better Breakfast
|
[
{
"docid": "MED-3875",
"text": "BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.",
"title": "Effect of mammalian lignans on the growth of prostate cancer cell lines."
},
{
"docid": "MED-3796",
"text": "Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.",
"title": "Effect of flax seed ingestion on the menstrual cycle."
},
{
"docid": "MED-3742",
"text": "Background: Dietary flavonoids have beneficial effects on blood pressure in intervention settings, but there is limited information on habitual intake and risk of hypertension in population-based studies. Objective: We examined the association between habitual flavonoid intake and incident hypertension in a prospective study in men and women. Design: A total of 87,242 women from the Nurses' Health Study (NHS) II, 46,672 women from the NHS I, and 23,043 men from the Health Professionals Follow-Up Study (HPFS) participated in the study. Total flavonoid and subclass intakes were calculated from semiquantitative food-frequency questionnaires collected every 4 y by using an updated and extended US Department of Agriculture database. Results: During 14 y of follow-up, 29,018 cases of hypertension in women and 5629 cases of hypertension in men were reported. In pooled multivariate-adjusted analyses, participants in the highest quintile of anthocyanin intake (predominantly from blueberries and strawberries) had an 8% reduction in risk of hypertension [relative risk (RR): 0.92; 95% CI: 0.86, 0.98; P < 0.03] compared with that for participants in the lowest quintile of anthocyanin intake; the risk reduction was 12% (RR: 0.88; 95% CI: 0.84, 0.93; P < 0.001) in participants ≤60 y of age and 0.96 (0.91, 1.02) in participants >60 y of age (P for age interaction = 0.02). Although intakes of other subclasses were not associated with hypertension, pooled analyses for individual compounds suggested a 5% (95% CI: 0.91, 0.99; P = 0.005) reduction in risk for the highest compared with the lowest quintiles of intake of the flavone apigenin. In participants ≤60 y of age, a 6% (95% CI: 0.88, 0.97; P = 0.002) reduction in risk was observed for the flavan-3-ol catechin when the highest and the lowest quintiles were compared. Conclusions: Anthocyanins and some flavone and flavan-3-ol compounds may contribute to the prevention of hypertension. These vasodilatory properties may result from specific structural similarities (including the B-ring hydroxylation and methyoxylation pattern).",
"title": "Habitual intake of flavonoid subclasses and incident hypertension in adults"
},
{
"docid": "MED-4233",
"text": "OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.",
"title": "Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l..."
},
{
"docid": "MED-3877",
"text": "OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.",
"title": "Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen."
},
{
"docid": "MED-3778",
"text": "Ovulatory function was prospectively assessed over 6 mo in 23 vegetarians and 22 nonvegetarians with clinically normal menstrual cycles. Subjects were 20-40 y of age, of stable weight (body mass index, in kg/m2, of 18-25), on current diets for > or = 2 y, and not using oral contraceptives. Quantitative analysis of basal body temperature records classified cycles as normally ovulatory, short luteal phase (< 10 d), or anovulatory. Subjects completed the Three-Factor Eating Questionnaire (subjects completed the Three-Factor Eating Questionnaire (subscales for restraint, hunger, and disinhibition) and kept three 3-d food records. Vegetarians had lower BMIs (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < 0.05), percentage body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < 0.05), and restraint scores (6.4 +/- 4.4 vs 9.5 +/- 3.7, P < 0.05). Mean cycle lengths were similar, but vegetarians had longer luteal phase lengths (11.2 +/- 2.6 vs 9.1 +/- 3.8 d, P < 0.05). Cycle types also differed (chi 2 = 9.64, P < 0.01): vegetarians had fewer anovulatory cycles (4.6% vs 15.1% of cycles). Compared with those with restraint scores below the median, highly restrained women had fewer ovulatory cycles (3.6 +/- 2.3 vs 5.0 +/- 1.4, P < 0.05) and shorter mean luteal phase lengths (7.4 +/- 4.1 vs 10.7 +/- 3.1 d, P < 0.05). We conclude that ovulatory disturbances and restrained eating are less common among vegetarians, and that restraint influences ovulatory function.",
"title": "Vegetarian vs nonvegetarian diets, dietary restraint, and subclinical ovulatory disturbances: prospective 6-mo study."
},
{
"docid": "MED-3876",
"text": "BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.",
"title": "Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom."
}
] |
[
{
"docid": "MED-4709",
"text": "BACKGROUND: Inflammation is crucial in all stages of atherosclerosis, and few studies have investigated the effect of dietary fat on markers of inflammation related to this disease during the postprandial period. OBJECTIVE: To evaluate the chronic effects of dietary fat on the postprandial expression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) in healthy subjects. DESIGN: 20 healthy men followed three different diets for 4 weeks each, according to a randomized crossover design: Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); CHO-rich and n-3 diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After 12-h fast, volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast: 35% SFA; olive oil breakfast: 36% MUFA; walnut breakfast: 16% PUFA, 4% alpha-linolenic acid (LNA). RESULTS: The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) expression than the olive oil or walnut breakfasts (P=0.014) in PBMCs. Moreover, we found a higher postprandial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast (P=0.025) in these cells. However, the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences (P=N.S.). CONCLUSION: Consumption of a butter-enriched meal elicits greater postprandial expression of proinflammatory cytokine mRNA in PBMCs, compared to the olive oil and walnut breakfasts.",
"title": "Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men."
},
{
"docid": "MED-3582",
"text": "Breakfasts of lentils or wholemeal bread of identical carbohydrate content were taken by seven healthy volunteers. The lentils produced a significant 71% (p less than 0.001) reduction in the blood glucose area and flattened the plasma insulin and gastric inhibitory polypeptide responses by comparison with the bread. In addition, the lentil breakfast was followed by a significantly flatter blood glucose response to the standard bread lunch which followed 4 h later (by 38%, p less than 0.01). The blood glucose pattern was mimicked by feeding the bread breakfast slowly over the 4 h before lunch. Giving a bread breakfast containing a quarter of the carbohydrate reduced the breakfast glucose profile but resulted in a significantly impaired blood glucose response to lunch (168% of control, p less than 0.01). These results, together with breath hydrogen studies, performed on a separate group of four volunteers, indicate that the flattened response to lentils is not due to carbohydrate malabsorption. Slow release or \"lente\" carbohydrate foods such as lentils may form a useful part of the diets of those with impaired carbohydrate tolerance.",
"title": "Slow release dietary carbohydrate improves second meal tolerance."
},
{
"docid": "MED-3476",
"text": "Fruit and vegetable consumption reduces the risk for cardiovascular disease development. The postprandial state is an important contributor to chronic disease development. Orange flavonoids may reduce postprandial oxidation. It was hypothesized that a mixture of orange flavonoids would reduce postprandial oxidation better than a single orange flavonoid or orange sugar and ascorbic acid, but not as well as orange juice, when consumed with a typical breakfast. A placebo-controlled crossover trial (16 male and female participants, 4 treatments, 4 visits) was carried out. Treatments were placebo (ascorbic acid and sugar equivalent to orange juice); placebo plus hesperidin; placebo plus hesperidin, luteolin, and naringenin (mixture; found to have synergistic antioxidant properties in vitro in previous work); and orange juice (positive control). Serum oxygen radical absorbance capacity (ORAC), total plasma phenolics (TP), and serum lipoprotein oxidation (LO) were measured after a 12-hour baseline fast and at 1, 2, and 3 hours after sample consumption. The placebo plus mixture and orange juice groups were significantly increased in ORAC and LO lag time. Data for TP were inconsistent with ORAC and LO. Contrary to previous studies attributing the protective postprandial effect to fructose and ascorbate in other fruit trials, orange phenolic compounds contribute directly to the postprandial oxidative protection of serum, despite an inconsistent change in serum TP. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Controlling for sugar and ascorbic acid, a mixture of flavonoids matching navel oranges significantly increases human postprandial serum antioxidan..."
},
{
"docid": "MED-3469",
"text": "The purpose of this study was to compare the effects of unsweetened fruit juice and regular, decaffeinated soda on postprandial serum glucose levels in individuals with non-insulin-dependent diabetes mellitus (NIDDM) when these liquids are ingested separately as part of mixed meals. Eighteen individuals with NIDDM consumed three test breakfasts calculated using the diabetic exchange meal-planning system. Foods were identical in each of the breakfasts except for foods in the fruit exchange. Carbohydrate-equivalent amounts of fresh orange slices, unsweetened orange juice, and regular, decaffeinated Coke were consumed in breakfasts 1, 2, and 3, respectively. Serum glucose samples were drawn at fasting and 1, 2, and 3 hours postprandially. No difference was found in the postprandial serum glucose response when Coke versus orange juice was consumed in the breakfast. These findings question the appropriateness of using unsweetened fruit juices in routine meal planning for individuals with NIDDM.",
"title": "Postprandial glycemic response to orange juice and nondiet cola: is there a difference?"
},
{
"docid": "MED-3580",
"text": "The effects of the glycemic index (GI) of carbohydrate eaten the previous night on the glycemic response to a standard test meal eaten subsequently in the morning (breakfast) was studied. On separate evenings normal subjects ate low- or high-GI test meals of the same nutrient composition. The dinners consisted of single foods in two experiments and mixed meals containing several foods in the third. The differences between the observed glycemic responses to low- and high-GI dinners were predicted by their GIs. The glycemic responses to breakfast were significantly lower on mornings after low-GI dinners than after high-GI dinners. Eating, at dinner, foods with different fiber contents but the same GI had no effect on postbreakfast glycemia. We conclude that the GI predicts the difference between glycemic responses of mixed dinner meals; breakfast carbohydrate tolerance is improved when low-GI foods are eaten the previous evening.",
"title": "Second-meal effect: low-glycemic-index foods eaten at dinner improve subsequent breakfast glycemic response."
},
{
"docid": "MED-1259",
"text": "We sought to determine whether consumption of blueberries could reduce postprandial oxidation when consumed with a typical high-carbohydrate, low-fat breakfast. Participants (n 14) received each of the three treatments over 3 weeks in a cross-over design. Treatments consisted of a high blueberry dose (75 g), a low blueberry dose (35 g) and a control (ascorbic acid and sugar content matching that of the high blueberry dose). Serum oxygen radical absorbance capacity (ORAC), serum lipoprotein oxidation (LO) and serum ascorbate, urate and glucose were measured at fasting, and at 1, 2 and 3 h after sample consumption. The mean serum ORAC was significantly higher in the 75 g group than in the control group during the first 2 h postprandially, while serum LO lag time showed a significant trend over the 3 h for both blueberry doses. Changes in serum ascorbate, urate and glucose were not significantly different among the groups. To our knowledge, this is the first report that has demonstrated that increased serum antioxidant capacity is not attributable to the fructose or ascorbate content of blueberries. In summary, a practically consumable quantity of blueberries (75 g) can provide statistically significant oxidative protection in vivo after a high-carbohydrate, low-fat breakfast. Though not tested directly, it is likely that the effects are due to phenolic compounds, either directly or indirectly, as they are a major family of compounds in blueberries with potential bioactive activity.",
"title": "Consumption of blueberries with a high-carbohydrate, low-fat breakfast decreases postprandial serum markers of oxidation."
},
{
"docid": "MED-984",
"text": "We investigated total, free and protein-bound plasma homocysteine, cysteine and cysteinylglycine in 13 subjects aged 24-29 y after a breakfast at 0900 h containing 15-18 g of protein and a dinner at 1500 h containing approximately 50 g of protein. Twelve subjects had normal fasting homocysteine (mean +/- SD, 7.6 +/- 1.1 mumol/L) and methionine concentrations (22.7 +/- 3.5 mumol/L) and were included in the statistical analyses. Breakfast caused a small but significant increase in plasma methionine (22.2 +/- 20.6%) and a brief, nonsignificant increase followed by a significant decline in free homocysteine. However, changes in total and bound homocysteine were small. After dinner, there was a marked increase in plasma methionine by 16.7 +/- 8.9 mumol/L (87.9 +/- 49%), which was associated with a rapid and marked increase in free homocysteine (33.7 +/- 19.6%, 4 h after dinner) and a moderate and slow increase in total (13.5 +/- 7.5%, 8 h) and protein-bound (12.6 +/- 9.4%, 8 h) homocysteine. After both meals, cysteine and cysteinylglycine concentrations seemed related to changes in homocysteine, because there were parallel fluctuations in the free:bound ratios of all three thiols. Dietary changes in plasma homocysteine will probably not affect the evaluation of vitamin deficiency states associated with moderate to severe hyperhomocysteinemia but may be of concern in the risk assessment of cardiovascular disease in patients with mild hyperhomocysteinemia. Synchronous fluctuations in the free:bound ratio of the plasma aminothiol compounds indicate that biological effects of homocysteine may be difficult to separate from effects due to associated changes in other aminothiol compounds.",
"title": "Plasma concentrations of homocysteine and other aminothiol compounds are related to food intake in healthy human subjects."
},
{
"docid": "MED-1533",
"text": "Snacks are an important part of children's dietary intake, but the role of dried fruit on energy intake in children is unknown. Therefore, the effect of ad libitum consumption of an after-school snack of raisins, grapes, potato chips, and chocolate chip cookies on appetite and energy intake in twenty-six 8- to 11-y-old normal-weight (15th to 85th percentile) children was examined. On 4 separate weekdays, 1 wk apart, children (11 M, 15 F) were given a standardized breakfast, morning snack (apple), and a standardized lunch. After school, children randomly received 1 of 4 ad libitum snacks and were instructed to eat until \"comfortably full.\" Appetite was measured before and 15, 30, and 45 min after snack consumption. Children consumed the least calories from raisins and grapes and the most from cookies (P < 0.001). However, weight of raisins consumed was similar to potato chips (about 75 g) and lower compared to grapes and cookies (P < 0.009). Raisins and grapes led to lower cumulative food intake (breakfast + morning snack + lunch + after-school snack) (P < 0.001), while the cookies increased cumulative food intake (P < 0.001) compared to the other snacks. Grapes lowered appetite compared to all other snacks (P < 0.001) when expressed as a change in appetite per kilocalorie of the snack. Ad libitum consumption of raisins has potential as an after-school snack to achieve low snack intake prior to dinner, similar to grapes, compared to potato chips, and cookies in children 8 to 11 y old. © 2013 Institute of Food Technologists®",
"title": "An after-school snack of raisins lowers cumulative food intake in young children."
},
{
"docid": "MED-5260",
"text": "OBJECTIVES: The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity. BACKGROUND: Endothelial-dependent vasodilatation is impaired during the postprandial state, and oxidative stress could play a key role in its development. METHODS: Twenty-one hypercholesterolemic volunteers received two breakfasts, using a randomized sequential crossover design. Both arms received the same olive oil, but one had its phenolic acid content reduced from 400 to 80 ppm. Ischemic reactive hyperemia (IRH) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake. Postprandial plasma concentrations of lipid fractions, lipoperoxides (LPO), 8-epi prostaglandin-F(2alpha), and nitrates/nitrites (NO(x)) were obtained at baseline and after 2 h of the fat meal. RESULTS: The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function, as well as a greater increase in concentrations of NO(x) (p < 0.001) and a lower increase in LPO (p < 0.005) and 8-epi prostaglandin-F2alpha (p < 0.001) than the ones induced by the low polyphenol fat meal. A positive correlation was found to exist between NO(x) and enhanced endothelial function at the second hour (r = 0.669; p < 0.01). Furthermore, a negative correlation was found between IRH and LPO (r = -0.203; p < 0.05) and 8-epi prostaglandin-F2alpha levels (r = -0.440; p < 0.05). CONCLUSIONS: A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postprandial state. This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites.",
"title": "Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients."
},
{
"docid": "MED-1610",
"text": "The effects of three different meat-containing breakfast meals (pork, beef or chicken) on acute satiety and appetite regulatory hormones were compared using a within-subjects study design. Thirty fasting non-smoking pre-menopausal women attended a research centre on three test days to consume, a meat-containing meal matched in energy (kJ) and protein content, palatability, and appearance. No difference was found between meat groups for either energy intake or macronutrient profile of food consumed at a subsequent ad libitum buffet lunch, or over the rest of the day. Visual Analogue Scale (VAS) ratings for hunger and satiety over an 180 min period did not differ between test meals. After consumption of the test meals, a significant difference was found in PYY response between pork and chicken meals (P=0.027) but not for levels of CCK, ghrelin, insulin or glucose. This study positions pork, beef, and chicken as equal in their effect on satiety and release of appetite-related intestinal hormones and of insulin. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Pork, beef and chicken have similar effects on acute satiety and hormonal markers of appetite."
},
{
"docid": "MED-827",
"text": "The phenotype of polycystic ovarian syndrome (PCOS) is known to worsen with weight gain, increased ingestion of carbohydrates and a sedentary lifestyle. The purpose of this study was to assess the dietary habits in a group of adolescent girls with PCOS. Adolescents with PCOS were recruited and asked to complete a questionnaire on their eating habits and a recall dietary diary, from which their caloric and macronutrient intake was calculated. Results were compared with those from a group of normal controls. Thirty-five women with PCOS and 46 controls were included. Girls with PCOS were less likely to have cereals for breakfast (20.7 versus 66.7%) and as a result consumed less fibre than controls. They were more likely to eat an evening meal (97.1 versus 78.3%) and eat this over an hour later when compared to controls. Despite having comparable body mass indexes, girls with PCOS ate a daily surplus calorie average of 3% versus controls that had a negative calorie intake of 0.72% (p = 0.047). Ameliorating eating habits early in adolescence in girls with PCOS may improve future metabolic concerns related to a genetic predisposition and worsened by an unhealthy lifestyle.",
"title": "Dietary habits in adolescent girls with polycystic ovarian syndrome."
},
{
"docid": "MED-1515",
"text": "Long periods of sedentary behaviour may adversely affect health irrespective of overall physical activity levels. This study compared the effects of sitting, standing and walking on postprandial lipaemia in healthy normolipidaemic Japanese men. 15 participants, aged 26.8±2.0 years (mean±SD), completed 3, 2-day trials in a random order: 1) sitting (control), 2) standing, and 3) walking. On day 1 of the sitting trial, participants rested. On day 1 of the standing trial, participants stood for six, 45-min periods. On day 1 of the walking trial, participants walked briskly for 30 min at approximately 60% of maximum heart rate. On day 2 of each trial, participants rested and consumed test meals for breakfast and lunch. Venous blood samples were collected in the morning and afternoon on day 1, and in the fasted state (0 h) and at 2, 4 and 6 h postprandially on day 2. On day 2 area under the serum triacylglycerol concentration vs. time curve was 18% lower on the walking trial than the sitting and standing trials (1-factor ANOVA, P=0.015). Hence postprandial lipaemia was not reduced after standing but was reduced after low-volume walking compared with sitting in healthy normolipidaemic Japanese men. © Georg Thieme Verlag KG Stuttgart · New York.",
"title": "Postprandial lipaemia: effects of sitting, standing and walking in healthy normolipidaemic humans."
},
{
"docid": "MED-4398",
"text": "BACKGROUND: Previous studies suggest possible associations between Western diet and acne. We examined data from the Nurses Health Study II to retrospectively evaluate whether intakes of dairy foods during high school were associated with physician-diagnosed severe teenage acne. METHODS: We studied 47,355 women who completed questionnaires on high school diet in 1998 and physician-diagnosed severe teenage acne in 1989. We estimated the prevalence ratios and 95% confidence intervals of acne history across categories of intakes. RESULTS: After accounting for age, age at menarche, body mass index, and energy intake, the multivariate prevalence ratio (95% confidence intervals; P value for test of trend) of acne, comparing extreme categories of intake, were: 1.22 (1.03, 1.44; .002) for total milk; 1.12 (1.00, 1.25; .56) for whole milk; 1.16 (1.01, 1.34; .25) for low-fat milk; and 1.44 (1.21, 1.72; .003) for skim milk. Instant breakfast drink, sherbet, cottage cheese, and cream cheese were also positively associated with acne. CONCLUSION: We found a positive association with acne for intake of total milk and skim milk. We hypothesize that the association with milk may be because of the presence of hormones and bioactive molecules in milk.",
"title": "High school dietary dairy intake and teenage acne."
},
{
"docid": "MED-2716",
"text": "BACKGROUND Many beliefs about obesity persist in the absence of supporting scientific evidence (presumptions); some persist despite contradicting evidence (myths). The promulgation of unsupported beliefs may yield poorly informed policy decisions, inaccurate clinical and public health recommendations, and an unproductive allocation of research resources and may divert attention away from useful, evidence-based information. METHODS Using Internet searches of popular media and scientific literature, we identified, reviewed, and classified obesity-related myths and presumptions. We also examined facts that are well supported by evidence, with an emphasis on those that have practical implications for public health, policy, or clinical recommendations. RESULTS We identified seven obesity-related myths concerning the effects of small sustained increases in energy intake or expenditure, establishment of realistic goals for weight loss, rapid weight loss, weight-loss readiness, physical-education classes, breast-feeding, and energy expended during sexual activity. We also identified six presumptions about the purported effects of regularly eating breakfast, early childhood experiences, eating fruits and vegetables, weight cycling, snacking, and the built (i.e., human-made) environment. Finally, we identified nine evidence-supported facts that are relevant for the formulation of sound public health, policy, or clinical recommendations. CONCLUSIONS False and scientifically unsupported beliefs about obesity are pervasive in both scientific literature and the popular press. (Funded by the National Institutes of Health.)",
"title": "Myths, Presumptions, and Facts about Obesity"
},
{
"docid": "MED-5131",
"text": "The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.",
"title": "Vitamin B12 sources and bioavailability."
},
{
"docid": "MED-5245",
"text": "BACKGROUND: Coffee and tea are believed to cause gastro-oesophageal reflux; however, the effects of these beverages and of their major component, caffeine, have not been quantified. The aim of this study was to evaluate gastro-oesophageal reflux induced by coffee and tea before and after a decaffeination process, and to compare it with water and water-containing caffeine. METHODS: Three-hour ambulatory pH-metry was performed on 16 healthy volunteers, who received 300 ml of (i) regular coffee, decaffeinated coffee or tap water (n = 16), (ii) normal tea, decaffeinated tea, tap water, or coffee adapted to normal tea in caffeine concentration (n = 6), and (iii) caffeine-free and caffeine-containing water (n = 8) together with a standardized breakfast. RESULTS: Regular coffee induced a significant (P < 0.05) gastro-oesophageal reflux compared with tap water and normal tea, which were not different from each other. Decaffeination of coffee significantly (P < 0.05) diminished gastro-oesophageal reflux, whereas decaffeination of tea or addition of caffeine to water had no effect. Coffee adapted to normal tea in caffeine concentration significantly (P < 0.05) increased gastro-oesophageal reflux. CONCLUSIONS: Coffee, in contrast to tea, increases gastro-oesophageal reflux, an effect that is less pronounced after decaffeination. Caffeine does not seem to be responsible for gastro-oesophageal reflux which must be attributed to other components of coffee.",
"title": "Effect of decaffeination of coffee or tea on gastro-oesophageal reflux."
},
{
"docid": "MED-885",
"text": "Oxalate bioavailability from sugar beet fibre (40 g), spinach (25 g) and a solution of sodium oxalate (182 mg) was tested in nine women using a triplicated 3 x 3 Latin square arrangement. Each test substance provided 120 mg oxalic acid. Throughout the study the volunteers consumed a control diet and the test substances were administered at breakfast on specified days. After an initial 2-day control period, oxalate was administered in three test periods that consisted of one test day followed by one control day. Urine collected during 24-hr periods was analysed daily for oxalate. Oxalate excretion did not differ among the five control days and was not increased significantly following the ingestion of sugar beet fibre by the volunteers. Oxalate excretion was greater (P less than 0.0001) for the mean of the spinach and sodium oxalate solution diets than for the mean of the sugar beet fibre and control diets. Oxalate bioavailability from sugar beet fibre was 0.7% compared with bioavailabilities of 4.5 and 6.2% for spinach and oxalate solutions, respectively. The low bioavailability of oxalate from sugar beet fibre may be attributable to its high ratio of minerals (calcium and magnesium) to oxalate, its complex fibre matrix or the loss of the soluble oxalate during processing of sugar beets.",
"title": "Bioavailability of oxalic acid from spinach, sugar beet fibre and a solution of sodium oxalate consumed by female volunteers."
},
{
"docid": "MED-2020",
"text": "OBJECTIVE: Wheat fiber appears to protect from cardiovascular disease despite its lack of consistent effect on serum lipids. We therefore wished to determine whether reported inconsistencies in the effect of wheat bran resulted from differences in particle size or its high gluten content. METHODS: Two studies were conducted. In one-month metabolic diets, 24 hyperlipidemic subjects consumed breads providing an additional 19 g/d dietary fiber as medium or ultra-fine wheat bran and extra protein (10% of energy as wheat gluten). In two-week ad libitum diets, 24 predominantly normolipidemic subjects consumed breakfast cereals providing an additional 19 g/d of dietary fiber as coarse or a mixture of ultra-fine and coarse wheat bran with no change in gluten intake. Both studies followed a randomized crossover design with control periods when subjects ate low-fiber breads and cereals respectively with no added gluten. Fasting blood lipids were measured on day zero and at the end of each phase. RESULTS: Wheat bran had no effect on total, LDL or HDL cholesterol irrespective of particle size or level of gluten in the diet. However, consumption of increased gluten in the metabolic study was associated with a 13+/-4% reduction in serum triglycerides (p = 0.005) which was not seen in the normal-gluten ad libitum study. CONCLUSIONS: The protective effect of wheat fiber in cardiovascular disease cannot be explained by an effect of wheat bran in reducing serum cholesterol although in hyperlipidemic subjects displacement of carbohydrate by gluten on the high-fiber phases was associated with lower serum triglycerides.",
"title": "Effect of wheat bran on serum lipids: influence of particle size and wheat protein."
},
{
"docid": "MED-1871",
"text": "In order to compare the antihypertensive effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa with captopril, a controlled and randomized clinical trial was done. Patients from 30 to 80 years old with diagnosed hypertension and without antihypertensive treatment for at least 1 month before were included. The experimental procedure consisted of the administration of an infusion prepared with 10 g of dry calyx from H. sabdariffa on 0.51 water (9.6 mg anthocyanins content), daily before breakfast, or captopril 25 mg twice a day, for 4 weeks. The outcome variables were tolerability, therapeutic effectiveness (diastolic reduction > or = 10 mm Hg) and, in the experimental group, urinary electrolytes modification. Ninety subjects were included, 15 withdrew from the study due to non-medical reasons; so, the analysis included 39 and 36 patients from the experimental and control group, respectively. The results showed that H. sabdariffa was able to decrease the systolic blood pressure (BP) from 139.05 to 123.73mm Hg (ANOVA p < 0.03) and the diastolic BP from 90.81 to 79.52mm Hg (ANOVA p < 0.06). At the end of the study, there were no significant differences between the BP detected in both treatment groups (ANOVA p > 0.25). The rates of therapeutic effectiveness were 0.7895 and 0.8438 with H. sabdariffa and captopril, respectively (chi2, p > 0.560), whilst the tolerability was 100% for both treatments. A natriuretic effect was observed with the experimental treatment. The obtained data confirm that the H. sabdariffa extract, standardized on 9.6mg of total anthocyanins, and captopril 50 mg/day, did not show significant differences relative to hypotensive effect, antihypertensive effectiveness, and tolerability.",
"title": "Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and ..."
},
{
"docid": "MED-2140",
"text": "Background Around the world, beans and rice are commonly consumed together as a meal. With type 2 diabetes increasing, the effect of this traditional diet pattern on glycemic response has not been studied fully. Methods We evaluated the glycemic response of bean and rice traditional meals compared to rice alone in adults with type 2 diabetes. Seventeen men and women with type 2 diabetes controlled by metformin (n = 14) or diet/exercise (n = 3) aged 35–70 years participated in the randomized 4 × 4 crossover trial. The white long grain rice control, pinto beans/rice, black beans/rice, red kidney beans/rice test meals, matched for 50 grams of available carbohydrate, were consumed at breakfast after a 12 hour fast. Capillary blood glucose concentrations at baseline and at 30 minute intervals up to 180 minutes postprandial were collected. MANOVA for repeated measures established glucose differences between treatments. Paired t tests identified differences between bean types and the rice control following a significant MANOVA. Results Postprandial net glucose values were significantly lower for the three bean/rice treatments in contrast to the rice control at 90, 120 and 150 minutes. Incremental area under the curve values were significantly lower for the pinto and black bean/rice meals compared to rice alone, but not for kidney beans. Conclusions Pinto, dark red kidney and black beans with rice attenuate the glycemic response compared to rice alone. Promotion of traditional foods may provide non-pharmaceutical management of type 2 diabetes and improve dietary adherence with cultural groups. Trial registration Clinical Trials number NCT01241253",
"title": "Bean and rice meals reduce postprandial glycemic response in adults with type 2 diabetes: a cross-over study"
},
{
"docid": "MED-2782",
"text": "BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.",
"title": "Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial."
},
{
"docid": "MED-3369",
"text": "Background: Strategies are needed to increase children's intake of a variety of vegetables, including vegetables that are not well liked. Objective: We investigated whether incorporating puréed vegetables into entrées to reduce the energy density (ED; in kcal/g) affected vegetable and energy intake over 1 d in preschool children. Design: In this crossover study, 3- to 5-y-old children (n = 40) were served all meals and snacks 1 d/wk for 3 wk. Across conditions, entrées at breakfast, lunch, dinner, and evening snack were reduced in ED by increasing the proportion of puréed vegetables. The conditions were 100% ED (standard), 85% ED (tripled vegetable content), and 75% ED (quadrupled vegetable content). Entrées were served with unmanipulated side dishes and snacks, and children were instructed to eat as much as they liked. Results: The daily vegetable intake increased significantly by 52 g (50%) in the 85% ED condition and by 73 g (73%) in the 75% ED condition compared with that in the standard condition (both P < 0.0001). The consumption of more vegetables in entrées did not affect the consumption of the vegetable side dishes. Children ate similar weights of food across conditions; thus, the daily energy intake decreased by 142 kcal (12%) from the 100% to 75% ED conditions (P < 0.05). Children rated their liking of manipulated foods similarly across ED amounts. Conclusion: The incorporation of substantial amounts of puréed vegetables to reduce the ED of foods is an effective strategy to increase the daily vegetable intake and decrease the energy intake in young children. This trial was registered at clinicaltrials.gov as NCT01252433.",
"title": "Hiding vegetables to reduce energy density: an effective strategy to increase children's vegetable intake and reduce energy intake"
},
{
"docid": "MED-3371",
"text": "Background: The overconsumption of energy-dense foods leads to excessive energy intakes. The substitution of low-energy-dense vegetables for foods higher in energy density can help decrease energy intakes but may be difficult to implement if individuals dislike the taste of vegetables. Objective: We investigated whether incorporating puréed vegetables to decrease the energy density of entrées at multiple meals reduced daily energy intakes and increased daily vegetable intakes. Design: In this crossover study, 20 men and 21 women ate ad libitum breakfast, lunch, and dinner in the laboratory once a week for 3 wk. Across conditions, entrées at meals varied in energy density from standard versions (100% condition) to reduced versions (85% and 75% conditions) by the covert incorporation of 3 or 4.5 times the amount of puréed vegetables. Entrées were accompanied by unmanipulated side dishes. Participants rated their hunger and fullness before and after meals. Results: Subjects consumed a consistent weight of foods across conditions of energy density; thus, the daily energy intake significantly decreased by 202 ± 60 kcal in the 85% condition (P < 0.001) and by 357 ± 47 kcal in the 75% condition (P < 0.0001). Daily vegetable consumption significantly increased from 270 ± 17 g of vegetables in the 100% condition to 487 ± 25 g of vegetables in the 75% condition (P < 0.0001). Despite the decreased energy intake, ratings of hunger and fullness did not significantly differ across conditions. Entrées were rated as similar in palatability across conditions. Conclusions: Large amounts of puréed vegetables can be incorporated into various foods to decrease the energy density. This strategy can lead to substantial reductions in energy intakes and increases in vegetable intakes. This trial was registered at clinicaltrials.gov as NCT01165086.",
"title": "Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults"
},
{
"docid": "MED-3581",
"text": "BACKGROUND: Low postprandial blood glucose is associated with low risk of metabolic diseases. A meal's ability to diminish the glucose response to carbohydrates eaten during the following meal is known as the \"second-meal effect\" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods consumed during the first meal has been suggested as the main mechanism for SME. However, LGI foods often increase colonic fermentation because of the presence of fiber and resistant starch. OBJECTIVE: The objective was to study the SME of greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals consisting of sponge cakes made with rapidly digestible, nonfermentable amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects were fed the same standard lunch containing 93 g available carbohydrates. Blood was collected for measurement of glucose, insulin, and nonesterified fatty acids (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation. Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the HGI-Lac meal, this effect was concomitant with low NEFA concentrations and delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of their effect on a food's glycemic index, have the potential to regulate postprandial responses to a second meal by reducing NEFA competition for glucose disposal and, to a minor extent, by affecting intestinal motility.",
"title": "Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect."
},
{
"docid": "MED-3771",
"text": "OBJECTIVE: Hyperosmotic stress on cells limits many aspects of cell function, metabolism and health. International data suggest that schoolchildren may be at risk of hyperosmotic stress on cells because of suboptimal water intake. The present study explored the cell hydration status of two samples of children in the USA. DESIGN: Cross-sectional study describing the urine osmolality (an index of hyperosmotic cell shrinkage) and water intake of convenience samples from Los Angeles (LA) and New York City (NYC). SETTING: Each participant collected a urine sample at an outpatient clinic on the way to school on a weekday morning in spring 2009. Each was instructed to wake, eat, drink and do as usual before school, and complete a dietary record form describing the type and amounts of all foods and beverages consumed after waking, before giving the sample. SUBJECTS: The children (9-11 years) in LA (n 337) and NYC (n 211) considered themselves healthy enough to go to school on the day they gave the urine sample. RESULTS: Elevated urine osmolality (>800 mmol/kg) was observed in 63 % and 66 % of participants in LA and NYC, respectively. In multivariable-adjusted logistic regression models, elevated urine osmolality was associated with not reporting intake of drinking water in the morning (LA: OR = 2·1, 95 % CI 1·2, 3·5; NYC: OR = 1·8, 95 % CI 1·0, 3·5). Although over 90 % of both samples had breakfast before giving the urine sample, 75 % did not drink water. CONCLUSIONS: Research is warranted to confirm these results and pursue their potential health implications.",
"title": "What is the cell hydration status of healthy children in the USA? Preliminary data on urine osmolality and water intake."
},
{
"docid": "MED-4412",
"text": "BACKGROUND & AIMS: The aim of this study was to investigate whether nutritional risk factors, especially black tea consumptions, are inversely associated with the development of chronic obstructive pulmonary disease (COPD) in male smokers. METHODS: Forty male smokers with clinical diagnosis of COPD (Group-I (GI)) and 36 healthy smokers without COPD (Group-II (GII)) were included in this study. We compared the dietary habits and food intakes of the two groups using an adaptation of the Arizona Food Frequency Questionnaire (AFFQ). Question form included a list of 65 food items formed from five main food groups (grain, meat and alternatives, dairy products, vegetables-fruits and fat) and 25 dietary habits. The data were evaluated by binary logistic regression analysis, receiver operating characteristic (ROC) curve, Kolmogorov-Smirnov, Student's t, Mann-Whitney, and Chi-square tests. RESULTS: When both groups compared, black tea consumptions (GI-700ml; GII-1600ml (OR: 0.635, P<0.001)), vegetable fruits scores (GI-54.30; GII-63.81 (OR: 0.863, P<0.001)), regularly breakfast habit (GI-24 patients; GII-36 cases (OR: 0.549, P<0.001)) and eating salty (GI-22 patients; GII-5 cases (P<0.001)) made significant differences. In ROC curves, the area under the curve of black tea (0.898 (95% CI: 0.819-0.977) and vegetables-fruits (0.833 (95% CI: 0.727-0.938) provided high accuracy to distinguish between COPD group and controls (P<0.001). CONCLUSIONS: High intakes of black tea and vegetables-fruits consumptions may be protecting male smokers from developing COPD.",
"title": "Nutritional risk factors for the development of chronic obstructive pulmonary disease (COPD) in male smokers."
},
{
"docid": "MED-5032",
"text": "The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and orange juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR] = 9.5, 95 percent confidence interval [CI] = 1.6-57.6 for 12 or more hot dogs per month, trend P = 0.01), and fathers' intake of hot dogs (OR = 11.0, CI = 1.2-98.7 for highest intake category, trend P = 0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.",
"title": "Processed meats and risk of childhood leukemia (California, USA)."
},
{
"docid": "MED-2371",
"text": "Background Limiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk. Objective To assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults. Methods Randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 ± 9.6 years; weight = 76.3 ± 21.8 kilograms; total cholesterol = 244 ± 24 mg/dL). In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD) and lipid panel. Results Single dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 ± 1.9 vs. 0.4 ± 2.4%; p = 0.99). Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 ± 1.2% vs. -0.1 ± 1.5%; p < 0.01) and lowered serum total cholesterol (-18 ± 18 vs. -5 ± 21 mg/dL; p < 0.01) and LDL (-14 ± 20 vs. -2 ± 19 mg/dL; p = 0.01). Study results (positive or negative) are expressed in terms of change relative to baseline. Conclusions Egg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.",
"title": "Daily egg consumption in hyperlipidemic adults - Effects on endothelial function and cardiovascular risk"
},
{
"docid": "MED-3201",
"text": "Background Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction. Methods Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed. Results The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%). Conclusions These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles. Trial registration ClinicalTrials.gov NCT00581074",
"title": "Effects of grapefruit, grapefruit juice and water preloads on energy balance, weight loss, body composition, and cardiometabolic risk in free-living obese adults"
},
{
"docid": "MED-4703",
"text": "OBJECTIVE: To investigate the potential of acetic acid supplementation as a means of lowering the glycaemic index (GI) of a bread meal, and to evaluate the possible dose-response effect on postprandial glycaemia, insulinaemia and satiety. SUBJECTS AND SETTING: In all, 12 healthy volunteers participated and the tests were performed at Applied Nutrition and Food Chemistry, Lund University, Sweden. INTERVENTION: Three levels of vinegar (18, 23 and 28 mmol acetic acid) were served with a portion of white wheat bread containing 50 g available carbohydrates as breakfast in randomized order after an overnight fast. Bread served without vinegar was used as a reference meal. Blood samples were taken during 120 min for analysis of glucose and insulin. Satiety was measured with a subjective rating scale. RESULTS: A significant dose-response relation was seen at 30 min for blood glucose and serum insulin responses; the higher the acetic acid level, the lower the metabolic responses. Furthermore, the rating of satiety was directly related to the acetic acid level. Compared with the reference meal, the highest level of vinegar significantly lowered the blood glucose response at 30 and 45 min, the insulin response at 15 and 30 min as well as increased the satiety score at 30, 90 and 120 min postprandially. The low and intermediate levels of vinegar also lowered the 30 min glucose and the 15 min insulin responses significantly compared with the reference meal. When GI and II (insulinaemic indices) were calculated using the 90 min incremental area, a significant lowering was found for the highest amount of acetic acid, although the corresponding values calculated at 120 min did not differ from the reference meal. CONCLUSION: Supplementation of a meal based on white wheat bread with vinegar reduced postprandial responses of blood glucose and insulin, and increased the subjective rating of satiety. There was an inverse dose-response relation between the level of acetic acid and glucose and insulin responses and a linear dose-response relation between acetic acid and satiety rating. The results indicate an interesting potential of fermented and pickled products containing acetic acid.",
"title": "Vinegar supplementation lowers glucose and insulin responses and increases satiety after a bread meal in healthy subjects."
}
] |
PLAIN-2626
|
Carcinogen Blocking Effects of Turmeric
|
[
{
"docid": "MED-5327",
"text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.",
"title": "The association between dietary patterns and mental health in early adolescence."
},
{
"docid": "MED-5329",
"text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.",
"title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet."
},
{
"docid": "MED-2602",
"text": "In this study, we investigated the molecular pathways targeted by curcumin during apoptosis of human melanoma cell lines. We found that curcumin caused cell death in eight melanoma cell lines, four with wild-type and four with mutant p53. We demonstrate that curcumin-induced apoptosis is both dose- and time-dependent. We found that curcumin did not induce p53, suggesting that curcumin activates other apoptosis pathways. Our data show that curcumin activates caspases-3 and -8 but not caspase-9, supporting the rationale that apoptosis occurs via a membrane-mediated mechanism. Both a caspase-8 and broad-based caspase inhibitor, but not a caspase-9 specific inhibitor, suppressed curcumin-induced cell death. To further support our hypothesis that curcumin induces activation of a death receptor pathway, we show that curcumin induces Fas receptor aggregation in a FasL-independent manner and that low-temperature incubation, previously shown to inhibit receptor aggregation, prevented curcumin-induced cell death. Moreover, we demonstrate that expression of dominant negative FADD significantly inhibited curcumin-induced cell death. In addition, our results indicate that curcumin also blocks the NF-kappaB cell survival pathway and suppresses the apoptotic inhibitor, XIAP. Since melanoma cells with mutant p53 are strongly resistant to conventional chemotherapy, curcumin may overcome the chemoresistance of these cells and provide potential new avenues for treatment.",
"title": "Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53."
},
{
"docid": "MED-5341",
"text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.",
"title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro."
},
{
"docid": "MED-2812",
"text": "Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Molecular mechanisms of curcumin action: gene expression."
},
{
"docid": "MED-2604",
"text": "Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.",
"title": "Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?"
},
{
"docid": "MED-2605",
"text": "Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is known to inhibit proliferation of cancer cells by arresting them at various phases of the cell cycle and to induce apoptosis in tumor cells. Curcumin-induced apoptosis mainly involves the activation of caspase-3 and mitochondria-mediated pathway in various cancer cells of different tissue origin. In the present study, the induction of apoptosis and cytotoxicity by curcumin in colon cancer colo 205 cells was investigated by using flow cytometry. The results demonstrated that curcumin induced cytotoxicity and apoptosis dose- and time-depedently. Curcumin induced the production of reactive oxygen species (ROS) and Ca+2, decreased the levels of mitochondria membrane potential and induced caspase-3 activity. Curcumin also promoted the expression of Bax, cytochrome C, p53 and p21 but inhibited the expression of Bcl-2. These observations suggest that curcumin may have a possible therapeutic potential in colon cancer patients.",
"title": "Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3."
},
{
"docid": "MED-5116",
"text": "BACKGROUND: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. METHODS: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n=1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n=173 deaths) and breast cancer-specific mortality (n=113 deaths) were determined through the National Death Index. RESULTS: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. CONCLUSION: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings.",
"title": "Dietary flavonoid intake and breast cancer survival among women on Long Island."
},
{
"docid": "MED-4051",
"text": "The food mutagens IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) are heterocyclic amines (HCA), generated when heating proteinaceous food. This study investigates the protective potential of the flavonoids quercetin (Q) and rutin (R) against oxidative stress induced in vitro by IQ and PhIP in lymphocytes from healthy individuals and untreated, newly diagnosed colon cancer patients using the Comet assay. In the presence of up to 500μM Q and R, the DNA damage resulting from a high dose of PhIP (75μM) or IQ (150μM) was significantly reduced (P<0.001) to levels comparable to six times lower IQ or 7.5 times lower PhIP doses. Lymphocytes from colon cancer patients had greater baseline DNA damage than those from healthy individuals (P<0.01) and this higher level of damage was also observed throughout in vitro treatment. Except for the >50years of age group and male gender, confounding factors such as smoking, drinking and/or dietary habits were not found to be significant. In conclusion, flavonoids reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients."
},
{
"docid": "MED-4197",
"text": "Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.",
"title": "Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation."
},
{
"docid": "MED-4058",
"text": "A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AαC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at level just above the LOQ (65 pg/g hair), indicating PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6-month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0, 0.080 to 800 µg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AαC and MeIQx were detected in fur at dosages ≥0.8 µg AαC/kg body weight and ≥8 µg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p-values <0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising long-lived biomarker with by which we can assess the exposure to PhIP, a potential human carcinogen.",
"title": "Biomonitoring of Carcinogenic Heterocyclic Aromatic Amines in Hair: A Validation Study"
},
{
"docid": "MED-2607",
"text": "Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications.",
"title": "New perspectives of curcumin in cancer prevention"
},
{
"docid": "MED-5339",
"text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.",
"title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat."
},
{
"docid": "MED-4047",
"text": "The total phenolic contents and antioxidant activities of garlics from California, Oregon, Washington, and New York were determined by Fourier transform infrared (FT-IR) spectroscopy (400-4000 cm(-1)). The total phenolic content was quantified [Folin-Ciocalteu assay (FC)] and three antioxidant activity assays, 2,2-diphenyl-picrylhydrazyl (DPPH) assay, Trolox equivalent antioxidant capacity (TEAC) assay, and ferric reducing antioxidant power (FRAP), were employed for reference measurements. Four independent partial least-squares regression (PLSR) models were constructed with spectra from 25 extracts and their corresponding FC, DPPH, TEAC, and FRAP with values for 20 additional extracts predicted (R > 0.95). The standard errors of calibration and standard error of cross-validation were <1.45 (TEAC), 0.36 (FRAP), and 0.33 μmol Trolox/g FW (DPPH) and 0.55 mg gallic acid/g FW (FC). Cluster and dendrogram analyses could segregate garlic grown at different locations. Hydroxyl and phenolic functional groups most closely correlated with garlic antioxidant activity.",
"title": "Determination of total phenolic content and antioxidant activity of garlic (Allium sativum) and elephant garlic (Allium ampeloprasum) by attenuated..."
},
{
"docid": "MED-4332",
"text": "There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce \"artificial\" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as \"scavenging\" the reactive intermediate(s).",
"title": "Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay."
},
{
"docid": "MED-4060",
"text": "Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are receiving heightened attention as a risk factor for human cancer. HAAs arise during the cooking of meats, fish, and poultry, and several HAAs also occur in tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and induce tumors at multiple sites in rodents. A number of epidemiologic studies have reported that frequent consumption of well-done cooked meats containing HAAs can result in elevated risks for colon, prostate, and mammary cancers. Moreover, DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs induce genetic damage even though the concentrations of these compounds in cooked meats are generally in the low parts-per-billion (ppb) range. With recent improvements in sensitivity of mass spectrometry instrumentation, HAAs, their metabolites, and DNA adducts can be detected at trace amounts in biological fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic studies will help to clarify the role of these dietary genotoxicants in the etiology of human cancer.",
"title": "Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats."
},
{
"docid": "MED-5335",
"text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Does a vegan diet reduce risk for Parkinson's disease?"
},
{
"docid": "MED-4194",
"text": "In this review recent publications are cited for a number of antimutagens. The molecules surveyed are potential or proven \"desmutagens\" or \"interceptors.\" These are biologically prevalent or synthetic molecules that are most often small metabolites proficient in binding to, or reacting with, mutagenic chemicals and free radicals. Many of this class of \"blocking agents\" are \"soft\" and \"hard\" nucleophiles with consequently varying abilities to react with particular classes of electrophiles, the major classes of direct-acting mutagens. Although they serve as a first line of defense against mutagens and carcinogens, many interceptor molecules are under-investigated with regard to their spectra of activity and their possible relevance to prophylaxis or treatment of human disease states.",
"title": "Antimutagens and anticarcinogens: a survey of putative interceptor molecules."
},
{
"docid": "MED-5322",
"text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.",
"title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting."
},
{
"docid": "MED-5324",
"text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.",
"title": "Effects of a high-fat meal on pulmonary function in healthy subjects."
},
{
"docid": "MED-2599",
"text": "Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.",
"title": "Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upre..."
},
{
"docid": "MED-5065",
"text": "Anthocyanins, belonging to the flavonoid family of phytochemicals, have received attention as agents that may have potential in preventing chronic diseases such as cardiovascular diseases and certain cancers. In the present study, an anthocyanin-rich extract from Concord grapes [referred to as Concord grape extract (CGE)] and the anthocyanin delphinidin were evaluated for their capacity to inhibit DNA adduct formation due to the environmental carcinogen benzo[a]pyrene (BP) in MCF-10F cells, a noncancerous, immortalized human breast epithelial cell line. CGE at 10 and 20 microg/mL and delphinidin at 0.6 microM concentrations significantly inhibited BP-DNA adduct formation. This was associated with a significant increase in activities of the phase II detoxification enzymes glutathione S-transferase and NAD(P)H:quinone reductase 1. In addition, these grape components also suppressed reactive oxygen species (ROS) formation, but did not induce antioxidant response element-dependent transcription. Taken together, these data suggest that CGE and a component grape anthocyanin have breast cancer chemopreventive potential due in part to their capacity to block carcinogen-DNA adduct formation, modulate activities of carcinogen-metabolizing enzymes, and suppress ROS in these noncancerous human breast cells.",
"title": "Anthocyanin-rich grape extract blocks breast cell DNA damage."
},
{
"docid": "MED-4050",
"text": "Green tea is a commonly consumed beverage in Asia and has been suggested to have anti-inflammatory and possible anti-carcinogenic properties in laboratory studies. We sought to examine the association between green tea consumption and risk of breast cancer incidence or recurrence, using all available epidemiologic evidence to date. We conducted a systematic search of five databases and performed a meta-analysis of studies of breast cancer risk and recurrence published between 1998 and 2009, encompassing 5,617 cases of breast cancer. Summary relative risks (RR) were calculated using a fixed effects model, and tests of heterogeneity across combined studies were conducted. We identified two studies of breast cancer recurrence and seven studies of breast cancer incidence. Increased green tea consumption (more than three cups a day) was inversely associated with breast cancer recurrence (Pooled RR = 0.73, 95% CI: 0.56-0.96). An analysis of case-control studies of breast cancer incidence suggested an inverse association with a pooled RR of 0.81 (95% CI: 0.75, 0.88) while no association was found among cohort studies of breast cancer incidence. Combining all studies of breast cancer incidence resulted in significant heterogeneity. Available epidemiologic evidence supports the hypothesis that increased green tea consumption may be inversely associated with risk of breast cancer recurrence. The association between green tea consumption and breast cancer incidence remains unclear based on the current evidence.",
"title": "Green tea consumption and breast cancer risk or recurrence: a meta-analysis."
},
{
"docid": "MED-5342",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-5337",
"text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.",
"title": "Intensive lifestyle changes may affect the progression of prostate cancer."
},
{
"docid": "MED-5064",
"text": "To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage, an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay. After consumption of the sprouts (300 g/p/d, n = 8), a reduction of DNA-migration (97%) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine (PhIP) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2). This effect protection may be due to inhibition of sulfotransferase 1A1, which plays a key role in the activation of PhIP. In addition, a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly (39%) lower after the intervention. These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase, but in vitro experiments indicate that sprouts contain compounds, which act as direct scavengers of reactive oxygen species. Serum vitamin C levels were increased by 37% after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels. Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage.",
"title": "Consumption of Brussels sprouts protects peripheral human lymphocytes against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative ..."
},
{
"docid": "MED-2816",
"text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.",
"title": "Plant-derived health: the effects of turmeric and curcuminoids."
},
{
"docid": "MED-5330",
"text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.",
"title": "Effect of a single high-fat meal on endothelial function in healthy subjects."
},
{
"docid": "MED-4195",
"text": "Chlorophyll (Chla) and chlorophyllin (CHL) were shown previously to reduce carcinogen bioavailability, biomarker damage, and tumorigenicity in trout and rats. These findings were partially extended to humans, where CHL reduced excretion of aflatoxin B(1) (AFB(1))-DNA repair products in Chinese unavoidably exposed to dietary AFB(1). However, neither AFB(1) pharmacokinetics nor Chla effects were examined. We conducted an unblinded crossover study to establish AFB(1) pharmacokinetic parameters among four human volunteers, and to explore possible effects of CHL or Chla cotreatment in three of those volunteers. For protocol 1, fasted subjects received an Institutional Review Board-approved dose of 14C-AFB(1) (30 ng, 5 nCi) by capsule with 100 mL water, followed by normal eating and drinking after 2 hours. Blood and cumulative urine samples were collected over 72 hours, and 14C- AFB(1) equivalents were determined by accelerator mass spectrometry. Protocols 2 and 3 were similar except capsules also contained 150 mg of purified Chla or CHL, respectively. Protocols were repeated thrice for each volunteer. The study revealed rapid human AFB(1) uptake (plasma k(a), 5.05 + or - 1.10 h(-1); T(max), 1.0 hour) and urinary elimination (95% complete by 24 hours) kinetics. Chla and CHL treatment each significantly impeded AFB(1) absorption and reduced Cmax and AUCs (plasma and urine) in one or more subjects. These initial results provide AFB(1) pharmacokinetic parameters previously unavailable for humans, and suggest that Chla or CHL co-consumption may limit the bioavailability of ingested aflatoxin in humans, as they do in animal models.",
"title": "Effects of chlorophyll and chlorophyllin on low-dose aflatoxin B(1) pharmacokinetics in human volunteers."
},
{
"docid": "MED-5325",
"text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.",
"title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)"
},
{
"docid": "MED-5328",
"text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.",
"title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2"
},
{
"docid": "MED-5363",
"text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.",
"title": "Dietary patterns and depressive symptoms among Japanese men and women."
},
{
"docid": "MED-2598",
"text": "Death receptors belong to the TNF receptor family and are characterised by an intracellular death domain that serves to recruit adapter proteins such as TRADD and FADD and cysteine proteases such as Caspase-8. Activation of Caspase-8 on the aggregated receptor leads to apoptosis. Triggering of death receptors is mediated through the binding of specific ligands of the TNF family, which are homotrimeric type-2 membrane proteins displaying three receptor binding sites. There are various means of modulating the activation of death receptors. The status of the ligand (membrane-bound vs. soluble) is critical in the activation of Fas and of TRAIL receptors. Cleavage of membrane-bound FasL to a soluble form (sFasL) does not affect its ability to bind to Fas but drastically decreases its cytotoxic activity. Conversely, cross-linking epitope-tagged sFasL with anti-tag antibodies to mimic membrane-bound ligand results in a 1000-fold increase in cytotoxicity. This suggests that more than three Fas molecules need to be aggregated to efficiently signal apoptosis. Death receptors can also be regulated by decoy receptors. The cytotoxic ligand TRAIL interacts with five receptors, only two of which (TRAIL-R1 and -R2) have a death domain. TRAIL-R3 is anchored to the membrane by a glycolipid and acts as a dominant negative inhibitor of TRAIL-mediated apoptosis when overexpressed on TRAIL-sensitive cells. Intracellular proteins interacting with the apoptotic pathway are potential modulators of death receptors. FLIP resembles Caspase-8 in structure but lacks protease activity. It interacts with both FADD and Caspase-8 to inhibits the apoptotic signal of death receptors and, at the same time, can activate other signalling pathways such as that leading to NF-kappa B activation.",
"title": "Apoptosis induced by death receptors."
},
{
"docid": "MED-2606",
"text": "Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.",
"title": "Effect of turmeric on urinary mutagens in smokers."
},
{
"docid": "MED-2608",
"text": "The effects of curcumin, the yellow pigment of the spice, turmeric (Curcuma longa) on the mutagenicity of several environmental mutagens were investigated in the Salmonella/microsome test with or without Aroclor 1254-induced rat-liver homogenate (S-9 mix). With Salmonella typhimurium strain TA98 in the presence of S-9 mix, curcumin inhibited the mutagenicity of bidi and cigarette smoke condensates, tobacco and masheri extracts, benzo[a]pyrne and dimethyl benzo[a]anthracene in a dose-dependent manner. Curcumin did not influence the mutagenicity without S-9 mix of sodium azide, monoacetylhydrazine and streptozocin in strain TA100 nor of 4-nitrophenylenediamine in strain TA98. Our observations indicate that curcumin may alter the metabolic activation and detoxification of mutagens.",
"title": "In vitro antimutagenicity of curcumin against environmental mutagens."
},
{
"docid": "MED-5323",
"text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Endocrine-disrupting chemicals and obesity development in humans: a review."
},
{
"docid": "MED-5331",
"text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.",
"title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland."
},
{
"docid": "MED-5340",
"text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.",
"title": "Renal function parameters of Thai vegans compared with non-vegans."
},
{
"docid": "MED-4053",
"text": "Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Occurrence of heterocyclic amines in cooked meat products."
},
{
"docid": "MED-5333",
"text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.",
"title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis."
},
{
"docid": "MED-5332",
"text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.",
"title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age."
},
{
"docid": "MED-5334",
"text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.",
"title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study."
},
{
"docid": "MED-5326",
"text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?"
},
{
"docid": "MED-4055",
"text": "Heterocyclic amines (HCAs) are formed when meat products such as beef, chicken, pork and fish are cooked at high temperatures. The most abundant HCA found in the human diet is 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). PhIP causes mammary carcinomas in female rats and mice, and is associated with an increased risk of developing colon, breast, and prostate cancer in humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by cytochrome b5 reductase producing superoxide anions and hydroxyl radicals causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent cancer in several animal models, presumably by metabolic modulation. We hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To test this hypothesis we treated normal breast epithelial (MCF-10A) cells with PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides was used as a surrogate for ROS. Lipid peroxides were detected using a PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM) and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay. PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the production of reactive oxygen species. Therefore, we propose that DAS can prevent PhIP-induced breast cancer.",
"title": "Diallyl sulfide inhibits PhIP-induced DNA strand breaks in normal human breast epithelial cells."
},
{
"docid": "MED-5338",
"text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.",
"title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease"
},
{
"docid": "MED-2603",
"text": "FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "FADD: a regulator of life and death."
},
{
"docid": "MED-4196",
"text": "Interest in dietary phytochemicals for potential cancer chemoprevention has increased substantially. Screening dietary compounds for chemopreventive activity however, requires a systematic and wide-ranging approach to encompass the complexity of carcinogenesis. We present some of the molecular pathways that underpin the broad biological processes involved in carcinogenesis. Oxidative stress, inflammation, and the evasion of apoptosis are important biological mechanisms by which carcinogenesis occurs. Subsequently, antioxidant, anti-inflammatory, and pro-apoptotic activity represent important activities for preventing, suppressing, or reversing the development of carcinogenesis. Ultimately, these mechanisms of action may provide a useful basis for screening novel phytochemicals for chemopreventive activity. In this review, we identify the important molecular processes that may be targeted in routine screenings of dietary phytochemicals to ultimately select the most effective potential candidates for cancer chemoprevention.",
"title": "Molecular pathways for cancer chemoprevention by dietary phytochemicals."
},
{
"docid": "MED-2601",
"text": "It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.",
"title": "Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pat..."
},
{
"docid": "MED-4049",
"text": "More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP’s mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1α, Sp1, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.",
"title": "Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine"
}
] |
[
{
"docid": "MED-2820",
"text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.",
"title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis"
},
{
"docid": "MED-2075",
"text": "Isothiocyanates are found in cruciferous vegetables such as broccoli, Brussels sprouts, cauliflower, and cabbage. Epidemiologic studies suggest that cruciferous vegetable intake may lower overall cancer risk, including colon and prostate cancer. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables and is especially high in broccoli and broccoli sprouts. SFN has proved to be an effective chemoprotective agent in cell culture, carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer. Early research focused on the “blocking activity” of SFN via Phase 2 enzyme induction, as well as inhibition of enzymes involved in carcinogen activation, but there has been growing interest in other mechanisms of chemoprotection by SFN. Recent studies suggest that SFN offers protection against tumor development during the “post-initiation” phase and mechanisms for suppression effects of SFN, including cell cycle arrest and apoptosis induction are of particular interest. In humans, a key factor in determining the efficacy of SFN as a chemoprevention agent is gaining an understanding of the metabolism, distribution and bioavailability of SFN and the factors that alter these parameters. This review discusses the established anti-cancer properties of SFN, with an emphasis on the possible chemoprevention mechanisms. The current status of SFN in human clinical trials also is included, with consideration of the chemistry, metabolism, absorption and factors influencing SFN bioavailability.",
"title": "Multi-targeted prevention of cancer by sulforaphane"
},
{
"docid": "MED-2831",
"text": "TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8",
"title": "Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers"
},
{
"docid": "MED-2794",
"text": "Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.",
"title": "Dietary turmeric potentially reduces the risk of cancer."
},
{
"docid": "MED-2067",
"text": "A number of natural compounds with inhibitory effects on tumorigenesis have been identified from our diet. Several studies have documented the cancer-preventive activity of a significant number of isothiocyanates (ITCs), the majority of which occur in plants, especially in Cruciferous vegetables. The most characterized ITC is sulforaphane (SFN). SFN has received a great deal of attention because of its ability to simultaneously modulate multiple cellular targets involved in cancer development, including: (i) DNA protection by modulating carcinogen-metabolizing enzymes and blocking the action of mutagens; (ii) inhibition of cell proliferation and induction of apoptosis, thereby retarding or eliminating clonal expansion of initiated, transformed, and/or neoplastic cells; (iii) inhibition of neoangiogenesis, progression of benign tumors to malignant tumors, and metastasis formation. SFN is therefore able to prevent, delay, or reverse preneoplastic lesions, as well as to act on cancer cells as a therapeutic agent. Taking into account this evidence and its favorable toxicological profile, SFN can be viewed as a conceptually promising agent in cancer prevention and/or therapy.",
"title": "Sulforaphane as a promising molecule for fighting cancer."
},
{
"docid": "MED-2814",
"text": "Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin in various cancers."
},
{
"docid": "MED-5197",
"text": "BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature. METHODS: We estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of grilled or barbecued and smoked meats were derived from the interviewer-administered questionnaire data. Dietary intakes of PAH and HCA were derived from the self-administered modified Block food frequency questionnaire of intake 1 year before reference date. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake). Postmenopausal women with low fruit and vegetable intake, but high lifetime intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI = 1.20-2.50). No associations were observed with the food frequency questionnaire-derived intake measures of PAHs and HCAs, with the possible exception of benzo(alpha)pyrene from meat among postmenopausal women whose tumors were positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI = 0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.",
"title": "Cooked meat and risk of breast cancer--lifetime versus recent dietary intake."
},
{
"docid": "MED-5000",
"text": "BACKGROUND: High oxalate intake resulting from consuming supplemental doses of cinnamon and turmeric may increase risk of hyperoxaluria, a significant risk factor for urolithiasis. OBJECTIVE: This study assessed urinary oxalate excretion from supplemental doses of cinnamon and turmeric as well as changes in fasting plasma glucose, cholesterol, and triacylglycerol concentrations. DESIGN: Eleven healthy subjects, aged 21-38 y, participated in an 8-wk, randomly assigned, crossover study that involved the ingestion of supplemental doses of cinnamon and turmeric for 4-wk periods that provided 55 mg oxalate/d. Oxalate load tests, which entailed the ingestion of a 63-mg dose of oxalate from the test spices, were performed after each 4-wk experimental period and at the study onset with water only (control treatment). Fasting plasma glucose and lipid concentrations were also assessed at these time points. RESULTS: Compared with the cinnamon and control treatments, turmeric ingestion led to a significantly higher urinary oxalate excretion during the oxalate load tests. There were no significant changes in fasting plasma glucose or lipids in conjunction with the 4-wk periods of either cinnamon or turmeric supplementation. CONCLUSIONS: The percentage of oxalate that was water soluble differed markedly between cinnamon (6%) and turmeric (91%), which appeared to be the primary cause of the greater urinary oxalate excretion/oxalate absorption from turmeric. The consumption of supplemental doses of turmeric, but not cinnamon, can significantly increase urinary oxalate levels, thereby increasing risk of kidney stone formation in susceptible individuals.",
"title": "Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects."
},
{
"docid": "MED-2786",
"text": "Alzheimer's disease (AD) is the most common form of dementia. There is limited choice in modern therapeutics, and drugs available have limited success with multiple side effects in addition to high cost. Hence, newer and alternate treatment options are being explored for effective and safer therapeutic targets to address AD. Turmeric possesses multiple medicinal uses including treatment for AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture that contributes to the pharmacological profile of parent curcuminoid mixture or turmeric. A careful literature study reveals that the other two constituents of the curcuminoid mixture also contribute significantly to the effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review that each component of the curcuminoid mixture plays a distinct role in making curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents turmeric in its medicinal value better than curcumin alone. The progress in understanding the disease etiology demands a multiple-site-targeted therapy, and the curcuminoid mixture of all components, each with different merits, makes this mixture more promising in combating the challenging disease. Copyright © 2013 John Wiley & Sons, Ltd.",
"title": "Therapeutic potential of turmeric in Alzheimer's disease: curcumin or curcuminoids?"
},
{
"docid": "MED-2819",
"text": "OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.",
"title": "Biological actions of curcumin on articular chondrocytes."
},
{
"docid": "MED-4777",
"text": "The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer.",
"title": "Green tea: nature's defense against malignancies."
},
{
"docid": "MED-1937",
"text": "We describe here three patients with the Alzheimer's Disease (AD) whose behavioral symptoms were improved remarkably as a result of the turmeric treatment, which is the traditional Indian medicine. Their cognitive decline and Behavioral and Psychological Symptoms of Dementia (BPSD) were very severe. All three patients exhibited irritability, agitation, anxiety, and apathy, two patients suffer from urinary incontinence and wonderings. They were prescribed turmeric powder capsules and started recovering from these symptoms without any adverse reaction in the clinical symptom and laboratory data. After 12 weeks of the treatment, total score of the Neuro-Psychiatric Inventory-brief questionnaire decreased significantly in both acuity of symptoms and burden of caregivers. In one case, the Mini-Mental State Examination (MMSE) score was up five points, from 12/30 to 17/30. In the other two cases, no significant change was seen in the MMSE; however, they came to recognize their family within 1 year treatment. All cases have been taking turmeric for more than 1 year, re-exacerbation of BPSD was not seen. The present cases suggest a significant improvement of the behavioral symptoms in the AD with the turmeric treatment, leading to probable benefit of the use of turmeric in individuals with the AD with BPSD.",
"title": "Effects of turmeric on Alzheimer's disease with behavioral and psychological symptoms of dementia"
},
{
"docid": "MED-1819",
"text": "Gemcitabine is a first line cancer drug widely used for the treatment of pancreatic cancer. However, its therapeutic efficiency is significantly limited by resistance of pancreatic cancer cells to this and other chemotherapeutic drugs. We have investigated the cytotoxic effect of Turmeric Force (TF), a supercritical and hydroethanolic extract of turmeric, alone and in combination with gemcitabine in two pancreatic carcinoma cell lines (BxPC3 and Panc-1). TF is highly cytotoxic to BxPC3 and Panc-1 cell lines with IC50 values of 1.0 and 1.22 microg/ml, respectively with superior cytotoxicity than curcumin. Gemcitabine IC50 value for both of these cell line is 0.03 microg/ml; however, 30-48% of the pancreatic cancer cells are resistant to gemcitabine even at concentrations >100 microg/ml. In comparison, TF induced cell death in 96% of the cells at 50 microg/ml. The combination of gemcitabine and TF was synergistic with IC90 levels achieved in both pancreatic cancer cell lines at lower concentrations. CalcuSyn analysis of cytotoxicity data showed that the Gemcitabine + Turmeric Force combination has strong synergism with combination index (CI) values of 0.050 and 0.183 in BxPC3 and Panc-1 lines, respectively at IC50 level. This synergistic effect is due to the increased inhibitory effect of the combination on nuclear factor-kappaB activity and signal transducer and activator of transcription factor 3 expression as compared to the single agent.",
"title": "Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines."
},
{
"docid": "MED-2825",
"text": "Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric."
},
{
"docid": "MED-2783",
"text": "Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Multitargeting by turmeric, the golden spice: From kitchen to clinic."
},
{
"docid": "MED-2801",
"text": "Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin and obesity."
},
{
"docid": "MED-2817",
"text": "Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin in inflammatory diseases."
},
{
"docid": "MED-2243",
"text": "An ethanol extract of turmeric (\"Curcuma longa\") as well as an ointment of curcumin (its active ingredient) were found to produce remarkable symptomatic relief in patients with external cancerous lesions. Reduction in smell were noted in 90% of the cases and reduction in itching in almost all cases. Dry lesions were observed in 70% of the cases, and a small number of patients (10%) had a reduction in lesion size and pain. In many patients the effect continued for several months. An adverse reaction was noticed in only one of the 62 patients evaluated.",
"title": "Turmeric and curcumin as topical agents in cancer therapy."
},
{
"docid": "MED-2811",
"text": "Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.",
"title": "Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations."
},
{
"docid": "MED-2813",
"text": "The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to \"get back to our roots.\"",
"title": "Curcumin: getting back to the roots."
},
{
"docid": "MED-3515",
"text": "Cluster headache (CH) is a primary headache syndrome that is classified with the trigeminal autonomic cephalalgias. CH treatment involves three steps: acute attack management, transitional therapy, and preventive therapy. Greater occipital nerve block has been shown to be an effective alternative bridge therapy to oral steroids in CH. Botulinum toxin type A has recently been studied as a new preventive treatment for patients with chronic CH, with limited success.",
"title": "The role of nerve blocks and botulinum toxin injections in the management of cluster headaches."
},
{
"docid": "MED-1623",
"text": "The artificial sweetener aspartame (L-aspartyl-L-phenylalanyl-methyl ester), is consumed, primarily in beverages, by a very large number of Americans, causing significant elevations in plasma and, probably, brain phenylalanine levels. Anecdotal reports suggest that some people suffer neurologic or behavioral reactions in association with aspartame consumption. Since phenylalanine can be neurotoxic and can affect the synthesis of inhibitory monoamine neurotransmitters, the phenylalanine in aspartame could conceiveably mediate neurologic effects. If mice are given aspartame in doses that elevate plasma phenylalanine levels more than those of tyrosine (which probably occurs after any aspartame dose in humans), the frequency of seizures following the administration of an epileptogenic drug, pentylenetetrazole, is enhanced. This effect is simulated by equimolar phenylalanine and blocked by concurrent administration of valine, which blocks phenylalanine's entry into the brain. Aspartame also potentiates the induction of seizures by inhaled fluorothyl or by electroconvulsive shock. Perhaps regulations concerning the sale of food additives should be modified to require the reporting of adverse reactions and the continuing conduct of mandated safety research.",
"title": "Possible neurologic effects of aspartame, a widely used food additive."
},
{
"docid": "MED-2824",
"text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.",
"title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution."
},
{
"docid": "MED-3609",
"text": "Zingerone a dietary compound was investigated for its ability to protect against radiation induced genotoxicity and apoptosis in human lymphocytes growing in vitro. The radiation antagonistic potential of zingerone was assessed by alkaline comet, cytokinesis-block micronucleus, apoptosis and reactive oxygen species inhibition assays. Treatment of lymphocytes with zingerone (10μg/ml) prior exposure to 2Gy gamma radiation resulted in a significant reduction of frequency of micronuclei as compared to the control set of cells evaluated by cytokinesis blocked micronucleus assay. Similarly, treatment of lymphocytes with zingerone prior to radiation exposure showed significant decrease in the DNA damage as assessed by comet parameters, such as percent tail DNA and Olive tail moment. Further, treatment with zingerone (10μg/ml) before irradiation significantly decreased the percentage of apoptotic cells analyzed microscopically method and by DNA ladder assay. Similarly, the radiation induced reactive oxygen species levels were significantly (P<0.01) inhibited by zingerone. Our study demonstrates the protective effect of zingerone against radiation induced DNA damage and antiapoptotic effect in human lymphocytes, which may be partly attributed to scavenging of radiation induced free radicals and also by the inhibition of radiation induced oxidative stress. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Protective effect of zingerone, a dietary compound against radiation induced genetic damage and apoptosis in human lymphocytes."
},
{
"docid": "MED-2830",
"text": "OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.",
"title": "Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks."
},
{
"docid": "MED-3161",
"text": "Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.",
"title": "Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic ..."
},
{
"docid": "MED-3763",
"text": "The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity."
},
{
"docid": "MED-4448",
"text": "Flavonoids have been hypothesized to reduce cancer risk. Previous epidemiological studies conducted to evaluate this hypothesis have not assessed all flavonoids, including classes that could contribute to intake among Americans, which would result in an underestimation of intake. This misclassification could mask variability among individuals, resulting in attenuated effect estimates for the association between flavonoids and cancer. To augment flavonoid and lignan intake estimates, we developed a database that can be used in conjunction with a food-frequency questionnaire (FFQ). Coupling information derived from the available literature with the U.S. Department of Agriculture databases, we estimated content of 6 flavonoid classes and lignans for 50 food group items. We combined these estimates with responses from a modified Block FFQ that was self-completed in 1996-1997 by a population-based sample of women without breast cancer on Long Island, New York (n = 1,500). Total flavonoid and lignan content of food items ranged from 0 to 129 mg/100 g, and the richest sources were tea, cherries, and grapefruit. Individual intake estimates, from highest to lowest, were flavan-3-ols, flavanones, flavonols, lignans, isoflavones, anthocyanidins, and flavones. Each class of flavonoids and lignans exhibited a wide range of intake levels. This database is useful to quantify flavonoid and lignan intake for other observational studies conducted in the United States that utilize the Block FFQ.",
"title": "Construction of a flavonoid database for assessing intake in a population-based sample of women on Long Island, New York."
},
{
"docid": "MED-3502",
"text": "In this article I review the association between exposure to carrageenan and the occurrence of colonic ulcerations and gastrointestinal neoplasms in animal models. Although the International Agency for Research on Cancer in 1982 identified sufficient evidence for the carcinogenicity of degraded carrageenan in animals to regard it as posing a carcinogenic risk to humans, carrageenan is still used widely as a thickener, stabilizer, and texturizer in a variety of processed foods prevalent in the Western diet. I reviewed experimental data pertaining to carrageenan's effects with particular attention to the occurrence of ulcerations and neoplasms in association with exposure to carrageenan. In addition, I reviewed from established sources mechanisms for production of degraded carrageenan from undegraded or native carrageenan and data with regard to carrageenan intake. Review of these data demonstrated that exposure to undegraded as well as to degraded carrageenan was associated with the occurrence of intestinal ulcerations and neoplasms. This association may be attributed to contamination of undegraded carrageenan by components of low molecular weight, spontaneous metabolism of undegraded carrageenan by acid hydrolysis under conditions of normal digestion, or the interactions with intestinal bacteria. Although in 1972, the U.S. Food and Drug Administration considered restricting dietary carrageenan to an average molecular weight > 100,000, this resolution did not prevail, and no subsequent regulation has restricted use. Because of the acknowledged carcinogenic properties of degraded carrageenan in animal models and the cancer-promoting effects of undegraded carrageenan in experimental models, the widespread use of carrageenan in the Western diet should be reconsidered.",
"title": "Review of harmful gastrointestinal effects of carrageenan in animal experiments."
},
{
"docid": "MED-4451",
"text": "Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.",
"title": "Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish."
}
] |
PLAIN-501
|
agave nectar
|
[
{
"docid": "MED-5056",
"text": "BACKGROUND: Oxidative damage is implicated in the etiology of cancer, cardiovascular disease, and other degenerative disorders. Recent nutritional research has focused on the antioxidant potential of foods, while current dietary recommendations are to increase the intake of antioxidant-rich foods rather than supplement specific nutrients. Many alternatives to refined sugar are available, including raw cane sugar, plant saps/syrups (eg, maple syrup, agave nectar), molasses, honey, and fruit sugars (eg, date sugar). Unrefined sweeteners were hypothesized to contain higher levels of antioxidants, similar to the contrast between whole and refined grain products. OBJECTIVE: To compare the total antioxidant content of natural sweeteners as alternatives to refined sugar. DESIGN: The ferric-reducing ability of plasma (FRAP) assay was used to estimate total antioxidant capacity. Major brands of 12 types of sweeteners as well as refined white sugar and corn syrup were sampled from retail outlets in the United States. RESULTS: Substantial differences in total antioxidant content of different sweeteners were found. Refined sugar, corn syrup, and agave nectar contained minimal antioxidant activity (<0.01 mmol FRAP/100 g); raw cane sugar had a higher FRAP (0.1 mmol/100 g). Dark and blackstrap molasses had the highest FRAP (4.6 to 4.9 mmol/100 g), while maple syrup, brown sugar, and honey showed intermediate antioxidant capacity (0.2 to 0.7 mmol FRAP/100 g). Based on an average intake of 130 g/day refined sugars and the antioxidant activity measured in typical diets, substituting alternative sweeteners could increase antioxidant intake an average of 2.6 mmol/day, similar to the amount found in a serving of berries or nuts. CONCLUSION: Many readily available alternatives to refined sugar offer the potential benefit of antioxidant activity.",
"title": "Total antioxidant content of alternatives to refined sugar."
}
] |
[
{
"docid": "MED-1671",
"text": "BACKGROUND: Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. OBJECTIVE: We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. DESIGN: Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS: In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. CONCLUSIONS: Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.",
"title": "Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women."
},
{
"docid": "MED-1439",
"text": "BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.",
"title": "Brain volume changes on longitudinal magnetic resonance imaging in normal older people."
},
{
"docid": "MED-1786",
"text": "Fertility status may predict later mortality, but no studies have examined the effect of semen quality on subsequent mortality. Men referred to the Copenhagen Sperm Analysis Laboratory by general practitioners and urologists from 1963 to 2001 were, through a unique personal identification number, linked to the Danish central registers that hold information on all cases of cancer, causes of death, and number of children in the Danish population. The men were followed until December 31, 2001, death, or censoring, whichever occurred first, and the total mortality and cause-specific mortality of the cohort were compared with those of all age-standardized Danish men or according to semen characteristics. Among 43,277 men without azospermia referred for infertility problems, mortality decreased as the sperm concentration increased up to a threshold of 40 million/mL. As the percentages of motile and morphologically normal spermatozoa and semen volume increased, mortality decreased in a dose-response manner (P(trend) < 0.05). The decrease in mortality among men with good semen quality was due to a decrease in a wide range of diseases and was found among men both with and without children; therefore, the decrease in mortality could not be attributed solely to lifestyle and/or social factors. Semen quality may therefore be a fundamental biomarker of overall male health.",
"title": "Good semen quality and life expectancy: a cohort study of 43,277 men."
},
{
"docid": "MED-1660",
"text": "OBJECTIVES: Atherosclerosis of arteries supplying the lumbar region has been suggested as a mechanism leading to intervertebral disc degeneration and sciatica. The study described here examined whether serum lipid levels or pharmacologically treated hyperlipidemia were associated with sciatica. METHODS: A nationally representative sample (n=8028) of Finns aged 30 years or over was interviewed and examined. Sciatica was assessed by a physician according to preset criteria. Information for the present purpose was available for 74.8% of the sample. RESULTS: The prevalence of sciatica was 3.3% for men and 2.2% for women. In men without hyperlipidemia treatment, sciatica was associated with total cholesterol (high vs. low tertile: OR 2.28, 95% CI 1.14-4.55), LDL cholesterol (2.12; 1.11-4.05), and triglycerides (1.92; 1.04-3.55), adjusted for age, BMI, exercise, smoking, heavy physical work, and education. HDL was not associated with sciatica. For men in the highest tertile of both total cholesterol and triglycerides, the OR of sciatica was 3.89 (1.68-8.99) in comparison to men with cholesterol in the lowest tertile and triglycerides in the lowest or the middle tertile. In similar analyses among women no associations were seen. Pharmacologically treated hyperlipidemia was associated with sciatica in women (2.02; 1.01-4.04), but not in men (1.71; 0.83-3.55). CONCLUSIONS: Independent of BMI and other possible confounders, clinically assessed sciatica in men was associated with levels of atherogenic serum lipids. Pharmacologically treated hyperlipidemia was associated with sciatica in women. The findings are in accordance with the atherosclerosis-sciatica hypothesis.",
"title": "Serum lipids in relation to sciatica among Finns."
},
{
"docid": "MED-2195",
"text": "The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected. © 2013 Institute of Food Technologists®",
"title": "The influence of deep frying using various vegetable oils on acrylamide formation in sweet potato (Ipomoea batatas L. Lam) chips."
},
{
"docid": "MED-2479",
"text": "BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.",
"title": "The intestinal microflora in allergic Estonian and Swedish 2-year-old children."
},
{
"docid": "MED-1852",
"text": "Aluminium (Al) migration from cans to beer and tea was studied along time. Analyses of Al in the canned drinks were performed till the sell-by date, and, in seven months, aluminium migration was found to increase 0.14 mg L(-1) in beer, and 0.6 mg L(-1) in tea. This study included dented cans from which aluminium migration into tea was found to be particularly severe. Al concentration in dented canned tea increased 9.6 mg L(-1) in seven months.",
"title": "Aluminium migration into beverages: are dented cans safe?"
},
{
"docid": "MED-4642",
"text": "The role of diet in breast cancer (BC) risk is unclear. Fiber could reduce BC risk, through the enterohepatic circulation of estrogens. We examined the relationship between diet and sex hormones in postmenopausal women with or without BC. Thirty-one postmenopausal women (10 omnivores, 11 vegetarians, and 10 BC omnivores) were recruited. Dietary records (5 days) and hormone levels (3 days) were evaluated on 4 occasions over 1 yr. Vegetarians showed a lower fat/fiber ratio, a higher intake of total and cereal fiber (g/d)/body weight (kg), a significantly lower level of plasma estrone-sulfate, estradiol, free-estradiol, free-testosterone, and ring D oxygenated estrogens, and a significantly higher level of sex-hormone-binding-globulin than BC subjects. Fiber was consumed in slightly larger amounts by omnivores than by BC subjects. Omnivores had significantly lower plasma testosterone and estrone-sulfate but higher sex-hormone-binding-globulin than BC subjects. No difference was found for the urinary 16-oxygenated estrogens. However, the 2-MeO-E1/2-OH-E1 ratio was significantly lower in omnivores than in BC group. This ratio is positively associated with the fat/fiber ratio. In conclusion, testosterone may contribute to causing alterations in the levels of catechol estrogens and 16-oxygenated estrogens. The fat/fiber ratio appears to be useful in evaluating dietary effects on estrogen metabolism.",
"title": "Diets and hormonal levels in postmenopausal women with or without breast cancer."
},
{
"docid": "MED-2058",
"text": "OBJECTIVE: To examine daily cows milk consumption and duration of breastfeeding in infants and young children with anal fissure and constipation. METHODS: Two groups of 30 consecutive children aged between 4 months and 3 years were evaluated retrospectively. Group I comprised children with chronic constipation and anal fissure in whom surgical causes were excluded, and group II comprised normal children. The daily consumption of cows milk, duration of breastfeeding and other clinical features of the children were investigated RESULTS: The mean daily consumption of cows milk was significantly higher in group I (756 mL, range 200-1500 mL) than group II (253 mL, range 0-1000 mL) (P < 0.001). Group I children were breastfed for a significantly shorter period (5.8 months, range 0-18 months) than group II (10.1 months, range 2-24 months) (P < 0.006). The odds ratios for the two factors - children consuming more than 200 mL of cows milk per day (25 children in group I, 11 children in group II) and breastfeeding for less than 4 months (16 children in group I, 5 children in group II) - were calculated to be 8.6 (95% confidence interval [CI]: 0.23-0.74, P = 0.0005) and 5.7 (95% CI: 0.37-0.66, P = 0.007), respectively. CONCLUSIONS: Infants and young children with chronic constipation and anal fissure may consume larger amounts of cows milk than children with a normal bowel habit. Additionally, shorter duration of breastfeeding and early bottle feeding with cows milk may play a role in the development of constipation and anal fissure in infants and young children.",
"title": "Cows milk consumption in constipation and anal fissure in infants and young children."
},
{
"docid": "MED-3733",
"text": "This study assessed the metabolic response to sweetened dried cranberries (SDC), raw cranberries (RC), and white bread (WB) in humans with type 2 diabetes. Development of palatable cranberry preparations associated with lower glycemic responses may be useful for improving fruit consumption and glycemic control among those with diabetes. In this trial, type 2 diabetics (n= 13) received WB (57 g, 160 cal, 1 g fiber), RC (55 g, 21 cal, 1 g fiber), SDC (40 g, 138 cal, 2.1 g fiber), and SDC containing less sugar (SDC-LS, 40 g, 113 cal, 1.8 g fiber + 10 g polydextrose). Plasma glucose (mmol/L) peaked significantly at 60 min for WB, and at 30 min for RC, SDC, and SDC-LS at 9.6 ± 0.4, 7.0 ± 0.4, 9.6 ± 0.5, and 8.7 ± 0.5, respectively, WB remained significantly elevated from the other treatments at 120 min. Plasma insulin (pmol/mL) peaked at 60 min for WB and SDC and at 30 min for RC and SDC-LS at 157 ± 15, 142 ± 27, 61 ± 8, and 97 ± 11, respectively. Plasma insulin for SDC-LS was significantly lower at 60 min than either WB or SDC. Insulin area under the curve (AUC) values for RC and SDC-LS were both significantly lower than WB or SDC. Phenolic content of SDC and SDC-LS was determined following extraction with 80% acetone prior to high-performance liquid chromatography (HPLC) and electronspray ionization-mass spectrometry (ESI-MS) and found to be rich in 5-caffeoylquinic cid, quercetin-3-galactoside, and quercetin-3-galactoside, and the proanthocyanidin dimer epicatechin. In conclusion, SDC-LS was associated with a favorable glycemic and insulinemic response in type 2 diabetics. Practical Application: This study compares phenolic content and glycemic responses among different cranberry products. The study seeks to expand the palatable and portable healthy food choices for persons with type 2 diabetes. The novel use of polydextrose as a bulking agent making possible a reduction in caloric content and potential glycemic response is also characterized in this study.",
"title": "Glycemic responses to sweetened dried and raw cranberries in humans with type 2 diabetes."
},
{
"docid": "MED-2673",
"text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.",
"title": "Determination of microbial transglutaminase in meat and meat products."
},
{
"docid": "MED-4834",
"text": "Soft drinks can be a major source of sucrose, which may influence serum lipid concentration. We have examined the association between intake frequency of various types of soft drinks and the concentration of serum triglycerides (TG) and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol in the cross-sectional Oslo Health Study. A total of 14 188 subjects of the altogether 18,770 participants of the study had data on intake frequency of colas and non-colas, with or without sugar. The population sample consisted of both sexes and 3 age groups: group 1 (30 years of age), group 2 (40 and 45 years of age), and group 3 (59-60 years of age). In both sexes, HDL decreased and TG increased significantly (p < 0.001) with increasing intake frequency of colas. In contrast, no consistent associations were found between the reported intake of non-cola soft drinks and the serum lipids. We found no significant differences related to the reported presence or absence of sugar in the soft drinks. In multiple linear regression analyses, the colas vs. serum lipid associations prevailed (p < 0.001) after including 13 possible confounders: sex; age group; time since last meal; physical activity; intake of alcohol, coffee, cheese, fruit and (or) berries, and fatty fish; smoking; length of education; use of cholesterol-lowering drugs; and intake of non-colas. Thus, the self-reported intake frequency of colas, but not other soft drinks, was negatively associated with serum HDL, and positively associated with TG and LDL.",
"title": "Cola intake and serum lipids in the Oslo Health Study."
},
{
"docid": "MED-1241",
"text": "PURPOSE: With little scientific evidence to support use of aromatherapy for postoperative nausea and/or vomiting (PONV) symptoms, this study evaluated controlled breathing with peppermint aromatherapy (AR) and controlled breathing alone (CB) for PONV relief. DESIGN: A single blind randomized control trial design was used. METHODS: On initial PONV complaint, symptomatic subjects received either CB (n = 16) or AR (n = 26) intervention based on randomization at enrollment. A second treatment was repeated at 5 minutes if indicated. Final assessment occurred 10 minutes post initial treatment. Rescue medication was offered for persistent symptoms. FINDINGS: Among eligible subjects, PONV incidence was 21.4% (42/196). Gender was the only risk factor contributing to PONV symptoms (P = .0024). Though not statistically significant, CB was more efficacious than AR, 62.5% versus 57.7%, respectively. CONCLUSIONS: CB can be initiated without delay as an alternative to prescribed antiemetics. Data also support use of peppermint AR in conjunction with CB for PONV relief. Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.",
"title": "Controlled breathing with or without peppermint aromatherapy for postoperative nausea and/or vomiting symptom relief: a randomized controlled trial."
},
{
"docid": "MED-1551",
"text": "In a controlled trial, 21 strict vegetarians were studied prospectively for eight weeks: a two-week control period of the usual vegetarian diet was followed by four weeks, during which 250 g of beef was added isocalorically to the daily vegetarian diet and then by two weeks of the control diet. Plasma high-density lipoprotein-cholesterol did not change during the study, whereas plasma total cholesterol rose significantly by 19% at the end of the meat-eating period. Systolic blood pressure (BP) increased significantly during the meat eating by 3% over control values, whereas diastolic BP showed no major changes. Plasma renin activity, prostaglandin A and E levels, and urinary kallikrein, norepinephrine, and epinephrine excretions were within normal limits and did not change notably throughout the trial. The study suggests an adverse effect of consumption of beef on plasma lipid and BP levels.",
"title": "Effect of ingestion of meat on plasma cholesterol of vegetarians."
},
{
"docid": "MED-2969",
"text": "OBJECTIVE: We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-kappaB (NF-kappaB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose. RESEARCH DESIGN AND METHODS: Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected. RESULTS: There was a significant increase in ROS generation by mononuclear cells (by 130 +/- 18%, P < 0.001), polymorph nuclear cells (by 95 +/- 22%, P < 0.01), and in NF-kappaB binding in mononuclear cells by 82 +/- 16% (P < 0.01) over the baseline after 2 h of glucose intake. These changes were absent following fructose, orange juice, or water intake. There was significantly lower ROS generation and NF-kappaB binding following orange juice, fructose, and water compared with glucose (P < 0.001 for all). Furthermore, incubation of mononuclear cells in vitro with 50 mmol/l of the flavonoids hesperetin or naringenin reduced ROS generation by 52 +/- 7% and 77 +/- 8% (P < 0.01), respectively, while fructose or ascorbic acid did not cause any change. CONCLUSIONS: Caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to its flavonoids content and might, therefore, represent a potentially safe energy source.",
"title": "Orange juice or fructose intake does not induce oxidative and inflammatory response."
},
{
"docid": "MED-870",
"text": "Ilex paraguariensis dried and minced leaves are made into a brewed tea, prepared in a sui generis manner by large populations in South America, having evolved from a tea drunk by the Guarani ethnic group to a beverage that has a social and almost ritualistic role in some South American modern societies. It is used both as a source of caffeine, in lieu or in parallel with tea and coffee, but also as a therapeutic agent for its alleged pharmacological properties. Although with some exceptions, research on biomedical properties of this herb has had a late start and strongly lags behind the impressive amount of literature on green tea and coffee. However, in the past 15 years, there was a several-fold increase in the literature studying Ilex paraguariensis properties showing effects such as antioxidant properties in chemical models and ex vivo lipoprotein studies, vaso-dilating and lipid reduction properties, antimutagenic effects, controversial association with oropharyngeal cancer, anti-glycation effects and weight reduction properties. Lately, promising results from human intervention studies have surfaced and the literature offers several developments on this area. The aim of this review is to provide a concise summary of the research published in the past three years, with an emphasis on translational studies, inflammation and lipid metabolism. Ilex paraguariensis reduces LDL-cholesterol levels in humans with Ilex paraguariensis dyslipoproteinemia and the effect is synergic with that of statins. Plasma antioxidant capacity as well as expression of antioxidant enzymes is positively modulated by intervention with Ilex paraguariensis in human cohorts. A review on the evidence implicating Ilex paraguariensis heavy consumption with some neoplasias show data that are inconclusive but indicate that contamination with alkylating agents during the drying process of the leaves should be avoided. On the other hand, several new studies confirm the antimutagenic effects of Ilex paraguariensis in different models, from DNA double breaks in cell culture models to mice studies. Novel interesting work has emerged showing significant effect on weight reduction both in mice and in rat models. Some mechanisms involved are inhibition of pancreatic lipase, activation of AMPK and uncoupling of electron transport. Intervention studies in animals have provided strong evidence of anti-inflammatory effects of Ilex paraguariensis, notably protecting cigarette-induced lung inflammation acting on macrophage migration and inactivating matrix-metalloproteinase. Research on the effects of Ilex paraguariensis in health and disease has confirmed its antioxidant, anti-inflammatory, antimutagenic and lipid-lowering activities. Although we are still waiting for the double-blind, randomized prospective clinical trial, the evidence seems to provide support for beneficial effects of mate drinking on chronic diseases with inflammatory component and lipid metabolism disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.",
"title": "Recent advances on Ilex paraguariensis research: minireview."
},
{
"docid": "MED-4412",
"text": "BACKGROUND & AIMS: The aim of this study was to investigate whether nutritional risk factors, especially black tea consumptions, are inversely associated with the development of chronic obstructive pulmonary disease (COPD) in male smokers. METHODS: Forty male smokers with clinical diagnosis of COPD (Group-I (GI)) and 36 healthy smokers without COPD (Group-II (GII)) were included in this study. We compared the dietary habits and food intakes of the two groups using an adaptation of the Arizona Food Frequency Questionnaire (AFFQ). Question form included a list of 65 food items formed from five main food groups (grain, meat and alternatives, dairy products, vegetables-fruits and fat) and 25 dietary habits. The data were evaluated by binary logistic regression analysis, receiver operating characteristic (ROC) curve, Kolmogorov-Smirnov, Student's t, Mann-Whitney, and Chi-square tests. RESULTS: When both groups compared, black tea consumptions (GI-700ml; GII-1600ml (OR: 0.635, P<0.001)), vegetable fruits scores (GI-54.30; GII-63.81 (OR: 0.863, P<0.001)), regularly breakfast habit (GI-24 patients; GII-36 cases (OR: 0.549, P<0.001)) and eating salty (GI-22 patients; GII-5 cases (P<0.001)) made significant differences. In ROC curves, the area under the curve of black tea (0.898 (95% CI: 0.819-0.977) and vegetables-fruits (0.833 (95% CI: 0.727-0.938) provided high accuracy to distinguish between COPD group and controls (P<0.001). CONCLUSIONS: High intakes of black tea and vegetables-fruits consumptions may be protecting male smokers from developing COPD.",
"title": "Nutritional risk factors for the development of chronic obstructive pulmonary disease (COPD) in male smokers."
},
{
"docid": "MED-3683",
"text": "BACKGROUND: The aim of this study was to investigate whether consumption of Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) could affect naturally acquired common cold infections in healthy subjects. METHODS: A randomised, parallel, double-blind placebo-controlled study was performed to investigate whether intake of this probiotic mixture could reduce the risk of common cold episodes, number of days with common cold symptoms, frequency and severity of symptoms, and cellular immune response in common cold infections. A total of 272 subjects were supplemented daily with either 10(9) cfu (colony forming units) of probiotics (N = 135) or control (N = 137) for a 12-week period. RESULTS: The incidence of acquiring one or more common cold episode was reduced from 67% in the control group to 55% in the probiotic group (p < 0.05). Also, the number of days with common cold symptoms were significantly (p < 0.05) reduced from 8.6 days in the control group to 6.2 days, in the probiotic group, during the 12-week period. The total symptom score was reduced during the study period from a mean of 44.4 for the control group to 33.6 for the probiotic group. The reduction in pharyngeal symptoms was significant (p < 0.05). In addition, the proliferation of B lymphocytes was significantly counteracted in the probiotic group (p < 0.05) in comparison with the control group. CONCLUSION: In conclusion, intake of the probiotic strains Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) reduces the risk of acquiring common cold infections.",
"title": "Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infe..."
},
{
"docid": "MED-2004",
"text": "The incidence and prevalence of diabetes (primarily type 2 diabetes) has risen sharply since 1990. It is projected to increase another 64% between 2010 and 2025, affecting 53.1 million people and resulting in medical and societal costs of a half trillion dollars a year. We know how to prevent many cases of diabetes and how to treat it effectively. Early appropriate treatment makes a significant difference in preventing major complications and reducing premature death, but it does not cure the disease. Early detection of prediabetes, in conjunction with lifestyle changes, can reduce the number of people with diabetes. A dramatic reduction in diabetes prevalence over time will require significant lifestyle changes on the part of society as a whole. The purpose of this study is to increase public awareness of the severity of regional diabetes trends by providing detailed forecasts for all states and several metropolitan areas for 2010, 2015, and 2025. A model was created to utilize the latest national diabetes and population data and projections, and to transform these into state and metropolitan area forecasts for the whole population and major subgroups. These forecasts were then summarized in easy-to-understand briefing papers for each state and selected metro areas, which are provided online for easy public access. This research is important because little data exist that project the future prevalence and potential costs of diabetes at the state and metro area level. With this data, key stakeholders can make informed decisions concerning diabetes, its impact on their communities, and resource allocation.",
"title": "Creating public awareness: state 2025 diabetes forecasts."
},
{
"docid": "MED-2346",
"text": "Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.",
"title": "Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity"
},
{
"docid": "MED-5230",
"text": "CONTEXT: Dietary composition may affect insulin secretion, and high insulin levels, in turn, may increase the risk for cardiovascular disease (CVD). OBJECTIVE: To examine the role of fiber consumption and its association with insulin levels, weight gain, and other CVD risk factors compared with other major dietary components. DESIGN AND SETTING: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter population-based cohort study of the change in CVD risk factors over 10 years (1985-1986 to 1995-1996) in Birmingham, Ala; Chicago, III; Minneapolis, Minn; and Oakland, Calif. PARTICIPANTS: A total of 2909 healthy black and white adults, 18 to 30 years of age at enrollment. MAIN OUTCOME MEASURES: Body weight, insulin levels, and other CVD risk factors at year 10, adjusted for baseline values. RESULTS: After adjustment for potential confounding factors, dietary fiber showed linear associations from lowest to highest quintiles of intake with the following: body weight (whites: 174.8-166.7 lb [78.3-75.0 kg], P<.001; blacks: 185.6-177.6 lb [83.5-79.9 kg], P = .001), waist-to-hip ratio (whites: 0.813-0.801, P = .004; blacks: 0.809-0.799, P = .05), fasting insulin adjusted for body mass index (whites: 77.8-72.2 pmol/L [11.2-10.4 microU/mL], P = .007; blacks: 92.4-82.6 pmol/L [13.3-11.9 microU/mL], P = .01) and 2-hour postglucose insulin adjusted for body mass index (whites: 261.1-234.7 pmol/L [37.6-33.8 microU/mL], P = .03; blacks: 370.2-259.7 pmol/L [53.3-37.4 microU/mL], P<.001). Fiber was also associated with blood pressure and levels of triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fibrinogen; these associations were substantially attenuated by adjustment for fasting insulin level. In comparison with fiber, intake of fat, carbohydrate, and protein had inconsistent or weak associations with all CVD risk factors. CONCLUSIONS: Fiber consumption predicted insulin levels, weight gain, and other CVD risk factors more strongly than did total or saturated fat consumption. High-fiber diets may protect against obesity and CVD by lowering insulin levels.",
"title": "Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults."
},
{
"docid": "MED-5249",
"text": "Coffee is the leading worldwide beverage after water and its trade exceeds US $10 billion worldwide. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health promoting potential; however, some researchers have argued about the association of coffee consumption with cardiovascular complications and cancer insurgence. The health-promoting properties of coffee are often attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, hydroxyhydroquinone (HHQ), etc. Many research investigations, epidemiological studies, and meta-analyses regarding coffee consumption revealed its inverse correlation with that of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer's disease. Moreover, it ameliorates oxidative stress because of its ability to induce mRNA and protein expression, and mediates Nrf2-ARE pathway stimulation. Furthermore, caffeine and its metabolites help in proper cognitive functionality. Coffee lipid fraction containing cafestol and kahweol act as a safeguard against some malignant cells by modulating the detoxifying enzymes. On the other hand, their higher levels raise serum cholesterol, posing a possible threat to coronary health, for example, myocardial and cerebral infarction, insomnia, and cardiovascular complications. Caffeine also affects adenosine receptors and its withdrawal is accompanied with muscle fatigue and allied problems in those addicted to coffee. An array of evidence showed that pregnant women or those with postmenopausal problems should avoid excessive consumption of coffee because of its interference with oral contraceptives or postmenopausal hormones. This review article is an attempt to disseminate general information, health claims, and obviously the risk factors associated with coffee consumption to scientists, allied stakeholders, and certainly readers. © Taylor and Francis Group, LLC",
"title": "Coffee and its consumption: benefits and risks."
},
{
"docid": "MED-1066",
"text": "The relations of dietary habits to insulin sensitivity and postprandial triglyceride metabolism were evaluated in 25 patients with nonalcoholic steatohepatitis (NASH) and 25 age-, body mass index (BMI)-, and gender-matched healthy controls. After a 7-day alimentary record, they underwent a standard oral glucose tolerance test (OGTT), and the insulin sensitivity index (ISI) was calculated from the OGTT; an oral fat load test was also performed in 15 patients and 15 controls. The dietary intake of NASH patients was richer in saturated fat (13.7% +/- 3.1% vs. 10.0% +/- 2.1% total kcal, respectively, P =.0001) and in cholesterol (506 +/- 108 vs. 405 +/- 111 mg/d, respectively, P =.002) and was poorer in polyunsaturated fat (10.0% +/- 3.5% vs. 14.5% +/- 4.0% total fat, respectively, P =.0001), fiber (12.9 +/- 4.1 vs. 23.2 +/- 7.8 g/d, respectively, P =.000), and antioxidant vitamins C (84.3 +/- 43.1 vs. 144.2 +/- 63.1 mg/d, respectively, P =.0001) and E (5.4 +/- 1.9 vs. 8.7 +/- 2.9 mg/d, respectively, P =.0001). The ISI was significantly lower in NASH patients than in controls. Postprandial total and very low density lipoproteins triglyceride at +4 hours and +6 hours, triglyceride area under the curve, and incremental triglyceride area under the curve were higher in NASH compared with controls. Saturated fat intake correlated with ISI, with the different features of the metabolic syndrome, and with the postprandial rise of triglyceride. Postprandial apolipoprotein (Apo) B48 and ApoB100 responses in NASH were flat and strikingly dissociated from the triglyceride response, suggesting a defect in ApoB secretion. In conclusion, dietary habits may promote steatohepatitis directly by modulating hepatic triglyceride accumulation and antioxidant activity as well as indirectly by affecting insulin sensitivity and postprandial triglyceride metabolism. Our findings provide further rationale for more specific alimentary interventions, particularly in nonobese, nondiabetic normolipidemic NASH patients.",
"title": "Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis."
},
{
"docid": "MED-1180",
"text": "The effects of extracts from five cultivars of strawberries on the proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated, and possible correlations with the levels of several antioxidants were analyzed. In addition, the effects of organic cultivation compared to conventional cultivation on the content of antioxidants in the strawberries and strawberry extracts on the cancer cell proliferation were investigated. The ratio of ascorbate to dehydroascorbate was significantly higher in the organically cultivated strawberries. The strawberry extracts decreased the proliferation of both HT29 cells and MCF-7 cells in a dose-dependent way. The inhibitory effect for the highest concentration of the extracts was in the range of 41-63% (average 53%) inhibition compared to controls for the HT29 cells and 26-56% (average 43%) for MCF-7 cells. The extracts from organically grown strawberries had a higher antiproliferative activity for both cell types at the highest concentration than the conventionally grown, and this might indicate a higher content of secondary metabolites with anticarcinogenic properties in the organically grown strawberries. For HT29 cells, there was a negative correlation at the highest extract concentration between the content of ascorbate or vitamin C and cancer cell proliferation, whereas for MCF-7 cells, a high ratio of ascorbate to dehydroascorbate correlated with a higher inhibition of cell proliferation at the second highest concentration. The significance of the effect of ascorbate on cancer cell proliferation might lie in a synergistic action with other compounds.",
"title": "Antioxidant levels and inhibition of cancer cell proliferation in vitro by extracts from organically and conventionally cultivated strawberries."
},
{
"docid": "MED-2086",
"text": "Endocrine research in the 1930s increased and extended the use of sex hormones as medical therapies in an unprecedented way, especially for female ailments. In the 1950s the therapeutic use of sex hormones extended to the treatment of 'tall' girls. Ambiguity in the definition of the 'tall' girl, the arbitrary nature of the treatment decision, and diversity in the therapeutic regimes highlight the problematic nature of this medical practice. Using linguistic repertoires to study the political and ideological implications found in the patterned use of language, this paper reports on a discourse analysis of the medical literature on treatment of tall girls between the 1950s and 1990s, when this treatment was at its peak. Three linguistic repertoires emerged: the institutional authority of medicine to determine the 'abnormality' of tall stature in females; the clinical knowledge and experience in the diagnosis of medical risk associated with tall stature in women; and using hormones as cosmetic therapy to (re)produce femininity in tall girls. All three related to the maintenance of the cultural representations and social expectations of femininity. With no evidence of psychological harm associated with tall stature in women, and no long-term studies of either effectiveness or benefit, over five decades clinicians persuaded themselves and their patients that tall stature required therapeutic intervention. The treatment of tall girls with high dose oestrogen must be viewed as the medicalisation of a normal physical attribute adversely related to the social construction of gender. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "The medicalisation of 'tall' girls: A discourse analysis of medical literature on the use of synthetic oestrogen to reduce female height."
},
{
"docid": "MED-5161",
"text": "Dietary flavonols and flavones are subgroups of flavonoids that have been suggested to decrease the risk of coronary heart disease (CHD). The authors prospectively evaluated intakes of flavonols and flavones in relation to risk of nonfatal myocardial infarction and fatal CHD in the Nurses' Health Study. They assessed dietary information from the study's 1990, 1994, and 1998 food frequency questionnaires and computed cumulative average intakes of flavonols and flavones. Cox proportional hazards regression with time-varying variables was used for analysis. During 12 years of follow-up (1990-2002), the authors documented 938 nonfatal myocardial infarctions and 324 CHD deaths among 66,360 women. They observed no association between flavonol or flavone intake and risk of nonfatal myocardial infarction or fatal CHD. However, a weak risk reduction for CHD death was found among women with a higher intake of kaempferol, an individual flavonol found primarily in broccoli and tea. Women in the highest quintile of kaempferol intake relative to those in the lowest had a multivariate relative risk of 0.66 (95% confidence interval: 0.48, 0.93; p for trend = 0.04). The lower risk associated with kaempferol intake was probably attributable to broccoli consumption. These prospective data do not support an inverse association between flavonol or flavone intake and CHD risk.",
"title": "Dietary intakes of flavonols and flavones and coronary heart disease in US women."
},
{
"docid": "MED-1449",
"text": "Amid soaring health spending, there is growing interest in workplace disease prevention and wellness programs to improve health and lower costs. In a critical meta-analysis of the literature on costs and savings associated with such programs, we found that medical costs fall by about $3.27 for every dollar spent on wellness programs and that absenteeism costs fall by about $2.73 for every dollar spent. Although further exploration of the mechanisms at work and broader applicability of the findings is needed, this return on investment suggests that the wider adoption of such programs could prove beneficial for budgets and productivity as well as health outcomes.",
"title": "Workplace wellness programs can generate savings."
},
{
"docid": "MED-1429",
"text": "The first four reviews in this series (Steinberg, D. 2004. J. Lipid Res. 45: 1583-1593; Steinberg, D. 2005. J. Lipid Res. 46: 179-190; Steinberg, D. 2005. J. Lipid Res. 46: 2037-2051; Steinberg, D. 2006. J. Lipid Res. 47: 1-14) traced the gradual accumulation of evidence, evidence of several different kinds, supporting the lipid hypothesis. They tracked the history from Anitschkow's 1913 classic work on the cholesterol-fed rabbit model to the breakthrough 1984 Coronary Primary Prevention Trial, the first large, randomized, double-blind primary intervention trial showing that decreasing blood cholesterol (using cholestyramine) significantly reduces coronary heart disease events. At that point, for the first time, decreasing blood cholesterol levels became an official national public health goal. Still, only a small fraction of patients at high risk were getting appropriate cholesterol-lowering treatment, and a number of important clinical questions remained unanswered. This final review in the series traces the early studies that led to the discovery of the statins and briefly reviews the now familiar large-scale clinical trials demonstrating their safety and their remarkable effectiveness in reducing coronary heart disease morbidity and mortality.",
"title": "Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the s..."
},
{
"docid": "MED-3320",
"text": "OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.",
"title": "Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry."
},
{
"docid": "MED-1711",
"text": "Summary Objectives The insulin-like growth factor (IGF) signaling pathway has been implicated in the pathogenesis of numerous tumor types, including non-small cell lung cancer (NSCLC). Figitumumab is a fully human IgG2 monoclonal antibody against IGF-1 receptor (IGF-1R). Methods This phase I, open-label, dose-escalation study (ClinicalTrials.gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m2) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC. Treatments were administered intravenously on day 1 of a 21-day cycle for four to six cycles. Pharmacokinetics, biomarkers, and antitumor activity were also evaluated. Results Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level. When given in combination, figitumumab plasma exposure increased in an approximately dose-proportional manner. The approximate 2-fold accumulation following repeated administration supported the 21-day regimen as appropriate for figitumumab administration. Serum total IGF-1 and IGF binding protein-3 concentrations increased following figitumumab dosing, but a clear dose-dependent relationship was not demonstrated. Seven of 18 evaluable patients experienced a partial response. Conclusions Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC. Further analysis of biomarker data is necessary for the development of figitumumab therapy.",
"title": "Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer"
}
] |
80187
|
Elvis Presley had a heart attack in the bathroom of Graceland on August 16, 1977.
|
[
{
"docid": "Elvis_Presley",
"text": "Elvis Aaron Presley ( January 8 , 1935 -- August 16 , 1977 ) was an American singer-songwriter and actor . Regarded as one of the most significant cultural icons of the 20th century , he is often referred to as the `` King of Rock and Roll '' , or simply `` the King '' . Presley was born in Tupelo , Mississippi , and relocated to Memphis , Tennessee , with his family when he was 13 years old . His music career began there in 1954 , when he recorded a song with producer Sam Phillips at Sun Records . Accompanied by guitarist Scotty Moore and bassist Bill Black , Presley was an early popularizer of rockabilly , an uptempo , backbeat-driven fusion of country music and rhythm and blues . RCA Victor acquired his contract in a deal arranged by Colonel Tom Parker , who managed the singer for more than two decades . Presley 's first RCA single , `` Heartbreak Hotel '' , was released in January 1956 and became a number-one hit in the United States . He was regarded as the leading figure of rock and roll after a series of successful network television appearances and chart-topping records . His energized interpretations of songs and sexually provocative performance style , combined with a singularly potent mix of influences across color lines that coincided with the dawn of the Civil Rights Movement , made him enormously popular -- and controversial . In November 1956 , Presley made his film debut in Love Me Tender . In 1958 , he was drafted into military service . He resumed his recording career two years later , producing some of his most commercially successful work before devoting much of the 1960s to making Hollywood films and their accompanying soundtrack albums , most of which were critically derided . In 1968 , following a seven-year break from live performances , he returned to the stage in the acclaimed televised comeback special Elvis , which led to an extended Las Vegas concert residency and a string of highly profitable tours . In 1973 , Presley featured in the first globally broadcast concert via satellite , Aloha from Hawaii . On August 16 , 1977 , he sustained a heart attack in the bathroom of his Graceland estate , and died as a result . His death came in the wake of many years of prescription drug abuse which lead to his poor health and death . Presley is one of the most celebrated and influential musicians of the 20th century . Commercially successful in many genres , including pop , blues and gospel , he is one of the best-selling solo artists in the history of recorded music , with estimated record sales of around 600 million units worldwide . He won three Grammys , also receiving the Grammy Lifetime Achievement Award at age 36 , and has been inducted into multiple music halls of fame .",
"title": ""
}
] |
[
{
"docid": "My_Farewell_to_Elvis",
"text": "My Farewell to Elvis is the 27th studio album by American country singer Merle Haggard , released in 1977 , his first for MCA Records . It reached Number 6 on the Country album chart . The single `` From Graceland to the Promised Land '' reached number 4 on the Billboard Country Singles chart . The album is a tribute to the music of the late Elvis Presley , who died on August 16 , 1977 .",
"title": ""
},
{
"docid": "From_Elvis_Presley_Boulevard,_Memphis,_Tennessee",
"text": "From Elvis Presley Boulevard , Memphis , Tennessee is an album by American singer and musician Elvis Presley , released on May 16 , 1976 on RCA Records . According to Sony music 's `` Elvis The Music '' site , the album was released on May 17 . Since music at this time period was normally released on Mondays , it is believed that the May 16th date is more accurate . It is often mistaken that this is a concert recording as the album states the songs were `` recorded live '' . While this is true , the songs were recorded live in the recording studio at a studio set up in Presley 's mansion , Graceland , not in front of an audience . Two songs recorded during the session , `` Moody Blue '' and `` She Thinks I Still Care '' would be released the following year on his final album , Moody Blue . From Elvis Presley Boulevard , Memphis , Tennessee was Presley 's fourth album to reach # 1 on the Billboard country music album sales chart within the last four years . `` Hurt '' was a top 10 hit on both the country and adult contemporary charts , while `` For the Heart '' stalled at # 45 on the country charts . The latter did make the pop top 30 . Both songs would again find success on the country charts in the '80s -- `` For the Heart '' became the first single for the Judds in 1983 , while Juice Newton took her version of `` Hurt '' to # 1 in 1986 . From Elvis Presley Boulevard , Memphis , Tennessee was certified Gold on October 10 , 1977 by the RIAA . In 2000 the album 's tracks were added to Moody Blue to create an expanded 19-track CD of the latter title . In 2000 a two-disc edition of From Elvis Presley Boulevard , Memphis , Tennessee was issued on the `` Follow That Dream '' label .",
"title": ""
},
{
"docid": "Simon_Vega",
"text": "Simon H. Vega ( October 8 , 1935 -- May 12 , 2017 ) was a high school teacher who became a personal friend of singer Elvis Presley while the two served together in the United States Army in Germany from 1958 -- 1960 . In 1993 , Vega turned his house into a museum called `` Little Graceland '' located in his native Los Fresnos in Cameron County north of Brownsville , Texas . `` Little Graceland '' is loosely patterned on Presley 's mansion , Graceland , in Memphis , Tennessee . Vega was one of three children born in Los Fresnos to Pablo Vega ( 1895 -- 1969 ) and the former Estefana Hinojosa ( 1900 -- 2003 ) , she a native of San Luis Potosí , Mexico . His sister is Matea V. Garcia of Chicago ; his brother now deceased , Jose Isabel Vega of Los Fresnos . He and his wife , Teresa Vega , named a son , Rene Elvis Vega , after Presley . In 1978 , a year after Presley 's early death , Vega composed a song , `` The Ballad of Elvis Presley '' . He produced three thousand copies and has five remaining ones for his personal collection . Little Graceland is a home converted into a shrine to the man dubbed `` The King '' of rock and roll music . The museum contains many pictures of Presley , some with Vega , which the museum owner considers among his most prized possessions . Vega , with assistance from the Los Fresnos Area Chamber of Commerce and the City of Los Fresnos ( meaning `` ash trees '' ) , holds two Elvis festivals annually in January and August , the months of Presley 's birth and death . The festivities include live music , food and beverages , a lookalike contest , a sing-alike competition , automobile shows , trivia questions , and museum tours . The highlight of the festivities is the impersonators that come from far and wide to perform the Elvis hits on stage . On February 6 , 1958 , Vega was inducted into the Army at Fort Carson , Colorado , and was sent to Fort Hood near Killeen , Texas , for his four-week basic training . During that same period of time , Presley arrived at Fort Hood from Fort Chaffee near Fort Smith , Arkansas . At Fort Hood , Vega introduced his wife Teresa to Presley for a photograph . Teresa recalls that Elvis was nervous while he placed his arm around her for the picture . After the picture was taken , Elvis responded , Gracias . The photo of Elvis and Teresa is among those in Little Graceland . Although Vega had met Elvis at Fort Hood , the two did not become friends until they reached the barracks in August 1958 at Freiburg in Baden-Württemberg , Germany . They were assigned to Company D Spearhead 3rd Army Division . While awaiting a meal , Vega reintroduced himself to Presley , and the two became `` army buddies '' who often shared guard duty . Vega recalls fondly that Presley wanted equal treatment from the other soldiers , not favoritism because of his celebrity status . When Presley died , Vega says that he was so personally devastated that he began collecting anything with a connection to his friend . Vega 's countless pieces of memorabilia are displayed in glass cases or line the walls of the museum . He has a bottle of `` Love Me Tender '' shampoo , the same name as a Presley song and film . There are key chains , playing cards , dolls , pocketknives , neckties , watches , and a complete set of Presley collector plates . Word of Little Graceland spread nationally , as vacationers and winter residents heading to South Padre Island on the Gulf of Mexico stopped to view the replica of the gates of Graceland in front of Vega 's house . Vega has also constructed a doghouse-size replica of Presley 's boyhood home in Tupelo , Mississippi . Vega considers Presley the unequaled entertainer of the 20th century who exuded charisma through his records and personal appearances . `` Once you got to know him , Elvis was a really good guy , but he was never an ordinary guy . Elvis liked to see people happy . That 's part of why he sang and entertained the people , '' says Vega . Despite heart and hip problems , Vega hosts some fifty visitors to his museum each week . Simon Vega passed away on Friday , May 12 , 2017 . He was buried on May 15 , 2017 at Los Cuates Cemetery in Los Fresnos .",
"title": ""
},
{
"docid": "Moody_Blue",
"text": "Moody Blue is the final studio album by American singer and musician Elvis Presley , released by RCA Records the month before his death in August 1977 . The album was a mixture of live and studio work , and included the four tracks from Presley 's final studio recording sessions in October 1976 and two tracks left over from the previous Graceland session in February 1976 . `` Moody Blue '' was a previously published hit song recorded at the earlier Graceland session and held over for this album . Also recorded at the February session was `` She Thinks I Still Care '' . `` Way Down '' became a hit after Presley 's death less than one month after this album 's publication . The album was certified Gold and Platinum on September 12 , 1977 and 2x Platinum on March 27 , 1992 by the RIAA .",
"title": ""
},
{
"docid": "Johnny_Harra",
"text": "Johnny Lee Harra ( born Harry Lee Lovett ; July 11 , 1946 -- March 30 , 2011 ) was an American Elvis impersonator . He began impersonating Elvis at the age of 11 and was cast as the 42-year-old Elvis in the 1981 docudrama This Is Elvis . Harra , one of four actors to portray Elvis in the movie , was featured in two scenes from the re-enactment of August 16 , 1977 , filmed at Graceland . After many years in seclusion he returned to the stage before the 25th anniversary of Elvis ' death . In year 1995 took second place as the best imitator of the world during the twentieth century . The title was usurped by a Colombian Harra was featured in newspapers and magazines , and on national TV shows like Merv Griffin , Johnny Carson and Dick Clark . Johnny traveled internationally performing his `` Profiles of Presley '' show . He died on March 30 , 2011 , aged 64 .",
"title": ""
},
{
"docid": "Elvis_Presley_Enterprises",
"text": "Elvis Presley Enterprises , Inc. ( EPE ) is a corporate entity created by `` The Elvis Presley Trust '' to conduct business and manage its assets , including Graceland . EPE 's business extends far beyond the Graceland operation , however , and includes worldwide licensing of Elvis-related products and ventures , the development of Elvis-related music , film , video , television and stage productions , the ongoing development of EPE 's Internet presence , the management of significant music publishing assets and more .",
"title": ""
},
{
"docid": "Way_Down",
"text": "`` Way Down '' is a song recorded by Elvis Presley . Recorded in October 1976 , it was his last single released before his death on August 16 , 1977 . The song was written by Layng Martine , Jr. and was later covered by Status Quo and Cliffhanger . Elvis recorded the song at his home studio in Graceland in late October , 1976 . Released as a single ( with `` Pledging My Love '' on the B-side ) on June 6 , 1977 , it was his single at the time of his death . It initially peaked at No. 31 on the Billboard Hot 100 chart dated August 6 , 1977 and had fallen to No. 53 on the chart for the week ending August 27 , 1977 . Thereafter , it reversed direction and reached an even higher peak at No. 18 on 24 September -- 1 October 1977 . `` Way Down '' reached No. 1 on the American Country chart the week he died . Overseas , the song hit the UK Singles Chart a few weeks later , almost seven years after his previous UK number-one single , `` The Wonder of You '' , in 1970 . His previous single , `` Moody Blue '' , had been a number-one hit on the US Country Charts earlier in 1977 . `` Way Down '' was reissued in April 2005 and reached No. 2 on the UK Singles Chart . The recording also featured J.D. Sumner singing the words `` way on down '' at the end of each chorus down to the note low C ( C2 ) . At the end of the song , this phrase is octaved , reaching a double low C ( C1 , three octaves below middle C ) . According to the Guinness Book of World Records it is the lowest recorded note ever produced by the human voice , first accomplished by Sumner in a 1966 recording of the hymn `` Blessed Assurance . ''",
"title": ""
},
{
"docid": "Way_Down_in_the_Jungle_Room",
"text": "Way Down in the Jungle Room is a compilation album by American singer Elvis Presley . It was released on August 5 , 2016 by RCA Records and Legacy Recordings . The album features master recordings and outtakes from two recording sessions on February 2 -- 8 , 1976 and October 28 -- 30 , 1976 in the Jungle Room , a recording studio set up by Elvis in the den of Graceland in Memphis , Tennessee . The first disc subtitled The Masters features material from these sessions that were later released on From Elvis Presley Boulevard , Memphis , Tennessee ( 1976 ) , and the subsequent final studio album , Moody Blue ( 1977 ) . The second disc , The Outtakes , features outtakes and `` in-the-studio dialog '' newly mixed by Matt Ross-Spang at the Sam Phillips Recording Studio .",
"title": ""
},
{
"docid": "Elvis_Presley_Forever_stamp",
"text": "The Elvis Presley Forever postage stamp is a part of the Music Icons series issued by the United States Postal Service . It features Presley in a 1955 black and white photography taken by William Speer . The design created by Antonio Alcalá and Leslie Badani also features a golden crown and the signature of Presley on the side . The stamp was dedicated on August 12 , 2015 during a ceremony in Graceland , attended by Priscilla Presley and Postmaster General Megan Brennan . The release of the stamp was accompanied by a hit compilation album , Elvis Forever , sold through post offices around the United States and on the internet . Other than the Rev. Martin Luther King and several US Presidents , Elvis Presley is the only US national who has been the subject of two commemorative stamps by the USPS . The first was issued in 1993 . The first stamps , and earliest known use ( EKU ) , were purchased August 10 , 2015 at the Mason , Tennessee post office by stamp collector David Saks .",
"title": ""
},
{
"docid": "Moody_Blue_(song)",
"text": "`` Moody Blue '' is a song made famous by Elvis Presley . The song was written by Mark James who also penned Elvis ' `` Suspicious Minds '' . `` Moody Blue '' was Presley 's last No. 1 hit in his lifetime , topping the Billboard magazine Hot Country Singles chart in February 1977 . `` Moody Blue '' also peaked at number thirty-one on the Hot 100 . RCA Records also issued an extremely limited quantity of the `` Moody Blue '' single in an experimental translucent blue vinyl pressing , with `` She Thinks I Still Care '' as the B-side . Six months after `` Moody Blue '' topped the chart , Presley was dead . The song was recorded in February 1976 in the Jungle Room of Presley 's Graceland home . The only time Elvis performed the song in its entirety was on February 21 , 1977 at a concert in Charlotte , North Carolina . He had attempted to perform the song February 20 at the same venue but revealed to the crowd that he had completely forgotten the song ; he returned on February 21 , lead sheet in hand , and performed the song with his eyes glued to the lyrics . Both the February 20 false-start and the February 21 performance were recorded on soundboard in good sound quality and were released officially in 2007 by the Follow That Dream label ; still photos of the February 21 performance also exist . The complete version was first released on bootleg by the Fort Baxter label in 1995 .",
"title": ""
},
{
"docid": "Elvis_Presley_House",
"text": "Elvis Presley House is a one-story ranch style house in a residential neighborhood in Memphis , Tennessee . Singer Elvis Presley lived here with his parents between March 1956 and March 1957 , before moving to Graceland .",
"title": ""
},
{
"docid": "Elvis_Recorded_Live_on_Stage_in_Memphis",
"text": "Elvis Recorded Live on Stage in Memphis is a live album by American singer and musician Elvis Presley , released on RCA Records in July 1974 . It was recorded on March 20 of the same year at the Mid-South Coliseum in Memphis , Tennessee , Presley 's hometown . The cover features of a photograph of Presley 's home , Graceland . The album was recorded on the same day as his Good Times album was released . Elvis Recorded Live on Stage in Memphis was Presley 's fifth live album in less than five years and the last to be issued in his lifetime . He earned his third Grammy Award for this album 's performance of `` How Great Thou Art '' . The album was certified gold by the Recording Industry Association of America on July 15 , 1999 . In the United States , Elvis Recorded Live on Stage in Memphis topped Billboards Country chart and reached the top 40 of the Top LPs & Tape listings ( now known as the Billboard 200 ) . It was Presley 's last album to reach the top 40 until Moody Blue in 1977 . Although the live album was not a major commercial success , it did produce the singer 's third and final Grammy Award winner , `` How Great Thou Art '' , which won for best inspirational performance . Two other gospel songs , `` Why Me Lord '' and `` Help Me '' , are given an inspired performance . Another highlight is the Sun years classic `` Trying to Get to You '' , a favorite live choice of Presley 's , which suggested that he still had the power to belt it out when he chose to . The live recording of `` Let Me Be There '' from this album was later used as filler on Presley 's final studio album , Moody Blue . It was also issued as a promotional single in 1974 , with the same song on both sides ( mono and stereo ) . In 2004 , FTD Records re-released Elvis Recorded Live on Stage in Memphis containing the entire concert , which had included performances of songs such as `` Suspicious Minds '' and `` Polk Salad Annie '' that had been omitted from the 1974 LP to avoid repetition with Presley 's previous live albums . On March 17 , 2014 , close to the 40th anniversary of the concert , Sony/RCA Legacy re-released the album as a two-CD set . Disc one corresponds with the FTD version , in that it features the complete show from the Mid-South Coliseum . The second disc consists of a near-identical concert recorded at the Richmond Coliseum just two days earlier ; as it had a similar setlist , this show is known as the `` test run '' for the Memphis concert , but was recorded only in mono . Disc two also includes several recently rediscovered studio rehearsal recordings from August 1974 . On release , the two-CD set re-entered the UK Albums Chart at number 74 .",
"title": ""
},
{
"docid": "It's_Easy_for_You",
"text": "`` It 's Easy for You '' is a song by American musician Elvis Presley , released in 1977 by RCA Records as the final track on his final studio album , Moody Blue . It was written by Andrew Lloyd Webber and Tim Rice and produced by Felton Jarvis . It was recorded in the ` Jungle Room ' of Presley 's Graceland mansion .",
"title": ""
},
{
"docid": "Graceland",
"text": "Graceland is a mansion on a 13.8 acre estate in Memphis , Tennessee that was owned by Elvis Presley . It is located at 3764 Elvis Presley Boulevard in the vast Whitehaven community , about 9 miles ( 14.5 km ) from Downtown and less than four miles ( 6 km ) north of the Mississippi border . It currently serves as a museum . It was opened to the public on June 7 , 1982 . The site was listed in the National Register of Historic Places on November 7 , 1991 , and declared a National Historic Landmark on March 27 , 2006 . Graceland is the second most-visited house in America with over 650,000 visitors a year ; second only to the White House .",
"title": ""
},
{
"docid": "Graceland_Too",
"text": "Graceland Too was Paul MacLeod 's two-story home and shrine to Elvis Presley in Holly Springs , Mississippi . It was open to the public twenty-four hours a day , every day , all year . The house was crammed with Elvis paraphernalia to the point of being a fire hazard . MacLeod was renowned for his eccentricity , based upon his reverence for Elvis , and his claim to drink at least two dozen cans of soda per day . The town 's assistant director of tourism , Suzann William , claims MacLeod is Holly Springs ' number one tourism attraction . The house was originally painted pink , then white , and in 2012 it became a vivid , Mediterranean blue with American Flags and painted navy blue pine trees . On July 15 , 2014 , a man named Dwight David Taylor Jr. was shot by MacLeod just inside of the front door of the house . According to police , Taylor banged on the door of the house around 11 p.m. asking for money . He tried to force his way into the home and broke the glass on the front door . After Taylor refused to leave , MacLeod shot him . Taylor died from a gunshot wound to the chest . MacLeod cooperated with police and was released . No charges were filed . On July 17 , 2014 , MacLeod was found dead on the porch by someone driving by the house around 7 a.m. MacLeod 's attorney , Phillip K. Knecht , said in a statement that MacLeod had been `` battling ill health for some time '' . He added , `` We ca n't be sure of anything right now , but nothing points to suicide or foul play . We await an official autopsy , but his ill health , combined with the stress from Monday 's tragedy , leads me to believe it was a very unfortunate natural occurrence '' . The contents of Graceland Too went up for auction on January 31 , 2015 . Well over 100 people showed up for the auction on the Graceland Too site , many having travelled hundreds of miles in the hope of buying an Elvis treasure or a memory of Graceland Too . Many in the crowd were disappointed and dispirited when the entire lot of items was sold for a reported $ 54,500 to an anonymous buyer from Georgia . Shortly after MacLeod 's death , it was revealed that documentary filmmakers had been working for five years on a film about MacLeod and Graceland Too . The same week as the auction an art photography book , Graceland Too Revisited , was published by authors/photographers Darrin Devault and Tom Graves . Because of a problem with the online bidding company during the first auction , the original $ 54,000 online bid for the contents of Graceland Too was negated , requiring a new auction . That auction was held on May 2 , 2015 . The vast majority of Graceland Too 's property was sold at that auction , including hundreds of Elvis Presley memorabilia that MacLeod had collected over the years . In December 2015 , Marie and Jeffrey Underwood , as well as members of the Friends of Graceland Too , purchased the house and all remaining property at a public auction for $ 5,500 .",
"title": ""
},
{
"docid": "Elvis_Presley's_Army_career",
"text": "American singer Elvis Presley served in the United States Army between March 1958 and March 1960 . At the time of his draft he was one of the most well-known names in the world of entertainment . Before entering the U.S. Army , Presley had caused national outrage with his sexually charged performances and rock and roll music . Many parents , religious leaders , and teachers groups saw his draft , removing him from public view , as a positive thing . Despite being offered the chance to enlist in Special Services to entertain the troops and live in priority housing , Presley decided to serve as a regular soldier . This earned him the respect of many of his fellow soldiers and people back home who had previously viewed him in a negative light . During his service , Presley 's life was affected in many ways , beginning with the death of his mother . Not long before he was to be stationed in Germany , Gladys Presley died of a heart attack brought on by Acute Hepatitis and Cirrhosis at age 46 . When he was stationed in West Germany , he met his future wife Priscilla Beaulieu and became dependent on stimulants and barbiturates . This unhealthy addiction eventually led to his divorce , and ultimately his death at age 42 in 1977 . After his release from military service , Presley found a new fan base among an older age group , thanks in part to his army career and releases of ballads over rock and roll songs .",
"title": ""
},
{
"docid": "Welcome_to_My_World_(Elvis_Presley_album)",
"text": "Welcome to My World was the title of a compilation album by American singer and musician Elvis Presley that was released by RCA Records in early 1977 , just months before his death . According to Elvis : The Illustrated Record by Roy Carr and Mick Farren , all but one track on this album had been previously released . That track is `` I Ca n't Stop Loving You '' , recorded during the afternoon performance at Madison Square Garden on June 10 , 1972 ; the remainder of the concert remained unreleased until the 1990s when it was issued as An Afternoon in the Garden . Welcome to My World was certified gold on September 30 , 1977 and platinum on January 14 , 1983 by the RIAA . One track , Your Cheatin ' Heart , dated back 19 years .",
"title": ""
},
{
"docid": "Graceland_(disambiguation)",
"text": "Graceland is the former estate of Elvis Presley . Graceland may also refer to : Graceland , Missouri , an unincorporated community Graceland ( Elkins , West Virginia ) , historic house in Elkins , West Virginia Graceland Cemetery in Chicago , Illinois Graceland Cemetery ( Washington , D.C. ) , a former cemetery in Washington , D.C. Graceland University , a private , liberal arts university in Lamoni , Iowa , and Independence , Missouri Graceland ( album ) , a 1986 album by Paul Simon `` Graceland '' ( song ) , the title track of that album GraceLand , a 2004 novel by Chris Abani Graceland ( TV series ) , a 2013 American television series",
"title": ""
},
{
"docid": "Priscilla_Presley",
"text": "Priscilla Ann Presley ( née Wagner ; born May 24 , 1945 ) is an American actress and business magnate . She is the former wife of the late entertainer Elvis Presley as well as co-founder and former chairwoman of Elvis Presley Enterprises ( EPE ) , the company that turned Graceland into one of the top tourist attractions in the United States . In her acting career , Presley starred with Leslie Nielsen in the three successful Naked Gun films , and played the role of Jenna Wade on the long-running television series Dallas .",
"title": ""
},
{
"docid": "Elvis_Presley's_Pink_Cadillac",
"text": "Elvis Presley 's iconic Pink Cadillac was a 1955 Cadillac Fleetwood . It set style for the era , was sung about in popular culture , and was copied by others around the world . The car is now preserved in the Graceland museum , in Memphis , Tennessee .",
"title": ""
},
{
"docid": "Had_a_Dream_(For_the_Heart)",
"text": "`` Had a Dream ( For the Heart ) '' is a song written by Dennis Linde . It was originally recorded by Elvis Presley as `` For the Heart '' on his 1976 album From Elvis Presley Boulevard , Memphis , Tennessee . Presley 's version , the B-side to the album 's single `` Hurt '' , peaked at number 45 on the Hot Country Songs charts that year . The Judds covered the song and released it as their debut single in December 1983 , from their album Wynonna & Naomi . The song reached number 17 on the same chart .",
"title": ""
},
{
"docid": "Pure_Gold_(Elvis_Presley_album)",
"text": "Pure Gold is a 1975 compilation album by American singer and musician Elvis Presley released as part of the RCA Records budget `` Pure Gold '' series of albums . Though at this point in his career , Presley was focused more on the country music market , where he had a string of chart-topping records in recent years , this collection focuses more on earlier material than recent hits . Considered a rather mediocre compilation album in terms of both content and sound quality , Pure Gold nevertheless sold extremely well in the wake of Elvis ' death in August 1977 .",
"title": ""
},
{
"docid": "Elvis_sightings",
"text": "A considerable number of people believe that Elvis Presley did not die in 1977 , but went into hiding for various reasons and is still alive . This notion was popularized by the books of Gail Brewer-Giorgio and other authors . Several people even claim to have seen Elvis after he was supposed to have died . One rash of alleged sightings took place in Kalamazoo , Michigan , in the late 1980s . Such reports encountered much public ridicule and became fodder for humorous publications like the Weekly World News . Elvis was rumored to have appeared in the background of an airport scene in the 1990 film Home Alone . In an interview with USA Today , director Chris Columbus responded `` If Elvis was on the set , I would have known '' . In June 2016 , a video of an elderly man in Graceland was alleged to be Elvis . Bill Bixby , who co-starred with Elvis in Clambake and Speedway , hosted two television specials investigating the subject : The Elvis Files ( 1991 ) , and The Elvis Conspiracy ( 1992 ) .",
"title": ""
},
{
"docid": "Fool's_Gold_Loaf",
"text": "Fool 's Gold Loaf is a sandwich made by the Colorado Mine Company , a restaurant in Denver , Colorado . The sandwich consists of a single warmed , hollowed-out loaf of bread filled with the contents of one jar of creamy peanut butter , one jar of grape jelly , and a pound of bacon . The sandwich 's connection to Elvis Presley is the source of its legend and prolonged interest . According to The Life and Cuisine of Elvis Presley , it was the focus of a midnight sandwich run by Elvis Presley and his friends . Taking his private jet from Graceland , Presley and his friends purchased 30 of the sandwiches and spent two hours eating them and drinking Perrier and champagne before flying home . The story became legend and the sandwich became the subject of continued media interest and part of numerous cookbooks , typically focused around Presley 's love of food .",
"title": ""
},
{
"docid": "Graceland_Wedding_Chapel",
"text": "Graceland Wedding Chapel is a wedding chapel located in Las Vegas , Nevada that has been the site of many celebrity weddings . Opened in the 1950s , it is one of the oldest wedding chapels in Las Vegas , and is known for weddings performed by Elvis impersonators . Presley himself gave the owners of the chapel permission to use the Graceland name .",
"title": ""
},
{
"docid": "Tourism_in_Memphis,_Tennessee",
"text": "Tourism in Memphis includes the points of interest in Memphis , Tennessee such as museums , fine art galleries , and parks , as well as Graceland ( the former home of Elvis Presley ) the Beale Street entertainment district , and sporting events ( see Sports in Memphis , Tennessee ) . The Memphis Brooks Museum of Art , founded in 1916 , is the oldest and largest fine art museum in the state of Tennessee . A smaller art museum , the Dixon Gallery and Gardens in east Memphis focuses on impressionism . Downtown Memphis is home to the Peabody Place Museum , the largest collection of 19th-century Chinese art in the nation . Graceland , the home of Rock 'n' Roll legend Elvis Presley , is one of the most visited houses in the United States ( after the White House and Biltmore Estate ) , attracting over 600,000 domestic and international visitors a year .",
"title": ""
},
{
"docid": "Ulysses_Jones,_Jr.",
"text": "Ulysses Jones , Jr. ( born June 7 , 1951 in Memphis , Tennessee , died November 9 , 2010 ) was an American politician and a Democratic member of the Tennessee House of Representatives for the 98th district , which encompasses a part of Shelby County , Tennessee . In the state House of Representatives , Ulysses Jones was the Chair of the House State and Local Government Committee and the Co-Chair of the Joint Lottery Oversight Committee . He was a member of numerous House committees : the Calendar and Rules Committee , the Education Committee , the K-12 Subcommittee , the Elections Subcommittee , the State Government Subcommittee , the Local Government Subcommittee , the Joint Lottery Scholarship Committee , the Joint Tennessee Education Lottery Corporation Committee , the Joint Select Oversight Committee on Education , and the Tennessee Commemorative Women 's Suffrage Commission . Ulysses Jones graduated from North Side High School . He attended the University of Memphis and Tennessee State University . He worked as a Battalion Chief for Memphis Fire Services . It has been alleged by Tim Willis , informant for Operation Tennessee Waltz , that Ulysses Jones took a bribe from E-Cycle , a fictitious company that had been set up by the FBI . Jones said in response that it had only been a campaign contribution , and that he would `` be willing to take a lie detector test , even by the FBI . '' When Elvis Presley died on August 16 , 1977 , Ulysses Jones and Charles Crossby were the two paramedics on the scene at Graceland when it was reported to Memphis Fire Department 's Engine House No. 29 that a person was having trouble breathing . Jones was also interviewed by Albert Goldman for his book `` Elvis '' , he also appeared on several TV shows talking about that day .",
"title": ""
},
{
"docid": "Wooden_Heart",
"text": "`` Wooden Heart '' ( '' '' lit . Must I then ) is a song best known for its use in the 1960 Elvis Presley film G.I. Blues . The song was a hit single for Presley in the UK Singles Chart , making No. 1 for six weeks there in March and April 1961 , but was not released on a single in the United States until November 1964 , where it was the B-side to `` Blue Christmas '' . Presley performed the song live during his Dinner Show concert at the Hilton Hotel in Las Vegas in 1975 , a recording available on the Elvis Presley live album Dinner At Eight . A cover version by Joe Dowell made it to number one in the US at the end of August 1961 , knocking Bobby Lewis ' `` Tossin ' and Turnin ' '' off the number-one spot of the Billboard Hot 100 after seven weeks . Dowell 's version also spent three weeks at number one on the Easy Listening chart . `` Wooden Heart '' , created by Fred Wise , Ben Weisman , Kay Twomey and German bandleader Bert Kaempfert , was based on a German folk song by Friedrich Silcher , `` Muss i denn '' , originating from the Rems Valley in Württemberg , southwest Germany . `` Wooden Heart '' features several lines from the original folk song , written in the German Swabian dialect , as spoken in Württemberg . Marlene Dietrich recorded a version of the song sometime before 1958 , pre-dating Presley , in the original German language , which appears as a B-side on a 1959 version of her single `` Lili Marlene '' , released by Philips in association with Columbia Records . The Elvis Presley version was published by Gladys Music , Elvis Presley 's publishing company . Bobby Vinton recorded his version in 1975 with those lines translated into Polish . The Elvis Presley version featured two parts in German , the first one is the first four lines of '' '' , whereas the second part appears towards the end and is based on a translation of the English version ( therefore not appearing in the original German folk lyrics ) . This part being '' '' This literally means `` Be good to me , Be good to me , Be to me how you really should , How you really should ... ''",
"title": ""
},
{
"docid": "Elvis_the_King",
"text": "Elvis the King is a box set comprising 18 singles of the recorded work of American singer and musician Elvis Presley , released in 2007 by RCA Records . The box set is available in both CD and 10 '' vinyl formats . The first release was Monday , August 13 , 2007 , marking 30 years -- to the week -- since the death of Elvis Presley . The second single was released on Thursday , August 16 , which is the exact anniversary of Presley 's death . From then on , the singles were released every Monday until December 2 , 2007 .",
"title": ""
},
{
"docid": "I'm_Leavin'_(Elvis_Presley_song)",
"text": "`` I 'm Leavin ' '' is a 1971 song by Elvis Presley . It was written by Sonny Charles and Michael Jarrett . The song was originally released in 1971 as a single , with `` Heart of Rome '' ( from the album Love Letters from Elvis ) on the B-side . In the United States `` I 'm Leavin ' '' reached number 36 on Billboard Hot 100 for the week of August 21 , 1971 . In the UK Singles Chart , it reached number 23 for the week of October 2 , 1971 . Later `` I 'm Leavin ' '' was included in the 1980 box set Elvis Aron Presley ( on the record 8 titled `` Lost Singles '' ) .",
"title": ""
}
] |
4036
|
Why are capital gains taxed at a lower rate than normal income?
|
[
{
"docid": "6891",
"text": "Were capital gains taxes not lower, companies would have an incentive to minimize the portion of the value they create that materializes as capital gains. They would do this by using more debt financing (since interest is deductible) than equity financing. This would have a destabilizing effect on the economy. Low capital gains taxes help encourage investment over spending. This is believed to improve economic growth. Given these factors, it is generally believed that the current capital gains tax rate is very close to the optimal rate. That is, a higher tax rate would not result in greater tax revenue. Bluntly, a higher income tax rate on earned income does not really discourage people from working harder and earning more money. But a higher rate on capital gains does discourage investment. Essentially, it's because investment is more discretionary.",
"title": ""
},
{
"docid": "384644",
"text": "Here are three key factors that you do not explicitly state: So while I cannot say exactly why the tax law is the way it is, I can infer that it encourages long-term investments rather than short-term, which would seem to be a good thing for society overall. The fast that capital gains are taxed at all somewhat discourages cashing out investments (although I suspect it's more of a nuisance factor - the cash received is likely more on an incentive that the tax is a disincentive).",
"title": ""
},
{
"docid": "530548",
"text": "Consider inflation. If you invest $10,000 today, you need to make a few hundred dollars interest just to make up for inflation - if there is 3% inflation then a change from $10,000 to $10,300 means you didn't actually make any money.",
"title": ""
},
{
"docid": "348982",
"text": "To me, the lower tax rate for capital gains is largely due to governments encouraging economic activity. Note that investments usually come from your normal income, which is already taxed. Capital gains tax is essentially punishing people who take the extra effort to put their money into work. If the tax rate is high, it would definitely cause people to rethink about investing, thus slowing the general economy down.",
"title": ""
},
{
"docid": "322049",
"text": "I think this question is very nearly off-topic for this site, but I also believe that a basic understanding of the why the tax structure is what it is can help someone new to investing to understand their actual tax liability. The attempt at an answer I provide below is from a Canadian & US context, but should be similar to how this is viewed elsewhere in the world. First note that capital gains today are much more fluid in concept than even 100 years ago. When the personal income tax was first introduced [to pay for WWI], a capital gain was viewed as a very deliberate action; the permanent sale of property. Capital gains were not taxed at all initially [in Canada until 1971], under the view that income taxes would have been paid on income-earning assets all along [through interest, dividends, and rent], and therefore taxing capital gains would be a form of 'double-taxation'. This active, permanent sale was also viewed as an action that an investor would need to work for. Therefore it was seen as foolish to prevent investors from taking positive economic action [redistributing their capital in the most effective way], simply to avoid the tax. However today, because of favourable taxation on capital gains, many financial products attempt to package and sell capital gains to investors. For example, many Canadian mutual funds buy and sell investments to earn capital gains, and distribute those capital gains to the owners of the mutual fund. This is no longer an active action taken by the investor, it is simply a function of passive investing. The line between what is a dividend and what is a capital gain has been blurred by these and similar advanced financial products. To the casual investor, there is no practical difference between receiving dividends or capital gain distributions, except for the tax impact. The notional gain realized on the sale of property includes inflation. Consider a rental property bought in 1930 for $100,000, and sold in 1960 for $180,000, assuming inflation between 1930 and 1960 was 70%. In 1960 dollars, the property was effectively bought for 170k. This means the true gain after accounting for inflation is only $10k. But, the notional gain is $80k, meaning a tax on that capital gain would be almost entirely a tax on inflation. This is viewed by many as being unfair, as it does not actually represent true income. I will pause to note that any tax on any investment at all, taxes inflation; interest, for example, is taxed in full even though it can be almost entirely inflationary, depending on economic conditions. A tax on capital gains may restrict market liquidity. A key difference between capital gains and interest/rent/dividends, is that other forms of investment income are taxed annually. If you hold a bond, you get taxed on interest from that bond. You cannot gain value from a bond, deferring tax until the date it matures [at least in Canada, you are deemed to accrue bond interest annually, even if it is a 0 coupon bond]. However, what if interest rates have gone down, increasing the value of your bond, and you want to sell it to invest in a business? You may choose not to do this, to avoid tax on that capital gain. If it were taxed as much as regular income, you might be even more inclined to never sell any asset until you absolutely have to, thus restricting the flow of capital in the market. I will pause here again, to note that laws could be enacted to minimize capital gains tax, as long as the money is reinvested immediately, thus reducing this impact. Political inertia / lobbying from key interests has a significant impact on the tax structure for investments. The fact remains that the capital gains tax is most significantly an impact on those with accrued wealth. It would take significant public support to increase capital gain tax rates, for any political party to enact such laws. When you get right down to it, tax laws are complex, and hard to push in the public eye. The general public barely understands that their effective tax rate is far lower than their top marginal tax rate. Any tax increases at all are often viewed negatively, even by those who would never personally pay any of that tax due to lack of investment income. Therefore such changes are typically made quietly, and with some level of bi-partisan support. If you feel the capital gains tax rules are illogical, just add it to the pile of such tax laws that exist today.",
"title": ""
},
{
"docid": "235004",
"text": "Every economy wants growth and for growth to come you need investments. So, you must provide some motive for people to risk their money (every investment has inherently a degree of risk or if you want uncertainty about the outcome). As a result the tax on capital gains is lower than on other types of income (because the risk is almost zero). The tax is considered in the calculation of the net interest rate. And you can see this as the interest which the investors demand in order to invest their money.",
"title": ""
},
{
"docid": "408983",
"text": "There are many reasons, which other answers have already discussed. I want to emphasize and elaborate on just one of the reasons, which is that it avoids double taxation, especially on corporate earnings. Generally, for corporations, its earnings are already taxed at around 40% (for the US - including State income taxes). When dividends are distributed out, it is taxed again at the individual level. The effect is the same when equity is sold and the distribution is captured as a capital gain. (I believe this is why the dividend and capital gain rates are the same in the US.) For a simplistic example, say there is a C Corporation with a single owner. The company earns $1,000,000 before income taxes. It pays 400,000 in taxes, and has retained earnings of $600,000. To get the money out, the owner can either distribute a dividend to herself, or sell her stake to another person. Either choice leads to $600,000 getting taxed at another 20%~30% or so at the individual level (depending on the State). If we calculate the effective rate, it is above 50%! Many people invest in stock, including mutual funds, and the dividends and capital gains are taxed at lower rates. Individual tax returns that contain no wage income often have very low average tax rates for this reason. However, the investments themselves are continuously paying out their own taxes, or accruing taxes in the form of future tax liability.",
"title": ""
},
{
"docid": "21810",
"text": "There are two alternative explanations: Choose the explanation you prefer based on your level of cynicism.",
"title": ""
}
] |
[
{
"docid": "420529",
"text": "I assume US as mhoran_psprep edited, although I'm not sure IRS necessarily means US. (It definitely used to also include Britain's Inland Revenue, but they changed.) (US) Stockbrokers do not normally withhold on either dividends/interest/distributions or realized capital gains, especially since gains might be reduced or eliminated by later losses. (They can be required to apply backup withholding to dividends and interest; don't ask how I know :-) You are normally required to pay most of your tax during the year, defined as within 10% or $1000 whichever is more, by withholding and/or estimated payments. Thus if the tax on your income including your recent gain will exceed your withholding by 10% and $1000, you should either adjust your withholding or make an estimated payment or some combination, although even if you have a job the last week of December is too late for you to adjust withholding significantly, or even to make a timely estimated payment if 'earlier in the year' means in an earlier quarter as defined for tax (Jan-Mar, Apr-May, June-Aug, Sept-Dec). See https://www.irs.gov/businesses/small-businesses-self-employed/estimated-taxes and for details its link to Publication 505. But a 'safe harbor' may apply since you say this is your first time to have capital gains. If you did not owe any income tax for last year (and were a citizen or resident), or (except very high earners) if you did owe tax and your withholding plus estimated payments this year is enough to pay last year's tax, you are exempt from the Form 2210 penalty and you have until the filing deadline (normally April 15 but this year April 18 due to weekend and holiday) to pay. The latter is likely if your job and therefore payroll income and withholding this year was the same or nearly the same as last year and there was no other big change other than the new capital gain. Also note that gains on investments held more than one year are classified as long-term and taxed at lower rates, which reduces the tax you will owe (all else equal) and thus the payments you need to make. But your wording 'bought and sold ... earlier this year' suggests your holding was not long-term, and short-term gains are taxed as 'ordinary' income. Added: if the state you live in has a state income tax similar considerations apply but to smaller amounts. TTBOMK all states tax capital gains (and other investment income, other than interest on exempt bonds), and don't necessarily give the lower rates for long-term gains. And all states I have lived in have 'must have withholding or estimated payments' rules generally similar to the Federal ones, though not identical.",
"title": ""
},
{
"docid": "519123",
"text": "\"I had been pondering this recently myself too. This question motivated me to do a little research. It appears that what happens is that (take a deep breath) the capital gain does push you into the next tax bracket, but the capital gain is always interpreted as the \"\"last\"\" income you received, so that if your non-capital-gains income is less than the threshold, it will all be taxed in the lower bracket, and only your capital gain will be taxed in the higher bracket (but it will be taxed at the capital-gains rate of that higher bracket). In short, a capital gain can only push capital gains into higher capital-gains tax brackets; it cannot push ordinary income into higher ordinary-income tax brackets. In addition, the amount of the capital gain is taxed in a marginal fashion, such that any portion of the gain that will \"\"fit\"\" into a lower bracket will be taxed at a lower level, with only the topmost portion of any gain being taxed at the top rate. This site is one claiming this: Will capital gain or dividend income push my other income into a higher tax bracket? No, the tax rates apply first to your “ordinary income” (income from sources other than long-term capital gains or qualifying dividends) so these items that are taxed at special rates won’t push your other income into a higher tax bracket. If my ordinary income puts me in the 15% tax bracket, can I receive an unlimited amount of long-term capital gain at the 0% rate? No, the 0% rate applies only to the amount of long-term capital gain and dividend income needed to “fill up” the 15% tax bracket. For example, if your ordinary income is $4,000 below the figure that would put you in the 25% bracket and you have a $10,000 long-term capital gain, you’ll pay 0% on $4,000 of your capital gain and 15% on the rest. There are several Bogleheads forum threads (here, here, here and here) that also touch on the same issue. The last of those links to the IRS capital gains worksheet. I traced through the logic and I believe it confirms this. Here's how it works: (In conclusion, we now know Mitt Romney's secret.)\"",
"title": ""
},
{
"docid": "57263",
"text": "\"US federal tax law distinguishes many types of income. For most people, most of their income is \"\"earned income\"\", money you were paid to do a job. Another category of income is \"\"capital gains\"\", money you made from the sale of an asset. For a variety of reasons, capital gains tax rates are lower than earned income tax rates. (For example, it is common that much of the gain is not real profit but inflation. If you buy an asset for $10,000 and sell it for $15,000, you pay capital gains tax on the $5,000 profit. But what if prices in general since you bought the asset have gone up 50%? Then your entire profit is really inflation, you didn't actually make any money -- but you still have to pay a tax on the paper gain.) So if you make your money by investing in assets -- buying and selling at a profit -- you will pay lower taxes than if you made the same amount of money by receiving a salary from a job, or by running a business where you sell your time and expertise rather than an asset. But money made from assets -- capital gains -- is not tax free. It's just a lower tax. It MIGHT be that when combined with other deductions and tax credits this would result in you paying no taxes in a particular year. Maybe you could avoid paying taxes forever if you can take advantage of tax loopholes. But for most people, making money from capital gains could result in lower taxes per dollar of income than someone doing more ordinary work. Or it could result in higher taxes, if you factor in inflation, net present value of money, and so on. BTW Warren Buffet's \"\"secretary\"\" is not a typist. She apparently makes at least $200,000 a year. http://www.forbes.com/sites/paulroderickgregory/2012/01/25/warren-buffetts-secretary-likely-makes-between-200000-and-500000year/#ab91f3718b8a. And side note: if Warren Buffet thinks he isn't paying enough in taxes, why doesn't he voluntarily pay more? The government has a web site where citizens can voluntarily pay additional taxes. In 2015 they received $3.9 million in such contributions. http://www.treasurydirect.gov/govt/reports/pd/gift/gift.htm\"",
"title": ""
},
{
"docid": "170717",
"text": "In the US, the key to understanding the benefits of retirement accounts is to understand capital gains taxes and how they work. Retirement accounts are designed for making investments throughout your career, then after several decades of contributions, withdrawing that money to pay for your needs when your full-time employment has concluded. Normally when you invest money in a brokerage account, if the value of your investment increases, and you sell in less than a year, those investments are considered short-term gains and taxed as ordinary income. If you hold that same investment for over a year, the same investment is taxed at a lower capital gains rate (depending on which tax bracket you are in during that year, the amount due could be up to 20%, but much lower than your regular income tax rate). When you place your money in a retirement account, you are choosing to either pay the tax due on the income when you put it in the account, or put the money in tax free and pay the tax when you withdraw (these are called tax-deferred accounts). When you have money invested several decades, the raw dollar amount increases greatly, but inflation is also reducing the value of those dollars. Imagine you bought some bonds that payed 4% over 40 years, but inflation was 2% during those same years. When you sell those bonds 40 years later, you will owe capital gains on the entire gain even though half of the gain came from inflation. Retirement accounts allow you to buy and sell according to your investment needs and goals without any consideration about whether the gains are short-term or long-term, and they also allow you to pay taxes just once, either when you put it in, or when you take it out, with no worries about whether you're paying taxes on inflated gains.",
"title": ""
},
{
"docid": "170318",
"text": "It depends on your investment profile but basically, dividends increase your taxable income. Anyone making an income will effectively get 'lower returns' on their investments due to this effect. If you had the choice between identical shares that either give a dividend or don't, you'll find that stock that pays a dividend has a lower price, and increases in value more slowly than stock that doesn't. (all other things being equal) There's a whole bunch of economic theory behind this but in short, the current stock price is a measure of how much the company is worth combined with an estimation of how much it will be worth in the future (NPV of all future dividends is the basic model). When the company makes profit, it can keep those profits, and invest in new projects or distribute a portion of those profits to shareholders (aka dividends). Distributing the value to shareholders reduces the value of the company somewhat, but the shareholders get the money now. If the company doesn't give dividends, it has a higher value which will be reflected in a higher stock price. So basically, all other things being equal (which they rarely are, but I digress) the price and growth difference reflects the fact that dividends are paying out now. (In other words, if you wanted non-dividend shares you could get them by buying dividend shares and re-investing the dividend as new shares every time there was a payout, and you could get dividend-share like properties by selling a percentage of non-dividend shares periodically). Dividend income is taxable as part of your income right away, however taxes on capital gains only happen when you sell the asset in question, and also has a lower tax rate. If you buy and hold Berkshire Hatheway, you will not have to pay taxes on the gains you get until you decide to sell the shares, and even then the tax rate will be lower. If you are investing for retirement, this is great, since your income from other sources will be lower, so you can afford to be taxed then. In many jurisdictions, income from capital gains is subject to a different tax rate than the rest of your income, for example in the US for most people with money to invest it's either 15% or 20%, which will be lower than normal income tax would be (since most people with money to invest would be making enough to be in a higher bracket). Say, for example, your income now is within the 25% bracket. Any dividend you get will be taxed at that rate, so let's say that the dividend is about 2% and the growth of the stock is about 4%. So, your effective growth rate after taxation is 5.5% -- you lose 0.5% from the 25% tax on the dividend. If, instead, you had stock with the same growth but no dividend it would grow at a rate of 6%. If you never withdrew the money, after 20 years, $1 in the dividend stock would be worth ~$2.92 (1.055^20), whereas $1 in the non-dividend stock would be worth ~$3.21 (1.06^20). You're talking about a difference of 30 cents per dollar invested, which doesn't seem huge but multiply it by 100,000 and you've got yourself enough money to renovate your house purely out of money that would have gone to the government instead. The advantage here is if you are saving up for retirement, when you retire you won't have much income so the tax on the gains (even ignoring the capital gains effect above) will definitely be less then when you were working, however if you had a dividend stock you would have been paying taxes on the dividend, at a higher rate, throughout the lifetime of the investment. So, there you go, that's what Mohnish Pabrai is talking about. There are some caveats to this. If the amount you are investing isn't large, and you are in a lower tax bracket, and the stock pays out relatively low dividends you won't really feel the difference much, even though it's there. Also, dividend vs. no dividend is hardly the highest priority when deciding what company to invest in, and you'll practically never be able to find identical companies that differ only on dividend/no dividend, so if you find a great buy you may not have a choice in the matter. Also, there has been a trend in recent years to also make capital gains tax progressive, so people who have a higher income will also pay more in capital gains, which negates part of the benefit of non-dividend stocks (but doesn't change the growth rate effects before the sale). There are also some theoretical arguments that dividend-paying companies should have stronger shareholders (since the company has less capital, it has to 'play nice' to get money either from new shares or from banks, which leads to less risky behavior) but it's not so cut-and-dried in real life.",
"title": ""
},
{
"docid": "169240",
"text": "You can keep the cash in your account as long as you want, but you have to pay a tax on what's called capital gains. To quote from Wikipedia: A capital gain is a profit that results from investments into a capital asset, such as stocks, bonds or real estate, which exceeds the purchase price. It is the difference between a higher selling price and a lower purchase price, resulting in a financial gain for the investor.[1] Conversely, a capital loss arises if the proceeds from the sale of a capital asset are less than the purchase price. Thus, buying/selling stock counts as investment income which would be a capital gain/loss. When you are filing taxes, you have to report net capital gain/loss. So you don't pay taxes on an individual stock sale or purchase - you pay tax on the sum of all your transactions. Note: You do not pay any tax if you have a net capital loss. Taxes are only on capital gains. The amount you are taxed depends on your tax bracket and your holding period. A short term capital gain is gain on an investment held for less than one year. These gains are taxed at your ordinary income tax rate. A long term capital gain is gain on an investment held for more than one year. These gains are taxed at a special rate: If your income tax rate is 10 or 15%, then long term gains are taxed at 0% i.e. no tax, otherwise the tax rate is 15%. So you're not taxed on specific stock sales - you're taxed on your total gain. There is no tax for a capital loss, and investors sometimes take profits from good investments and take losses from bad investments to lower their total capital gain so they won't be taxed as much. The tax rate is expected to change in 2013, but the current ratios could be extended. Until then, however, the rate is as is. Of course, this all applies if you live in the United States. Other countries have different measures. Hope it helps! Wikipedia has a great chart to refer to: http://en.wikipedia.org/wiki/Capital_gains_tax_in_the_United_States.",
"title": ""
},
{
"docid": "149305",
"text": "\"Appreciation of a Capital Asset is a Capital Gain. In the United States, Capital Gains get favorable tax treatment after being held for 12 months. From the IRS newsroom: Capital gains and losses are classified as long-term or short-term, depending on how long you hold the property before you sell it. If you hold it more than one year, your capital gain or loss is long-term. If you hold it one year or less, your capital gain or loss is short-term. The tax rates that apply to net capital gain are generally lower than the tax rates that apply to other income. For 2009, the maximum capital gains rate for most people is15%. For lower-income individuals, the rate may be 0% on some or all of the net capital gain. Special types of net capital gain can be taxed at 25% or 28%. The IRS defines a Capital Asset as \"\"most property you own\"\" with a list of exclusions found in Schedule D Instructions. None of the exclusions listed relate to Bond ETFs.\"",
"title": ""
},
{
"docid": "459589",
"text": "Yes, you may make non-deductible contributions to an IRA. The main benefit of a non-deductible IRA is tax-deferred earnings. If the investment pays out dividends, they will be kept in the IRA (whether you take them in cash and put them in a Cash Management Account, or you automatically reinvest them). You do not get taxed on these earnings until you withdraw from the IRA during retirement. If your income at that time is significantly lower than your income while you're working, you will be in a lower tax bracket (unless tax rates change drastically between now and then), so the taxes you pay on these earnings will be lower than if you'd invested outside the IRA and paid taxes along the way. You also get the benefit of compounding of the tax-deferred earnings. There's one caveat -- when you withdraw from the IRA, all the growth is treated as ordinary income. Even if some of it is capital gains, it will be taxed at your ordinary income rate, not your capital gains rate. So this is most beneficial for investments that produce dividends. If you have a mix of deductible and non-deductible contributions to your IRA, the tax on the principle portion of your withdrawals is pro-rated based on the ratio of deductible to total contributions. This ensures that you eventually get taxed for the deductible portion (it's not really tax-free, it's tax-deferred), but don't get taxed twice for the non-deductible portion. Another option, if your 401(k) plan allows it, is to make after-tax contributions to the 401(k). At the end of the year, you can make an in-service distribution of these contributions and their earnings from the 401(k) to a Roth Conversion IRA. This allows you to contribute to a Roth IRA even if you're above the income limit for normal Roth IRA contributions. You can also do this even if you're also making non-deductible contributions to your regular IRA.",
"title": ""
},
{
"docid": "7423",
"text": "\"If you sell an asset for more than you paid for it, the excess amount realized is called a capital gain and is generally considered a form of income for tax purposes. Generally, one pays income tax on realized capital gains, unless the sale is exempt—such as the sale of one's principal residence. Capital gains tax can also be avoided or deferred by holding assets in a tax-advantaged investment account like a TFSA or RRSP. When taxable, the effective income tax rate on capital gains income is half the normal rate due to the capital gains inclusion rate. Capital gains income is generally not considered to be employment, \"\"earned\"\", or \"\"working\"\" income. However, individuals who, say, trade stocks frequently and earn a substantial portion of their income that way may have their gains considered employment income and subject to regular income tax instead of the better rate. I suggest you contact Service Canada and ask them about the impact of a one-time sale of personal property that would result in a realized capital gain. While you would owe income tax on the capital gain, it might not have any impact on your disability benefits, because it would not be earned or employment income. You should also check with your private insurer; they may also consider the sale a capital gain and not employment income, however, only they would be able to tell you for sure whether it would have any possible effect on your benefits.\"",
"title": ""
},
{
"docid": "558867",
"text": "I'm not sure where you are, but in the United States capital gains are taxed at a lower rate than other types of income. On the 1040, captial gains income is separated from earned income, and income tax is calculated just on earned income. Then capital gains tax is calculated on capital gains income, and then added to income tax afterward.",
"title": ""
},
{
"docid": "60929",
"text": "\"In a Traditional IRA contributions are often tax-deductible. For instance, if a taxpayer contributes $4,000 to a traditional IRA and is in the twenty-five percent marginal tax bracket, then a $1,000 benefit ($1,000 reduced tax liability) will be realized for the year. So that's why they tax you as income, because they didn't tax that income before. If a taxpayer expects to be in a lower tax bracket in retirement than during the working years, then this is one advantage for using a Traditional IRA vs a Roth. Distributions are taxed as ordinary income. So it depends on your tax bracket UPDATE FOR COMMENT: Currently you may have heard on the news about \"\"the fiscal cliff\"\" - CNBC at the end of the year. This is due to the fact that the Bush tax-cuts are set to expire and if they expire. Many tax rates will change. But here is the info as of right now: Dividends: From 2003 to 2007, qualified dividends were taxed at 15% or 5% depending on the individual's ordinary income tax bracket, and from 2008 to 2012, the tax rate on qualified dividends was reduced to 0% for taxpayers in the 10% and 15% ordinary income tax brackets. After 2012, dividends will be taxed at the taxpayer's ordinary income tax rate, regardless of his or her tax bracket. - If the Bush tax cuts are allowed to expire. - Reference - Wikipedia Capital Gains tax rates can be seen here - the Capital Gains tax rate is relative to your Ordinary Income tax rate For Example: this year long term gains will be 0% if you fall in the 15% ordinary tax bracket. NOTE: These rates can change every year so any future rates might be different from the current year.\"",
"title": ""
},
{
"docid": "598596",
"text": "In most jurisdictions, you want to split the transactions. Why? Because you want to report capital gains on your investment income, and this will almost always be taxed at a lower rate than employment income. See Wikipedia's article for more information about capital gains. In Canada, you pay tax on 50% of your realized capital gains. There are also ways to shelter your gains from tax; in Canada, TFSA, in the US, I believe these are 'roth' accounts. I actually think you have to split the transactions, at least in Canada and the U.S., though I'm not absolutely sure. Regardless, you want to do so if you plan on making money with your investments. If you plan on making a loss, please contact me as I'm happy to accept the money you are planning on throwing away.",
"title": ""
},
{
"docid": "314342",
"text": "\"Many individual states, counties, and cities have their own income taxes, payroll taxes, sales taxes, property taxes, etc., you will need to consult your state and local government websites for information about additional taxes that apply based on your locale. Wages, Salaries, Tips, Cash bonuses and other taxable employee pay, Strike benefits, Long-term disability, Earnings from self employment Earned income is subject to payroll taxes such as: Earned income is also subject to income taxes which are progressively higher depending on the amount earned minus tax credits, exemptions, and/or deductions depending on how you file. There are 7 tax rates that get progressively larger as your income rises but only applies to the income in each bracket. 10% for the first 18,650 (2017) through 39.6% for any income above 470,700. The full list of rates is in the above linked article about payroll taxes. Earned income is required for contributions to an IRA. You cannot contribute more to an IRA than you have earned in a given year. Interest, Ordinary Dividends, Short-term Capital Gains, Retirement income (pensions, distributions from tax deferred accounts, social security), Unemployment benefits, Worker's Compensation, Alimony/Child support, Income earned while in prison, Non-taxable military pay, most rental income, and S-Corp passthrough income Ordinary income is taxed the same as earned income with the exception that social security taxes do not apply. This is the \"\"pure taxable income\"\" referred to in the other linked question. Dividends paid by US Corporations and qualified foreign corporations to stock-holders (that are held for a certain period of time before the dividend is paid) are taxed at the Long-term Capital Gains rate explained below. Ordinary dividends like the interest earned in your bank account are included with ordinary income. Stocks, Bonds, Real estate, Carried interest -- Held for more than a year Income from assets that increase in value while being held for over a year. Long term capital gains justified by the idea that they encourage people to hold stock and make long term investments rather than buying and then quickly reselling for a short-term profit. The lower tax rates also reflect the fact that many of these assets are already taxed as they are appreciating in value. Real-estate is usually taxed through local property taxes. Equity in US corporations realized by rising stock prices and dividends that are returned to stock holders reflect earnings from a corporation that are already taxed at the 35% Corporate tax rate. Taxing Capital gains as ordinary income would be a second tax on those same profits. Another problem with Long-term capital gains tax is that a big portion of the gains for assets held for multiple decades are not real gains. Inflation increases the price of assets held for longer periods, but you are still taxed on the full gain even if it would be a loss when inflation is calculated. Capital gains are also taxed differently depending on your income level. If you are in the 10% or 15% brackets then Long-term capital gains are assessed at 0%. If you are in the 25%, 28%, 33%, or 35% brackets, they are assessed at 15%. Only those in the 39.6% bracket pay 20%. Capital assets sold at a profit held for less than a year Income from buying and selling any assets such as real-estate, stock, bonds, etc., that you hold for less than a year before selling. After adding up all gains and losses during the year, the net gain is taxed as ordinary income. Collectibles held for more than a year are not considered capital assets and are still taxed at ordinary income rates.\"",
"title": ""
},
{
"docid": "66858",
"text": "\"Long-term capital gains, which is often the main element of investment income for investors who are not high-frequency day traders, are taxed at a single rate that is often substantially below the marginal rate they would otherwise be taxed at, particularly for wealthy individuals. There are a few rationales behind this treatment; the two most common are that the government wants to encourage long-term investments (as opposed to short-term speculation), and that capital gains are a kind of double taxation (from one point of view) as they are coming from income that has already been taxed once before (as wage or ordinary income). The latter in particular is highly controversial, but this is one of the more divisive political issues in the taxation front - one party would eliminate the tax entirely, the other would eliminate the difference. For most individuals, the majority of their long-term capital gains are taxed at 15% up to almost half of a million dollars total AGI, which is a fairly low rate - it's equivalent to the rate a taxpayer would pay on up to $37,000 in wage income (after deductions/exemptions/etc.). You can see from this table in Wikipedia that it is much preferred to pay long-term capital gains rates when possible - at every point it's at least 10% lower than the tax rate for ordinary income. Ordinary income includes wages and many other sources of income - basically, anything that is not long term capital gains. Wage income is taxed at this rate, and also subject to some non-income-tax taxes (FICA and Medicare in particular); other sources of ordinary income are not subject to those taxes (including IRA income). Short term capital gains are generally included in this bucket. Qualified Dividends are treated similarly to long-term capital gains (as they are of a similar nature), and taxed accordingly. The \"\"Net Investment Tax\"\" is basically applying the Medicare tax to investment income for higher-income taxpayers ($125k single, $250k joint). It's on top of capital gains rates for them. It came about through the Affordable Care Act, and is one of the first provisions likely to be repealed by the new Congress (as it can be repealed through the budgeting provision). It seems likely that 2017 taxes will not contain this provision.\"",
"title": ""
},
{
"docid": "453639",
"text": "(All for US.) Yes you (will) have a realized long-term capital gain, which is taxable. Long-term gains (including those distributed by a mutual fund or other RIC, and also 'qualified' dividends, both not relevant here) are taxed at lower rates than 'ordinary' income but are still bracketed almost (not quite) like ordinary income, not always 15%. Specifically if your ordinary taxable income (after deductions and exemptions, equivalent to line 43 minus LTCG/QD) 'ends' in the 25% to 33% brackets, your LTCG/QD income is taxed at 15% unless the total of ordinary+preferred reaches the top of those brackets, then any remainder at 20%. These brackets depend on your filing status and are adjusted yearly for inflation, for 2016 they are: * single 37,650 to 413,350 * married-joint or widow(er) 75,300 to 413,350 * head-of-household 50,400 to 441,000 (special) * married-separate 37,650 to 206,675 which I'd guess covers at least the middle three quintiles of the earning/taxpaying population. OTOH if your ordinary income ends below the 25% bracket, your LTCG/QD income that 'fits' in the lower bracket(s) is taxed at 0% (not at all) and only the portion that would be in the ordinary 25%-and-up brackets is taxed at 15%. IF your ordinary taxable income this year was below those brackets, or you expect next year it will be (possibly due to status/exemption/deduction changes as well as income change), then if all else is equal you are better off realizing the stock gain in the year(s) where some (or more) of it fits in the 0% bracket. If you're over about $400k a similar calculation applies, but you can afford more reliable advice than potential dogs on the Internet. (update) Near dupe found: see also How are long-term capital gains taxed if the gain pushes income into a new tax bracket? Also, a warning on estimated payments: in general you are required to pay most of your income tax liability during the year (not wait until April 15); if you underpay by more than 10% or $1000 (whichever is larger) you usually owe a penalty, computed on Form 2210 whose name(?) is frequently and roundly cursed. For most people, whose income is (mostly) from a job, this is handled by payroll withholding which normally comes out close enough to your liability. If you have other income, like investments (as here) or self-employment or pension/retirement/disability/etc, you are supposed to either make estimated payments each 'quarter' (the IRS' quarters are shifted slightly from everyone else's), or increase your withholding, or a combination. For a large income 'lump' in December that wasn't planned in advance, it won't be practical to adjust withholding. However, if this is the only year increased, there is a safe harbor: if your withholding this year (2016) is enough to pay last year's tax (2015) -- which for most people it is, unless you got a pay cut this year, or a (filed) status change like marrying or having a child -- you get until next April 15 (or next business day -- in 2017 it is actually April 18) to pay the additional amount of this year's tax (2016) without underpayment penalty. However, if you split the gain so that both 2016 and 2017 have income and (thus) taxes higher than normal for you, you will need to make estimated payment(s) and/or increase withholding for 2017. PS: congratulations on your gain -- and on the patience to hold anything for 10 years!",
"title": ""
},
{
"docid": "537916",
"text": "\"Do I have to pay the stock investment income tax if I bought some stocks in 2016, it made some profits but I didn't sell them at the end of 2016? You pay capital gains taxes only when you sell the stocks. When you sell the stock within a year you will pay the short term capital gains rate which is the same rate as your ordinary income. If the stock pays dividends, however, you will have to pay taxes in the year that the dividend was paid out to you. I bought some stocks in 2011, sold them in 2012 and made some gains. Which year of do I pay the tax for the gains I made? You would pay in 2012, likely at the short term gain rate. I bought some stocks, sold them and made some gains, then use the money plus the gains to buy some other stocks before the end of the same year. Do I have to pay the tax for the gains I made in that year? Yes. There is a specific exception called the \"\"Wash Sale Rule\"\", but that would only apply if you lost money on the original sale and bought a substantially similar or same stock within 30 days. Do I get taxed more for the money I made from buying and selling stocks, even if the gains is only in hundreds? More than what? You pay taxes based on the profit you make from the investment. If you held it less than a year it is the same tax rate as your regular income. If you held it longer you pay a lower tax rate which is usually lower than your regular tax rate.\"",
"title": ""
},
{
"docid": "118878",
"text": "\"The scenario you mention regarding capital gains is pretty much the core of the issue. Here's a run-down from PolitiFact.com that explains it a bit. It's important to focus on it being the tax rate, not the tax amount (which I think you get, but I want to reinforce that for other readers). Basically, most of Buffett's income comes from capital gains and dividends, income from investments he makes with the money he already has. Income earned by buying and selling stocks or from stock dividends is generally taxed at 15 percent, the rate for long-term capital gains and qualified dividends. Buffett also mentioned that some of the \"\"mega-rich\"\" are hedge fund managers \"\"who earn billions from our daily labors but are allowed to classify our income as 'carried interest,' thereby getting a bargain 15 percent tax rate.\"\" We don't know the taxes paid by Buffett's secretary, who was mentioned by Obama but not by Buffett. Buffet's secretary would have to make a high salary, or else typical deductions (such as the child tax credit) would offset taxes owed. Let's say the secretary is a particularly well-compensated executive assistant, making adjusted income more than $83,600 in income. (Yes, that sounds like a lot to us, too, but remember: We're talking about the secretary to one of the richest people in the world.) In that case, marginal tax rates of 28 percent would apply. Then, there would be payroll taxes of 6.25 percent on the first $106,800, money that goes to Social Security, and another 1.45 percent on all income, which goes to Medicare. The secretary’s overall tax rate would be lower than 28 percent, since not all the income would be taxed at that rate, only the income above $83,600. Buffett, meanwhile, would pay very little, if anything, in payroll taxes. In the New York Times op-ed, Buffett said he paid 17.4 percent in taxes. Thinking of the secretary, it gets a little complicated, given how the tax brackets work, but basically, people who make between $100,000 and $200,000 are paying around 20 percent in federal taxes, including payroll and income taxes, according to an analysis from the nonpartisan Tax Policy Center. So in this case, the secretary's rate is higher because so much of Buffett's income comes from investments and is taxed at the lower capital gains rate. Here's Buffet's original Op-Ed in the NYT for those of you that aren't familiar.\"",
"title": ""
},
{
"docid": "177298",
"text": "Long-term capital gains, as you note, get special tax treatment. They are lower than regular income tax rates. Short-term capital gains aren't penalized, they are just treated as regular income under the regular rates. So, from a tax perspective, the day-trader gets by the same way as the rest of us because they are paying the same rates on the same progressive income tax scale.",
"title": ""
},
{
"docid": "553253",
"text": "E.g. I buy 1 stock unit for $100.00 and sell it later for $150.00 => income taxes arise. Correct. You pay tax on your gains, i.e.: the different between net proceeds and gross costs (proceeds sans fees, acquisition costs including fees). I buy 1 stock unit for $150.00 and sell it later for $100.00 => no income taxes here. Not correct. The loss is deductible from other capital gains, and if no other capital gains - from your income (up to $3000 a year, until exhausted). Also, there are two different tax rate sets for capital gains: short term (holding up to 1 year) and long term (more than that). Short term capital gains tax matches ordinary income brackets, whereas long term capital gains tax brackets are much lower.",
"title": ""
},
{
"docid": "155053",
"text": "\"There is not a special rate for short-term capital gains. Only long-term gains have a special rate. Short-term gains are taxed at your ordinary-income rate (see here). Hence if you're in the 25% bracket, your short-term gain would be taxed at 25%. The IRA withdrawal, as you already mentioned, would be taxed at 25%, plus a 10% penalty, for 35% total. Thus the bite on the IRA withdrawal is larger than that on a non-IRA withdrawal. As for the estimated tax issue, I don't think there will be a significant difference there. The reason is that (traditional) IRA withdrawals count as ordinary taxable income (see here). This means that, when you withdraw the funds from your IRA, you will increase your income. If that increase pushes you too far beyond what your withholding is accounting for, then you owe estimated tax. In other words, whether you get the money by selling stocks in a taxable account or by withdrawing them from an IRA, you still increase your taxable income, and thus potentially expose yourself to the estimated tax obligation. (In fact, there may be a difference. As you note, you will pay tax at the capital gains rate on gains from selling in a taxable account. But if you sell the stocks inside the IRA and withdraw, that is ordinary income. However, since ordinary income is taxed at a higher rate than long-term capital gains, you will potentially pay more tax on the IRA withdrawal, since it will be taxed at the higher rate, if your gains are long-term rather than short term. This is doubly true if you withdraw early, incurring the extra 10% penalty. See this question for some more discussion of this issue.) In addition, I think you may be somewhat misunderstanding the nature of estimated tax. The IRS will not \"\"ask\"\" you for a quarterly estimated tax when you sell stock. The IRS does not monitor your activity and send you a bill each quarter. They may indeed check whether your reported income jibes with info they received from your bank, etc., but they'll still do that regardless of whether you got that income by selling in a taxable account or withdrawing money from an IRA, because both of those increase your taxable income. Quarterly estimated tax is not an extra tax; it is just you paying your normal income tax over the course of the year instead of all at once. If your withholdings will not cover enough of your tax liability, you must figure that out yourself and pay the estimated tax (see here); if you don't do so, you may be assessed a penalty. It doesn't matter how you got the money; if your taxable income is too high relative to your withheld tax, then you have to pay the estimated tax. Typically tax will be withheld from your IRA distribution, but if it's not withheld, you'll still owe it as estimated tax.\"",
"title": ""
},
{
"docid": "494935",
"text": "I understand the frustration, American politics is pretty utterly fucked isn't it? > Anyway, I think we should be doing our best to incentivize corporate formation by lowering corporate taxes to zero and moving the incidence of taxation directly to capital. That's interesting, and I've heard it before. Is something [like this writer](http://www.theatlantic.com/business/archive/2010/10/why-we-should-eliminate-the-corporate-income-tax/65351/) outlines what you are thinking? Essentially remove corporate taxes, and then tax dividends and capital gains as normal income?",
"title": ""
},
{
"docid": "581866",
"text": "To try to answer the three explicit questions: Every share of stock is treated proportionately: each share is assigned the same dollar amount of investment (1/176th part of the contribution in the example), and has the same discount amount (15% of $20 or $25, depending on when you sell, usually). So if you immediately sell 120 shares at $25, you have taxable income on the gain for those shares (120*($25-$17)). Either selling immediately or holding for the long term period (12-18 mo) can be advantageous, just in different ways. Selling immediately avoids a risk of a decline in the price of the stock, and allows you to invest elsewhere and earn income on the proceeds for the next 12-18 months that you would not otherwise have had. The downside is that all of your gain ($25-$17 per share) is taxed as ordinary income. Holding for the full period is advantageous in that only the discount (15% of $20 or $25) will be taxed as ordinary income and the rest of the gain (sell price minus $20 or $25) will be taxed at long-term capital gain tax rates, which generally are lower than ordinary rates (all taxes are due in the year you do sell). The catch is you will sell at different price, higher or lower, and thus have a risk of loss (or gain). You will never be (Federally) double taxed in any scenario. The $3000 you put in will not be taxed after all is sold, as it is a return of your capital investment. All money you receive in excess of the $3000 will be taxed, in all scenarios, just potentially at different rates, ordinary or capital gain. (All this ignores AMT considerations, which you likely are not subject to.)",
"title": ""
},
{
"docid": "405342",
"text": "\"If you only have to pay 23k federal taxes on 100k, that means you are in the long term capital gains tax rate, which is the lower of the tax rates available. First you get your federal income tax marginal tax rate, and then find the matching long term capital gains tax rate. For example, if your marginal federal income tax rate is 28%, your capital gains tax rate would be 15%. Or rather, if the amount of the gain would put you in the 28% rate, then your long term capital gains tax rate is 15%. You can reduce that by having more losses. If you have anything else invested anywhere that is taking a loss, then you can sell that this year and it will offset the other gains you have realized. The only note is that your losses have to be long term capital losses too. Tax loss harvesting takes this to an extreme where you sell something at a loss to lock in the tax loss, but you didn't really want to get rid of that investment, so then you buy a nearly identical investment. ie. if you owned shares of \"\"Direxion Tech Sector ETF\"\" and it was at a loss, you would sell that and then immediately buy \"\"ProShares Tech Sector ETF\"\", the competing product that does the exact same thing. Then there is charity. This still requires spending money and you not having it any longer. If you feel that a cause can use the money more directly than the US government, you can donate an appreciated asset to the charity - not report a gain and also take a charitable deduction.\"",
"title": ""
},
{
"docid": "532657",
"text": "\"To keep it simple, I will keep the focus between a Trad IRA and a normal Taxable account (Roth's and 401(k) add more complications that make another problem). I will also assume, based on the question, that you aren't able to deduct the IRA contributions. Also, a Roth is better in every way than a non-deductible Trad IRA so the \"\"backdoor Roth\"\" mentioned in other answers is probably the way to go and this is more of an academic exercise. Ok, so why bother with the IRA if you're taxed anyway? Because you aren't taxed as you go! With a normal non-tax-advantaged account you have to pay taxes every year on any realized capital gains and dividends (including fund distributions). Because of the compounding nature of savings, delaying paying taxes is in your best interest. Simple example: Taxable Account: IRA Account: Now, this is a very simplified example. If you're more tax-conscious (i.e. more buy-and-holding), you can delay paying some of the long-term cap gains in the taxable account, but any short-term cap gains (including distributions from the underlying funds) will be at your marginal income tax rate. A few other observations: EDIT: I set up a spreadsheet where each year I deposited $1000 for 35 years. Each year, the balance in the IRA account grows by 5%, but the taxable only by 5%*(1-0.15) = 4.25% due to the effect of taxes. At the end of 35 years, my simulation assumes you pay 15% on all the gains in the IRA, which would likely not be the case, but easier than forecasting through retirement and demonstrates what I'm trying to show. Here's plot showing the balance in the various accounts, the blue is the IRA account, orange the taxable account, and grey is the effective balance of the IRA, after paying taxes on the gains: And here's a plot of the advantage of the IRA (after paying taxes on the gains), vs the taxable account: Whether that's worth it to you or anyone depends on some the assumptions in the simulation, especially effective tax rates, and growth rates, as well as any personal issues. Some people may be less likely to raid an IRA account, for example, than a normal account. Conversely, if you have a project coming up, you may need something a bit more liquid than an IRA.\"",
"title": ""
},
{
"docid": "42521",
"text": "\"If you sell a stock, with no distributions, then your gain is taxable under §1001. But not all realized gains will be recognized as taxable. And some gains which are arguably not realized, will be recognized as taxable. The stock is usually a capital asset for investors, who will generate capital gains under §1(h), but dealers, traders, and hedgers will get different treatment. If you are an investor, and you held the stock for a year or more, then you can get the beneficial capital gain rates (e.g. 20% instead of 39.6%). If the asset was held short-term, less than a year, then your tax will generally be calculated at the higher ordinary income rates. There is also the problem of the net investment tax under §1411. I am eliding many exceptions, qualifications, and permutations of these rules. If you receive a §316 dividend from a stock, then that is §61 income. Qualified dividends are ordinary income but will generally be taxed at capital gains rates under §1(h)(11). Distributions in redemption of your stock are usually treated as sales of stock. Non-dividend distributions (that are not redemptions) will reduce your basis in the stock to zero (no tax due) and past zero will be treated as gain from a sale. If you exchange stock in a tax-free reorganization (i.e. contribute your company stock in exchange for an acquirer's stock), you have what would normally be considered a realized gain on the exchange, but the differential will not be recognized, if done correctly. If you hold your shares and never sell them, but you engage in other dealings (short sales, options, collars, wash sales, etc.) that impact those shares, then you can sometimes be deemed to have recognized gain on shares that were never sold or exchanged. A more fundamental principle of income tax design is that not all realized gains will be recognized. IRC §1001(c) says that all realized gains are recognized, except as otherwise provided; that \"\"otherwise\"\" is substantial and far-ranging.\"",
"title": ""
},
{
"docid": "393964",
"text": "> Which of course explains why Biloxi is an economic powerhouse and no one has ever heard of New York City or San Francisco. Lower taxes states like Texas are faring better economically compared to other states with high taxes. > **[No-Tax Texas Out-Competes High-Tax Arkansas](http://www.cato.org/blog/no-tax-texas-out-competes-high-tax-arkansas)** > By Daniel J. Mitchell > Writing in National Review, **Greg Kaza discusses how Texas has been growing faster and creating more jobs than Arkansas. Much of the credit, he writes, is due to the fact that Texas has no state income tax while Arkansas penalizes workers with a tax rate of 7 percent:** > Employment growth in Texas has been significantly higher than in Arkansas during periods of economic expansion. The population in Dallas has nearly tripled in the post-WWII period, while the population in Little Rock has barely doubled in size. Per capita personal income in Texas is 94 percent of the U.S total. In Arkansas it’s 77 percent of the nation’s total, a level that has hardly budged since the 1970s. > The list of statistical disparities is long, and there’s a good reason why: While Arkansas and Texas share a common border, each taxes income and capital in radically different ways. **Arkansas has a top income-tax rate of 7 percent, the highest among the bordering states. Texas, however, does not impose an income tax. The imbalance is the same for capital gains: Arkansas taxes them. Texas does not. As a result, we can see a very basic economic principle at work: Talent and capital always will flow toward higher returns.**",
"title": ""
},
{
"docid": "175563",
"text": "In response to your points #1 and #2: In general, yes it is true that capital gains are only subject to half one's marginal rate of income tax. That doesn't mean 50% of the gain is due as tax... rather, it means that if one's marginal tax rate (tax bracket) on the next $10K would have been, say, 32%, then one is taxed on the gain at 16%. (The percentages are examples, not factual.) However, because these are employee stock options, the tax treatment is different than for a capital gain! Details: On the Federal tax return are lines for reporting Security option benefits (Line 101) and Security options deductions (Line 249). The distinction between a regular capital gain and an employee stock option benefits is important. In many cases the net effect may be the same as a capital gain, but the income is characterized differently and there are cases where it matters. Somebody who is about to or has realized employee stock option benefits should seek professional tax advice. In response to your next two points: No, one cannot transfer a capital gain or other investment income into a TFSA immediately after-the-fact in order to receive the tax-free benefits of the TFSA on that income. Only income and gains earned within a TFSA are free from tax – i.e. The options would have to have been in the TFSA before being exercised. Once a gain or other investment income has been realized in a non-sheltered account, it is considered taxable. The horse has already left the barn, so to speak! However, despite the above, there is another strategy available: One can create an offsetting deduction by contributing some of the realized gain into an RRSP. The RRSP contribution, assuming room is available, would yield a tax deduction to offset some tax due on the gain. However, the RRSP only defers income tax; upon withdrawal of funds, ordinary income tax is due (hopefully, at a lower marginal rate in retirement.) There is no minimum amount of time that money or assets have to be inside a TFSA to benefit from the tax-free nature of the account. However, there are limits on how much money you can move into a TFSA in any given year, and many folks weren't aware of the rules. p.s. Let me add once more that this is a case where I suggest seeking professional tax advice.",
"title": ""
},
{
"docid": "115264",
"text": "I think that author does a disservice by writing such seemingly sensible articles without actually knowing how things work. If I didn’t know better, I would think this guy was teaching me something. It’s a shame he did not do research before he started writing. Let’s say you buy a classic car. You take super good care of it, all original, mint condition. You paid cash for it out of your savings. This is a balance sheet transaction that has nothing to do with income. You traded your cash asset for a classic car asset. Now let’s say this car is so rare and you keep it in such good condition that it gains value every year. Maybe it was worth $15k when you bought it, but this year it’s already worth $17k. Great job on making a great purchase! But is that $2k gain counted as income to you? No, it is not. The value of that asset on your balance sheet went up, but you did not make anything off of that increase in value because you have not sold it. If you had to pay taxes on the increase in value every year, those taxes would essentially force you to sell that car to pay the taxes just because you took care of it. Additionally, in the long term, no one would want to own anything, so this would destroy the value of everyone’s stuff, but I digress. In this example, amazon stock is the car. The author is seeing the increase in stock value adding to the balance sheets of the investors who bought the stock and confusing that with income. Back to our example, let’s say your car increased in value $2k a year for two years and you decide to sell it for $19k - now we are about to realize some income! Since you bought it for $15k and sold for $19k, you earned an income of the difference, or $4k. Your income wasn’t $19k, because you originally put $15k in cash into the car. That cash was already saved from income you made in the past, and it is not counted again as income in this sale. Because you did not work for this new car sale income, but it was derived from asset growth, the income is called capital gains. You invested your capital ($15k) into the asset (car), and that asset appreciated. When you sold it, you received capital (money) back in exchange for that asset. The capital you received is more than what you invested, which is to say you gained $4k of capital by investing in and then selling your asset (car). Because you held the car for two years, you qualify for lower long term capital gains tax rate on that $4k. Had you sold it after year 1, you would’ve paid your regular normal income tax rate on those capital gains. Either way, you owe the tax when you sell the asset, not when it appreciates. I’m sure you realize this already, but if we change the car to amazon stock in my story, this is exactly how it works with investors. The author gets several things wrong 1 - amazon profits are not passed through to shareholders for income tax purposes. If amazon paid dividends, those dividends would be taxed at payout at the long term capital gains rate, and they would be paid out of cash amazon has left after it already paid corporate taxes on profits. Amazon has decided they can add more value to investors by using cash to grow instead of paying dividends. When the investors sell the stock, they will owe capital gains on the growth of that stock. If amazon is correct that using cash to grow, then investors will effectively pay more when they sell the stock than they would pay today if dividends were paid. 2 - asset appreciation is not income. Those investors will realize the income when they sell the stock, and they will pay the tax then. 3 - he is missing the point entirely on why amazon runs a low profit or how business strategy translates into financials. Low prices are not a function of low profitability. Low profitability could be an adverse result of low pricing, but being low profit in order to be low price is a ridiculous and failing strategy. Amazon’s low pricing is a function of their unparalleled buying power, unparalleled consumer and product data, amazing logistics prowess, clever loyalty programs like amazon prime, and many other brilliant things they’ve done. Their low profitability is a function of their investment in things like amazon fresh, amazon Alexa, drone delivery, automated convenience stores, building out cloud computing infrastructure, and many other R&D projects, $4 billion in original content spending for amazon prime video, and all kinds of expenditures years ahead of when they become profitable. By the time consumers want it, amazon already built it three years ago - this is the power of amazon. Sometimes multi billion dollar experiments fail, and all that money was for nothing. Sometimes they lose money for a few years and then become the infrastructure that runs a third of the internet. Amazon does not let fear of failure stop them, they invest in growth with their cash. This is how Bezos thinks - how do we build the future, not how can I avoid tax I do need to make a disclaimer here - there could be special tax treatment of classic cars that makes my example not work. Also classic cars may not appreciate in value. I don’t know anything about classic cars, I just picked a politically neutral thing to put in my story and made some assumptions to illustrate how capital gains work. My story is definitely how stocks work, and probably cars, but I just want to point out that I don’t know shit about car collecting.",
"title": ""
},
{
"docid": "125601",
"text": "If you put it in a normal account it is (1) taxed as ordinary income now and then (2) any growth is taxed again at the capital gains rate. Additionally, (3) any dividends will be taxed each year. If you put it in a 401(k), you will only be taxed once, at the ordinary income rate. Mathematically, if you start with X and have a regular tax rate of t and capital gains rate of g and your investments return r and there are n years to retirement, then your total wealth if you put it in a mutual fund (ignoring annual taxes on dividends) will be While if you used a 401(k) it would simply be The whole g term (along with any annual taxes on dividends) is gone in the second case and that's potentially a lot of taxes. The 401(k) is much better in terms of total wealth unless tax rates dramatically rise between now and when you retire so that the t in the second case is much higher than in the first. This is virtually never the case for people retiring now. Of course, what tax rates the future holds, we do not know.",
"title": ""
},
{
"docid": "93205",
"text": "For some reason this can result in either the flow through income being UNTAXED or the flow through income being taxed as a capital gains. Either way this allows a lower tax rate for LLC profits. I'm not sure that correct. I know it has something to do with capital accounts. This is incorrect. As to capital accounts - these are accounts representing the members/partners' capital in the enterprise, and have nothing to do with the tax treatment of the earnings. Undistributed earnings add to the capital accounts, but they're still taxed. Also, is it true that if the LLC loses money, that loss can be offset against other taxable income resulting in a lower total taxation? It can offset taxable income of the same kind, just like any other losses on your tax return. Generally, flow-through taxation of partnerships means that the income is taxed to the partner with the original attributes. If it is capital gains - it is taxed as capital gains. If it is earned income - it is taxed as earned income. Going through LLC/partnership doesn't re-characterize the income (going through corporation - does, in many cases).",
"title": ""
}
] |
PLAIN-693
|
biomagnification
|
[
{
"docid": "MED-1267",
"text": "β-methylamino-L-alanine (BMAA), a neurotoxic nonprotein amino acid produced by most cyanobacteria, has been proposed to be the causative agent of devastating neurodegenerative diseases on the island of Guam in the Pacific Ocean. Because cyanobacteria are widespread globally, we hypothesized that BMAA might occur and bioaccumulate in other ecosystems. Here we demonstrate, based on a recently developed extraction and HPLC-MS/MS method and long-term monitoring of BMAA in cyanobacterial populations of a temperate aquatic ecosystem (Baltic Sea, 2007–2008), that BMAA is biosynthesized by cyanobacterial genera dominating the massive surface blooms of this water body. BMAA also was found at higher concentrations in organisms of higher trophic levels that directly or indirectly feed on cyanobacteria, such as zooplankton and various vertebrates (fish) and invertebrates (mussels, oysters). Pelagic and benthic fish species used for human consumption were included. The highest BMAA levels were detected in the muscle and brain of bottom-dwelling fishes. The discovery of regular biosynthesis of the neurotoxin BMAA in a large temperate aquatic ecosystem combined with its possible transfer and bioaccumulation within major food webs, some ending in human consumption, is alarming and requires attention.",
"title": "From the Cover: Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure"
},
{
"docid": "MED-2644",
"text": "Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.",
"title": "p-Nonyl-phenol: an estrogenic xenobiotic released from \"modified\" polystyrene."
},
{
"docid": "MED-2652",
"text": "The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.",
"title": "Xeno-estrogenic compounds in precipitation."
},
{
"docid": "MED-2655",
"text": "Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.",
"title": "Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial"
},
{
"docid": "MED-2660",
"text": "BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids.",
"title": "Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men."
},
{
"docid": "MED-1266",
"text": "There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis). The non-protein amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer’s disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin.",
"title": "The Cyanobacteria Derived Toxin Beta-N-Methylamino-L-Alanine and Amyotrophic Lateral Sclerosis"
},
{
"docid": "MED-1276",
"text": "Previous evidence for spatial clustering of amyotrophic lateral sclerosis is inconclusive. Studies that have identified apparent clusters have often been based on a small number of cases, which means the results may have occurred by chance processes. Also, most studies have used the geographic location at the time of death as the basis for cluster detection, rather than exploring clusters at other points in the life cycle. In this study, the authors examine 1,000 cases of amyotrophic lateral sclerosis distributed throughout Finland who died between June 1985 and December 1995. Using a spatial-scan statistic, the authors examine whether there are significant clusters of the disease at both time of birth and time of death. Two significant, neighboring clusters were identified in southeast and south-central Finland at the time of death. A single significant cluster was identified in southeast Finland at the time of birth, closely matching one of the clusters identified at the time of death. These results are based on a large sample of cases, and they provide convincing evidence of spatial clustering of this condition. The results demonstrate also that, if the cluster analysis is conducted at different stages of the cases' life cycle, different conclusions about where potential risk factors may exist might result.",
"title": "Spatial clustering of amyotrophic lateral sclerosis in Finland at place of birth and place of death."
},
{
"docid": "MED-2657",
"text": "BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel",
"title": "Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis."
},
{
"docid": "MED-2479",
"text": "BACKGROUND: The prevalence of allergic diseases seems to have increased particularly over the past 35-40 years. Furthermore, allergic disease is less common among children in the formerly socialist countries of central and Eastern Europe as compared with Western Europe. It has been suggested that a reduced microbial stimulation during infancy and early childhood would result in a slower postnatal maturation of the immune system and development of an optimal balance between TH1- and TH2-like immunity. AIMS: To test the hypothesis that allergic disease among children may be associated with differences in their intestinal microflora in two countries with a low (Estonia) and a high (Sweden) prevalence of allergy. METHODS: From a prospective study of the development of allergy in relation to environmental factors, 29 Estonian and 33 Swedish 2-year-old children were selected. They were either nonallergic (n = 36) or had a confirmed diagnosis of allergy (n = 27) as verified by typical history and at least one positive skin prick test to egg or cow's milk. Weighed samples of faeces were serially diluted (10-2-10-9) and grown under anaerobic conditions. The counts of the various genera and species were calculated for each child. In addition, the relative amounts of the particular microbes were expressed as a proportion of the total count. RESULTS: The allergic children in Estonia and Sweden were less often colonized with lactobacilli (P < 0.01), as compared with the nonallergic children in the two countries. In contrast, the allergic children harboured higher counts of aerobic micro-organisms (P < 0. 05), particularly coliforms (P < 0.01) and Staphylococcus aureus (P < 0.05). The proportions of aerobic bacteria of the intestinal flora were also higher in the allergic children (P < 0.05), while the opposite was true for anaerobes (P < 0.05). Similarly, in the allergic children the proportions of coliforms were higher (P < 0. 05) and bacteroides lower (P < 0.05) than in the nonallergic children. CONCLUSIONS: Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood, similar to what has been shown in rodents. The role of intestinal microflora in relation to the development of infant immunity and the possible consequences for allergic diseases later in life requires further study, particularly as it would be readily available for intervention as a means for primary prevention of allergy by the administration of probiotic bacteria.",
"title": "The intestinal microflora in allergic Estonian and Swedish 2-year-old children."
},
{
"docid": "MED-4726",
"text": "The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'-dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane, oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet; n 13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, beta-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0.045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on beta-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.",
"title": "Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies."
},
{
"docid": "MED-1272",
"text": "Cyanobacteria produce many neurotoxins including beta-methylamino-L-alanine (BMAA) that has been liked to amyotrophic lateral sclerosis (ALS) and neurodegenerative disease. A number of ALS cases have been diagnosed among residents of Enfield, NH, a town encompassing a lake with a history of cyanobacteria algal blooms. To investigate an association between toxic cyanobacterial blooms in New Hampshire and development of ALS, we reviewed records from our institution and other community databases to obtain demographic information on patients diagnosed with ALS within New England. We identified nine ALS patients who lived near Lake Mascoma in Enfield, NH, an incidence of sporadic ALS that is 10 to 25 times the expected incidence of 2/100,000/year. We suggest that the high incidence of ALS in this potential cluster could be directly related to chronic exposure to cyanobacterial neurotoxins such as BMAA. Possible routes of toxin exposure include inhalation of aerosolized toxins, consuming fish, or ingestion of lake water. Further investigation, including analysis of brain tissue for cyanobacterial toxins, will be helpful to test for an association between BMAA and ALS.",
"title": "A cluster of amyotrophic lateral sclerosis in New Hampshire: a possible role for toxic cyanobacteria blooms."
},
{
"docid": "MED-4739",
"text": "Contemporary reproductive aged women and their offspring are facing an unprecedented onslaught of toxicant exposures from myriad sources in their day-to-day life. Public health recommendations regarding optimal diet and nutrition in pregnancy must incorporate several considerations including safety of available foodstuffs, cultural practices and lifestyle issues. Gestational consumption of contaminated seafood remains a potential source of toxicant exposure, including mercury, for the developing child. Health care professionals responsible for the care of women and their developing children need to become apprised of: a) risks associated with toxicant bioaccumulation in pregnancy; b) ongoing information emerging in the important field of reproductive toxicology; and c) strategies within the clinical setting to facilitate nutritional sufficiency and precautionary avoidance of adverse exposure among young women.",
"title": "Nowhere to hide: Chemical toxicants and the unborn child."
},
{
"docid": "MED-2464",
"text": "BACKGROUND: In recent decades, children's diet quality has changed and asthma prevalence has increased, although it remains unclear if these events are associated. OBJECTIVE: To examine children's total and component diet quality and asthma and airway hyperresponsiveness (AHR), a proxy for asthma severity. METHODS: Food frequency questionnaires adapted from the Nurses' Health Study and supplemented with foods whose nutrients which have garnered interest of late in relation to asthma were administered. From these data, diet quality scores (total and component), based on the Youth Healthy Eating Index (YHEI adapted) were developed. Asthma assessments were performed by pediatric allergists and classified by atopic status: Allergic asthma (≥1 positive skin prick test to common allergens >3 mm compared to negative control) versus non-allergic asthma (negative skin prick test). AHR was assessed via the Cockcroft technique. Participants included 270 boys (30% with asthma) and 206 girls (33% with asthma) involved in the 1995 Manitoba Prospective Cohort Study nested case-control study. Logistic regression was used to examine associations between diet quality and asthma, and multinomial logistic regression was used to examine associations between diet quality and AHR. RESULTS: Four hundred seventy six children (56.7% boys) were seen at 12.6 ± 0.5 years. Asthma and AHR prevalence were 26.2 and 53.8%, respectively. In fully adjusted models, high vegetable intake was protective against allergic asthma (OR 0.49; 95% CI 0.29-0.84; P < 0.009) and moderate/severe AHR (OR 0.58; 0.37-0.91; P < 0.019). CONCLUSIONS: Vegetable intake is inversely associated with allergic asthma and moderate/severe AHR. Copyright © 2012 Wiley Periodicals, Inc.",
"title": "Low vegetable intake is associated with allergic asthma and moderate-to-severe airway hyperresponsiveness."
},
{
"docid": "MED-1273",
"text": "From 1975 to 1983, six cases of amyotrophic lateral sclerosis (ALS) were diagnosed in long-term residents of Two Rivers, Wis; the probability that this occurred due to chance was less than .05. To investigate potential risk factors for ALS, we conducted a case-control study using two control subjects matched to each case patient for age, gender, and duration of residence in Two Rivers. Physical trauma, the frequent consumption of freshly caught Lake Michigan fish, and a family history of cancer were reported more often by case patients than control subjects. These findings support previous studies proposing a role for trauma in ALS pathogenesis and suggest that the causative role of diet should be further explored. Continued surveillance for and epidemiologic investigation of ALS clusters with subsequent retrospective analysis may provide clues concerning the cause of ALS.",
"title": "Amyotrophic lateral sclerosis. A case-control study following detection of a cluster in a small Wisconsin community."
},
{
"docid": "MED-1285",
"text": "The Chamorro people of Guam have been afflicted with a complex of neurodegenerative diseases (now known as ALS-PDC) with similarities to ALS, AD, and PD at a far higher rate than other populations throughout the world. Chamorro consumption of flying foxes may have generated sufficiently high cumulative doses of plant neurotoxins to result in ALS-PDC neuropathologies, since the flying foxes forage on neurotoxic cycad seeds.",
"title": "Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam."
},
{
"docid": "MED-2495",
"text": "We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood. Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n=162, 2-3years; n=180), and blood parameters were examined at three years of age (n=114). The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa. Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections. Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine. No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles. Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist int..."
},
{
"docid": "MED-2653",
"text": "Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 microg/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 microg/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats.",
"title": "Nonylphenol and octylphenol in human breast milk."
},
{
"docid": "MED-2396",
"text": "Rates of type 2 diabetes mellitus (T2DM), both in the United States and worldwide, have been rising at an alarming rate over the last two decades. Because this disease is viewed as primarily being attributable to unhealthy lifestyle habits, a great deal of emphasis has been placed on encouraging increased exercise, better dietary habits, and weight loss. Recent studies reveal that the presence of several persistent organic pollutants (POPs) can confer greater risk for developing the disease than some of the established lifestyle risk factors. In fact, evidence suggests the hypothesis that obesity might only be a significant risk factor when adipose tissue contains high amounts of POPs. Chlorinated pesticides and polychlorinated biphenyls, in particular, have been strongly linked to the development of metabolic syndrome, insulin resistance, and T2DM. In addition to reviewing the evidence associating POPs to these conditions, this article explores the possible contribution of farmed Atlantic salmon - a significant and common dietary source of POPs - with blood sugar dysregulation conditions.",
"title": "The role of persistent organic pollutants in the worldwide epidemic of type 2 diabetes mellitus and the possible connection to Farmed Atlantic Salm..."
},
{
"docid": "MED-2389",
"text": "Background: Prospective data regarding persistent organic pollutants (POPs) and risk of type 2 diabetes (T2D) are limited, and the results for individual POPs are not entirely consistent across studies. Objectives: We prospectively examined plasma POP concentrations in relation to incident T2D and summarized existing evidence in a meta-analysis. Methods: Plasma polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) concentrations were measured in 1,095 women who were free of diabetes at blood draw in 1989–1990 and participated in two case–control studies in the Nurses’ Health Study. We identified 48 incident T2D cases through 30 June 2008. We conducted a literature search in PubMed and EMBASE through December 2011 to identify prospective studies on POPs in relation to diabetes. We used a fixed-effects model to summarize results. Results: After multivariable adjustment, plasma HCB concentration was positively associated with incident T2D [pooled odds ratio (OR) 3.59 (95% CI: 1.49, 8.64, ptrend = 0.003) comparing extreme tertiles]. Other POPs were not significantly associated with diabetes. After pooling our results with those of six published prospective studies that included 842 diabetes cases in total, we found that HCB and total PCBs both were associated with diabetes: the pooled ORs were 2.00 (95% CI: 1.13, 3.53; I2 = 21.4%, pheterogeneity = 0.28) and 1.70 (95% CI: 1.28, 2.27; I2 = 16.3%, pheterogeneity = 0.30) for HCB and total PCBs, respectively. Conclusions: These findings support an association between POP exposure and the risk of T2D.",
"title": "Persistent Organic Pollutants and Type 2 Diabetes: A Prospective Analysis in the Nurses’ Health Study and Meta-analysis"
},
{
"docid": "MED-3687",
"text": "This study was aimed at determining the probiotic potential of a large number of autochthonous lactic acid bacteria isolated from fruit and vegetables. Survival under simulated gastric and intestinal conditions showed that 35% of the strains, mainly belonging to the species Lactobacillus plantarum maintained high cell densities. Selected strains did not affect the immune-mediation by Caco-2 cells. All strains stimulated all 27 immune-mediators by peripheral blood mononuclear cells (PBMC). A significant (P<0.05; P<0.01) increase of the major part of cytokines and growth factors was found. A few chemokines were stimulated. Immune-mediators with pro-inflammatory activity (IL-17, EOTAXIN and IFNγ) were significantly (P<0.01) stimulated by all strains, followed by IL-1b>IP-10>IL-6>MIP1α. Stimulation of IL-12, IL-2 and IL-7 was strain dependent. Only a few strains increased the synthesis of cytokines with anti-inflammatory activity. Six L. plantarum strains were further selected. Four were defined as the strongly adhesive strains (more than 40 bacteria adhering to one Caco-2 cell), and 2 as the adhesive strains (5-40 bacteria adhering to one Caco-2 cell). Five strains grew and acidified chemically defined medium with fructo-oligosaccharides (FOS) as the only carbon source. End-products of FOS fermentation were found. All strains inhibited enterohemorragic Escherichia coli K12 and Bacillus megaterium F6 isolated from human sources. The results of this study showed that some autochthonous lactic acid bacteria from raw fruit and vegetables have functional features to be considered as novel probiotic candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Novel probiotic candidates for humans isolated from raw fruits and vegetables."
},
{
"docid": "MED-4729",
"text": "In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources.",
"title": "Do Organohalogen Contaminants Contribute to Histopathology in Liver from East Greenland Polar Bears (Ursus maritimus)?"
},
{
"docid": "MED-2662",
"text": "A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.",
"title": "Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7)."
},
{
"docid": "MED-2650",
"text": "Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.",
"title": "Inadvertent exposure to xenoestrogens."
},
{
"docid": "MED-4876",
"text": "OBJECTIVE: The aim of this study was to screen for and quantify the neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) in a cohort of autopsy specimens taken from Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and non-neurological controls. BMAA is produced by cyanobacteria found in a variety of freshwater, marine, and terrestrial habitats. The possibility of geographically broad human exposure to BMAA had been suggested by the discovery of BMAA in brain tissues of Chamorro patients with ALS/Parkinsonism dementia complex from Guam and more recently in AD patients from North America. These observations warranted an independent study of possible BMAA exposures outside of the Guam ecosystem. METHODS: Postmortem brain specimens were taken from neuropathologically confirmed cases of 13 ALS, 12 AD, 8 HD patients, and 12 age-matched non-neurological controls. BMAA was quantified using a validated fluorescent HPLC method previously used to detect BMAA in patients from Guam. Tandem mass spectrometric (MS) analysis was carried out to confirm the identification of BMAA in neurological specimens. RESULTS: We detected and quantified BMAA in neuroproteins from postmortem brain tissue of patients from the United States who died with sporadic AD and ALS but not HD. Incidental detections observed in two out of the 24 regions were analyzed from the controls. The concentrations of BMAA were below what had been reported previously in Chamarro ALS/ Parkinsonism dementia complex patients, but demonstrated a twofold range across disease and regional brain area comparisons. The presence of BMAA in these patients was confirmed by triple quadrupole liquid chromatography/mass spectrometry/mass spectrometry. CONCLUSIONS: The occurrence of BMAA in North American ALS and AD patients suggests the possibility of a gene/environment interaction, with BMAA triggering neurodegeneration in vulnerable individuals. (c) 2009 The Authors Journal compilation (c) 2009 Blackwell Munksgaard.",
"title": "Cyanobacterial neurotoxin BMAA in ALS and Alzheimer's disease."
},
{
"docid": "MED-2654",
"text": "4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated.",
"title": "Endocrine disrupting nonylphenols are ubiquitous in food."
},
{
"docid": "MED-2643",
"text": "The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.",
"title": "Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action"
},
{
"docid": "MED-2627",
"text": "Human exposure to endocrine disrupters (EDs) is widespread and is considered to pose a growing threat to human health. Recent advances in molecular and genetic research and better understanding of mechanisms of blastic cell transformation have led to efforts to improve cancer risk assessment for populations exposed to this family of xenobiotics. In risk assessment, low dose extrapolation of cancer incidence data from both experimental animals and epidemiology studies has been largely based on models assuming linear correlation at low doses, despite existence of evidence showing otherwise. Another weakness of ED risk assessment is poor exposure data in ecological studies. Those are frequently rough estimates derived from contaminated items of local food basket surveys. Polyhalogenated hydrocarbons are treated as examples. There is growing sense of urgency to develop a biologically based dose response model of cancer risk, integrating emerging data from molecular biology and epidemiology to provide more realistic data for risk assessors, public, public health managers and environmental issues administrators.",
"title": "Human exposure to endocrine disrupters: carcinogenic risk assessment."
},
{
"docid": "MED-2391",
"text": "Objectives The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. Methods In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. Results Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p′- dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. Conclusion Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.",
"title": "Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA"
},
{
"docid": "MED-2661",
"text": "This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.",
"title": "Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy)."
},
{
"docid": "MED-2649",
"text": "Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.",
"title": "Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study"
},
{
"docid": "MED-2646",
"text": "BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.",
"title": "Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA..."
},
{
"docid": "MED-1289",
"text": "As root symbionts of cycad trees, cyanobacteria of the genus Nostoc produce β-methylamino-l-alanine (BMAA), a neurotoxic nonprotein amino acid. The biomagnification of BMAA through the Guam ecosystem fits a classic triangle of increasing concentrations of toxic compounds up the food chain. However, because BMAA is polar and nonlipophilic, a mechanism for its biomagnification through increasing trophic levels has been unclear. We report that BMAA occurs not only as a free amino acid in the Guam ecosystem but also can be released from a bound form by acid hydrolysis. After first removing free amino acids from tissue samples of various trophic levels (cyanobacteria, root symbioses, cycad seeds, cycad flour, flying foxes eaten by the Chamorro people, and brain tissues of Chamorros who died from amyotrophic lateral sclerosis/Parkinsonism dementia complex), we then hydrolyzed the remaining fraction and found BMAA concentrations increased 10- to 240-fold. This bound form of BMAA may function as an endogenous neurotoxic reservoir, accumulating and being transported between trophic levels and subsequently being released during digestion and protein metabolism. Within brain tissues, the endogenous neurotoxic reservoir can slowly release free BMAA, thereby causing incipient and recurrent neurological damage over years or even decades, which may explain the observed long latency period for neurological disease onset among the Chamorro people. The presence of BMAA in brain tissues from Canadian patients who died of Alzheimer's disease suggests that exposure to cyanobacterial neurotoxins occurs outside of Guam.",
"title": "A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam"
},
{
"docid": "MED-2395",
"text": "OBJECTIVE: Low-level exposure to some persistent organic pollutants (POPs) has recently become a focus because of their possible link with the risk of diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional associations of the serum concentrations of POPs with diabetes prevalence were investigated in 2,016 adult participants in the National Health and Nutrition Examination Survey 1999-2002. Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'-dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they were detectable in >or=80% of participants. RESULTS: Compared with subjects with serum concentrations below the limit of detection, after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of all six POPs. When the participants were classified according to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7 (P for trend < 0.001). The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals. CONCLUSIONS: There were striking dose-response relations between serum concentrations of six selected POPs and the prevalence of diabetes. The strong graded association could offer a compelling challenge to future epidemiologic and toxicological research.",
"title": "A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Ex..."
},
{
"docid": "MED-2493",
"text": "There is now compelling evidence that developmental exposure to chemicals from our environment contributes to disease later in life, with animal models supporting this concept in reproductive, metabolic, and neurodegenerative diseases. In contrast, data regarding how developmental exposures impact the susceptibility of the immune system to functional alterations later in life are surprisingly scant. Given that the immune system forms an integrated network that detects and destroys invading pathogens and cancer cells, it provides the body’s first line of defense. Thus, the consequences of early-life exposures that reduce immune function are profound. This review summarizes available data for pollutants such as cigarette smoke and dioxin-like compounds, which consistently support the idea that developmental exposures critically impact the immune system. These findings suggest that exposure to common chemicals from our daily environment represent overlooked contributors to the fact that infectious diseases remain among the top five causes of death worldwide.",
"title": "Environmental toxicants and the developing immune system: a missing link in the global battle against infectious disease?"
},
{
"docid": "MED-1288",
"text": "Beta-methylamino-L-alanine (BMAA) occurs in higher levels in museum specimens of the Guamanian flying fox than in the cycad seeds the flying foxes feed on, confirming the hypothesis that cycad neurotoxins are biomagnified within the Guam ecosystem. Consumption of a single flying fox may have resulted in an equivalent BMAA dose obtained from eating 174 to 1,014 kg of processed cycad flour. Traditional feasting on flying foxes may be related to the prevalence of neuropathologic disease in Guam.",
"title": "Biomagnification of cycad neurotoxins in flying foxes: implications for ALS-PDC in Guam."
},
{
"docid": "MED-2658",
"text": "The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.",
"title": "Alkylphenols--potential modulators of the allergic response."
},
{
"docid": "MED-2388",
"text": "Insulin resistance and the defective function of pancreatic β-cells can occur several years before the development of type 2 diabetes. It is necessary to investigate and clarify the integrated effects of moderate-to-high exposure to dioxins and mercury on the pancreatic endocrine function. This cross-sectional study investigated 1449 non-diabetic residents near a deserted pentachlorophenol and chloralkali factory. Metabolic syndrome related factors were measured to examine associations with serum dioxin and blood mercury. We also investigated associations between insulin resistance (HOMA-IR > 75th percentile), defective pancreatic β-cells function (HOMA β-cell > 75th percentile), serum dioxins and blood mercury. After adjusting for confounding factors, we found that insulin resistance increased with serum dioxins (b = 0.13, P < 0.001) and blood mercury (b = 0.01, P < 0.001). Moreover, participants with higher serum dioxins or blood mercury were at a significantly increasing risk for insulin resistance (P(trend) < 0.001). The joint highest tertile of serum dioxins and blood mercury was associated with elevated HOMA-IR at 11 times the odds of the joint lowest tertile (AOR 11.00, 95% CI: 4.87, 26.63). We hypothesize that simultaneous exposure to dioxins and mercury heightens the risk of insulin resistance more than does individual exposure. Copyright © 2010 Elsevier B.V. All rights reserved.",
"title": "Simultaneous exposure of non-diabetics to high levels of dioxins and mercury increases their risk of insulin resistance."
},
{
"docid": "MED-1277",
"text": "There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS) is caused by gene-environment interactions. Mutations in genes underlying familial ALS (fALS) have been discovered in only 5-10% of the total population of ALS patients. Relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron death leading to the syndrome of ALS, although exposure to chemicals including lead and pesticides, and to agricultural environments, smoking, certain sports, and trauma have all been identified with an increased risk of ALS. There is a need for research to quantify the relative roles of each of the identified risk factors for ALS. Recent evidence has strengthened the theory that chronic environmental exposure to the neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) produced by cyanobacteria may be an environmental risk factor for ALS. Here we describe methods that may be used to assess exposure to cyanobacteria, and hence potentially to BMAA, namely an epidemiologic questionnaire and direct and indirect methods for estimating the cyanobacterial load in ecosystems. Rigorous epidemiologic studies could determine the risks associated with exposure to cyanobacteria, and if combined with genetic analysis of ALS cases and controls could reveal etiologically important gene-environment interactions in genetically vulnerable individuals.",
"title": "Is exposure to cyanobacteria an environmental risk factor for amyotrophic lateral sclerosis and other neurodegenerative diseases?"
},
{
"docid": "MED-1278",
"text": "The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks and monkeys have shown that it can cause neurodegenerative symptoms such as ataxia and convulsions. Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential.",
"title": "Does α-Amino-β-methylaminopropionic Acid (BMAA) Play a Role in Neurodegeneration?"
},
{
"docid": "MED-2461",
"text": "This study aimed to evaluate the association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan. An in-class interview survey elicited experiences of asthma and respiratory symptoms and consumption frequencies of the major food categories in 2290 fifth graders. Respiratory symptoms surveyed included persistent cough, chest tightness, wheezing with cold, wheezing without cold, dyspnea-associated wheezing, and exercise-induced cough or wheezing. Results showed that the consumption of sweetened beverages had the strongest association with respiratory symptoms and was positively associated with six of the seven respiratory symptoms (all p < 0.05). The adjusted odds ratios (aOR) ranged from 1.05 (95% confidence interval (CI = 1.01-1.09) for exercise-induced cough to 1.09 (95% CI = 1.03-1.16) for wheezing without cold. Egg consumption was associated with 5 of the 7 respiratory symptoms. Consumptions of seafood, soy products, and fruits were each negatively associated with one of the seven respiratory symptoms (all p < 0.05). Consumption of seafood was negatively associated with physician-diagnosed asthma and consumptions of sweetened beverages and eggs were positively associated with suspected asthma (p < 0.05). In conclusion, the study suggests that diet is associated with the respiratory symptoms in schoolchildren in Taipei. Consumptions of sweetened beverages and eggs are associated with increased risk of respiratory symptoms and asthma whereas consumptions of soy products and fruits are associated with reduced risk of respiratory symptoms.",
"title": "The association of diet with respiratory symptoms and asthma in schoolchildren in Taipei, Taiwan."
},
{
"docid": "MED-2469",
"text": "The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.",
"title": "An anthroposophic lifestyle and intestinal microflora in infancy."
},
{
"docid": "MED-1265",
"text": "Determination of the environmental factors involved in neurodegenerative diseases has been elusive. Methylmercury and β-N-methylamino-L-alanine (BMAA) have both been implicated in this role. Exposure of primary cortical cultures to these compounds independently induced concentration-dependent neurotoxicity. Importantly, concentrations of BMAA (10-100 μM) that caused no toxicity alone potentiated methylmercury (3 μM) toxicity. In addition, concentrations of BMAA and methylmercury that had no effect by themselves on the main cellular antioxidant glutathione together decreased glutathione levels. Furthermore, the combined toxicity of methylmercury and BMAA was attenuated by the cell permeant form of glutathione, glutathione monoethyl ester. The results indicate a synergistic toxic effect of the environmental neurotoxins BMAA and methylmercury, and that the interaction is at the level of glutathione depletion.",
"title": "Synergistic toxicity of the environmental neurotoxins methylmercury and β-N-methylamino-L-alanine."
},
{
"docid": "MED-2407",
"text": "Background Persistent organic pollutants (POPs) are hazardous chemicals omnipresent in our food chain, which have been internationally regulated to ensure public health. Initially described for their potency to affect reproduction and promote cancer, recent studies have highlighted an unexpected implication of POPs in the development of metabolic diseases like type 2 diabetes and obesity. Based on this novel knowledge, this article aims at stimulating discussion and evaluating the effectiveness of current POP legislation to protect humans against the risk of metabolic diseases. Furthermore, the regulation of POPs in animal food products in the European Union (EU) is addressed, with a special focus on marine food since it may represent a major source of POP exposure to humans. Discussion There is mounting scientific evidence showing that current POP risk assessment and regulation cannot effectively protect humans against metabolic disorders. Better regulatory control of POPs in dietary products should be of high public health priority. Summary The general population is exposed to sufficient POPs, both in term of concentration and diversity, to induce metabolic disorders. This situation should attract the greatest attention from the public health and governmental authorities.",
"title": "Public health concern behind the exposure to persistent organic pollutants and the risk of metabolic diseases"
},
{
"docid": "MED-2651",
"text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.",
"title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan."
},
{
"docid": "MED-2497",
"text": "The birth cohort BraMat (n = 205; a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health) was established to study whether prenatal exposure to toxicants from the maternal diet affects immunological health outcomes in children. We here report on the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide generated in food during heat treatment. The frequency of common infections, eczema or itchiness, and periods of more than 10 days of dry cough, chest tightness or wheeze (called wheeze) in the children during the first year of life was assessed by questionnaire data (n = 195). Prenatal dietary exposure to the toxicants was estimated using a validated food frequency questionnaire from MoBa. Prenatal exposure to PCBs and dioxins was found to be associated with increased risk of wheeze and exanthema subitum, and also with increased frequency of upper respiratory tract infections. We found no associations between prenatal exposure to acrylamide and the health outcomes investigated. Our results suggest that prenatal dietary exposure to dioxins and PCBs may increase the risk of wheeze and infectious diseases during the first year of life. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants."
},
{
"docid": "MED-4740",
"text": "The US Environmental Protection Agency's 2004 Dioxin Reassessment included a characterization of background exposures to dioxin-like compounds, including an estimate of an average background intake dose and an average background body burden. These quantities were derived from data generated in the mid-1990s. Studies conducted in the 2000s were gathered in an attempt to update the estimates generated by the Reassessment. While these studies suggest declines in the average background dose and body burden, a precise quantification of this decline, much less a conclusion that a decline has indeed occurred, cannot be made because of the inconsistency of study design and data sources, and the treatment of non-detects in the generation of congener average concentrations. The average background intake of the Reassessment was 61.0 pg TEQ/day, and using more current data, the average background intake was 40.6 pg TEQ/day. The average body burden from the surveys in the mid-1990s was 22.9 pg TEQ/g lipid weight (pg/g lwt). More recent blood concentration data, from NHANES 2001/2, suggest an adult average at 21.7 pg/g TEQ lwt. These TEQ values include the 17 dioxin and furan congeners and 3 coplanar PCBs, and were generated substituting ND=(1/2)DL or ND=DL/sq rt (2). Results are provided for ND=0 and analyses conducted to evaluate the impacts of this substitution. A more detailed examination of beef and pork data from similarly designed national statistical surveys show that declines in pork are statistically significant while the beef concentrations appeared to have remained constant between the time periods.",
"title": "Evaluation of background exposures of Americans to dioxin-like compounds in the 1990s and the 2000s."
},
{
"docid": "MED-4730",
"text": "We successfully optimized an analytical method using gel permeation chromatography followed by direct sample introduction comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry to quantify multiple groups of targeted persistent organic pollutants and halogenated natural products (HNPs) simultaneously in fish oil samples. This new method has a wider analytical scope than the traditional approach to use multiple methods to cover each class of compounds. Our analysis revealed that the relatively more volatile and lighter organic compounds, such as polychlorinated biphenyls (PCBs), organochlorine pesticides, and other smaller organohalogen compounds, were still present in two brands of \"PCB-free\" cod liver oils, albeit at much lower levels than in an untreated commercial sample. Moreover, the less volatile organic compounds, such as polybrominated diphenyl ethers and brominated HNPs, were detected at similar levels in all three cod liver oils. This suggests that the commercial molecular distillation treatment used for removal of organic/inorganic toxic contaminants is only effective for the lighter organic contaminants.",
"title": "Simultaneous quantitation of multiple classes of organohalogen compounds in fish oils with direct sample introduction comprehensive two-dimensional..."
},
{
"docid": "MED-1281",
"text": "The calcium ion (Ca2+) is a ubiquitous second messenger that is crucial for the regulation of a wide variety of cellular processes. The diverse transient signals transduced by Ca2+ are mediated by intracellular Ca2+-binding proteins, also known as Ca2+ sensors. A key obstacle to studying many Ca2+-sensing proteins is the difficulty in identifying the numerous downstream target interactions that respond to Ca2+-induced conformational changes. Among a number of Ca2+ sensors in the eukaryotic cell, calmodulin (CaM) is the most widespread and the best studied. Employing the mRNA display technique, we have scanned the human proteome for CaM-binding proteins and have identified and characterized a large number of both known and previously uncharacterized proteins that interact with CaM in a Ca2+-dependent manner. The interactions of several identified proteins with Ca2+/CaM were confirmed by using pull-down assays and coimmunoprecipitation. Many of the CaM-binding proteins identified belong to protein families such as the DEAD/H box proteins, ribosomal proteins, proteasome 26S subunits, and deubiquitinating enzymes, suggesting the possible involvement of Ca2+/CaM in different signaling pathways. The selection method described herein could be used to identify the binding partners of other calcium sensors on the proteome-wide scale.",
"title": "Scanning the human proteome for calmodulin-binding proteins"
},
{
"docid": "MED-1287",
"text": "Recent studies demonstrate that most cyanobacteria produce the neurotoxin beta-N-methylamino-L-alanine (BMAA) and that it can biomagnify in at least one terrestrial food chain. BMAA has been implicated as a significant environmental risk in the development of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis (ALS). We examined several blooms of cyanobacteria in South Florida, and the BMAA content of resident animals, including species used as human food. A wide range of BMAA concentrations were found, ranging from below assay detection limits to approximately 7000 μg/g, a concentration associated with a potential long-term human health hazard.",
"title": "Cyanobacterial Blooms and the Occurrence of the neurotoxin beta-N-methylamino-L-alanine (BMAA) in South Florida Aquatic Food Webs"
},
{
"docid": "MED-2648",
"text": "The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.",
"title": "Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals"
},
{
"docid": "MED-1284",
"text": "We conducted an investigation of the levels of the neurotoxin 2-amino-3-(methylamino)-propanoic acid (BMAA) in cycad flour. Analysis of 30 flour samples processed from the endosperm of Cycas circinalis seeds collected on Guam indicated that more than 87% of the total BMAA content was removed during processing. Furthermore, in 1/2 the samples almost all (greater than 99%) of the total BMAA was removed. We found no significant regional differences in the BMAA content of flour prepared from cycad seeds collected from several villages on Guam. Testing of different samples prepared by the same Chamorro woman over 2 years suggests that the washing procedure probably varies in thoroughness from preparation to preparation but is routinely efficient in removing at least 85% of the total BMAA from all batches. Analysis of a flour sample that had undergone only 24 hours of soaking indicated that this single wash removed 90% of the total BMAA. We conclude that processed cycad flour as prepared by the Chamorros of Guam and Rota contains extremely low levels of BMAA, which are in the order of only 0.005% by weight (mean values for all samples). Thus, even when cycad flour is a dietary staple and eaten regularly, it seems unlikely that these low levels could cause the delayed and widespread neurofibrillary degeneration of nerve cells observed in amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam (ALS-PD).",
"title": "2-Amino-3-(methylamino)-propanoic acid (BMAA) in cycad flour: an unlikely cause of amyotrophic lateral sclerosis and parkinsonism-dementia of Guam."
},
{
"docid": "MED-2468",
"text": "BACKGROUND AND METHODS: We estimated the prevalence of self-reported asthma in adult Indians and examined several risk factors influencing disease prevalence. Analysis is based on 99 574 women and 56 742 men aged 20–49 years included in India’s third National Family Health Survey, 2005–2006. Multiple logistic regression analysis was used to estimate the prevalence odds ratios for asthma, adjusting for various risk factors. RESULTS: The prevalence of self-reported asthma was 1.8% (95%CI 1.6–2.0) among men and 1.9% (95%CI 1.8–2.0) among women, with higher rates in rural than in urban areas and marked geographic differences. After adjustment for known asthma risk factors, women were 1.2 times more likely to have asthma than men. Daily/weekly consumption of milk/milk products, green leafy vegetables and fruits were associated with a lower asthma risk, whereas consumption of chicken/meat, a lower body mass index (BMI; <16 kg/m2, OR 2.08, 95%CI 1.73–2.50) as well as a higher BMI (>30 kg/m2, OR 1.67, 95%CI 1.36–2.06), current tobacco smoking (OR 1.30, 95%CI 1.12–1.50) and ever use of alcohol (OR 1.21, 95%CI 1.05–1.39) were associated with an increased asthma risk. CONCLUSIONS: There are wide regional variations in the prevalence of asthma in India. With the exception of the findings for BMI, however, most of the associations of asthma with the risk factors are relatively weak and account for only a small proportion of cases. RÉSUMÉ CONTEXTE ET MÉTHODES: Nous avons estimé la prévalence auto-rapportée de l’asthme chez les Indiens adultes et examiné plusieurs facteurs de risque influençant la prévalence de la maladie. L’analyse repose sur 99 574 femmes et 56 742 hommes âgés de 20 à 49 ans et inclus dans la troisième Enquête Nationale des Familles en Inde, 2005–2006. On a utilisé l’analyse de régression logistique multiple pour estimer les odds ratio de prévalence pour l’asthme, après ajustement pour divers facteurs de risque. RÉSULTATS: La prévalence auto-rapportée de l’asthme est de 1,8% (IC95% 1,6–2,0) parmi les hommes et de 1,9% (IC95% 1,8–2,0) parmi les femmes, les taux étant plus élevés dans les zones rurales que dans les zones urbaines, et les différences géographiques étant marquées. Après ajustement pour les facteurs de risque d’asthme connus, les femmes sont 1,2 fois plus susceptibles de souffrir de l’asthme que les hommes. La consommation quotidienne ou hebdomadaire de lait/produits laitiers, de légumes à feuilles vertes et de fruits est en association avec un risque plus faible d’asthme alors que la consommation de poulet ou de viande, un index de masse corporelle (BMI) plus bas (<16 kg/m2, OR 2,08 ; IC95% 1,73–2,50) ainsi qu’un BMI plus élevé (>30 kg/m2, OR 1,67 ; IC95% 1,36–2,06), le fait de fumer du tabac actuellement (OR 1,30 ; IC95% 1,12–1,50) et l’utilisation de l’alcool à un moment quelconque (OR 1,21 ; IC95% 1,05–1,39) sont en association avec un risque accru d’asthme. La prévalence de l’asthme en Inde varie largement selon les régions. Toutefois, à l’exception des observations sur le BMI, l’association de l’asthme avec les facteurs de risque est relativement faible et ne rend compte que d’une petite proportion des cas seulement. RESUMEN MARCO DE REFERENCIA Y MÉTODOS: Se calculó la prevalencia de asma autorreferida en los adultos en la India y se evaluaron varios factores de riesgo que influyen sobre la prevalencia de la enfermedad. El estudio se basó en las 99 574 mujeres y los 56 742 hombres de 20 a 49 años de edad que participaron en la tercera Encuesta Nacional sobre la Salud de la Familia en la India entre el 2005 y el 2006. Mediante un análisis de regresión logística multifactorial se calculó la prevalencia de asma y el cociente de posibilidades de padecerla, al corregir diversos factores de riesgo. RESULTADOS: La prevalencia de asma autorreferida fue 1,8% en los hombres (intervalo de confianza [IC] del 95% 1,6 a 2,0) y 1,9% en las mujeres (IC95% 1,8 a 2,0); se observaron tasas más altas en las zonas rurales que en las zonas urbanas y se presentaron diferencias geográficas considerables. Tras corregir en función de algunos factores de riesgo de padecer asma conocidos, las mujeres presentaron una probabilidad 1,2 veces superior a los hombres de sufrir la enfermedad. El consumo diario o semanal de leche o productos lácteos, hortalizas de hojas verdes y frutas se asoció con un menor riesgo de asma y el consumo de carne de pollo o de res, un bajo índice de masa corporal (<16 kg/m2; OR 2,08; IC95% 1,73 a 2,50) igual que un alto índice de masa corporal (>30 kg/m2; OR 1,67; IC95% 1,36 a 2,06), el tabaquismo actual (OR 1,30; IC95% 1,12 a 1,50) y el consumo de alcohol en algún momento de la vida (OR 1,21; IC95% 1,05 a 1,39) se asociaron con un mayor riesgo de padecer la enfermedad. CONCLUSIÓN: Existen amplias variaciones geográficas en la prevalencia de asma en la India. Sin embargo, con la excepción del índice de masa corporal, la mayor parte de las asociaciones del asma con los factores de riesgo fueron débiles y explican solo una pequeña proporción de los casos.",
"title": "Prevalence and risk factors for self-reported asthma in an adult Indian population: a cross-sectional survey"
},
{
"docid": "MED-118",
"text": "The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.",
"title": "Alkylphenols in human milk and their relations to dietary habits in central Taiwan."
},
{
"docid": "MED-2472",
"text": "Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.",
"title": "Vegan regimen with reduced medication in the treatment of bronchial asthma."
},
{
"docid": "MED-2385",
"text": "The purpose of this investigation was to estimate the total hair mercury of diseased people (not including patients of mercury poisoning such as Minamata disease). Hair samples were collected from 133 diseased volunteers in Tokyo and the surrounding areas from Oct. 1992 to June 1993. The total mercury concentrations in the hair of ordinary diseased people (atopic dermatitis, asthma, dementia, cerebral infarct, osteoporosis, hypertension and diabetes) were from 2.08 ppm to 36.5 ppm. Those values were considerably higher than that of healthy people of the same age groups. However, the uptake routes and the metabolic mechanism of high hair mercury concentrations in diseased people are not clear.",
"title": "Concentration of mercury in hair of diseased people in Japan."
},
{
"docid": "MED-1274",
"text": "Sharks are among the most threatened groups of marine species. Populations are declining globally to support the growing demand for shark fin soup. Sharks are known to bioaccumulate toxins that may pose health risks to consumers of shark products. The feeding habits of sharks are varied, including fish, mammals, crustaceans and plankton. The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) has been detected in species of free-living marine cyanobacteria and may bioaccumulate in the marine food web. In this study, we sampled fin clips from seven different species of sharks in South Florida to survey the occurrence of BMAA using HPLC-FD and Triple Quadrupole LC/MS/MS methods. BMAA was detected in the fins of all species examined with concentrations ranging from 144 to 1836 ng/mg wet weight. Since BMAA has been linked to neurodegenerative diseases, these results may have important relevance to human health. We suggest that consumption of shark fins may increase the risk for human exposure to the cyanobacterial neurotoxin BMAA.",
"title": "Cyanobacterial Neurotoxin β-N-Methylamino-L-alanine (BMAA) in Shark Fins"
},
{
"docid": "MED-1279",
"text": "Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome which has no known cause, except for a small proportion of cases which are genetically inherited. The development of ALS likely involves both genetic and environmental risk factors. Environmental risk factors implicated in ALS have included heavy metals, trauma, pesticides, electrical injuries, electromagnetic radiation and the cyanobacterial-derived neurotoxin beta-N-methylamino-L-alanine (BMAA). To investigate possible environmental risks, a number of epidemiological studies of ALS have been conducted. Some of these studies employ spatial analysis techniques that examine for spatial clusters of ALS and can help guide further research into identifying environmental exposures. Despite identifying geographical disparities in the distribution of ALS cases, these studies have not provided any clear associations with environmental factors. We review the literature on important studies of spatial clustering of ALS and explore the hypothesized link between the neurotoxin BMAA and ALS.",
"title": "Spatial clustering of amyotrophic lateral sclerosis and the potential role of BMAA."
},
{
"docid": "MED-2656",
"text": "The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.",
"title": "Effects of intestinal microflora and the environment on the development of asthma and allergy."
},
{
"docid": "MED-2482",
"text": "Previous studies have suggested that probiotic administration may have therapeutic and/or preventive effects on atopic dermatitis in infants; however, its role in allergic airway diseases remains controversial. To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis (AR). We conducted a randomized, double-blind, placebo-controlled study on school children (age, 6-12 years) with asthma and AR. The eligible study subjects received either L. gasseri A5 (n = 49) or a placebo (n = 56) daily for 2 months. Pulmonary function tests were performed, and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period. Diary cards with records of the day- and nighttime peak expiratory flow rates (PEFR), symptoms of asthma, and AR scores of the patients were used for measuring the outcome of the treatment. Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells (PBMCs) were determined before and after the probiotic treatments. Our results showed the pulmonary function and PEFR increased significantly, and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls. Further, there was a significant reduction in the TNF-α, IFN-γ, IL-12, and IL-13 production by the PBMCs following the probiotic treatment. In conclusion, probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR.",
"title": "Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis."
},
{
"docid": "MED-2474",
"text": "This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.",
"title": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis."
},
{
"docid": "MED-1280",
"text": "Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, β-N-methylamino-l-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure.",
"title": "Diverse taxa of cyanobacteria produce β-N-methylamino-l-alanine, a neurotoxic amino acid"
},
{
"docid": "MED-2659",
"text": "U.S. and European regulators and researchers disagree over risks of a common class of surfactants.",
"title": "European bans on surfactant trigger transatlantic debate."
},
{
"docid": "MED-4731",
"text": "BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.",
"title": "No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-..."
},
{
"docid": "MED-1282",
"text": "Excitement about neurogenetics in the last two decades has diverted attention from environmental causes of sporadic ALS. Fifty years ago endemic foci of ALS with a frequency one hundred times that in the rest of the world attracted attention since they offered the possibility of finding the cause for non-endemic ALS throughout the world. Research on Guam suggested that ALS, Parkinson's disease and dementia (the ALS/PDC complex) was due to a neurotoxic non-protein amino acid, beta-methylamino-L-alanine (BMAA), in the seeds of the cycad Cycas micronesica. Recent discoveries that found that BMAA is produced by symbiotic cyanobacteria within specialized roots of the cycads; that the concentration of protein-bound BMAA is up to a hundred-fold greater than free BMAA in the seeds and flour; that various animals forage on the seeds (flying foxes, pigs, deer), leading to biomagnification up the food chain in Guam; and that protein-bound BMAA occurs in the brains of Guamanians dying of ALS/PDC (average concentration 627 microg/g, 5 mM) but not in control brains have rekindled interest in BMAA as a possible trigger for Guamanian ALS/PDC. Perhaps most intriguing is the finding that BMAA is present in brain tissues of North American patients who had died of Alzheimer's disease (average concentration 95 microg/g, 0.8mM); this suggests a possible etiological role for BMAA in non-Guamanian neurodegenerative diseases. Cyanobacteria are ubiquitous throughout the world, so it is possible that all humans are exposed to low amounts of cyanobacterial BMAA, that protein-bound BMAA in human brains is a reservoir for chronic neurotoxicity, and that cyanobacterial BMAA is a major cause of progressive neurodegenerative diseases including ALS worldwide. Though Montine et al., using different HPLC method and assay techniques from those used by Cox and colleagues, were unable to reproduce the findings of Murch et al., Mash and colleagues using the original techniques of Murch et al. have recently confirmed the presence of protein-bound BMAA in the brains of North American patients dying with ALS and Alzheimer's disease (concentrations >100 microg/g) but not in the brains of non-neurological controls or Huntington's disease. We hypothesize that individuals who develop neurodegenerations may have a genetic susceptibility because of inability to prevent BMAA accumulation in brain proteins and that the particular pattern of neurodegeneration that develops depends on the polygenic background of the individual.",
"title": "Beyond Guam: the cyanobacteria/BMAA hypothesis of the cause of ALS and other neurodegenerative diseases."
},
{
"docid": "MED-1283",
"text": "Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. The current status of the epidemiology, challenges to its study, and novel study design options are discussed in this paper. We focus on recent results from large-scale population based prospective studies, case-control studies and population based registries, risk factors, and neuropathologic findings in chronic traumatic encephalomyelopathy. We identify areas of interest for future research, including time-trends in the incidence and prevalence of ALS; the meaning of lifetime risk; the phenotypic description of ALS; the definition of familial versus sporadic ALS, syndromic aspects of ALS; specific risk factors such as military service, life style factors such as smoking, the use of statins, and the presence of β-N-methylamino-L-alanine (BMAA), an excitotoxic amino acid derivative possibly produced by cyanobacteria found in almost every terrestrial and aquatic habitat; the emergence and disappearance of an endemic ALS in areas of the Pacific; and gene-environment interactions in the etiology of ALS. To move the epidemiology forward, we suggest using well-characterized cohorts of newly diagnosed ALS patients to identify risk and prognostic factors; storing biological material for future studies; building on the National ALS Registry as a resource of future studies; working in multidisciplinary consortia; and addressing the possible early life etiology of ALS.",
"title": "Current pathways for epidemiological research in amyotrophic lateral sclerosis."
},
{
"docid": "MED-4741",
"text": "BACKGROUND: Previous studies have suggested that egg consumption may increase the risk of colorectal cancer and some other cancers. However, the evidence is still limited. To further explore the association between egg intake and cancer risk we conducted a case-control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls. RESULTS: In the multivariable model with adjustment for age, sex (when applicable), residence, education, income, interviewer, smoking, alcohol intake, intake of fruits and vegetables, grains, dairy products, fatty foods, meat, energy intake and BMI, there was a significant increase in the odds of cancers of the oral cavity and pharynx (OR= 2.02, 95% CI: 1.19-3.44), upper aerodigestive tract (OR= 1.67, 95% CI: 1.17-2.37), colorectum (OR= 1.64, 95% CI: 1.02-2.63), lung (OR= 1.59, 95% CI: 1.10-2.29), breast (OR= 2.86, 95% CI: 1.66-4.92), prostate (OR= 1.89, 95% CI: 1.15-3.10), bladder (OR= 2.23, 95% CI: 1.30-3.83) and all cancer sites combined (OR= 1.71, 95% CI: 1.35-2.17) with a high vs low egg intake. CONCLUSIONS: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.",
"title": "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay."
},
{
"docid": "MED-2476",
"text": "An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.",
"title": "Diet, infection and wheezy illness: lessons from adults."
},
{
"docid": "MED-2475",
"text": "Current understanding of the use of exclusion diets in the management of asthma in children is limited and controversial. The aim of this study was to examine the effects of excluding eggs and milk on the occurrence of symptoms in children with asthma and involved 22 children aged between three and 14 years clinically diagnosed as having mild to moderate disease. The investigation was single blind and prospective, and parents were given the option of volunteering to join the 'experiment' group, avoiding eggs, milk and their products for eight weeks, or the 'control' group, who consumed their customary food. Thirteen children were recruited to the experimental group and nine to the control group. A trained paediatrician at the beginning and end of the study period assessed the children. A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.",
"title": "The effects of exclusion of dietary egg and milk in the management of asthmatic children: a pilot study."
},
{
"docid": "MED-2494",
"text": "Background In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. Methods We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2–4 years, n=207), school-age children (5–7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. Results Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. Conclusions Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake.",
"title": "Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment"
},
{
"docid": "MED-2647",
"text": "Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.",
"title": "Dietary exposure to xenoestrogens in New Zealand."
},
{
"docid": "MED-4943",
"text": "Fish and seal oil dietary supplements, marketed to be rich in omega-3 fatty acids, are frequently consumed by Canadians. Samples of these supplements (n = 30) were collected in Vancouver, Canada, between 2005 and 2007. All oil supplements were analyzed for polychlorinated biphenyls (PCBs) and organochlorine insecticides (OCs) and each sample was found to contain detectable residues. The highest SigmaPCB and SigmaDDT (1,1,1-trichloro-di-(4-chlorophenyl)ethane) concentrations (10400 ng/g and 3310 ng/g, respectively) were found in a shark oil sample while lowest levels were found in supplements prepared using mixed fish oils (anchovy, mackerel, and sardine) (0.711 ng SigmaPCB/g and 0.189 ng SigmaDDT/g). Mean SigmaPCB concentrations in oil supplements were 34.5, 24.2, 25.1, 95.3, 12.0, 5260, 321, and 519 ng/g in unidentified fish, mixed fish containing no salmon, mixed fish with salmon, salmon, vegetable with mixed fish, shark, menhaden (n = 1), and seal (n = 1), respectively. Maximum concentrations of the other OCs were generally observed in the seal oil. The hexachlorinated PCB congeners were the dominant contributors to SigmaPCB levels, while SigmaDDT was the greatest contributor to organochlorine levels. Intake estimates were made using maximum dosages on manufacturers' labels and results varied widely due to the large difference in residue concentrations obtained. Average SigmaPCB and SigmaDDT intakes were calculated to be 736 +/- 2840 ng/d and 304 +/- 948 ng/d, respectively.",
"title": "Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides."
},
{
"docid": "MED-2386",
"text": "OBJECTIVE Emerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively determine associations of mercury exposure, as assessed by biomarker measurement, with incident diabetes. RESEARCH DESIGN AND METHODS We used neutron activation analysis to measure toenail mercury, an objective biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline in two separate U.S. prospective cohorts. Incident diabetes was identified from biennial questionnaires and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Associations of mercury exposure with incident diabetes were assessed using Cox proportional hazards. RESULTS During mean ± SD follow-up of 19.7 ± 7.0 years, 1,010 new cases of diabetes were diagnosed. The 95th percentile of toenail mercury was 1.32 μg/g in men and 0.76 μg/g in women, corresponding to exposures ∼3.5-fold and 2-fold higher than the U.S. Environmental Protection Agency reference dose. In multivariable analyses, toenail mercury concentrations were not associated with higher incidence of diabetes in women, men, or both cohorts combined. Comparing the highest to lowest quintile of exposure, the hazard ratio (95% CI) for incident diabetes was 0.86 (0.66–1.11) in women, 0.69 (0.42–1.15) in men, and 0.77 (0.61–0.98) in the combined cohorts. Findings were similar when more extreme categories (deciles) of mercury were compared, and in analyses stratified by fish or omega-3 consumption, BMI, and age. CONCLUSIONS These findings from two separate large prospective cohorts do not support adverse effects of methylmercury on development of diabetes in men or women at usual levels of exposure seen in these populations.",
"title": "Methylmercury Exposure and Incident Diabetes in U.S. Men and Women in Two Prospective Cohorts"
},
{
"docid": "MED-1268",
"text": "Most amyotrophic lateral sclerosis (ALS) cases occur sporadically. Some environmental triggers have been implicated, including beta-methylamino-L-alanine (BMAA), a cyanobacteria produced neurotoxin. This study aimed to identify environmental risk factors common to three sporadic ALS patients who lived in Annapolis, Maryland, USA and developed the disease within a relatively short time and within close proximity to each other. A questionnaire was used to identify potential risk factors for ALS among the cohort of patients. One common factor among the ALS patients was the frequent consumption of blue crab. Samples of blue crab from the patients' local fish market were tested for BMAA using LC-MS/MS. BMAA was identified in these Chesapeake Bay blue crabs. We conclude that the presence of BMAA in the Chesapeake Bay food web and the lifetime consumption of blue crab contaminated with BMAA may be a common risk factor for sporadic ALS in all three patients. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Linking β-methylamino-L-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD."
},
{
"docid": "MED-2496",
"text": "Persistent organic pollutants (POPs) exert harmful effects on cognitive, endocrine and immune functions and bioaccumulate in the environment and human tissues. The aim of this study was to investigate the body burden of several POPs in the adult population (n=246) and their association to diet and other lifestyle factors in a Swedish national survey. Serum concentrations of several polychlorinated biphenyls (PCBs), and the pesticides hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), chlordane compounds and dichlorodiphenyldichloroethylene (DDE) were determined by liquid-liquid extraction, silica column cleanup and gas chromatography high resolution mass spectrometry. Diet was assessed using 4-day food records and complementary dietary and lifestyle factors by questionnaire. Fish intake was additionally assessed by plasma fatty acid composition. Clustering of the compounds revealed that PCBs were separated into two clusters, one including low-chlorinated PCB 28 and 52, and the other high-chlorinated mono- and di-ortho PCBs, suggesting similarities and dissimilarities in exposure sources and possibly also toxicokinetics. Men had 24% and 32% higher levels of PCB 138-180 and chlordane compounds, respectively, compared with women. This may partly be explained by elimination of the POPs among women reporting a history of breastfeeding. The proportion of very long-chain n-3 fatty acids in plasma were positively correlated with the pollutants: r=0.24 (PCB 28), r=0.33 (PCB 118), r=0.35 (PCB 138-180), r=0.29 (HCB), r=0.18 (β-HCH), r=0.34 (chlordane compounds), r=0.34 (p,p'-DDE), p≤0.005. Individuals consuming fatty Baltic fish≥1 time per months had 45% higher serum levels of PCB 118 compared with non-consumers. Levels of PCB 28 were associated with the age of the residential building. To conclude, the population-distributed approach of surveying dietary habits, lifestyle factors and POP body burdens, made it possible to identify personal characteristics associated with the POP body burdens in Sweden. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Fish intake and breastfeeding time are associated with serum concentrations of organochlorines in a Swedish population."
},
{
"docid": "MED-4804",
"text": "BACKGROUND: Alcohol-based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact. METHODS: Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap-and-water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer. RESULTS: Plain water rubbing reduced palmar culture counts by a mean (+/- standard deviation [SD]) of 1.57 +/- 0.11 log10 colony-forming units (CFU) per cm2, and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (+/- SD) of 0.89 +/- 0.34 log10 CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 +/- 0.20 log10 CFU per cm2 (P = .005), Endure for a reduction of 0.37 +/- 0.42 log10 CFU per cm2 (P = .010), and Purell for a reduction of 0.14 +/- 0.33 log10 CFU per cm2 (P = .005). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing (P = .040). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients. CONCLUSIONS: Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.",
"title": "Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands."
},
{
"docid": "MED-2471",
"text": "The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One showed large worldwide variations in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, up to 10 to 20 fold between countries. Ecological analyses were undertaken with ISAAC Phase One data to explore factors that may have contributed to these variations, and are summarised and reviewed here. In ISAAC Phase One the prevalence of symptoms in the past 12 months of asthma, rhinoconjunctivitis and eczema were estimated from studies in 463,801 children aged 13 - 14 years in 155 centres in 56 countries, and in 257,800 children aged 6-7 years in 91 centres in 38 countries. Ecological analyses were undertaken between symptom prevalence and the following: Gross National Product per capita (GNP), food intake, immunisation rates, tuberculosis notifications, climatic factors, tobacco consumption, pollen, antibiotic sales, paracetamol sales, and outdoor air pollution. Symptom prevalence of all three conditions was positively associated with GNP, trans fatty acids, paracetamol, and women smoking, and inversely associated with food of plant origin, pollen, immunisations, tuberculosis notifications, air pollution, and men smoking. The magnitude of these associations was small, but consistent in direction between conditions. There were mixed associations of climate and antibiotic sales with symptom prevalence. The potential causality of these associations warrant further investigation. Factors which prevent the development of these conditions, or where there is an absence of a positive correlation at a population level may be as important from the policy viewpoint as a focus on the positive risk factors. Interventions based on small associations may have the potential for a large public health benefit.",
"title": "Which population level environmental factors are associated with asthma, rhinoconjunctivitis and eczema? Review of the ecological analyses of ISAAC Phase One"
},
{
"docid": "MED-1271",
"text": "Background Dietary exposure to the cyanotoxin BMAA is suspected to be the cause of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and North America, this toxin has been identified in the marine environment of amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures have been described. Objectives We aimed at identifying cluster(s) of amyotrophic lateral sclerosis in the Hérault district, a coastal district from Southern France, and to search, in the identified area(s), for the existence of a potential dietary source of BMAA. Methods A spatio-temporal cluster analysis was performed in the district, considering all incident amyotrophic lateral sclerosis cases identified from 1994 to 2009 by our expert center. We investigated the cluster area with serial collections of oysters and mussels that were subsequently analyzed blind for BMAA concentrations. Results We found one significant amyotrophic lateral sclerosis cluster (p = 0.0024), surrounding the Thau lagoon, the most important area of shellfish production and consumption along the French Mediterranean coast. BMAA was identified in mussels (1.8 µg/g to 6.0 µg/g) and oysters (0.6 µg/g to 1.6 µg/g). The highest concentrations of BMAA were measured during summer when the highest picocyanobacteria abundances were recorded. Conclusions While it is not possible to ascertain a direct link between shellfish consumption and the existence of this ALS cluster, these results add new data to the potential association of BMAA with sporadic amyotrophic lateral sclerosis, one of the most severe neurodegenerative disorder.",
"title": "Dietary BMAA Exposure in an Amyotrophic Lateral Sclerosis Cluster from Southern France"
},
{
"docid": "MED-2484",
"text": "Paediatric asthma is a major clinical concern worldwide and represents a huge burden on family and society. It accounts for a large number of lost school days and may deprive the child of both academic achievement and social interaction. Childhood asthma also places strain on healthcare resources as a result of doctor and hospital visits and the cost of treatment. The prevalence of asthma varies worldwide, possibly because of different exposure to respiratory infection, indoor and outdoor pollution, and diet. Certain risk factors appear to predispose children to developing asthma and atopic disease, including incidence and severity of wheezing, atopy, maternal smoking, and number of fever episodes. This paper discusses the burden, prevalence, and risk factors associated with paediatric asthma.",
"title": "The burden of childhood asthma"
},
{
"docid": "MED-1290",
"text": "Although the cyanobacteria/BMAA hypothesis of the cause of ALS and other age-related neurodegenerative diseases remains to be proven, it is not too early to ask whether treatment would be possible if the hypothesis were correct. This paper reviews the possible ways that chronic BMAA neurotoxicity could be prevented or treated.",
"title": "Possible therapy for ALS based on the cyanobacteria/BMAA hypothesis."
},
{
"docid": "MED-2645",
"text": "The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.",
"title": "Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment."
},
{
"docid": "MED-4732",
"text": "Background Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives In this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis. Methods PCB-77 or 2,2′,4,4,5,5′-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR)−/− mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE−/− mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis. Results Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol–3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor γ, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR−/− mice. ApoE−/− mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. Conclusions Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.",
"title": "Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis"
},
{
"docid": "MED-4551",
"text": "Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S",
"title": "Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He..."
}
] |
[
{
"docid": "MED-3628",
"text": "The distribution and behaviour of the natural-series alpha-emitter polonium-210 in the marine environment has been under study for many years primarily due to its enhanced bioaccumulation, its strong affinity for binding with certain internal tissues, and its importance as a contributor to the natural radiation dose received by marine biota as well as humans consuming seafoods. Results from studies spanning nearly 5 decades show that (210)Po concentrations in organisms vary widely among the different phylogenic groups as well as between the different tissues of a given species. Such variation results in (210)Po concentration factors ranging from approximately 10(3) to over 10(6) depending upon the organism or tissue considered. (210)Po/(210)Pb ratios in marine species are generally greater than unity and tend to increase up the food chain indicating that (210)Po is preferentially taken up by organisms compared to its progenitor (210)Pb. The effective transfer of (210)Po up the food chain is primarily due to the high degree of assimilation of the radionuclide from ingested food and its subsequent strong retention in the organisms. In some cases this mechanism may lead to an apparent biomagnification of (210)Po at the higher trophic level. Various pelagic species release (210)Po and (210)Pb packaged in organic biodetrital particles that sink and remove these radionuclides from the upper water column, a biogeochemical process which, coupled with scavenging rates of this radionuclide pair, is being examined as a possible proxy for estimating downward organic carbon fluxes in the sea. Data related to preferential bioaccumulation in various organisms, their tissues, resultant radiation doses to these species, and the processes by which (210)Po is transferred and recycled through the food web are discussed. In addition, the main gaps in our present knowledge and proposed areas for future studies on the biogeochemical behaviour of (210)Po and its use as a tracer of oceanographic processes are highlighted in this review. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "210Po in the marine environment with emphasis on its behaviour within the biosphere."
},
{
"docid": "MED-3271",
"text": "Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.",
"title": "Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?"
},
{
"docid": "MED-761",
"text": "OBJECTIVES: To determine the counseling practices of a group of internists in the areas of smoking, exercise, and alcohol and seat belt use, and to determine the associations among physicians' personal health habits and their counseling practices. DESIGN: A random stratified sample of members and fellows of the American College of Physicians in 21 regions selected to represent all areas of the United States. Because of the relatively small proportion of women in this group, they were oversampled. SETTING: Physicians' practices. PARTICIPANTS: One thousand three hundred and forty-nine internists (members or fellows of the College) returned questionnaires, for a response rate of 75%; 52% defined themselves as general internists. INTERVENTIONS: A questionnaire was used to obtain information on internists' use of cigarettes, alcohol, and seat belts and their level of physical activity. Data were obtained on the indications used for counseling and the aggressiveness of counseling about each of these four habits. MEASUREMENTS AND MAIN RESULTS: Bivariate and logistic regression analyses were used to compare the tendencies of internist subgroups both in using various indications for counseling and in the thoroughness of counseling. Generalists were more likely than specialists to counsel at least once all patients who were at risk and to be more aggressive in counseling. Ninety percent of respondents counseled all of their patients who smoked, but 64.5% never discussed the use of seat belts. Only 3.8% of these internists currently smoked cigarettes, 11.3% drank alcohol daily, 38.7% were extremely or quite active, and 87.3% used seat belts all or most of the time. Among men internists, for every habit except alcohol use, personal health practices were substantially associated with counseling patients; for example, nonsmoking internists were more likely to counsel smokers, and very physically active internists were more likely to counsel about exercise. Among women internists, being very physically active was associated with counseling more patients about exercise and alcohol use. CONCLUSIONS: The low level of self-reported counseling among these internists suggests that further emphasis on training in these skills is needed. The association between personal and professional practices suggests that medical schools and housestaff training programs should support health promotion activities for future internists.",
"title": "The counseling practices of internists."
},
{
"docid": "MED-4455",
"text": "The importance of dietary sulforaphane in helping maintain good health continues to gain support within the health-care community and awareness among U.S. consumers. In addition to the traditional avenue for obtaining sulforaphane, namely, the consumption of appropriate cruciferous vegetables, other consumer products containing added glucoraphanin, the natural precursor to sulforaphane, are now appearing in the United States. Crucifer seeds are a likely source for obtaining glucoraphanin, owing to a higher concentration of glucoraphanin and the relative ease of processing seeds as compared to vegetative parts. Seeds of several commonly consumed crucifers were analyzed not only for glucoraphanin but also for components that might have negative health implications, such as certain indole-containing glucosinolates and erucic acid-containing lipids. Glucoraphanin, 4-hydroxyglucobrassicin, other glucosinolates, and lipid erucic acid were quantified in seeds of 33 commercially available cultivars of broccoli, 4 cultivars each of kohlrabi, radish, cauliflower, Brussels sprouts, kale, and cabbage, and 2 cultivars of raab.",
"title": "Glucoraphanin and 4-hydroxyglucobrassicin contents in seeds of 59 cultivars of broccoli, raab, kohlrabi, radish, cauliflower, brussels sprouts, kal..."
},
{
"docid": "MED-3654",
"text": "Nutrient profiling of foods, described as the science of ranking foods based on their nutrient content, is fast becoming the basis for regulating nutrition labels, health claims, and marketing and advertising to children. A number of nutrient profile models have now been developed by research scientists, regulatory agencies, and by the food industry. Whereas some of these models have focused on nutrients to limit, others have emphasized nutrients known to be beneficial to health, or some combination of both. Although nutrient profile models are often tailored to specific goals, the development process ought to follow the same science-driven rules. These include the selection of index nutrients and reference amounts, the development of an appropriate algorithm for calculating nutrient density, and the validation of the chosen nutrient profile model against healthy diets. It is extremely important that nutrient profiles be validated rather than merely compared to prevailing public opinion. Regulatory agencies should act only when they are satisfied that the scientific process has been followed, that the algorithms are transparent, and that the profile model has been validated with respect to objective measures of a healthy diet.",
"title": "Nutrient profiling of foods: creating a nutrient-rich food index."
},
{
"docid": "MED-4724",
"text": "We report on the case of an infant who was hospitalized because of failure to thrive, megaloblastic anemia, and delayed psychomotor development. He was 10 months old and had been exclusively breast-fed by his vegan mother. Investigations showed vitamin B(12) deficiency with hematocytopenia and pervasive developmental disorders as well as vitamin K and vitamin D deficiencies. The infant's mother presented the same deficiencies. Introduction of vitamin supplementation normalized the biological disorders, and the infant showed weight gain and neurological improvement. This case highlights that a vegan diet during pregnancy followed by exclusive breast-feeding can induce nutritional deficiencies in the newborn, with clinical consequences. Detecting mother and child vitamin deficiencies and preventing them is essential.",
"title": "[Consequences of exclusive breast-feeding in vegan mother newborn--case report]."
},
{
"docid": "MED-5280",
"text": "BACKGROUND: Hypertriglyceridemia is now accepted as a risk factor for coronary heart disease, although the mechanism behind the increased risk is not well understood. The present study was undertaken to investigate the effects of triglyceridemia on endothelial function, because impaired endothelial function is considered a marker of atherogenesis. METHODS AND RESULTS: Flow- and nitroglycerin-induced dilatation of the brachial artery was investigated noninvasively by high-resolution ultrasound technique in seven young, healthy men without risk factors for coronary heart disease. Transient triglyceridemia was induced by infusion of a triglyceride emulsion, Intralipid, which raised free fatty acid concentrations twofold and triglyceride levels fourfold. Flow-induced vasodilatation decreased from 7.1+/-3.0% to 1.6+/-2.6% (P<.0002), whereas nitroglycerin-induced vasodilatation decreased from 20.5+/-5.8% to 11.5+/-3.2% (P<.002) before and after 1 hour of infusion of Intralipid, respectively. CONCLUSIONS: Transient triglyceridemia decreases vascular reactivity, presumably by both endothelium-dependent and endothelium-independent mechanisms.",
"title": "Transient triglyceridemia decreases vascular reactivity in young, healthy men without risk factors for coronary heart disease."
},
{
"docid": "MED-709",
"text": "The sub-chronic effect of Hibiscus sabdariffa (HS) calyx aqueous extract on the rat testes was investigated with a view to evaluate the pharmacological basis for the use of HS calyx extract as an aphrodisiac. Three test groups received different doses of 1.15, 2.30, and 4.60 g/kg based on the LD(50). The extracts were dissolved in the drinking water. The control group was given equivalent volume of water only. The animals were allowed free access to drinking solution during the 12-week period of exposure. At the expiration of the treatment period, animals were sacrificed, testes excised and weighed, and epididymal sperm number recorded. The testes were processed for histological examination. Results did not show any significant (P>0.05) change in the absolute and relative testicular weights. There was, however, a significant (P<0.05) decrease in the epididymal sperm counts in the 4.6 g/kg group, compared to the control. The 1.15 g/kg dose group showed distortion of tubules and a disruption of normal epithelial organization, while the 2.3 g/kg dose showed hyperplasia of testis with thickening of the basement membrane. The 4.6 g/kg dose group, on the other hand, showed disintegration of sperm cells. The results indicate that aqueous HS calyx extract induces testicular toxicity in rats.",
"title": "Testicular effects of sub-chronic administration of Hibiscus sabdariffa calyx aqueous extract in rats."
},
{
"docid": "MED-1301",
"text": "PURPOSE: There is evidence that dietary habits contribute to the presence and severity of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to explore any associations between consumption of grains and the development and severity of NAFLD. METHODS: Seventy-three consecutive NAFLD patients were enrolled. Additionally, 58 controls matched for age, sex and body mass index with 58 patients were also included. Consumption of grains was estimated through a semi-quantitative food frequency questionnaire. Medical history, anthropometric indices, body composition analysis, physical activity data, biochemical and inflammatory markers were available for all the participants. Liver stiffness measurement by transient elastography was performed in 58 and liver biopsy in 34 patients. RESULTS: In patients, consumption of whole grains was associated with lower abdominal fat level (β = -0.24, p = 0.02) and lower levels of insulin resistance index (β = -0.28, p = 0.009), while it also correlated inversely with interleukin-6 levels (ρ = -0.23, p = 0.05). Consumption of whole grains was associated with lower likelihood of having histological steatohepatitis (OR 0.97, 95% CI 0.94-1.000), after adjusting for sex and energy intake, but the association became weaker after further adjusting for abdominal fat or interleukin-6 levels. In the case-control analysis, consumption of refined grains was associated with higher odds of having NAFLD (OR 1.021, 95% CI 1.001-1.042), after adjusting for age, sex, energy intake, abdominal fat level, HOMA-IR, LDL, adiponectin and TNF-α. CONCLUSIONS: Although refined grain consumption increased the likelihood of having NAFLD, whole-grain consumption favorably affected clinical characteristics of patients with NAFLD and tended to be associated with less severe disease.",
"title": "The impact of cereal grain consumption on the development and severity of non-alcoholic fatty liver disease."
},
{
"docid": "MED-14",
"text": "BACKGROUND: Preclinical studies have shown that statins, particularly simvastatin, can prevent growth in breast cancer cell lines and animal models. We investigated whether statins used after breast cancer diagnosis reduced the risk of breast cancer-specific, or all-cause, mortality in a large cohort of breast cancer patients. METHODS: A cohort of 17,880 breast cancer patients, newly diagnosed between 1998 and 2009, was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2013), identifying 3694 deaths, including 1469 deaths attributable to breast cancer. Unadjusted and adjusted hazard ratios (HRs) for breast cancer-specific, and all-cause, mortality in statin users after breast cancer diagnosis were calculated using time-dependent Cox regression models. Sensitivity analyses were conducted using multiple imputation methods, propensity score methods and a case-control approach. RESULTS: There was some evidence that statin use after a diagnosis of breast cancer had reduced mortality due to breast cancer and all causes (fully adjusted HR = 0.84 [95% confidence interval = 0.68-1.04] and 0.84 [0.72-0.97], respectively). These associations were more marked for simvastatin 0.79 (0.63-1.00) and 0.81 (0.70-0.95), respectively. CONCLUSIONS: In this large population-based breast cancer cohort, there was some evidence of reduced mortality in statin users after breast cancer diagnosis. However, these associations were weak in magnitude and were attenuated in some sensitivity analyses.",
"title": "Statin use after diagnosis of breast cancer and survival: a population-based cohort study."
},
{
"docid": "MED-2586",
"text": "A systematic review and meta-analysis were carried out to study the effects of low-carbohydrate diet (LCD) on weight loss and cardiovascular risk factors (search performed on PubMed, Cochrane Central Register of Controlled Trials and Scopus databases). A total of 23 reports, corresponding to 17 clinical investigations, were identified as meeting the pre-specified criteria. Meta-analysis carried out on data obtained in 1,141 obese patients, showed the LCD to be associated with significant decreases in body weight (-7.04 kg [95% CI -7.20/-6.88]), body mass index (-2.09 kg m(-2) [95% CI -2.15/-2.04]), abdominal circumference (-5.74 cm [95% CI -6.07/-5.41]), systolic blood pressure (-4.81 mm Hg [95% CI -5.33/-4.29]), diastolic blood pressure (-3.10 mm Hg [95% CI -3.45/-2.74]), plasma triglycerides (-29.71 mg dL(-1) [95% CI -31.99/-27.44]), fasting plasma glucose (-1.05 mg dL(-1) [95% CI -1.67/-0.44]), glycated haemoglobin (-0.21% [95% CI -0.24/-0.18]), plasma insulin (-2.24 micro IU mL(-1) [95% CI -2.65/-1.82]) and plasma C-reactive protein, as well as an increase in high-density lipoprotein cholesterol (1.73 mg dL(-1) [95%CI 1.44/2.01]). Low-density lipoprotein cholesterol and creatinine did not change significantly, whereas limited data exist concerning plasma uric acid. LCD was shown to have favourable effects on body weight and major cardiovascular risk factors; however the effects on long-term health are unknown. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.",
"title": "Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors."
},
{
"docid": "MED-2110",
"text": "Almost all types of newborn respiratory failure are reversible. However, supportive treatment (oxygen and positive airway pressure) can damage the lung, and newborn respiratory failure remains a major cause of morbidity and death in infants. Prolonged extracorporeal membrane oxygenation (ECMO) provides life support while allowing the lung to \"rest.\" We have used ECMO in 45 moribund newborn infants; 25 survived. Neonatologists referred patients who were unresponsive to maximal therapy. The right atrium and aortic arch were cannulated via the jugular vein and carotid artery. Heparin was infused continuously to main activated clotting time at 200 to 300 seconds. Airway oxygenation and pressure were reduced to low levels. Primary diagnoses were hyaline membrane disease, 14 (6 survived, 8 died); meconium aspiration, 22 (15 survived, 7 died); persistent fetal circulation including diaphragmatic hernia, 5 (3 survived, 2 died); and sepsis, 4 (1 survived, 3 died). Growth, development, and brain and lung function are normal in 20 of 25 survivors. ECMO decreased newborn respiratory failure mortality and morbidity rates in this phase I trial. A controlled randomized study is underway. The results suggest that ECMO may be effective in older patients if used before irreversible lung damage occurs.",
"title": "Extracorporeal membrane oxygenation for newborn respiratory failure: forty-five cases."
},
{
"docid": "MED-5216",
"text": "Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stern efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.",
"title": "Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies"
},
{
"docid": "MED-2066",
"text": "Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.",
"title": "Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health."
},
{
"docid": "MED-1572",
"text": "Ciguatera fish poisoning results from the bioconcentration of a variety of toxins produced by marine dinoflagellates. Signs and symptoms vary widely, but it usually presents as gastrointestinal and neurologic complaints beginning shortly after the ingestion of fish containing the toxins. Symptoms may persist for months and sometimes even years. Although cases have been reported throughout the United States, epidemics are most common along tropical and subtropical coasts and usually involve the ingestion of large carnivorous fish. We review the literature and report the first epidemic of 25 cases of ciguatera fish poisoning presenting to area hospitals in Southern California that were successfully tracked by the Department of Health Services and isolated to fish caught off the coast of Baja California, Mexico.",
"title": "Ciguatera fish poisoning. A southern California epidemic."
},
{
"docid": "MED-884",
"text": "Approximately 75% of all kidney stones are composed primarily of calcium oxalate, and hyperoxaluria is a primary risk factor for this disorder. Nine types of raw and cooked vegetables were analyzed for oxalate using an enzymatic method. There was a high proportion of water-soluble oxalate in most of the tested raw vegetables. Boiling markedly reduced soluble oxalate content by 30-87% and was more effective than steaming (5-53%) and baking (used only for potatoes, no oxalate loss). An assessment of the oxalate content of cooking water used for boiling and steaming revealed an approximately 100% recovery of oxalate losses. The losses of insoluble oxalate during cooking varied greatly, ranging from 0 to 74%. Because soluble sources of oxalate appear to be better absorbed than insoluble sources, employing cooking methods that significantly reduce soluble oxalate may be an effective strategy for decreasing oxaluria in individuals predisposed to the development of kidney stones.",
"title": "Effect of different cooking methods on vegetable oxalate content."
},
{
"docid": "MED-2218",
"text": "OBJECTIVE: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere. DESIGN AND SETTING: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria. PARTICIPANTS: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions. MAIN OUTCOME MEASURES: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated. RESULTS: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia. CONCLUSIONS: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.",
"title": "Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study."
},
{
"docid": "MED-4722",
"text": "BACKGROUND: There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.",
"title": "Dietary protein and bone health: a systematic review and meta-analysis."
},
{
"docid": "MED-5162",
"text": "A study was performed to investigate the antimutagenic effect of broccoli flower head by the Ames Salmonella reverse mutation assay. Broccoli flower head being the most highly edible part in the plant was analysed for its antimutagenic effect. Without isolating the phytomolecules, the crude ethanol extract of broccoli flower head was tested for suppressing the mutagenic effect induced by certain chemical mutagens. Three strains - TA 98, TA102 and TA 1535 were used in the study. The tester strains were challenged with their respective mutagens. These were challenged with the ethanol extract of broccoli flower head at concentrations of 23 and 46 mg/plate. The plates were incubated for 72 h and the revertant colonies were counted. The crude extract did not prove to be promutagenic. The ethanol extract of the broccoli flower head at 46 mg/plate suppressed the mutagenic effect induced by the corresponding positive mutagens on all the three tester strains used in this study. The crude extract of broccoli flower head alone was not cytotoxic even at the maximum concentration tested (46 mg/plate). In conclusion, the ethanol extract of broccoli at 46 mg/plate suggests their diverse antimutagenic potential against the mutagenic chemicals employed in this study. (c) 2007 John Wiley & Sons, Ltd.",
"title": "Antimutagenic effect of broccoli flower head by the ames salmonella reverse mutation assay."
},
{
"docid": "MED-4711",
"text": "Licorice is a common Chinese medicinal herb with antitumor activity. Some components in licorice root have been shown to induce cell cycle arrest or apoptosis in cancer cells. This paper demonstrates for the first time that licorice Glycyrrhiza glabra and its component licochalcone-A (LA) can induce autophagy in addition to apoptosis in human LNCaP prostate cancer cells. Exposure of cells to licorice or LA resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine (MDC) staining, formation of acidic vesicular organelles (AVOs), and autophagosome membrane association of microtubule-associated protein 1 light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, as well as ultrastructural observation of autophagic vacuoles by transmission electron microscopy. Autophagy induction was accompanied by down-regulation of Bcl-2 and inhibition of the mammalian target of rapamycin (mTOR) pathway. In summary, licorice can induce caspase-dependent and autophagy-related cell death in LNCaP cells.",
"title": "Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway."
},
{
"docid": "MED-3091",
"text": "Phosphate toxicity is an important determinant of mortality in patients with chronic kidney disease (CKD), particularly those undergoing hemodialysis treatments. CKD patients are advised to take a low phosphate-containing diet, and are additionally prescribed with phosphate-lowering drugs. Since these patients usually seek guidance from their physicians and nurses for their dietary options, we conducted a survey to determine the levels of awareness regarding the high phosphate content in commercially processed food and drinks among medical and nursing students at the Hirosaki University School of Medicine in Japan. For this survey, 190 medical and nursing students (average age 21.7±3 years) were randomly selected, and provided with a list of questions aimed at evaluating their awareness of food and drinks containing artificially added phosphate ingredients. While 98.9% of these students were aware of the presence of sugar in commercially available soda drinks, only 6.9% were aware of the presence of phosphate (phosphoric acid). Similarly, only 11.6% of these students were aware of the presence of phosphate in commercially processed food, such as hamburgers and pizza. Moreover, around two thirds of the surveyed students (67.7%) were unaware of the harmful effects of unrestricted consumption of phosphate-containing food and drinks. About 28% of the surveyed students consume such “fast food” once a week, while 40% drink at least 1∼5 cans of soda drinks/week. After realizing the potential long-term risks of consuming excessive phosphate-containing food and drinks, 40.5% of the survey participants considered reducing their phosphate intake by minimizing the consumption of commercially processed “fast food” items and soda drinks. Moreover, another 48.4% of students showed interest in obtaining more information on the negative health effects of consuming excessive amounts of phosphate. This survey emphasizes the need for educational initiative to raise awareness of the health risks posed by excessive consumption of phosphate additives.",
"title": "Lack of Awareness among Future Medical Professionals about the Risk of Consuming Hidden Phosphate-Containing Processed Food and Drinks"
},
{
"docid": "MED-1354",
"text": "Context Antidepressant medications represent the best established treatment for Major Depressive Disorder (MDD), but there is little evidence that they have a specific pharmacological effect relative to pill-placebo for patients with less severe depression. Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. Data Sources Pubmed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. Study Selection Randomized placebo-controlled trials of FDA approved antidepressants in the treatment of Major or Minor Depressive Disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, included a medication vs placebo comparison for at least 6 weeks, did not exclude patients on the basis of a placebo washout period, and utilized the Hamilton Rating Scale for Depression. Data from six studies (718 patients) were included. Data Extraction Individual patient-level data were obtained from study authors. Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with Hamilton scores below 23, Cohen’s d-type effect sizes for the difference between medication and placebo were estimated to be < .20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline Hamilton severity and crossed the NICE threshold for a clinically significant difference at a baseline score of 25. Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms, and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.",
"title": "Antidepressant Drug effects and Depression Severity: A Patient-Level Meta-Analysis"
},
{
"docid": "MED-2372",
"text": "BACKGROUND: Because of egg cholesterol content, reduction in egg consumption is generally recommended to reduce risk of cardiovascular disease. Recently, however, evidence has been accumulating to suggest that dietary cholesterol is less relevant to cardiovascular risk than dietary saturated fat. This randomized controlled crossover trial was conducted to determine the effects of egg ingestion on endothelial function, a reliable index of cardiovascular risk. METHODS: Forty-nine healthy adults (mean age 56 years, 40% females) underwent a baseline brachial artery reactivity study (BARS), and were assigned to two eggs or oats daily for 6 weeks in random sequence with a 4-week washout. A BARS was done at the end of each treatment phase, measuring flow-mediated vasodilation (FMD) in the brachial artery using a high-frequency ultrasound. RESULTS: FMD was stable in both egg and oat groups, and between-treatment differences were not significant (egg -0.96%, oatmeal -0.79%; p value >0.05). Six weeks of egg ingestion had no effect on total cholesterol (baseline: 203.8 mg/dl; post-treatment: 205.3) or LDL (baseline: 124.8 mg/dl; post-treatment: 129.1). In contrast, 6 weeks of oats lowered total cholesterol (to 194 mg/dl; p = 0.0017) and LDL (to 116.6 mg/dl; p = 0.012). There were no differences in body mass index (BMI), triglyceride, HDL or SBP levels between egg and oat treatment assignments. CONCLUSION: Short-term egg consumption does not adversely affect endothelial function in healthy adults, supporting the view that dietary cholesterol may be less detrimental to cardiovascular health than previously thought.",
"title": "Egg consumption and endothelial function: a randomized controlled crossover trial."
},
{
"docid": "MED-5095",
"text": "Docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for eye and brain development and ongoing visual, cognitive, and cardiovascular health. Unlike fish-sourced oils, the bioavailability of DHA from vegetarian-sourced (algal) oils has not been formally assessed. We assessed bioequivalence of DHA oils in capsules from two different algal strains versus bioavailability from an algal-DHA-fortified food. Our 28-day randomized, placebo-controlled, parallel group study compared bioavailability of (a) two different algal DHA oils in capsules (\"DHASCO-T\" and \"DHASCO-S\") at doses of 200, 600, and 1,000 mg DHA per day (n = 12 per group) and of (b) an algal-DHA-fortified food (n = 12). Bioequivalence was based on changes in plasma phospholipid and erythrocyte DHA levels. Effects on arachidonic acid (ARA), docosapentaenoic acid-n-6 (DPAn-6), and eicosapentaenoic acid (EPA) were also determined. Both DHASCO-T and DHASCO-S capsules produced equivalent DHA levels in plasma phospholipids and erythrocytes. DHA response was dose-dependent and linear over the dose range, plasma phospholipid DHA increased by 1.17, 2.28 and 3.03 g per 100 g fatty acid at 200, 600, and 1,000 mg dose, respectively. Snack bars fortified with DHASCO-S oil also delivered equivalent amounts of DHA on a DHA dose basis. Adverse event monitoring revealed an excellent safety and tolerability profile. Two different algal oil capsule supplements and an algal oil-fortified food represent bioequivalent and safe sources of DHA.",
"title": "Bioequivalence of Docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food."
},
{
"docid": "MED-1839",
"text": "Ten subjects with normal renal function were given different single doses of aluminium containing antacids (1, 4, or 8 tablets). The antacid tablets (aluminium content 244 mg tablet-1) were chewed and swallowed either with water, with orange juice, or with citric acid solution. There was a marked increase in serum concentration of aluminium when the antacids was ingested with citric acid (P less than 0.001) or with orange juice (P less than 0.05). When antacids were taken with water, a slight, but significant increase in serum aluminium concentration was seen with 4, but not with 1 or with 8 tablets. Following all doses of antacid, a significant increase in 24 h urinary excretion of aluminium was seen. The estimated absorption of aluminium was 8 and 50 times higher when antacids were taken with orange juice or with citric acid, respectively, than when taken with water. Thus, measurable quantities of aluminium are absorbed from single oral doses of antacids. The absorption is substantially enhanced by concomitant ingestion of citric acid.",
"title": "Gastrointestinal absorption of aluminium from single doses of aluminium containing antacids in man."
},
{
"docid": "MED-5358",
"text": "Alkylresorcinols (ARs) are shown to be good biomarkers of consumption of rye and whole-grain wheat products in man. The aim of this pilot study was to investigate AR metabolites as potential biomarkers of breast cancer (BC) risk in Finnish women since intake of cereal fiber and its components has been proposed to reduce this risk through an effect on the enterohepatic circulation of estrogens. This was a cross-sectional and observational pilot study. A total of 20 omnivores, 20 vegetarians, and 16 BC women (6-12 mo after operation) were investigated on 2 occasions 6 mo apart. Dietary intake (5-days record), plasma/urinary AR metabolites [3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA)] and plasma/urinary enterolactone were measured. The groups were compared using nonparametric tests. We observed that plasma DHBA (P = 0.007; P = 0.03), plasma DHPPA (P = 0.02; P = 0.01), urinary DHBA (P = 0.001; P = 0.003), urinary DHPPA (P = 0.001; P = 0.001), and cereal fiber intake (P = 0.007; P = 0.003) were significantly lower in the BC group compared to the vegetarian and omnivore groups, respectively. Based on measurements of AR metabolites in urine and in plasma, whole-grain rye and wheat cereal fiber intake is low in BC subjects. Thus, urinary and plasma AR metabolites may be used as potential biomarkers of BC risk in women. This novel approach will likely also facilitate studies of associations between rye and whole-grain wheat cereal fiber intake and other diseases. Our findings should, however, be confirmed with larger subject populations.",
"title": "Plasma and urinary alkylresorcinol metabolites as potential biomarkers of breast cancer risk in Finnish women: a pilot study."
},
{
"docid": "MED-4517",
"text": "Low fecal weight and slow bowel transit time are thought to be associated with bowel cancer risk, but few published data defining bowel habits in different communities exist. Therefore, data on stool weight were collected from 20 populations in 12 countries to define this risk more accurately, and the relationship between stool weight and dietary intake of nonstarch polysaccharides (NSP) (dietary fiber) was quantified. In 220 healthy U.K. adults undertaking careful fecal collections, median daily stool weight was 106 g/day (men, 104 g/day; women, 99 g/day; P = 0.02) and whole-gut transit time was 60 hours (men, 55 hours; women, 72 hours; P = 0.05); 17% of women, but only 1% of men, passed < 50 g stool/day. Data from other populations of the world show average stool weight to vary from 72 to 470 g/day and to be inversely related to colon cancer risk (r = -0.78). Meta-analysis of 11 studies in which daily fecal weight was measured accurately in 26 groups of people (n = 206) on controlled diets of known NSP content shows a significant correlation between fiber intake and mean daily stool weight (r = 0.84). Stool weight in many Westernized populations is low (80-120 g/day), and this is associated with increased colon cancer risk. Fecal output is increased by dietary NSP. Diets characterized by high NSP intake (approximately 18 g/day) are associated with stool weights of 150 g/day and should reduce the risk of bowel cancer.",
"title": "Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber)"
},
{
"docid": "MED-3309",
"text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.",
"title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"
},
{
"docid": "MED-4893",
"text": "Background Prospective studies evaluating associations between food intake and risk of heart failure (HF) in diverse populations are needed. Objectives Relationships between incident HF (death or hospitalization) and intake of seven food categories (whole grains, fruits/vegetables, fish, nuts, high-fat dairy, eggs, red meat) were investigated in an observational cohort of 14,153 African-American and white adults, age 45 to 64 years, sampled from four US communities. Methods Between baseline (1987–1989) and Exam 3 (1993–1995), dietary intake was based on responses to a 66-item food frequency questionnaire administered at baseline; thereafter, intake was based on averaged baseline and Exam 3 responses. Hazard ratios (HR [95% CI]) for HF were calculated per 1–daily serving difference in food group intake. Results During a mean of 13 years, 1,140 HF hospitalizations were identified. After multivariable adjustment (energy intake, demographics, lifestyle factors, prevalent cardiovascular disease, diabetes, hypertension), HF risk was lower with greater whole-grain intake (0.93 [0.87, 0.99]), but HF risk was higher with greater intake of eggs (1.23 [1.08, 1.41]) and high-fat dairy (1.08 [1.01, 1.16]). These associations remained significant independent of intakes of the five other food categories, which were not associated with HF. Conclusions In this large, population-based sample of African-American and white adults, whole-grain intake was associated with lower HF risk, whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders.",
"title": "Incident Heart Failure Is Associated with Lower Whole-Grain Intake and Greater High-Fat Dairy and Egg Intake in the Atherosclerosis Risk in Communities (ARIC) Study"
},
{
"docid": "MED-4411",
"text": "Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.",
"title": "Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial."
}
] |
PLAIN-2524
|
Are GMOs Safe? The Case of Bt Corn
|
[
{
"docid": "MED-1733",
"text": "INTRODUCTION: Glyphosate-surfactant herbicide (GlySH) is widely used as a non-selective herbicide. Most intoxicated cases are from ingestion, inhalation, and skin exposure. Intramuscular injection of GlySH has never been reported. We present a case of GlySH intoxication via intramuscular injection. CASE REPORT: A 42-year-old woman came to the emergency department complaining of painful swelling of left upper limb for 12 h. She had performed an intramuscular injection of 6 mL of GlySH over the lateral aspect of the left elbow 15 h previously. Physical examination disclosed painful swelling over left distal arm, elbow, and forearm with three needle punctures. CT scan revealed ill-defined areas of heterogeneous high density with marked swelling at subcutaneous tissue over posterior aspect of the elbow. DISCUSSION: The mechanism of toxicity of GlySH is complicated and surfactant was thought to play an important role in GlySH intoxication. Intramuscular GlySH poisoning is different from oral GlySH intoxication. Care should be taken when monitoring acute rhabdomyolysis and compartment syndrome, which may develop rapidly and contribute to the surfactant component of glyphosate formulation.",
"title": "Rhabdomyolysis from an intramuscular injection of glyphosate-surfactant herbicide."
},
{
"docid": "MED-1753",
"text": "Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology. Copyright © 2012. Published by Elsevier Inc.",
"title": "The current state of GMO governance: are we ready for GM animals?"
},
{
"docid": "MED-1754",
"text": "Conspiracist ideation has been repeatedly implicated in the rejection of scientific propositions, although empirical evidence to date has been sparse. A recent study involving visitors to climate blogs found that conspiracist ideation was associated with the rejection of climate science and the rejection of other scientific propositions such as the link between lung cancer and smoking, and between HIV and AIDS (Lewandowsky et al., in press; LOG12 from here on). This article analyses the response of the climate blogosphere to the publication of LOG12. We identify and trace the hypotheses that emerged in response to LOG12 and that questioned the validity of the paper’s conclusions. Using established criteria to identify conspiracist ideation, we show that many of the hypotheses exhibited conspiratorial content and counterfactual thinking. For example, whereas hypotheses were initially narrowly focused on LOG12, some ultimately grew in scope to include actors beyond the authors of LOG12, such as university executives, a media organization, and the Australian government. The overall pattern of the blogosphere’s response to LOG12 illustrates the possible role of conspiracist ideation in the rejection of science, although alternative scholarly interpretations may be advanced in the future.",
"title": "Recursive Fury: Conspiracist Ideation in the Blogosphere in Response to Research on Conspiracist Ideation"
},
{
"docid": "MED-1752",
"text": "The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals. Using degenerate polymerase chain reaction, we have identified a new murine TGF-beta family member, growth/differentiation factor-8 (GDF-8), which is expressed specifically in developing and adult skeletal muscle. During early stages of embryogenesis, GDF-8 expression is restricted to the myotome compartment of developing somites. At later stages and in adult animals, GDF-8 is expressed in many different muscles throughout the body. To determine the biological function of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null animals are significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass. Individual muscles of mutant animals weigh 2-3 times more than those of wild-type animals, and the increase in mass appears to result from a combination of muscle cell hyperplasia and hypertrophy. These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth.",
"title": "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member."
},
{
"docid": "MED-2763",
"text": "Despite compelling statistics that show we could eliminate 80%of all heart disease and strokes, 90% of all diabetes, and 60% of all cancers with basic lifestyle changes, we have failed to motivate the public to make these changes and failed to motivate policy makers to make healthy choices the easiest choice. Dr. Katz suggests we have failed because we have focused too much on statistics and too little on passion. He implores all of us to tap into people's passion by connecting each of these statistics with a human story.",
"title": "Facing the facelessness of public health: what's the public got to do with it?"
},
{
"docid": "MED-1728",
"text": "The United States Environmental Protection Agency and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. Glyphosate is widely considered by regulatory authorities and scientific bodies to have no carcinogenic potential, based primarily on results of carcinogenicity studies of rats and mice. To examine potential cancer risks in humans, we reviewed the epidemiologic literature to evaluate whether exposure to glyphosate is associated causally with cancer risk in humans. We also reviewed relevant methodological and biomonitoring studies of glyphosate. Seven cohort studies and fourteen case-control studies examined the association between glyphosate and one or more cancer outcomes. Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate. Data from biomonitoring studies underscore the importance of exposure assessment in epidemiologic studies, and indicate that studies should incorporate not only duration and frequency of pesticide use, but also type of pesticide formulation. Because generic exposure assessments likely lead to exposure misclassification, it is recommended that exposure algorithms be validated with biomonitoring data. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Epidemiologic studies of glyphosate and cancer: a review."
},
{
"docid": "MED-1749",
"text": "Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada."
},
{
"docid": "MED-1748",
"text": "Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly precise log-normal distribution in the plasma samples while non-plasma (cord blood) control sample was found to be free of plant DNA.",
"title": "Complete Genes May Pass from Food to Human Blood"
},
{
"docid": "MED-1732",
"text": "Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Glyphosate induces human breast cancer cells growth via estrogen receptors."
},
{
"docid": "MED-1729",
"text": "We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.3 births per 1,000, with 83% of the total reported birth defects confirmed by medical records. Inclusion of children identified with birth or developmental disorders within the first 3 years of life and later led to a rate of 47.0 per 1,000 (72 children from 1,532 live births). Conceptions in spring resulted in significantly more children with birth defects than found in any other season (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n = 28 children). Forty-two percent of the children from families with recurrent birth defects were conceived in spring, a significantly higher rate than that for any other season. Three families in the kinships defined contributed a first-degree relative other than a sibling with the same or similar birth defect, consistent with a Mendelian inheritance pattern. The remaining nine families did not follow a Mendelian inheritance pattern. The sex ratio of children with birth defects born to applicator families shows a male predominance (1.75 to 1) across specific pesticide class use and exposure categories exclusive of fungicides. In the fungicide exposure category, normal female births significantly exceed male births (1.25 to 1). Similarly, the proportion of male to female children with birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic and neurobehavioral developmental effects clustered among the children born to applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6 (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out that (a) herbicides applied in the spring may be a factor in the birth defects observed and (b) fungicides can be a significant factor in the determination of sex of the children of the families of the RRV. Thus, two distinct classes of pesticides seem to have adverse effects on different reproductive outcomes. Biologically based confirmatory studies are needed.",
"title": "Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA."
},
{
"docid": "MED-1730",
"text": "The United States (US) Environmental Protection Agency (EPA) and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. To examine potential health risks in humans, we searched and reviewed the literature to evaluate whether exposure to glyphosate is associated causally with non-cancer health risks in humans. We also reviewed biomonitoring studies of glyphosate to allow for a more comprehensive discussion of issues related to exposure assessment and misclassification. Cohort, case-control and cross-sectional studies on glyphosate and non-cancer outcomes evaluated a variety of endpoints, including non-cancer respiratory conditions, diabetes, myocardial infarction, reproductive and developmental outcomes, rheumatoid arthritis, thyroid disease, and Parkinson's disease. Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0. Because accurate exposure measurement is crucial for valid results, it is recommended that pesticide-specific exposure algorithms be developed and validated. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Epidemiologic studies of glyphosate and non-cancer health outcomes: a review."
},
{
"docid": "MED-1726",
"text": "Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.",
"title": "Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles"
},
{
"docid": "MED-1738",
"text": "Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.",
"title": "Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis."
},
{
"docid": "MED-1747",
"text": "Knowledge of the US Public Health Syphilis Study at Tuskegee is sometime cited as a principal reason for the relatively low participation rates seen among racial/ethnic minorities, particularly African Americans, in biomedical research. However, only a few studies have actually explored this possibility. We use data from a random digit dial telephone survey of 510 African-Americans and 253 Latinos, age 18 to 45 years, to investigate associations between knowledge of the USPHS Syphilis Study at Tuskegee and endorsement of HIV/AIDS conspiracy theories. All respondents were drawn from an area of low-income, predominantly race-segregated inner city households in Los Angeles. Results indicate that African Americans were significantly more likely than Latinos to endorse HIV/AIDS conspiracy theories. Further, African Americans were more aware of the USPHS Syphilis Study at Tuskegee (SST). Nevertheless, 72% of African Americans and 94% of Latinos reported that they have never heard of the Syphilis Study at Tuskegee. Further, while awareness of the Syphilis Study at Tuskegee was a significant predictor of endorsing HIV/AIDS conspiracy theories, results suggest that other factors may be more important in accounting for low biomedical and behavioral study participation rates.",
"title": "Is there a legacy of the U.S. Public Health Syphilis Study at Tuskegee in HIV/AIDS-related beliefs among heterosexual African-Americans and Latinos?"
},
{
"docid": "MED-1725",
"text": "Methods: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable. Results: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these \"potentially carcinogenic\" pesticides suggested a positive trend of risk with exposure to increasing numbers. Conclusion: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.",
"title": "Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men"
},
{
"docid": "MED-1751",
"text": "There are many ways to categorise conspiracy theories. In the present study, we examined individual and demographic predictors of beliefs in commercial conspiracy theories among a British sample of over 300 women and men. Results showed many people were cynical and sceptical with regard to advertising tricks, as well as the tactics of organisations like banks and alcohol, drug and tobacco companies. Beliefs sorted into four identifiable clusters, labelled sneakiness, manipulative, change-the-rules and suppression/prevention. The high alpha for the overall scale suggested general beliefs in commercial conspiracy. Regressions suggested that those people who were less religious, more left-wing, more pessimistic, less (self-defined as) wealthy, less Neurotic and less Open-to-Experience believed there was more commercial conspiracy. Overall the individual difference variables explained relatively little of the variance in these beliefs. The implications of these findings for the literature on conspiracy theories are discussed. Limitations of the study are also discussed.",
"title": "Commercial conspiracy theories: a pilot study"
},
{
"docid": "MED-1731",
"text": "Glyphosate surfactant herbicide (GlySH) toxicity is an uncommon poisoning. We report two fatalities involving suicidal ingestion of this herbicide. Both deaths occurred despite early recognition of the serious nature of the poisoning and aggressive treatment. The deaths in this series are analysed in the context of a review of existing literature. Although traditionally regarded as minimally toxic, many deaths have been reported following suicidal ingestion. Severe GlySH toxicity may be refractory even to the most intensive supportive care. The triad of pulmonary oedema, metabolic acidosis and hyperkalaemia portends poor outcome. While containing a carbon phosphorus moiety, GlySH does not exhibit organophosphate toxicity. A clinical guide to assessing severity of GlySH toxicity is proposed and treatment modalities discussed.",
"title": "Glyphosate herbicide formulation: a potentially lethal ingestion."
},
{
"docid": "MED-1750",
"text": "The discovery of myostatin and our introduction to the “Mighty Mouse” over a decade ago spurred both basic and applied research and impacted popular culture as well. The myostatin-null genotype produces “double muscling” in mice and livestock and was recently described in a child. The field’s rapid growth is by no means surprising considering the potential benefits of enhancing muscle growth in clinical and agricultural settings. Indeed, several recent studies suggest that blocking myostatin’s inhibitory effects could improve the clinical treatment of several muscle growth disorders, whereas comparative studies suggest that these actions are at least partly conserved. Thus, neutralizing myostatin’s effects could also have agricultural significance. Extrapolating between studies that use different vertebrate models, particularly fish and mammals, is somewhat confusing because whole genome duplication events have resulted in the production and retention of up to four unique myostatin genes in some fish species. Such comparisons, however, suggest that myostatin’s actions may not be limited to skeletal muscle per se, but may additionally influence other tissues including cardiac muscle, adipocytes, and the brain. Thus, therapeutic intervention in the clinic or on the farm must consider the potential of alternative side effects that could impact these or other tissues. In addition, the presence of multiple and actively diversifying myostatin genes in most fish species provides a unique opportunity to study adaptive molecular evolution. It may also provide insight into myostatin’s nonmuscle actions as results from these and other comparative studies gain visibility in biomedical fields.",
"title": "Clinical, Agricultural, and Evolutionary Biology of Myostatin: A Comparative Review"
}
] |
[
{
"docid": "MED-2054",
"text": "OBJECTIVE: To determine the prevalence of constipation in children <or=2 years, describe the symptoms of constipation, and review how often specific interventions were effective. STUDY DESIGN: Retrospective chart review. RESULTS: Of 4,157 children <2 years of age, 185 children had constipation. The prevalence rate for constipation in the first year of life was 2.9%, and in the second year of life, the rate was 10.1%. Functional constipation was the cause in 97% of the children. Boys and girls were affected with equal frequency. Constipation was caused by an underlying organic disease in 1.6% of cases, and 97% of the children had functional constipation. Dietary changes and corn syrup were the initial treatment suggestions for 116 children; 93% of these children underwent follow-up examinations, and the constipation resolved in 25% of the children. Of 100 children treated with milk of magnesia or polyethylene glycol 3350 without electrolytes, 93 children underwent follow-up examinations, and the constipation was resolved with treatment in 92% of the children. CONCLUSIONS: Dietary changes, corn syrup, or both resolved constipation in 25% of children, and laxatives resolved constipation in 92% of children. Both milk of magnesia and polyethylene glycol were efficient and safe in infants and toddlers.",
"title": "Prevalence, symptoms and outcome of constipation in infants and toddlers."
},
{
"docid": "MED-1860",
"text": "To compare the antihypertensive effectiveness of sour tea (ST; Hibiscus sabdariffa) with black tea (BT) infusion in diabetic patients, this double-blind randomized controlled trial was carried out. Sixty diabetic patients with mild hypertension, without taking antihypertensive or antihyperlipidaemic medicines, were recruited in the study. The patients were randomly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month. Their blood pressure (BP) was measured on days 0, 15 and 30 of the study. The mean of systolic BP (SBP) in the ST group decreased from 134.4+/-11.8 mm Hg at the beginning of the study to 112.7+/-5.7 mm Hg after 1 month (P-value <0.001), whereas this measure changed from 118.6+/-14.9 to 127.3+/-8.7 mm Hg (P-value=0.002) in the BT group during the same period. The intervention had no statistically significant effect on the mean of diastolic BP (DBP) in either the ST or BT group. The mean pulse pressure (PP) of the patients in the ST group decreased from 52.2+/-12.2 to 34.5+/-9.3 mm Hg (P-value <0.001) during the study, whereas in the BT group, it increased from 41.9+/-11.7 to 47.3+/-9.6 mm Hg (P-value=0.01). In conclusion, consuming ST infusion had positive effects on BP in type II diabetic patients with mild hypertension. This study supports the results of similar studies in which antihypertensive effects have been shown for ST.",
"title": "The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes."
},
{
"docid": "MED-3843",
"text": "PURPOSE: Phytoestrogens are plant-derived, non-steroidal phytochemicals with anticarcinogenic potential. The major structural classes are the isoflavones and lignans. The aim of this study was to compare the effect of the plant-derived lignans secoisolariciresinol and matairesinol with the human lignans enterodiol and enterolactone as well as with 17β estradiol and tamoxifen on cell proliferation of breast carcinoma cell lines. METHODS: The influence of the lignans, 17β estradiol and tamoxifen on cell proliferation was determined using the BrdU test in MCF 7 and BT 20 cell lines. RESULTS: Enterodiol and enterolactone induced a stronger inhibition of cell growth in MCF 7 and BT 20 cells than secoisolariciresinol and matairesinol. The inhibition effects were less expressed in the BT 20 than in the MCF 7 cells. CONCLUSIONS: The human lignans enterodiol and enterolactone are more biologically active than their precursors secoisolariciresinol and matairesinol, and may be defined as the real drugs in cancer prevention.",
"title": "Antiproliferative activity of lignans against the breast carcinoma cell lines MCF 7 and BT 20."
},
{
"docid": "MED-1867",
"text": "OBJECTIVES: There is increasing evidence that intake of sour tea (Hibiscus sabdariffa) has hypoglycemic and hypolipidemic effects and may benefit patients suffering from metabolic disorders such as diabetes. The objective of the present study was to investigate the hypolipidemic effects of sour tea in patients with diabetes and compare them with those of black tea. DESIGN: In this sequential randomized controlled clinical trial, 60 patients with diabetes were recruited and randomly assigned into two groups: sour tea (ST) and black tea (BT). They were instructed to consume sour tea or black tea two times a day for 1 month. OUTCOME MEASURES: Fasting blood samples were taken at the beginning and at the end of the study for evaluation of lipids, lipoproteins, and apoproteins. RESULTS: Fifty-three (53) patients concluded the study. In the ST group, mean of high-density lipoprotein-cholesterol (HDLc) increased significantly (p = 0.002) at the end of the study, whereas changes in apolipoprotein-A1, and lipoprotein (a) were not significant. Also, a significant decrease in the mean of total cholesterol, low density lipoprotein-cholesterol, triglycerides, and Apo-B100 were seen in this group. In the BT group, only HDLc showed significant change (p = 0.002) at the end of the study and changes in the other measures were not statistically significant. CONCLUSIONS: The results of the present study showed that ST has a significant effect on blood lipid profile in patients with diabetes.",
"title": "Effects of sour tea (Hibiscus sabdariffa) on lipid profile and lipoproteins in patients with type II diabetes."
},
{
"docid": "MED-2490",
"text": "Background: Rice can be a major source of inorganic arsenic (Asi) for many sub-populations. Rice products are also used as ingredients in prepared foods, some of which may not be obviously rice based. Organic brown rice syrup (OBRS) is used as a sweetener in organic food products as an alternative to high-fructose corn syrup. We hypothesized that OBRS introduces As into these products. Objective: We determined the concentration and speciation of As in commercially available brown rice syrups and in products containing OBRS, including toddler formula, cereal/energy bars, and high-energy foods used by endurance athletes. Methods: We used inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography coupled to ICP-MS to determine total As (Astotal) concentrations and As speciation in products purchased via the Internet or in stores in the Hanover, New Hampshire, area. Discussion: We found that OBRS can contain high concentrations of Asi and dimethyl-arsenate (DMA). An “organic” toddler milk formula containing OBRS as the primary ingredient had Astotal concentrations up to six times the U.S. Environmental Protection Agency safe drinking water limit. Cereal bars and high-energy foods containing OBRS also had higher As concentrations than equivalent products that did not contain OBRS. Asi was the main As species in most food products tested in this study. Conclusions: There are currently no U.S. regulations applicable to As in food, but our findings suggest that the OBRS products we evaluated may introduce significant concentrations of Asi into an individual’s diet. Thus, we conclude that there is an urgent need for regulatory limits on As in food.",
"title": "Arsenic, Organic Foods, and Brown Rice Syrup"
},
{
"docid": "MED-913",
"text": "In recent years, there has been a notable concern on the safety of genetically modified (GM) foods/plants, an important and complex area of research, which demands rigorous standards. Diverse groups including consumers and environmental Non Governmental Organizations (NGO) have suggested that all GM foods/plants should be subjected to long-term animal feeding studies before approval for human consumption. In 2000 and 2006, we reviewed the information published in international scientific journals, noting that the number of references concerning human and animal toxicological/health risks studies on GM foods/plants was very limited. The main goal of the present review was to assess the current state-of-the-art regarding the potential adverse effects/safety assessment of GM plants for human consumption. The number of citations found in databases (PubMed and Scopus) has dramatically increased since 2006. However, new information on products such as potatoes, cucumber, peas or tomatoes, among others was not available. Corn/maize, rice, and soybeans were included in the present review. An equilibrium in the number research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was currently observed. Nevertheless, it should be noted that most of these studies have been conducted by biotechnology companies responsible of commercializing these GM plants. These findings suggest a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. All this recent information is herein critically reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "A literature review on the safety assessment of genetically modified plants."
},
{
"docid": "MED-2895",
"text": "PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight \"retinal responders\" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two \"retinal nonresponders\" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one \"serum and retinal nonresponder\" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.",
"title": "Dietary modification of human macular pigment density."
},
{
"docid": "MED-5032",
"text": "The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and orange juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR] = 9.5, 95 percent confidence interval [CI] = 1.6-57.6 for 12 or more hot dogs per month, trend P = 0.01), and fathers' intake of hot dogs (OR = 11.0, CI = 1.2-98.7 for highest intake category, trend P = 0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.",
"title": "Processed meats and risk of childhood leukemia (California, USA)."
},
{
"docid": "MED-5012",
"text": "This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.",
"title": "The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol."
},
{
"docid": "MED-5167",
"text": "OBJECTIVES: The phytoestrogen (plant estrogen) genistein, present in soy products, is of interest because in utero exposure to genistein can cause hypospadias in our mouse model and maternal consumption of soy is prevalent in human populations. Another compound of interest is the fungicide vinclozolin, which also causes hypospadias in the mouse and rat and can occur concurrently with genistein in the diet as a residue on exposed foods. A study in the United Kingdom found no relationship between a maternal organic vegetarian diet and hypospadias frequency, but women who consumed nonorganic vegetarian diets had a greater percentage of sons with hypospadias. Because nonorganic diets can include residues of pesticides such as vinclozolin, we sought to assess the interaction of realistic daily exposures to genistein and vinclozolin and their effects on the incidence of hypospadias. METHODS: Pregnant mice were fed a soy-free diet and orally gavaged from gestational days 13 to 17 with 0.17 mg/kg/day of genistein, 10 mg/kg/day of vinclozolin, or genistein and vinclozolin together at the same doses, all in 100 microL of corn oil. The controls received the corn oil vehicle. The male fetuses were examined at gestational day 19 for hypospadias, both macroscopically and histologically. RESULTS: We identified no hypospadias in the corn oil group. The incidence of hypospadias was 25% with genistein alone, 42% with vinclozolin alone, and 41% with genistein and vinclozolin together. CONCLUSIONS: These findings support the idea that exposure to these compounds during gestation could contribute to the development of hypospadias.",
"title": "Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin."
},
{
"docid": "MED-906",
"text": "Annatto dye is an orange-yellow food coloring extracted from the seeds of the tree Bixa orellana. It is commonly used in cheeses, snack foods, beverages, and cereals. Previously reported adverse reactions associated with annatto dye have included urticaria and angioedema. We present a patient who developed urticaria, angioedema, and severe hypotension within 20 minutes following ingestion of milk and Fiber One cereal, which contained annatto dye. Subsequent skin tests to milk, wheat, and corn were negative. The patient had a strong positive skin test to annatto dye, while controls had no response. The nondialyzable fraction of annatto dye on SDS-PAGE demonstrated two protein staining bands in the range of 50 kD. Immunoblotting demonstrated patient IgE-specific for one of these bands, while controls showed no binding. Annatto dye may contain contaminating or residual seed proteins to which our patient developed IgE hypersensitivity. Annatto dye is a potential rare cause of anaphylaxis.",
"title": "Anaphylaxis to annatto dye: a case report."
},
{
"docid": "MED-1710",
"text": "Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50% of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. The intake of soft drinks has increased 5-fold between 1950 and 2000. Most meta-analyses have shown that the risk of obesity, diabetes, cardiovascular disease, and metabolic syndrome are related to consumption of beverages sweetened with sugar or high-fructose corn syrup. Calorically sweetened beverage intake has also been related to the risk of nonalcoholic fatty liver disease, and, in men, gout. Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are “add-on” calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50% of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. When it is taken up by the liver, ATP decreases rapidly as the phosphate is transferred to fructose in a form that makes it easy to convert to lipid precursors. Fructose intake enhances lipogenesis and the production of uric acid. By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.",
"title": "Energy and Fructose From Beverages Sweetened With Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People"
},
{
"docid": "MED-5034",
"text": "The association between cured and broiled meat consumption by the mother during pregnancy and by the child was examined in relation to childhood cancer. Five meat groups (ham, bacon, or sausage; hot dogs; hamburgers; bologna, pastrami, corned beef, salami, or lunch meat; charcoal broiled foods) were assessed. Exposures among 234 cancer cases (including 56 acute lymphocytic leukemia [ALL], 45 brain tumor) and 206 controls selected by random-digit dialing in the Denver, Colorado (United States) standard metropolitan statistical area were compared, with adjustment for confounders. Maternal hot-dog consumption of one or more times per week was associated with childhood brain tumors (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.0-5.4). Among children, eating hamburgers one or more times per week was associated with risk of ALL (OR = 2.0, CI = 0.9-4.6) and eating hot dogs one or more times per week was associated with brain tumors (OR = 2.1, CI = 0.7-6.1). Among children, the combination of no vitamins and eating meats was associated more strongly with both ALL and brain cancer than either no vitamins or meat consumption alone, producing ORs of two to seven. The results linking hot dogs and brain tumors (replicating an earlier study) and the apparent synergism between no vitamins and meat consumption suggest a possible adverse effect of dietary nitrites and nitrosamines.",
"title": "Cured and broiled meat consumption in relation to childhood cancer: Denver, Colorado (United States)"
},
{
"docid": "MED-5157",
"text": "BACKGROUND/AIMS: Herbal agents are popular and perceived as safe because they are supposedly 'natural'. We report 10 cases of toxic hepatitis implicating Herbalife products. METHODS: To determine the prevalence and outcome of hepatotoxicity due to Herbalife products. A questionnaire was sent to all public Swiss hospitals. Reported cases were subjected to causality assessment using the CIOMS criteria. RESULTS: Twelve cases of toxic hepatitis implicating Herbalife preparations (1998-2004) were retrieved, 10 sufficiently documented to permit causality analysis. Median age of patients was 51 years (range 30-69) and latency to onset was 5 months (0.5-144). Liver biopsy (7/10) showed hepatic necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis in five patients. One patient with fulminant liver failure was successfully transplanted; the explant showed giant cell hepatitis. Sinusoidal obstruction syndrome was observed in one case. Three patients without liver biopsy presented with hepatocellular (2) or mixed (1) liver injury. Causality assessment of adverse drug reaction was classified as certain in two, probable in seven and possible in one case(s), respectively. CONCLUSIONS: We present a case series of toxic hepatitis implicating Herbalife products. Liver toxicity may be severe. A more detailed declaration of components and pro-active role of regulatory agencies would be desirable.",
"title": "Herbal does not mean innocuous: ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife products."
},
{
"docid": "MED-3660",
"text": "Lavender essential oil has been used as an anxiolytic drug, a mood stabilizer, a sedative, spasmolytic, antihypertensive, antimicrobial, analgesic agent as well as a wound healing accelerator. We have studied for the first time the efficacy of lavender essential oil inhalation for the treatment of migraine in a placebo-controlled clinical trial. METHODS: Forty-seven patients with definite diagnosis of migraine headache were divided into cases and controls. Cases inhaled lavender essential oil for 15 min, whereas the control group used liquid paraffin for the same time period. Patients were asked to record their headache severity and associated symptoms in 30-min intervals for a total of 2 h. We matched the two groups for key confounding factors. RESULTS: The mean reduction of headache severity in cases was 3.6 ± 2.8 based on Visual Analogue Scale score. The reduction was 1.6 ± 1.6 in controls. This difference between the controls and cases was statistically significant with p < 0.0001. From 129 headache attacks in cases, 92 responded entirely or partially to lavender. In the control group, 32 out of 68 recorded headache attacks responded to placebo. The percentage of responders was significantly higher in the lavender group than the placebo group (p = 0.001). CONCLUSION: The present study suggests that inhalation of lavender essential oil may be an effective and safe treatment modality in acute management of migraine headaches. Copyright © 2012 S. Karger AG, Basel.",
"title": "Lavender essential oil in the treatment of migraine headache: a placebo-controlled clinical trial."
},
{
"docid": "MED-3143",
"text": "BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.",
"title": "Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial."
},
{
"docid": "MED-5056",
"text": "BACKGROUND: Oxidative damage is implicated in the etiology of cancer, cardiovascular disease, and other degenerative disorders. Recent nutritional research has focused on the antioxidant potential of foods, while current dietary recommendations are to increase the intake of antioxidant-rich foods rather than supplement specific nutrients. Many alternatives to refined sugar are available, including raw cane sugar, plant saps/syrups (eg, maple syrup, agave nectar), molasses, honey, and fruit sugars (eg, date sugar). Unrefined sweeteners were hypothesized to contain higher levels of antioxidants, similar to the contrast between whole and refined grain products. OBJECTIVE: To compare the total antioxidant content of natural sweeteners as alternatives to refined sugar. DESIGN: The ferric-reducing ability of plasma (FRAP) assay was used to estimate total antioxidant capacity. Major brands of 12 types of sweeteners as well as refined white sugar and corn syrup were sampled from retail outlets in the United States. RESULTS: Substantial differences in total antioxidant content of different sweeteners were found. Refined sugar, corn syrup, and agave nectar contained minimal antioxidant activity (<0.01 mmol FRAP/100 g); raw cane sugar had a higher FRAP (0.1 mmol/100 g). Dark and blackstrap molasses had the highest FRAP (4.6 to 4.9 mmol/100 g), while maple syrup, brown sugar, and honey showed intermediate antioxidant capacity (0.2 to 0.7 mmol FRAP/100 g). Based on an average intake of 130 g/day refined sugars and the antioxidant activity measured in typical diets, substituting alternative sweeteners could increase antioxidant intake an average of 2.6 mmol/day, similar to the amount found in a serving of berries or nuts. CONCLUSION: Many readily available alternatives to refined sugar offer the potential benefit of antioxidant activity.",
"title": "Total antioxidant content of alternatives to refined sugar."
},
{
"docid": "MED-2093",
"text": "Chlorhexidine (CHX) is one of the most commonly prescribed antiseptic agents in the dental field. It has a long-lasting antibacterial activity with a broad-spectrum of action and it has been shown to reduce plaque, gingival inflammation and bleeding. Its use is considered a powerful adjuvant to mechanical oral hygiene (brushing and flossing), especially in those cases in which it cannot be performed correctly. Available as mouthwash, gel, aerosol, spray and disks, CHX is considered a safe compound, with minimal and transitory local and systemic side effects. Data support its periodic use as an adjuvant to normal brushing and flossing in subjects unable to maintain proper oral hygiene due to physical and/or mental impairment, or lack of motivation, or decreased salivary rate. CHX is also a useful alternative to mechanical oral hygiene procedures in those cases in which they are contraindicated, e.g. after a surgical procedure, or as a preoperative rinse before procedures in which use of a dental dam is not possible. The aim of this article is to offer a complete review of literature regarding the characteristics, the applications and the problems associated with the use of chlorhexidine in the dental field.",
"title": "Chlorhexidine (CHX) in dentistry: state of the art."
},
{
"docid": "MED-2150",
"text": "Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9–15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996–2001) obtained intake data on a variety of foods. Beginning in 2005, women (18–30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53–0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13–0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43–0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16–0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.",
"title": "Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women"
},
{
"docid": "MED-5123",
"text": "The present paper explores the level of evidence required to justify giving dietary advice to the public. There are important practical differences between the development of public health nutrition guidelines and guidelines for clinical practice. While the gold standard for evidence for clinical practice guidelines is a meta-analysis of a number of randomised controlled trials, this is often unrealistic and sometimes unethical for the evaluation of public health nutrition interventions. Hence, epidemiological studies make up the bulk of evidence for nutrition guidelines. Tea and coffee are an interesting case study in relation to this issue. They are two of the most commonly consumed beverages worldwide, yet there is little dietary advice on their use. The evidence for a relationship between coffee or tea consumption and several diseases is discussed. The available studies, predominantly epidemiological, together with animal and in vitro studies, indicate that coffee and tea are both safe beverages. However, tea is the healthier option because it has a possible role in the prevention of several cancers and CVD. While the evidence for such relationships is not strong, the public will continue to drink both tea and coffee, and will continue to ask nutritionists to make recommendations. It is therefore argued that advice should be given on the best available data, as waiting for complete data to become available could have severe consequences for public health.",
"title": "Tea or coffee? A case study on evidence for dietary advice."
},
{
"docid": "MED-4373",
"text": "The use of nutritional supplements in the general population and in cancer patients has become very popular. These supplements are not perceived as medications and are presumed to be safe by cancer patients, who may however be at risk for hypercalcemia. We note that many of our patients who have developed symptomatic hypercalcemia were taking vitamin D, calcium, or shark cartilage supplements. We report eight cases of hypercalcemia in cancer patients seen at the Cleveland Clinic Foundation in whom these nutritional supplements may have contributed to the prevalence or severity of hypercalcemia.",
"title": "Dangerous nutrition? Calcium, vitamin D, and shark cartilage nutritional supplements and cancer-related hypercalcemia."
},
{
"docid": "MED-717",
"text": "OBJECTIVE: Fructose intake has increased considerably in the United States, primarily as a result of increased consumption of high-fructose corn syrup, fruits and juices, and crystalline fructose. The purpose was to determine how often fructose, in amounts commonly consumed, would result in malabsorption and/or symptoms in healthy persons. DESIGN: Fructose absorption was measured using 3-hour breath hydrogen tests and symptom scores were used to rate subjective responses for gas, borborygmus, abdominal pain, and loose stools. SUBJECTS/SETTING: The study included 15 normal, free-living volunteers from a medical center community and was performed in a gastrointestinal specialty clinic. INTERVENTION: Subjects consumed 25- and 50-g doses of crystalline fructose with water after an overnight fast on separate test days. MAIN OUTCOME MEASURES: Mean peak breath hydrogen, time of peak, area under the curve (AUC) for breath hydrogen and gastrointestinal symptoms were measured during a 3-hour period after subjects consumed both 25- and 50-g doses of fructose. STATISTICAL ANALYSES: Differences in mean breath hydrogen, AUC, and symptom scores between doses were analyzed using paired t tests. Correlations among peak breath hydrogen, AUC, and symptoms were also evaluated. RESULTS: More than half of the 15 adults tested showed evidence of fructose malabsorption after 25 g fructose and greater than two thirds showed malabsorption after 50 g fructose. AUC, representing overall breath hydrogen response, was significantly greater after the 50-g dose. Overall symptom scores were significantly greater than baseline after each dose, but scores were only marginally greater after 50 g than 25 g. Peak hydrogen levels and AUC were highly correlated, but neither was significantly related to symptoms. CONCLUSIONS: Fructose, in amounts commonly consumed, may result in mild gastrointestinal distress in normal people. Additional study is warranted to evaluate the response to fructose-glucose mixtures (as in high-fructose corn syrup) and fructose taken with food in both normal people and those with gastrointestinal dysfunction. Because breath hydrogen peaks occurred at 90 to 114 minutes and were highly correlated with 180-minute breath hydrogen AUC, the use of peak hydrogen measures may be considered to shorten the duration of the exam.",
"title": "Fructose intake at current levels in the United States may cause gastrointestinal distress in normal adults."
},
{
"docid": "MED-3732",
"text": "Background Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct dissection of the submucosa and large lesions can be resected en bloc. ESD is not limited by resection size, increases histologically complete resection rates and may reduce the local recurrence. Nevertheless, the technique is time-consuming, technically demanding and associated with a high complication rate. To reduce the risk of complications, different devices and technical advances have been proposed with conflicting results and, still, ESD en bloc resections of huge lesions are associated with increased complications. Case Presentation We successfully used a combined ESD/EMR technique for huge rectal laterally spreading tumors (LSTs). ESD was used for circumferential resection of 2/3 of the lesion followed by piecemeal resection (2-3 pieces) of the central part of the tumour. In all three patients we obtained the complete dissection of the polyp and the complete histological evaluation in absence of complications and recurrence at 6 months' follow up. Conclusions In the treatment of rectal LSTs, the combined treatment - ESD/EMR resection may be considered a suitable therapeutic option, indicated in selected cases as an alternative to surgery, in which the two techniques are neither reliable nor safe separately. However, to confirm our results, larger trials with longer follow up are required together with improvement of the technique and of the technical devices.",
"title": "Rectal laterally spreading tumors successfully treated in two steps by endoscopic submucosal dissection and endoscopic mucosal resection"
},
{
"docid": "MED-3385",
"text": "Diacetyl-containing butter flavor was identified as the cause of an outbreak of bronchiolitis obliterans (BO) and other lung diseases in popcorn-plant workers. Litigation documents show that the outbreak was both predictable and preventable. The industry trade organization was aware of BO cases in workers at butter-flavoring and popcorn-manufacturing plants but often failed to implement industrial hygiene improvements and actively hid pertinent warning information. Due to weaknesses in the organization and mandates of regulatory bodies, organizations such as NIOSH, OSHA, the FDA, particularly the \"generally recognized as safe\" (GRAS) system, and the EPA failed to detect and prevent the outbreak, which highlights the need for systemic changes in food-product regulation, including the need for corporations to act responsibly, for stronger regulations with active enforcement, for a restructuring of the GRAS system, and for criminal penalties against corporations and professionals who knowingly hide information relevant to worker protection.",
"title": "Popcorn-worker lung caused by corporate and regulatory negligence: an avoidable tragedy."
},
{
"docid": "MED-3554",
"text": "A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.",
"title": "A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer."
},
{
"docid": "MED-2742",
"text": "A national telephone survey was conducted of 1,620 randomly selected U.S. residents who spoke English, were at least 18 years old, and resided in households with kitchen facilities. Respondents were interviewed about their recognition of foodborne pathogens, foods at risk for transmitting infection, knowledge of safe food handling, and food-handling practices. One-third of the respondents who prepared meals reported unsafe food hygiene practices: e.g., they did not wash hands or take precautions to prevent cross-contamination from raw meat. Unsafe practices were reported more often by men, adults 18 to 29 years of age, and occasional food preparers than by women, persons 30 years old or older, and frequent food preparers. Respondents who identified a food vehicle for Salmonella spp. were more likely to report washing their hands and cleaning cutting boards after preparing raw meat and poultry. The results raise concerns about consumer food-handling practices. The influence of food safety training, food-handling experience, and age on food-handling practices should be studied further. Awareness of a food vehicle for Salmonella spp., for example, may indicate knowledge of the etiology of foodborne disease that promotes safe food handling. Understanding the factors associated with safe food handling will assist in development of effective safe-food instruction programs.",
"title": "Consumer knowledge of foodborne microbial hazards and food-handling practices."
},
{
"docid": "MED-2743",
"text": "In June 2012, the Oregon Health Authority and the Washington State Department of Health noted an increase in the number of Salmonella enterica serotype Heidelberg clinical isolates sharing an identical pulsed-field gel electrophoresis (PFGE) pattern. In 2004, this pattern had been linked to chicken from Foster Farms by the Washington State Department of Health; preliminary 2012 interviews with infected persons also indicated exposure to Foster Farms chicken. On August 2, 2012, CDC's PulseNet* detected a cluster of 19 Salmonella Heidelberg clinical isolates matching the outbreak pattern. This report summarizes the investigation by CDC, state and local health departments, the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS), and the Food and Drug Administration (FDA) and reinforces the importance of safe food handling to prevent illness. A total of 134 cases from 13 states were identified, including 33 patients who were hospitalized. This multifaceted investigation used standard epidemiologic and laboratory data along with patient shopper card purchase information, and PFGE data from the retail meat component of the National Antimicrobial Resistance Monitoring System (NARMS)†, a relatively novel tool in outbreak investigation, to link the outbreak strain to chicken from Foster Farms.",
"title": "Outbreak of Salmonella Heidelberg infections linked to a single poultry producer -- 13 states, 2012-2013."
},
{
"docid": "MED-2738",
"text": "Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers.",
"title": "Trends in U.S. consumers' safe handling and consumption of food and their risk perceptions, 1988 through 2010."
},
{
"docid": "MED-5345",
"text": "Five years ago, the Institute of Medicine (IOM) called for a national effort to make health care safe. Although progress since then has been slow, the IOM report truly \"changed the conversation\" to a focus on changing systems, stimulated a broad array of stakeholders to engage in patient safety, and motivated hospitals to adopt new safe practices. The pace of change is likely to accelerate, particularly in implementation of electronic health records, diffusion of safe practices, team training, and full disclosure to patients following injury. If directed toward hospitals that actually achieve high levels of safety, pay for performance could provide additional incentives. But improvement of the magnitude envisioned by the IOM requires a national commitment to strict, ambitious, quantitative, and well-tracked national goals. The Agency for Healthcare Research and Quality should bring together all stakeholders, including payers, to agree on a set of explicit and ambitious goals for patient safety to be reached by 2010.",
"title": "Five years after To Err Is Human: what have we learned?"
},
{
"docid": "MED-3382",
"text": "Artificial food colors (AFCs) have not been established as the main cause of attention-deficit hyperactivity disorder (ADHD), but accumulated evidence suggests that a subgroup shows significant symptom improvement when consuming an AFC-free diet and reacts with ADHD-type symptoms on challenge with AFCs. Of children with suspected sensitivities, 65% to 89% reacted when challenged with at least 100 mg of AFC. Oligoantigenic diet studies suggested that some children in addition to being sensitive to AFCs are also sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and orange. Some studies found \"cosensitivity\" to be more the rule than the exception. Recently, 2 large studies demonstrated behavioral sensitivity to AFCs and benzoate in children both with and without ADHD. A trial elimination diet is appropriate for children who have not responded satisfactorily to conventional treatment or whose parents wish to pursue a dietary investigation.",
"title": "Dietary sensitivities and ADHD symptoms: thirty-five years of research."
}
] |
714
|
Low expression of miR7a does not repress target genes or exert a biological function in testis.
|
[
{
"docid": "18421962",
"text": "Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a microRNA (miRNA) through their binding sites and that changes in ceRNA abundances from individual genes can modulate the activity of miRNAs. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target site abundance through expression of an miR-122 target in hepatocytes and livers and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target site abundance (≥1.5 × 10(5) added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect.",
"title": "Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance."
}
] |
[
{
"docid": "15635366",
"text": "L3mbtl2 has been implicated in transcriptional repression and chromatin compaction but its biological function has not been defined. Here we show that disruption of L3mbtl2 results in embryonic lethality with failure of gastrulation. This correlates with compromised proliferation and abnormal differentiation of L3mbtl2(-/-) embryonic stem (ES) cells. L3mbtl2 regulates genes by recruiting a Polycomb Repressive Complex1 (PRC1)-related complex, resembling the previously described E2F6-complex, and including G9A, Hdac1, and Ring1b. The presence of L3mbtl2 at target genes is associated with H3K9 dimethylation, low histone acetylation, and H2AK119 ubiquitination, but the latter is neither dependent on L3mbtl2 nor sufficient for repression. Genome-wide studies revealed that the L3mbtl2-dependent complex predominantly regulates genes not bound by canonical PRC1 and PRC2. However, some developmental regulators are repressed by the combined activity of all three complexes. Together, we have uncovered a highly selective, essential role for an atypical PRC1-family complex in ES cells and early development.",
"title": "The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development."
},
{
"docid": "6828370",
"text": "The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.",
"title": "A coding-independent function of gene and pseudogene mRNAs regulates tumour biology"
},
{
"docid": "18895793",
"text": "The relationship between chromatin structure and gene expression is a subject of intense study. The universal transcriptional activator Gal4 removes promoter nucleosomes as it triggers transcription, but how it does so has remained obscure. The reverse process, repression of transcription, has often been correlated with the presence of nucleosomes. But it is not known whether nucleosomes are required for that effect. A new quantitative assay describes, for any given location, the fraction of DNA molecules in the population that bears a nucleosome at any given instant. This allows us to follow the time courses of nucleosome removal and reformation, in wild-type and mutant cells, upon activation (by galactose) and repression (by glucose) of the GAL genes of yeast. We show that upon being freed of its inhibitor Gal80 by the action of galactose, Gal4 quickly recruits SWI/SNF to the genes, and that nucleosome \"remodeler\" rapidly removes promoter nucleosomes. In the absence of SWI/SNF, Gal4's action also results in nucleosome removal and the activation of transcription, but both processes are significantly delayed. Addition of glucose to cells growing in galactose represses transcription. But if galactose remains present, Gal4 continues to work, recruiting SWI/SNF and maintaining the promoter nucleosome-free despite it being repressed. This requirement for galactose is obviated in a mutant in which Gal4 works constitutively. These results show how an activator's recruiting function can control chromatin structure both during gene activation and repression. Thus, both under activating and repressing conditions, the activator can recruit an enzymatic machine that removes promoter nucleosomes. Our results show that whereas promoter nucleosome removal invariably accompanies activation, reformation of nucleosomes is not required for repression. The finding that there are two routes to nucleosome removal and activation of transcription-one that requires the action of SWI/SNF recruited by the activator, and a slower one that does not-clarifies our understanding of the early events of gene activation, and in particular corrects earlier reports that SWI/SNF plays no role in GAL gene induction. Our finding that chromatin structure is irrelevant for repression as studied here-that is, repression sets in as efficiently whether or not promoter nucleosomes are allowed to reform-contradicts the widely held, but little tested, idea that nucleosomes are required for repression. These findings were made possible by our nucleosome occupancy assay. The assay, we believe, will prove useful in studying other outstanding issues in the field.",
"title": "Activator Control of Nucleosome Occupancy in Activation and Repression of Transcription"
},
{
"docid": "6820680",
"text": "MicroRNAs (miRNAs) are short noncoding RNAs that exert posttranscriptional gene silencing and regulate gene expression. In addition to the hundreds of conserved cellular miRNAs that have been identified, miRNAs of viral origin have been isolated and found to modulate both the viral life cycle and the cellular transcriptome. Thus far, detection of virus-derived miRNAs has been largely limited to DNA viruses, suggesting that RNA viruses may be unable to exploit this aspect of transcriptional regulation. Lack of RNA virus-produced miRNAs has been attributed to the replicative constraints that would incur following RNase III processing of a genomic hairpin. To ascertain whether the generation of viral miRNAs is limited to DNA viruses, we investigated whether influenza virus could be designed to deliver functional miRNAs without affecting replication. Here, we describe a modified influenza A virus that expresses cellular microRNA-124 (miR-124). Insertion of the miR-124 hairpin into an intron of the nuclear export protein transcript resulted in endogenous processing and functional miR-124. We demonstrate that a viral RNA genome incorporating a hairpin does not result in segment instability or miRNA-mediated genomic targeting, thereby permitting the virus to produce a miRNA without having a negative impact on viral replication. This work demonstrates that RNA viruses can produce functional miRNAs and suggests that this level of transcriptional regulation may extend beyond DNA viruses.",
"title": "Engineered RNA viral synthesis of microRNAs."
},
{
"docid": "10024681",
"text": "Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.",
"title": "Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer"
},
{
"docid": "16550075",
"text": "BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1alpha and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.",
"title": "BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control."
},
{
"docid": "23581096",
"text": "The SRY gene on the mammalian Y chromosome undoubtedly acts to determine testis, but it is still quite unclear how. It was originally supposed that SRY acts directly to activate other genes in the testis-determining pathway. This paper presents an alternative hypothesis that SRY functions indirectly, by interacting with related genes SOX3 (from which SRY evolved) and SOX9 (which appears to be intimately involved in vertebrate gonad differentiation). Specifically, I propose that in females SOX3 inhibits SOX9 function, but in males, SRY inhibits SOX3 and permits SOX9 to enact its testis-determining role. This hypothesis makes testable predictions of the phenotypes of XX and XY individuals with deficiencies or overproduction of any of the three genes, and is able to account for the difficult cases of XX(SRY-) males and transdifferentiation in the absence of SRY. The hypothesis also suggests a way that the dominant SRY sex-determining system of present-day mammals may have evolved from an ancient system relying on SOX3 dosage.",
"title": "Interactions between SRY and SOX genes in mammalian sex determination."
},
{
"docid": "20028729",
"text": "Nuclear receptors regulate many biologically important processes in development and homeostasis by their bimodal function as repressors and activators of gene transcription. A finely tuned modulation of the transcriptional activities of nuclear receptors is crucial for determining highly specific and diversified programmes of gene expression. Recent studies have provided insights into the molecular mechanisms that are required to switch between repression and activation functions, the combinatorial roles of the multiple cofactor complexes that are required for mediating transcriptional regulation, and the central question of how several different signalling pathways can be integrated at the nuclear level to achieve specific profiles of gene expression.",
"title": "Controlling nuclear receptors: the circular logic of cofactor cycles"
},
{
"docid": "2000038",
"text": "MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression.",
"title": "MicroRNAs can generate thresholds in target gene expression"
},
{
"docid": "6455142",
"text": "Although regulation of histone methylation is believed to contribute to embryonic stem cell (ESC) self-renewal, the mechanisms remain obscure. We show here that the histone H3 trimethyl lysine 4 (H3K4me3) demethylase, KDM5B, is a downstream Nanog target and critical for ESC self-renewal. Although KDM5B is believed to function as a promoter-bound repressor, we find that it paradoxically functions as an activator of a gene network associated with self-renewal. ChIP-Seq reveals that KDM5B is predominantly targeted to intragenic regions and that it is recruited to H3K36me3 via an interaction with the chromodomain protein MRG15. Depletion of KDM5B or MRG15 increases intragenic H3K4me3, increases cryptic intragenic transcription, and inhibits transcriptional elongation of KDM5B target genes. We propose that KDM5B activates self-renewal-associated gene expression by repressing cryptic initiation and maintaining an H3K4me3 gradient important for productive transcriptional elongation.",
"title": "KDM5B regulates embryonic stem cell self-renewal and represses cryptic intragenic transcription."
},
{
"docid": "4434951",
"text": "BACKGROUND Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging \"clock\", a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 df/df mutation, calorie restriction and rapamycin. RESULTS In wild-type mice fed an unsupplemented ad libitum diet, age-associated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver function. Genes harbouring hypomethylated enhancers were enriched for genes that change expression with age. Hypermethylation was enriched at CpG islands marked with bivalent activating and repressing histone modifications and resembled hypermethylation in liver cancer. Age-associated methylation changes are suppressed in Ames dwarf and calorie restricted mice and more selectively and less specifically in rapamycin treated mice. CONCLUSIONS Age-associated hypo- and hypermethylation events occur at distinct regulatory features of the genome. Distinct longevity-promoting interventions, specifically genetic, dietary and drug interventions, suppress some age-associated methylation changes, consistent with the idea that these interventions exert their beneficial effects, in part, by modulation of the epigenome. This study is a foundation to understand the epigenetic contribution to healthy aging and longevity and the molecular basis of the DNA methylation clock.",
"title": "Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions"
},
{
"docid": "15058155",
"text": "EBI2, aka GPR183, is a G-couple receptor originally identified in 1993 as one of main genes induced in Burkitt's lymphoma cell line BL41 by Epstein-Barr virus (EBV) infection. After it was reported in 2009 that the receptor played a key role in regulating B cell migration and responses, we initiated an effort in looking for its endogenous ligand. In 2011 we and another group reported the identification of 7α, 25-dihydroxyxcholesterol (7α, 25-OHC), an oxysterol, as the likely physiological ligand of EBI2. A few subsequently published studies further elucidated how 7α, 25-OHC bound to EBI2, and how a gradient of 7α, 25-OHC could be generated in vivo and regulated migration, activation, and functions of B cells, T cells, dendritic cells (DCs), monocytes/macrophages, and astrocytes. The identification of 7α, 25-OHC as a G protein-coupled receptor ligand revealed a previously unknown signaling system of oxysterols, a class of molecules which exert profound biological functions. Dysregulation of the synthesis or functions of these molecules is believed to contribute to inflammation and autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, cancer as well as metabolic diseases such as diabetes, obesity, and dyslipidemia. Therefore EBI2 may represent a promising target for therapeutic interventions for human diseases.",
"title": "7α, 25-dihydroxycholesterol-mediated activation of EBI2 in immune regulation and diseases"
},
{
"docid": "21487212",
"text": "Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.",
"title": "Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting."
},
{
"docid": "9159495",
"text": "Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline.",
"title": "A microRNA feedback loop regulates global microRNA abundance during aging."
},
{
"docid": "37204802",
"text": "Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an α-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53 hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its negative regulator MDMX, and represses transcriptional activity of p53. Depletion of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase, promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell proliferation and tumorigenesis in vivo, and significantly, the expression of JMJD6 is markedly up-regulated in various types of human cancer especially in colon cancer, and high nuclear JMJD6 protein is strongly correlated with aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a novel posttranslational modification for p53 and support the pursuit of JMJD6 as a potential biomarker for colon cancer aggressiveness and a potential target for colon cancer intervention.",
"title": "JMJD6 Promotes Colon Carcinogenesis through Negative Regulation of p53 by Hydroxylation"
},
{
"docid": "14380875",
"text": "Glucocorticoids repress NFkappaB-mediated activation of proinflammatory genes such as interleukin-8 (IL-8) and ICAM-1. Our experiments suggest that the glucocorticoid receptor (GR) confers this effect by associating through protein-protein interactions with NFkappaB bound at each of these genes. That is, we show that the GR zinc binding region (ZBR), which includes the DNA binding and dimerization functions of the receptor, binds directly to the dimerization domain of the RelA subunit of NFkappaB in vitro and that the ZBR is sufficient to associate with RelA bound at NFkappaB response elements in vivo. Moreover, we demonstrate in vivo and in vitro that GR does not disrupt DNA binding by NFkappaB. In transient transfections, we found that the GR ligand binding domain is essential for repression of NFkappaB but not for association with it and that GR can repress an NFkappaB derivative bearing a heterologous activation domain. We used chromatin immunoprecipitation assays in untransfected A549 cells to infer the mechanism by which the tethered GR represses NFkappaB-activated transcription. As expected, we found that the inflammatory signal TNFalpha stimulated preinitiation complex (PIC) assembly at the IL-8 and ICAM-1 promoters and that the largest subunit of RNA polymerase II (pol II) in those complexes became phosphorylated at serines 2 and 5 in its carboxy-terminal domain (CTD) heptapeptide repeats (YSPTSPS); these modifications are required for transcription initiation. Remarkably, GR did not inhibit PIC assembly under repressing conditions, but rather interfered with phosphorylation of serine 2 of the pol II CTD.",
"title": "The Glucocorticoid Receptor Inhibits"
},
{
"docid": "43156471",
"text": "We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast (Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 (class III) and Hos2 (class I) have a role in preventing histone loss; Clr6 (class I) is the principal enzyme in promoter-localized repression. Hos2 has an unexpected role in promoting high expression of growth-related genes by deacetylating H4K16Ac in their open reading frames. Clr3 (class II) acts cooperatively with Sir2 throughout the genome, including the silent regions: rDNA, centromeres, mat2/3 and telomeres. The most significant acetylation sites are H3K14Ac for Clr3 and H3K9Ac for Sir2 at their genomic targets. Clr3 also affects subtelomeric regions which contain clustered stress- and meiosis-induced genes. Thus, this combined genomic approach has uncovered different roles for fission yeast HDACs at the silent regions in repression and activation of gene expression.",
"title": "Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast."
},
{
"docid": "13777706",
"text": "Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism.",
"title": "Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs"
},
{
"docid": "18358026",
"text": "Cancer cells simultaneously harbor global losses and gains in DNA methylation. We demonstrate that inducing cellular oxidative stress by hydrogen peroxide treatment recruits DNA methyltransferase 1 (DNMT1) to damaged chromatin. DNMT1 becomes part of a complex(es) containing DNMT3B and members of the polycomb repressive complex 4. Hydrogen peroxide treatment causes relocalization of these proteins from non-GC-rich to GC-rich areas. Key components are similarly enriched at gene promoters in an in vivo colitis model. Although high-expression genes enriched for members of the complex have histone mark and nascent transcription changes, CpG island-containing low-expression genes gain promoter DNA methylation. Thus, oxidative damage induces formation and relocalization of a silencing complex that may explain cancer-specific aberrant DNA methylation and transcriptional silencing.",
"title": "Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands."
},
{
"docid": "9752604",
"text": "In light of the emerging interplay between redox and metabolic signaling pathways we investigated the potential cross talk between nuclear factor E2-related factor 2 (Nrf2) and AMP-activated kinase (AMPK), central regulators of the cellular redox and energy balance, respectively. Making use of xanthohumol (XN) as an activator of both the AMPK and the Nrf2 signaling pathway we show that AMPK exerts a positive influence on Nrf2/heme oxygenase (HO)-1 signaling in mouse embryonic fibroblasts. Genetic ablation and pharmacological inhibition of AMPK blunts Nrf2-dependent HO-1 expression by XN already at the mRNA level. XN leads to AMPK activation via interference with mitochondrial function and activation of liver kinase B1 as upstream AMPK kinase. The subsequent AMPK-mediated enhancement of the Nrf2/HO-1 response does not depend on inhibition of the mammalian target of rapamycin, inhibition of glycogen synthase kinase 3β, or altered abundance of Nrf2 (total and nuclear). However, reduced endoplasmic reticulum stress was identified and elaborated as a step in the AMPK-augmented Nrf2/HO-1 response. Overall, we shed more light on the hitherto incompletely understood cross talk between the LKB1/AMPK and the Nrf2/HO-1 axis revealing for the first time involvement of the unfolded protein response as an additional player and suggesting tight cooperation between signaling pathways controlling cellular redox, energy, or protein homeostasis.",
"title": "Activated AMPK boosts the Nrf2/HO-1 signaling axis—A role for the unfolded protein response"
},
{
"docid": "4455466",
"text": "Recognition of modified histones by ‘reader’ proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific ‘Ser 31’ residue in a composite pocket formed by the tandem bromo–PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression.",
"title": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression"
},
{
"docid": "7645565",
"text": "Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC).",
"title": "Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6"
},
{
"docid": "18882947",
"text": "The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1(-/-) mice have previously been characterized and show developmental blocks at the CD4-CD8- double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1(-/-) mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1(-/-) mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and loss of Tcf1 functionally act as collaborating oncogenic events. Tcf1 deficiency predisposes to the development of thymic lymphomas by ectopic up-regulation of Lef1 due to lack of Tcf1 repressive isoforms and frequently by cooperating activating mutations in Notch1. Tcf1 therefore functions as a T-cell-specific tumor suppressor gene, besides its established role as a Wnt responsive transcription factor. Thus, Tcf1 acts as a molecular switch between proliferative and repressive signals during T-lymphocyte development in the thymus.",
"title": "The Nuclear Effector of Wnt-Signaling, Tcf1, Functions as a T-Cell–Specific Tumor Suppressor for Development of Lymphomas"
},
{
"docid": "23356816",
"text": "The mammalian A-type cyclin family consists of two members, cyclin A1 (encoded by Ccna1) and cyclin A2 (encoded by Ccna2). Cyclin A2 promotes both G1/S and G2/M transitions, and targeted deletion of Ccna2 in mouse is embryonic lethal. Cyclin A1 is expressed in mice exclusively in the germ cell lineage and is expressed in humans at highest levels in the testis and certain myeloid leukaemia cells. To investigate the role of cyclin A1 and possible redundancy among the cyclins in vivo, we generated mice bearing a null mutation of Ccna1. Ccna1-/- males were sterile due to a block of spermatogenesis before the first meiotic division, whereas females were normal. Meiosis arrest in Ccna1–/– males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase. Cyclin A1 is therefore essential for spermatocyte passage into the first meiotic division in male mice, a function that cannot be complemented by the concurrently expressed B-type cyclins.",
"title": "Cyclin A1 is required for meiosis in the male mouse"
},
{
"docid": "8909176",
"text": "Maltose metabolism of baker's yeast (Saccharomyces cerevisiae) in lean dough is negatively influenced by glucose repression, thereby delaying the dough fermentation. To improve maltose metabolism and leavening ability, it is necessary to alleviate glucose repression. The Snf1 protein kinase is well known to be essential for the response to glucose repression and required for transcription of glucose-repressed genes including the maltose-utilization genes (MAL). In this study, the SNF1 overexpression and deletion industrial baker's yeast strains were constructed and characterized in terms of maltose utilization, growth and fermentation characteristics, mRNA levels of MAL genes (MAL62 encoding the maltase and MAL61 encoding the maltose permease) and maltase and maltose permease activities. Our results suggest that overexpression of SNF1 was effective to glucose derepression for enhancing MAL expression levels and enzymes (maltase and maltose permease) activities. These enhancements could result in an 18% increase in maltose metabolism of industrial baker's yeast in LSMLD medium (the low sugar model liquid dough fermentation medium) containing glucose and maltose and a 15% increase in leavening ability in lean dough. These findings provide a valuable insight of breeding industrial baker's yeast for rapid fermentation.",
"title": "Effects of SNF1 on Maltose Metabolism and Leavening Ability of Baker's Yeast in Lean Dough."
},
{
"docid": "8331432",
"text": "The transcription factor HNF3 and linker histones H1 and H5 possess winged-helix DNA-binding domains, yet HNF3 and other fork head-related proteins activate genes during development whereas linker histones compact DNA in chromatin and repress gene expression. We compared how the two classes of factors interact with chromatin templates and found that HNF3 binds DNA at the side of nucleosome cores, similarly to what has been reported for linker histone. A nucleosome structural binding site for HNF3 is occupied at the albumin transcriptional enhancer in active and potentially active chromatin, but not in inactive chromatin in vivo. While wild-type HNF3 protein does not compact DNA extending from the nucleosome, as does linker histone, site-directed mutants of HNF3 can compact nucleosomal DNA if they contain basic amino acids at positions previously shown to be essential for nucleosomal DNA compaction by linker histones. The results illustrate how transcription factors can possess special nucleosome-binding activities that are not predicted from studies of factor interactions with free DNA.",
"title": "Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome."
},
{
"docid": "12652963",
"text": "MicroRNAs (miRNAs) are ∼22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels.",
"title": "miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA."
},
{
"docid": "37438296",
"text": "Age-dependent decline in skeletal muscle function leads to several inherited and acquired muscular disorders in elderly individuals. The levels of microRNAs (miRNAs) could be altered during muscle maintenance and repair. We therefore performed a comprehensive investigation for miRNAs from five different periods of bovine skeletal muscle development using next-generation small RNA sequencing. In total, 511 miRNAs, including one putatively novel miRNA, were identified. Thirty-six miRNAs were differentially expressed between prenatal and postnatal stages of muscle development including several myomiRs (miR-1, miR-206 and let-7 families). Compared with miRNA expression between different muscle tissues, 14 miRNAs were up-regulated and 22 miRNAs were down-regulated in the muscle of postnatal stage. In addition, a novel miRNA was predicted and submitted to the miRBase database as bta-mir-10020. A dual luciferase reporter assay was used to demonstrate that bta-mir-10020 directly targeted the 3'-UTR of the bovine ANGPT1 gene. The overexpression of bta-mir-10020 significantly decreased the DsRed fluorescence in the wild-type expression cassette compared to the mutant type. Using three computational approaches - miranda, pita and rnahybrid - these differentially expressed miRNAs were also predicted to target 3609 bovine genes. Disease and biological function analyses and the KEGG pathway analysis revealed that these targets were statistically enriched in functionality for muscle growth and disease. Our miRNA expression analysis findings from different states of muscle development and aging significantly expand the repertoire of bovine miRNAs now shown to be expressed in muscle and could contribute to further studies on growth and developmental disorders in this tissue type.",
"title": "Altered microRNA expression in bovine skeletal muscle with age."
},
{
"docid": "27949347",
"text": "TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?",
"title": "Putting p53 in Context"
},
{
"docid": "31882215",
"text": "We describe robust induction of autophagy during the reprogramming of mouse fibroblasts to induced pluripotent stem cells by four reprogramming factors (Sox2, Oct4, Klf4 and c-Myc), henceforth 4F. This process occurs independently of p53 activation, and is mediated by the synergistic downregulation of mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy-related genes. The 4F coordinately repress mTORC1, but bifurcate in their regulation of autophagy-related genes, with Klf4 and c-Myc inducing them but Sox2 and Oct4 inhibiting them. On one hand, inhibition of mTORC1 facilitates reprogramming by promoting cell reshaping (mitochondrial remodelling and cell size reduction). On the other hand, mTORC1 paradoxically impairs reprogramming by triggering autophagy. Autophagy does not participate in cell reshaping in reprogramming but instead degrades p62, whose accumulation in autophagy-deficient cells facilitates reprogramming. Our results thus reveal a complex signalling network involving mTORC1 inhibition and autophagy induction in the early phase of reprogramming, whose delicate balance ultimately determines reprogramming efficiency.",
"title": "Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming"
}
] |
7132
|
When buying a call option, is the financial stability of the option writer relevant?
|
[
{
"docid": "376136",
"text": "In the case of regulated, exchange-traded options, the writer of an options contract is obliged to maintain a margin with their broker, and the broker is obliged to maintain a margin with the clearing house. (Institutional writers of options will deal directly with the clearing house.) In the event that the writer is unable to make a daily margin call, the broker (or clearing house) may automatically close out (all of) their positions using existing margin held. If there was a shortfall, the broker (or clearing house) would be left to persue the client (writer) to make good on their obligations. None of this effects the position of the original buyer of the options contract. Effectively, the buyer's counterparty is their broker's clearing house account.",
"title": ""
},
{
"docid": "31587",
"text": "Exchange traded options are issued in a way that there is no counter party risk. Consider, stocks and options are held in street name. So, for example, if I am short and you are long shares, no matter what happens on my end, your shares are yours. To be complete, it's possible to enter into a direct deal, where you have a contract for some non-standard option, but that would be very rare for the average investor.",
"title": ""
}
] |
[
{
"docid": "507828",
"text": "\"I'm adding to @Dilip's basic answer, to cover the additional points in your question. I'll assume you are referring to publicly traded stock options, such as those found on the CBOE, and not an option contract entered into privately between two specific counterparties (e.g. as in an employer stock option plan). Since you are not obligated to exercise a call option you purchased on the market, you don't need to maintain funds on account for possible exercising. You could instead let the option expire, or resell the option, neither of which requires funds available for purchase of the underlying shares. However, should you actually choose to exercise the call option (and usually this is done close to expiration, if at all), you will be required to fund your account much like if you bought the underlying shares in the first place. Call your broker to determine the exact rules and timing for when they need the money for a call-option exercise. And to expand on the idea of \"\"cancelling\"\" an option you purchased: No, you cannot \"\"cancel\"\" an option contract, per se. But, you are permitted to sell the call option to somebody else willing to buy, via the market. When you sell your call option, you'll either make or lose money on the sale – depending on the price of the underlying shares at the time (are they in- or out- of the money?), volatility in the market, and remaining time value. Once you sell, you're back to \"\"no position\"\". That's not the same as \"\"cancelled\"\", but you are out of the trade, whether at profit or loss. Furthermore, the option writer (i.e. the seller who \"\"sold to open\"\" a position, in writing the call in the first place) is also not permitted to cancel the option he wrote. However, the option writer is permitted to close out the original short position by simply buying back a matching call option on the market. Again, this would occur at either profit or loss based on market prices at the time. This second kind of buy order – i.e. made by someone who initially wrote a call option – is called a \"\"buy to close\"\", meaning the purchase of an offsetting position. (The other kind of buy is the \"\"buy to open\"\".) Then, consider: Since an option buyer is free to re-sell the option purchased, and since an option writer (who \"\"sold to open\"\" the new contract) is also free to buy back an offsetting option, a process known as clearing is required to match remaining buyers exercising the call options held with the remaining option writers having open short positions for the contract. For CBOE options, this clearing is performed by the Options Clearing Corporation. Here's how it works (see here): What is the OCC? The Options Clearing Corporation is the sole issuer of all securities options listed at the CBOE, four other U.S. stock exchanges and the National Association of Securities Dealers, Inc. (NASD), and is the entity through which all CBOE option transactions are ultimately cleared. As the issuer of all options, OCC essentially takes the opposite side of every option traded. Because OCC basically becomes the buyer for every seller and the seller for every buyer, it allows options traders to buy and sell in a secondary market without having to find the original opposite party. [...] [emphasis above is mine] When a call option writer must deliver shares to a call option buyer exercising a call, it's called assignment. (I have been assigned before, and it isn't pleasant to see a position called away that otherwise would have been very profitable if the call weren't written in the first place!) Also, re: \"\"I know my counter party cannot sell his shares\"\" ... that's not strictly true. You are thinking of a covered call. But, an option writer doesn't necessarily need to own the underlying shares. Look up Naked call (Wikipedia). Naked calls aren't frequently undertaken because a naked call \"\"is one of the riskiest options strategies because it carries unlimited risk\"\". The average individual trader isn't usually permitted by their broker to enter such an order, but there are market participants who can do such a trade. Finally, you can learn more about options at The Options Industry Council (OIC).\"",
"title": ""
},
{
"docid": "134752",
"text": "You appear to be thinking of option writers as if they were individuals with small, nondiversified, holdings and a particular view on what the underlying is going to do. This is not the best way to think about them. Option writers are typically large institutions with large portfolios and that provide services in all sorts of different areas. At the same time as they are writing calls on a particular stock, they are writing puts on it and options on other stocks. They are buying and selling the underlying and all kinds of different derivatives. They are not necessarily writing the option because they are expecting or hoping to benefit from a price move. It's just small part of their business. They write the option if the option price is good enough that they think they are selling it for very slightly more than it's worth. Asking why an option writer creates a call is like asking why a grocery store keeps buying groceries from their distributors. Don't they know the price of food may not always rise? Sure, but their business is selling the food for slightly more than they pay for it, not speculating on what will happen to its price. Most option writers are doing the same thing, except what they are buying and selling is sets of cash flows and risk. As a general rule, the business model of option writers is to profit from the few cents of spread or mispricing, not from aggregate changes in the price of the underlying. They should and often do maintain balanced portfolios so their option writing activities don't expose them to a lot of risk. Also note that there could be lots of reasons for writing options, even if you do have a particular view. For example, perhaps the option writer thinks volatility of the underlying will decrease. Writing a call could be part of an overall strategy that profits from this view.",
"title": ""
},
{
"docid": "557356",
"text": "\"There are two reasons why most options aren't exercised. The first is obvious, and the second, less so. The obvious: An option that's practically worthless doesn't get exercised. Options that reach expiry and remain unexercised are almost always worthless bets that simply didn't pay off. This includes calls with strikes above the current underlying price, and puts with strikes below it. A heck of a lot of options. If an option with value was somehow left to expire, it was probably a mistake, or else the transaction costs outweighed the value remaining; not quite worthless, but not \"\"worth it\"\" either. The less obvious: An option with value can be cancelled any time before expiration. A trader that buys an option may at some point show a gain sooner than anticipated, or a loss in excess of his tolerance. If a gain, he may want to sell before expiry to realize the gain sooner. Similarly, if a loss, he may want to take the loss sooner. In both cases, his capital is freed up and he can take another position. And — this is the key part — the other end matched up with that option sale is often a buyer that had created (written) exactly such an option contract in the first place – the option writer – and who is looking to get out of his position. Option writers are the traders responsible, in the first place, for creating options and increasing the \"\"open interest.\"\" Anybody with the right kind and level of options trading account can do this. A trader that writes an option does so by instructing his broker to \"\"sell to open\"\" a new instance of the option. The trader then has a short position (negative quantity) in that option, and all the while may be subject to the obligations that match the option's exercise rights. The only way for the option writer to get out of that short position and its obligations are these: Not by choice: To get assigned. That is to say: a buyer exercised the option. The writer has to fulfill his obligation by delivering the underlying (if a call) to the option holder, or buying the underlying (if a put) from the option holder. Not by choice: The option expires worthless. This is the ideal scenario for a writer because 100% of the premium received (less transaction costs) is profit. By choice: The writer is free to buy back exactly the same kind of option before expiry using a \"\"buy to close\"\" order with their broker. Once the option has been purchased with a \"\"buy to close\"\", it eliminates the short position and obligation. The option is cancelled. The open interest declines. Options thus cancelled just don't live long enough to either expire or be exercised.\"",
"title": ""
},
{
"docid": "512310",
"text": "Think of options as insurance. An insurance company makes money by selling the policies at a rate slightly higher than the average payout. Most options expire worthless. This is because most options are purchased by hedge funds. To 'hedge' means taking out insurance in case your position goes against you. So the sellers of options obtain a price that covers their (averaged) losses plus provides them with a profit for their trouble. An option has an amount that it declines in value each day (called theta). At the expiration date the option is worth zero (if it is out-of-the-money). So it is option writers that, typically, make money in the options market (as they are the sellers of insurance). If they didn't make money selling options they would not sell them. For example, the February call option on SPY strike 200 traded at 8.81 on 12/30. Since then it has crumbled in value to 0.14. The option writer currently stands to make a huge profit. So, just as with insurance, you (generally) never make money by buying insurance. But the sellers of insurance tend to make money as do the writers of options. Edit: Theta @ Investopedia",
"title": ""
},
{
"docid": "46291",
"text": "Think of it this way: 1) You buy 1k in call options that will let you buy 100k of stock when they expire in the money in a year. 2) You take the 99k you would have spent on the stock and invest it in a risk free savings account. 3) Assume the person who sold you the call, immediately hedges the position by buying 100k of stock to deliver when the options expire. The amount of money you could make on risk free interest needs to be comparable to the premium you paid the option writer for tying up their capital, or they wouldn't have made the trade. So higher risk free rates would mean a higher call price. NOTE: The numbers are not equal because of the risk in writing the option, but they will move the same direction.",
"title": ""
},
{
"docid": "238474",
"text": "If it helps you to think about it, long is equivalent to betting for the upside and short is equivalent to betting for the downside. If you are long on options, then you expect the value of such options to increase. If you are long an option, then you own the option. If you are short an option, then generally you sold the option. Someone who is short a call (sometimes called the writer or occasionally the issuer) has sold a call option to someone who is now long a call. Buying a call option that will increase in value is itself a form of investment, just as it's investment to buy stock or other instruments hoping they will appreciate in value. An option's value will rise or fall with the underlying, so being long an option is a way to be long in the underlying. Someone can be long in a stock by buying the stock, or long in a call by buying call options in the stock. The long call generally requires less initial investment than buying the underlying, and lets the option-holder avoid the asset downside during the option term. The risk is that the asset may not appreciate to the point that the call option will pay off. In the conceptual sense, a share of stock is a particular right to the profits and assets of a corporation, both in form of dividends and in liquidation. An option is a particular right to the the share of stock. It's just a further way to formalize and subdivide the various property rights that exist in a corporation. If you can buy a piece of paper with particular rights to corporate profits and assets, then you can buy another piece of paper with particular rights to the former piece of paper.",
"title": ""
},
{
"docid": "119976",
"text": "\"One alternative strategy you may want to consider is writing covered calls on the stock you have \"\"just sitting there\"\". This will allow you to earn a return (the premium from the calls) without necessarily having to give up your holding. As a brief overview, \"\"options\"\" are derivatives that give the holder the right (or option) to buy or sell shares at a specified price. Holders of call options with a strike prike $x on a particular security have the right to purchase that security at the strike price $x. Conversely, holders of put options with a strike price of $x have the right to sell that security at the strike price $x. Always on the other side of a call or put option is a person that has sold the option, which is called \"\"writing\"\" the option. If this person writes a call option, then he will be obligated to sell a certain amount of stock (100 shares per contract) at the strike price if that option is exercised. A writer of a put option will be obligated to by 100 shares per contract at the strike price if that option is exercised. Covered calls involve writing call contracts on stock that you own. For example, say you own 100 shares of AAPL, and that AAPL is currently trading for $330. You decide to write a Jan 21, 2012 call on these shares at a strike price of $340, earning you a premium of say $300. Two things can now happen: if the price of AAPL is not at least $340 on January 21, then the options are \"\"out of the money\"\" and will expire unexercised (why exercise an option to buy at $340 when you can buy at the currently cheaper market price?). You keep your AAPL stock plus the $300 premium you earn. If, however, the price of AAPL is greater than $340, the option will be exercised and you will now be required to sell the shares you own at $340. You will earn a return of $10/share ($340-$330), plus the $300 premium from the call option. You still make out in the end, but have unfortunately incurred an opportunity cost, as had you not written the call option you would have been able to sell at the market price, which is higher than the $340 strike price. Covered calls are considered relatively safe and conservative, however the strategy is most effective for stocks that are expected to stay within a relatively narrow price range for the duration of the contract. They do provide one option of earning additional money on stocks you are currently holding, albeit at the risk of giving up some returns if the stock price rises above the strike price.\"",
"title": ""
},
{
"docid": "349974",
"text": "\"It will be helpful to establish some definitions: Long \"\"Long\"\" is financial slang for \"\"to have possession of an asset\"\", legally, and \"\"to debit an asset\"\", financially. Short \"\"Short\"\" is financial slang for \"\"to be liable for an asset\"\", legally, and \"\"to credit an asset\"\", financially. Option \"\"Option\"\" is financial slang for \"\"to have the right but not obligation to force the liable to perform action\"\", legally. Without limits and when taken to absurdity, this can mean slavery. For equities, this means \"\"to have the right but not the obligation to force the liable to buy/sell a specified asset at a specified price with a specified expiration for that right\"\" for a call/put, respectively. By the above, a call option is \"\"the right but not the obligation to force the liable to buy a specified asset at a specified price with a specified expiration for that right\"\". By the definition of \"\"long\"\" above, a call option is actually not long the underlying. By the definitions above and with a narrower scope applied to equities & indexes, to be \"\"long\"\" the call means \"\"to have the right but not the obligation to force the liable to buy a specified asset at a specified price with a specified expiration for that right\"\" while to be \"\"short\"\" the call means \"\"to have the obligation to be forced to sell a specified asset at a specified price with a specified expiration for that right\"\". So, to be \"\"long\"\" a call means to simply own the call.\"",
"title": ""
},
{
"docid": "277359",
"text": "Think about it this way. If the strike price is $200, and cost of the option is $0.05. $200 + $0.05 is $200.05. That does not mean that the price of buying the option is more. Neither is the option writer going to pay you $70 to buy the contract. When you are buying options, you can only have a limited downside and that is the premium that you pay for it. In case of the $115 contract, your total loss could be a maximum of $19.3. In case of the $130 contract, your total loss could be a maximum of $9.3. This is due to the fact that the chances of AAPL going to hit $130 is less than the chance of AAPL hitting $115. Therefore, option writers offer the lower probability contracts at a lower price. Long story short, you do not pay for the Strike price. You only pay the premium and that premium keeps getting lower with and increase in Strike price(Or decrease if it is a put option). Strike price is just a number that you expect the stock or index to break. I would suggest you to read up a little more on pricing from here",
"title": ""
},
{
"docid": "193303",
"text": "The value of an option has 2 components, the extrinsic or time value element and the intrinsic value from the difference in the strike price and the underlying asset price. With either an American or European option the intrinsic value of a call option can be 'locked in' any time by selling the same amount of the underlying asset (whether that be a stock, a future etc). Further, the time value of any option can be monitised by delta hedging the option, i.e. buying or selling an amount of the underlying asset weighted by the measure of certainty (delta) of the option being in the money at expiry. Instead, the extra value of the American option comes from the financial benefit of being able to realise the value of the underlying asset early. For a dividend paying stock this will predominantly be the dividend. But for non-dividend paying stocks or futures, the buyer of an in-the-money option can realise their intrinsic gains on the option early and earn interest on the profits today. But what they sacrifice is the timevalue of the option. However when an option becomes very in the money and the delta approaches 1 or -1, the discounting of the intrinsic value (i.e. the extra amount a future cash flow is worth each day as we draw closer to payment) becomes larger than the 'theta' or time value decay of the option. Then it becomes optimal to early exercise, abandon the optionality and realise the monetary gains upfront. For a non-dividend paying stock, the value of the American call option is actually the same as the European. The spot price of the stock will be lower than the forward price at expiry discounted by the risk free rate (or your cost of funding). This will exactly offset the monetary gain by exercising early and banking the proceeds. However for an option on a future, the value today of the underlying asset (the future) is the same as at expiry and its possible to fully realise the interest earned on the money received today. Hence the American call option is worth more. For both examples the American put option is worth more, slightly more so for the stock. As the stock's spot price is lower than the forward price, the owner of the put option realises a higher (undiscounted) intrinsic profit from selling the stock at the higher strike price today than waiting till expiry, as well as realising the interest earned. Liquidity may influence the perceived value of being able to exercise early but its not a tangible factor that is added to the commonly used maths of the option valuation, and isn't really a consideration for most of the assets that have tradeable option markets. It's also important to remember at any point in the life of the option, you don't know the future price path. You're only modelling the distribution of probable outcomes. What subsequently happens after you early exercise an American option no longer has any bearing on its value; this is now zero! Whether the stock subsequently crashes in price is irrelevent. What is relevant is that when you early exercise a call you 'give up' all potential upside protected by the limit to your downside from the strike price.",
"title": ""
},
{
"docid": "519781",
"text": "\"When the buyout happens, the $30 strike is worth $10, as it's in the money, you get $10 ($1000 per contract). Yes, the $40 strike is pretty worthless, it actually dropped in value today. Some deals are worded as an offer or intention, so a new offer can come in. This appears to be a done deal. From Chapter 8 of CHARACTERISTICS AND RISKS OF STANDARDIZED OPTIONS - FEB 1994 with supplemental updates 1997 through 2012; \"\"In certain unusual circumstances, it might not be possible for uncovered call writers of physical delivery stock and stock index options to obtain the underlying equity securities in order to meet their settlement obligations following exercise. This could happen, for example, in the event of a successful tender offer for all or substantially all of the outstanding shares of an underlying security or if trading in an underlying security were enjoined or suspended. In situations of that type, OCC may impose special exercise settlement procedures. These special procedures, applicable only to calls and only when an assigned writer is unable to obtain the underlying security, may involve the suspension of the settlement obligations of the holder and writer and/or the fixing of cash settlement prices in lieu of delivery of the underlying security. In such circumstances, OCC might also prohibit the exercise of puts by holders who would be unable to deliver the underlying security on the exercise settlement date. When special exercise settlement procedures are imposed, OCC will announce to its Clearing Members how settlements are to be handled. Investors may obtain that information from their brokerage firms.\"\" I believe this confirms my observation. Happy to discuss if a reader feels otherwise.\"",
"title": ""
},
{
"docid": "573077",
"text": "\"Being \"\"Long\"\" something means you own it. Being \"\"Short\"\" something means you have created an obligation that you have sold to someone else. If I am long 100 shares of MSFT, that means that I possess 100 shares of MSFT. If I am short 100 shares of MSFT, that means that my broker let me borrow 100 shares of MSFT, and I chose to sell them. While I am short 100 shares of MSFT, I owe 100 shares of MSFT to my broker whenever he demands them back. Until he demands them back, I owe interest on the value of those 100 shares. You short a stock when you feel it is about to drop in price. The idea there is that if MSFT is at $50 and I short it, I borrow 100 shares from my broker and sell for $5000. If MSFT falls to $48 the next day, I buy back the 100 shares and give them back to my broker. I pocket the difference ($50 - $48 = $2/share x 100 shares = $200), minus interest owed. Call and Put options. People manage the risk of owning a stock or speculate on the future move of a stock by buying and selling calls and puts. Call and Put options have 3 important components. The stock symbol they are actionable against (MSFT in this case), the \"\"strike price\"\" - $52 in this case, and an expiration, June. If you buy a MSFT June $52 Call, you are buying the right to purchase MSFT stock before June options expiration (3rd Saturday of the month). They are priced per share (let's say this one cost $0.10/share), and sold in 100 share blocks called a \"\"contract\"\". If you buy 1 MSFT June $52 call in this scenario, it would cost you 100 shares x $0.10/share = $10. If you own this call and the stock spikes to $56 before June, you may exercise your right to purchase this stock (for $52), then immediately sell the stock (at the current price of $56) for a profit of $4 / share ($400 in this case), minus commissions. This is an overly simplified view of this transaction, as this rarely happens, but I have explained it so you understand the value of the option. Typically the exercise of the option is not used, but the option is sold to another party for an equivalent value. You can also sell a Call. Let's say you own 100 shares of MSFT and you would like to make an extra $0.10 a share because you DON'T think the stock price will be up to $52/share by the end of June. So you go to your online brokerage and sell one contract, and receive the $0.10 premium per share, being $10. If the end of June comes and nobody exercises the option you sold, you get to keep the $10 as pure profit (minus commission)! If they do exercise their option, your broker makes you sell your 100 shares of MSFT to that party for the $52 price. If the stock shot up to $56, you don't get to gain from that price move, as you have already committed to selling it to somebody at the $52 price. Again, this exercise scenario is overly simplified, but you should understand the process. A Put is the opposite of a Call. If you own 100 shares of MSFT, and you fear a fall in price, you may buy a PUT with a strike price at your threshold of pain. You might buy a $48 June MSFT Put because you fear the stock falling before June. If the stock does fall below the $48, you are guaranteed that somebody will buy yours at $48, limiting your loss. You will have paid a premium for this right (maybe $0.52/share for example). If the stock never gets down to $48 at the end of June, your option to sell is then worthless, as who would sell their stock at $48 when the market will pay you more? Owning a Put can be treated like owning insurance on the stock from a loss in stock price. Alternatively, if you think there is no way possible it will get down to $48 before the end of June, you may SELL a $48 MSFT June Put. HOWEVER, if the stock does dip down below $48, somebody will exercise their option and force you to buy their stock for $48. Imagine a scenario that MSFT drops to $30 on some drastically terrible news. While everybody else may buy the stock at $30, you are obligated to buy shares for $48. Not good! When you sold the option, somebody paid you a premium for buying that right from you. Often times you will always keep this premium. Sometimes though, you will have to buy a stock at a steep price compared to market. Now options strategies are combinations of buying and selling calls and puts on the same stock. Example -- I could buy a $52 MSFT June Call, and sell a $55 MSFT June Call. I would pay money for the $52 Call that I am long, and receive money for the $55 Call that I am short. The money I receive from the short $55 Call helps offset the cost of buying the $52 Call. If the stock were to go up, I would enjoy the profit within in $52-$55 range, essentially, maxing out my profit at $3/share - what the long/short call spread cost me. There are dozens of strategies of mixing and matching long and short calls and puts depending on what you expect the stock to do, and what you want to profit or protect yourself from. A derivative is any financial device that is derived from some other factor. Options are one of the most simple types of derivatives. The value of the option is derived from the real stock price. Bingo? That's a derivative. Lotto? That is also a derivative. Power companies buy weather derivatives to hedge their energy requirements. There are people selling derivatives based on the number of sunny days in Omaha. Remember those calls and puts on stock prices? There are people that sell calls and puts based on the number of sunny days in Omaha. Sounds kind of ridiculous -- but now imagine that you are a solar power company that gets \"\"free\"\" electricity from the sun and they sell that to their customers. On cloudy days, the solar power company is still on the hook to provide energy to their customers, but they must buy it from a more expensive source. If they own the \"\"Sunny Days in Omaha\"\" derivative, they can make money for every cloudy day over the annual average, thus, hedging their obligation for providing more expensive electricity on cloudy days. For that derivative to work, somebody in the derivative market puts a price on what he believes the odds are of too many cloudy days happening, and somebody who wants to protect his interests from an over abundance of cloudy days purchases this derivative. The energy company buying this derivative has a known cost for the cost of the derivative and works this into their business model. Knowing that they will be compensated for any excessive cloudy days allows them to stabilize their pricing and reduce their risk. The person selling the derivative profits if the number of sunny days is higher than average. The people selling these types of derivatives study the weather in order to make their offers appropriately. This particular example is a fictitious one (I don't believe there is a derivative called \"\"Sunny days in Omaha\"\"), but the concept is real, and the derivatives are based on anything from sunny days, to BLS unemployment statistics, to the apartment vacancy rate of NYC, to the cost of a gallon of milk in Maine. For every situation, somebody is looking to protect themselves from something, and somebody else believes they can profit from it. Now these examples are highly simplified, many derivatives are highly technical, comprised of multiple indicators as a part of its risk profile, and extremely difficult to explain. These things might sound ridiculous, but if you ran a lemonade stand in Omaha, that sunny days derivative just might be your best friend...\"",
"title": ""
},
{
"docid": "594303",
"text": "Options, both puts and calls, are typically written/sold at different strike prices. For example, even though the stock of XYZ is currently trading at $12.50, there could be put options for prices ranging from $0.50 to $30.00, just as an example. There are several factors that go into determining the strike prices at which people are willing to write options. The writer/seller of an option is the person on the other side of the trade that has the opposite opinion of you. If you are interested in purchasing a put on a stock to hedge your downside, that means the writer/seller of the put is betting that you are wrong and that the stock price will rise instead.",
"title": ""
},
{
"docid": "201794",
"text": "Suppose you're writing a put with a strike price of 80. Say the share's(underlying asset) price goes down to 70. So the holder of the put will exercise the option. Ie he has a 'right to sell' a share worth 70 for rs 80. Whereas a put option writer has an 'obligation to buy' at rs 80 a share trading at rs 70. Always think from the perspective of the holder. If the holder exercises the option, the writer will suffer a loss. Maximum loss he suffers will be the break even FSP, which is Strike price reduced by the premium paid.. If he doesn't exercise the option the writer will make a profit, which can maximum be the put premium received.",
"title": ""
},
{
"docid": "22916",
"text": "On expiry, with the underlying share price at $46, we have : You ask : How come they substract 600-100. Why ? Because you have sold the $45 call to open you position, you must now buy it back to close your position. This will cost you $100, so you are debited for $100 and this debit is being represented as a negative (subtracted); i.e., -$100 Because you have purchased the $40 call to open your position, you must now sell it to close your position. Upon selling this option you will receive $600, so you are credited with $600 and this credit is represented as a positive (added) ; i.e., +$600. Therefore, upon settlement, closing your position will get you $600-$100 = $500. This is the first point you are questioning. (However, you should also note that this is the value of the spread at settlement and it does not include the costs of opening the spread position, which are given as $200, so you net profit is $500-$200 = $300.) You then comment : I know I am selling 45 Call that means : As a writer: I want stock price to go down or stay at strike. As a buyer: I want stock price to go up. Here, note that for every penny that the underlying share price rises above $45, the money you will pay to buy back your short $45 call option will be offset by the money you will receive by selling the long $40 call option. Your $40 call option is covering the losses on your short $45 call option. No matter how high the underlying price settles above $45, you will receive the same $500 net credit on settlement. For example, if the underlying price settles at $50, then you will receive a credit of $1000 for selling your $40 call, but you will incur a debit of $500 against for buying back your short $45 call. The net being $500 = $1000-$500. This point is made in response to your comments posted under Dr. Jones answer.",
"title": ""
},
{
"docid": "576976",
"text": "\"Am I getting it right that in India in terms of short selling in F&O market its what in the rest of the world is called naked short and you actually make promise to depositary that you will deliver that security you sold on settlement without actually owning the security or going through SLB mechanism? In Future and Options; there is no concept of short selling. You buy a future for a security / index. On the settlement day; the exchange determines the settlement price. The trade is closed in cash. i.e. Based on the settlement price, you [and the other party] will either get money [other party looses money] or you loose money [other party gets the money]. Similarly for Options; on expiry, the all \"\"In Money\"\" [or At Money] Options are settled in cash and you are credit with funds [the option writer is debited with funds]. If the option is \"\"out of money\"\" it expires and you loose the premium you paid to exercise the option.\"",
"title": ""
},
{
"docid": "190484",
"text": "There are really only two options: invoiced, or paid. Everything else is not relevant from a tax or accounting point of view. Of course, if you're invoicing as you go along or collecting deposits once things are in your order books, then that amount of money is relevant. Working things out according to when you invoice is called working on an accrual basis. Working it out according to when you get paid is called working on a cash basis. Wikipedia explains the distinction, which also applies to your expenses: when did you incur them (get the bill) vs when you did you pay it. In some jurisdictions and for some kinds of companies, you can choose which of these two bases to work on (but no other basis.) There is advice on the UK government website about keeping your accounts. It includes a link to a PDF and on page 15 of that 100 page PDF it states: 2.14 The financial statements, with the exception of cash flow information, shall be prepared on the accruals basis of accounting. HENCE, ALL INCOME AND CHARGES RELATING TO THE FINANCIAL YEARTO WHICH THE ACCOUNTS RELATE MUST BE TAKEN INTO ACCOUNT, WITHOUT REGARD TO THE DATE OF PAYMENT OR RECEIPT. That seems pretty clear to me. When you invoice. Period.",
"title": ""
},
{
"docid": "478600",
"text": "\"The tax comes when you close the position. If the option expires worthless it's as if you bought it back for $0. There's a short-term capital gain for the difference between your short-sale price and your buyback price on the option. I believe the capital gain is always short-term because short sales are treated as short-term even if you hold them open more than one year. If the option is exercised (calling away your stock) then you add the premium to your sale price on the stock and then compute the capital gain. So in this case you can end up treating the premium as a long-term capital gain. See IRS pub 550 http://www.irs.gov/publications/p550/ch04.html#en_US_2010_publink100010619 Search for \"\"Writers of puts and calls\"\"\"",
"title": ""
},
{
"docid": "143655",
"text": "\"An option is a financial instrument instrument that gives you the right, but not the obligation, to do some transaction in the future at a given price. An employee stock option is a kind of \"\"call option\"\" -- it gives you the right, but not the obligation, to buy the stock at a certain price (the \"\"exercise price\"\", usually set as the price of the stock when the option was granted). The idea is that you would \"\"exercise\"\" the option (buy the stock at the given price as provided by the option), if the value of the stock is higher than the exercise price, and not if it is lower. The option is gifted to you. But that does not mean you get any stock. If and when you choose to exercise the option, you would buy the stock with your own money. At what time you can exercise the option (and how many shares you can exercise at a given time) will be specified in the agreement. Usually, you can only exercise a particular share after it has \"\"vested\"\" (according to some vesting schedule), and you lose the ability to exercise after you no longer work for the company (plus perhaps a grace period), or after the option expires.\"",
"title": ""
},
{
"docid": "155461",
"text": "\"There are no \"\"rules\"\" about how the price should act after an IPO, so there are no guarantee that a \"\"pop\"\" would appear at the opening day. But when an IPO is done, it's typically underpriced. On average, the shares are 10% up at the end of the first day after the IPO (I don't have the source that, I just remember that from some finance course). Also, after the IPO, the underwriter can be asked to support the trading of the share for a certain period of time. That is the so called stabilizing agent. They have few obligations like: This price support in often done by a repurchase of some of the shares of poorly performing IPO. EDIT: Informations about the overallotment pool. When the IPO is done, a certain number of client buy the shares issued by the company. The underwriter, with the clients, can decide to create an overallotment pool, where the clients would get a little more shares (hence \"\"overallotment\"\"), but this time the shares are not issued by the company but by the underwriter. To put it another way, the underwriter oversell and becomes short by a certain number of shares (limited to 15% of the IPO). In exchange for the risk taken by this overallotment, the underwriter gets a greenshoe option from the clients, that will allows the underwriter to buy back the oversold shares, at the price of the IPO, from the clients. The idea behind this option is to avoid a market exposure for the underwriter. So, after the IPO: If the price goes down, the underwriter buys back on the market the overshorted shares and makes a profits. If the price goes up, the company exercise the greenshoe option buy the shares at the IPO prices (throught the overallotment pool, that is, the additional shares that the clients wanted ) to avoid suffering a loss.\"",
"title": ""
},
{
"docid": "336011",
"text": "\"No. The more legs you add onto your trade, the more commissions you will pay entering and exiting the trade and the more opportunity for slippage. So lets head the other direction. Can we make a simple, risk-free option trade, with as few legs as possible? The (not really) surprising answer is \"\"yes\"\", but there is no free lunch, as you will see. According to financial theory any riskless position will earn the risk free rate, which right now is almost nothing, nada, 0%. Let's test this out with a little example. In theory, a riskless position can be constructed from buying a stock, selling a call option, and buying a put option. This combination should earn the risk free rate. Selling the call option means you get money now but agree to let someone else have the stock at an agreed contract price if the price goes up. Buying the put option means you pay money now but can sell the stock to someone at a pre-agreed contract price if you want to do so, which would only be when the price declines below the contract price. To start our risk free trade, buy Google stock, GOOG, at the Oct 3 Close: 495.52 x 100sh = $49,552 The example has 100 shares for compatibility with the options contracts which require 100 share blocks. we will sell a call and buy a put @ contract price of $500 for Jan 19,2013. Therefore we will receive $50,000 for certain on Jan 19,2013, unless the options clearing system fails, because of say, global financial collapse, or war with Aztec spacecraft. According to google finance, if we had sold a call today at the close we would receive the bid, which is 89.00/share, or $8,900 total. And if we had bought a put today at the close we would pay the ask, which is 91.90/share, or $9190 total. So, to receive $50,000 for certain on Jan 19,2013 we could pay $49,552 for the GOOG stock, minus $8,900 for the money we received selling the call option, plus a payment of $9190 for the put option we need to protect the value. The total is $49,842. If we pay $49,842 today, plus execute the option strategy shown, we would have $50,000 on Jan 19,2013. This is a profit of $158, the options commissions are going to be around $20-$30, so in total the profit is around $120 after commissions. On the other hand, ~$50,000 in a bank CD for 12 months at 1.1% will yield $550 in similarly risk-free interest. Given that it is difficult to actually make these trades simultaneously, in practice, with the prices jumping all around, I would say if you really want a low risk option trade then a bank CD looks like the safer bet. This isn't to say you can't find another combination of stock and contract price that does better than a bank CD -- but I doubt it will ever be better by very much and still difficult to monitor and align the trades in practice.\"",
"title": ""
},
{
"docid": "201736",
"text": "What is a good resource to learn about options trading strategies? Options are a quite advanced investment form, and you'd do well to learn a lot about them before attempting to dive into this fairly illiquid market. Yale's online course in financial markets covers the Options Market and is a good starting point to make sure you've got all the basics. You may be familiar with most of it, but it's a decent refresher on lingo and Black-Scholes. How can I use options to establish some cash flow from long standing investments while minimizing capital gains expenses? This question seems designed to get people to talk about covered calls. Essentially, you sell call contracts: you let people buy things you already have at a price in the future, at their whim. They pay you for this option, though usually not much if the options aren't in the money. You can think of this as trading any return above the call option for a bit of extra cash. I don't invest with taxable accounts, but there are significant tax consequences for options. Because they expire, there will be turnover in your portfolio, and up front income when you take the sell side. So if you trade in options with close expiration dates, you'll probably end up with a lot of short-term capital gains, which are treated as normal income. One strategy is to trade in broad-based stock index options, which have favorable tax treatments. Some people have abused this though to disguise normal income as capital gains, so it could go away. Obviously the easy approach is to just use a tax advantaged account for options trading. An ETF might also be able to handle the turnover on your behalf, for example VIX is a series of options on S&P500 options. A second strategy I've heard of is buying calls and puts at a given strike price. For example, if you bought Dec '13 calls and puts on SPX @ 115 today, it would cost you about $35 dollars. If the price moves more than 35 dollars away from 115 by DEC '13 (in either direction), you've made a profit. If you reflect on that for a bit, you'll see why VIX is considered a volatility index. I guess I should mention that shorting a stock and buying a put option at the market price are very similar, with the exception that your loss is limited to the price of the option. Is there ever an instance where options investing is not speculative? The term 'speculative' is not well defined. For many people, the answer is no. It's very easy to just buy put options and wait for prices to fall, or call options and wait for prices to rise. Moreover, the second strategy above essentially gives you similar performance to a stock without paying full price. These all fall under the headline of increasing a risk portfolio rather than decreasing it, which I figure is a decent definition of speculation. On the other hand, there are ways to use options minimize risk rather than increase it. You can buy underwater options as portfolio insurance, if your portfolio drops below a certain amount, you still have the right to sell it at a higher one. And the Case-Schiller index is run in part, on the hopes that one day there might be a thriving market for real estate options (or futures). When you buy a home or lend money to someone to buy one, you could buy regional Case-Schiller options to protect you if the regional market tanks. But in all of these cases, it's required for someone else to take the opposite trade. Risk isn't reduced, it's traded around. So technically, there is a speculative element to these as well. I think the proper question here is whether speculation is present, but whether speculation can be put to good ends. Without speculators, the already very thin market for options would shrivel faster.",
"title": ""
},
{
"docid": "154989",
"text": "\"Whether or not you make money here depends on whether you are buying or selling the option when you open your position. You certainly would not make money in the scenario where you are buying options at the open. If fact you would end up loosing quite a lot of money. You do not specify whether you are buying or selling the options, so let's assume that you are buying both the call and the put. We'll look a profitable trade at the bottom of my answer. Buying an in-the-money Call option with a strike price of $90 when the underlying asset price is $150 would cost you a small fraction over $6000 = (100 x $60) since the intrinsic value value of the option is $60. Add to this cost any commission charged by your broker. Buying an out-of-the-money Put option with a strike price of $110 when the underlying asset price is $150 would cost you a \"\"small\"\" premium - lets say a premium of something like $0.50. The option has no intrinsic value, only time value and a volatility value, so the exact cost would depend on the time to expiry and the implied volatility of the underlying asset. Since the strike price is \"\"well out of the money\"\", being about 27% below the underlying asset price, the premium would be small. So, assuming the premium of $0.50, you would pay $50 for the option plus any commission applicable. The cash settlement on expiry, with an underlying settlement price of $100, would be a premium of $10 for each of the two options, so you would receive cash of 100 x ($10 + $10) = $2000, less any commission applicable. However, you have paid $6000 + $50 to purchase the options, so you realise a net loss of $6050 - $2000 = $4050 plus any commissions applicable. Thus, you would make a profit on the put option, but you would realise a very large loss on the call option. On the other hand, if you open your position by selling the call option and buying the put option, then you would make money. For the sale of the call option you would receive about $6000. For the purchase of the put option you would pay about $50. On settlement, you would pay $1000 to buy back the call option and you would receive about $1000 when selling the put option. Thus you net profit would be about ($6000 - $1000) for the call position, and ($1000 - $50) for the put position. The net profit would then total $5950 less an commissions payable.\"",
"title": ""
},
{
"docid": "387147",
"text": "\"Write means sell to open. It is called that because options writers are creating (i.e. writing) new contracts. No such thing as \"\"reading\"\" an option.\"",
"title": ""
},
{
"docid": "176161",
"text": "\"To understand the VXX ETF, you need to understand VIX futures, to understand VIX futures you need to understand VIX, to understand VIX you need to understand options pricing formulas such as the \"\"Black Scholes\"\" formula Those are your prerequisites. Learn at your own pace. Short Answer: When you buy VXX you are buying the underlying are front month VIX futures. Limited by the supply of the ETF's NAV (Net Asset Value) units. It is assumed that the ETF manager is actually buying and selling more VIX front month futures to back the underlying ETF. Long Answer: Assume nobody knows what an options contract should be worth. Therefore formulas have been devised to standardize how to price an options contract. The Black-Scholes formula is widely used, one of the variables in this formula is \"\"Implied Volatility\"\", which basically accounts for the mispricing of options when the other variables (Intrinsic Value, delta, gamma, theta...) don't completely explain how much the option is worth. People are willing to pay more for options when the perception is that they will be more profitable, \"\"implied volatility\"\" tracks these changes in an option's demand, where the rest of the black-scholes formula creates a price for an option that will always be the same. Each stock in the market that also trades standardized options will have implied volatility which can be computed from the price of those options. The \"\"Volatility Index\"\" (VIX), looks at the implied volatility of MANY STOCK's options contracts. Specifically the \"\"implied volatility of out the money puts on the S&P 500\"\". If you don't know what that quoted part of the sentence means, then you have at least five other individual questions to ask before you re-read this answer and understand the relevance of these followup questions: Why would people buy out-the-money puts on the S&P 500? Why would people pay more for out-the-money puts on the S&P 500 on some days and pay less for them on other days? This is really the key to the whole puzzle. Anyway, now that we have this data, people wanted to speculate on the future value of the VIX. So VIX futures contracts began trading and with it there came a liquid market. There doesn't need to be anything physical to back a financial product anymore. A lot of people don't trade futures, retail investors have practically only heard of \"\"the stock market\"\". So one investment bank decided to make a fund that only holds VIX futures that expire within a month. (front month futures). They split that fund up into shares and listed it on the stock market, like alchemy the VXX was formed. Volatility studies are fascinating, and get way more complex than this now that the VXX ETF also has liquid options contracts trading on it too, and there are leveraged VIX ETF funds that also trade options\"",
"title": ""
},
{
"docid": "118360",
"text": "First, it depends on your broker. Full service firms will tear you a new one, discount brokers may charge ~nothing. You'll have to check with your broker on assignment fees. Theoretically, this is the case of the opposite of my answer in this question: Are underlying assets supposed to be sold/bought immediately after being bought/sold in call/put option? Your trading strategy/reasoning for your covered call notwithstanding, in your case, as an option writer covering in the money calls, you want to hold and pray that your option expires worthless. As I said in the other answer, there is always a theoretical premium of option price + exercise price to underlying prices, no matter how slight, right up until expiration, so on that basis, it doesn't pay to close out the option. However, there's a reality that I didn't mention in the other answer: if it's a deep in the money option, you can actually put a bid < stock price - exercise price - trade fee and hope for the best since the market makers rarely bid above stock price - exercise price for illiquid options, but it's unlikely that you'll beat the market makers + hft. They're systems are too fast. I know the philly exchange allows you to put in implied volatility orders, but they're expensive, and I couldn't tell you if a broker/exchange allows for dynamic orders with the equation I specified above, but it may be worth a shot to check out; however, it's unlikely that such a low order would ever be filled since you'll at best be lined up with the market makers, and it would require a big player dumping all its' holdings at once to get to your order. If you're doing a traditional, true-blue covered call, there's absolutely nothing wrong being assigned except for the tax implications. When your counterparty calls away your underlyings, it is a sell for tax purposes. If you're not covering with the underlying but with a more complex spread, things could get hairy for you real quick if someone were to exercise on you, but that's always a risk. If your broker is extremely strict, they may close the rest of your spread for you at the offer. In illiquid markets, that would be a huge percentage loss considering the wide bid/ask spreads.",
"title": ""
},
{
"docid": "427145",
"text": "In Australia there are 2 type of warrants (I don't know if it is the same in the US, UK and other countries), the first are trading warrants and the second are instalment warrants. The trading warrants are exactly what it says, they are used for trading. They are similar to option and have calls and puts. As Cameron says, they differ from exchange traded options in that they are issued by the financial companies whereas options are generally written by other investors. Instalment warrants on the other hand are usually bought and sold by investors with a longer term view. There are no calls and puts and you can just go long with them. They are also issued by financial companies, and how they work is best explained through an example: if I was to buy a stock directly say I would be paying $50 per share, however an instalment warrant in the underlying stock may be offered for $27 per warrant. I could buy the warrant directly from the company when it is issued or on the secondary market just like shares. I would pay the $27 per warrant upfront, and then in 2 years time when the warrant expires I have the choice to purchase the underlying stock for the strike price of say $28, roll over to a new issue of warrants, sell it back on the secondary market, or let it expire, in which case I would receive any intrinsic value left in the warrant. You would have noticed that the warrant purchase price plus the strike price adds up to more than the share price ($55 compared to $50). This is the interest component inherent in the warrant which covers the borrowing costs until expiry, when you pay the second portion (the strike price) and receive the underlying shares. Another difference between Instalment warrants and trading warrants (and options) is that with instalment warrants you still get the full dividends just like the shares, but at a higher yield than the shares.",
"title": ""
},
{
"docid": "166597",
"text": "Options are contractual instruments. Most options you'll run into are contracts which allow you to buy or sell stock at a given price at some time in the future, if you feel like it (it gives you the option). These are Call and Put options, respectively (for buying the stock and selling the stock). If you have a lot of money in an index fund ETF, you may be able to protect your portfolio against a market decline by (e.g.) buying Put options against the ETF for a substantially lower price than the index fund currently trades at. If the market crashes and your fund falls in value significantly, you can exercise the options, selling the fund at the price that your option has specified (to the counter-party of your contract). This is the risk that the option mitigates against. Even if you don't have one particular fund with your investments, you could still buy a put option on a similar fund, and resell it to another person in lieu of exercise (they would be capable of buying the stock and performing the exercise themselves for profit if necessary). In general, if you are buying an option for safety, it should be an option either on something you own, or something whose price behavior will mimic something you own. You will note that options are linked to the price of stocks. Futures are contracts whose values are linked to the price of other things, typically commodities such as oil, gold, or orange juice. Their behaviors may diverge. With an option you can have a contractual guarantee on the exact investment you're trying to protect. (Additionally, many commodities' value may fall at the same time that stock investments fall: during economic contractions which reduce industrial activity, resulting in lower profits for firms and less demand for commodities.) You may also note that there are other structures that options may have - PUT options on index funds or similar instruments are probably most specifically relevant to your interests. The downside of protecting yourself with options is that it costs money to buy this option, and the option eventually expires, so you may lose money. Essentially, you are buying safety and risk-tolerance from the option contract's counterparty, and safety is not free. I cannot inform you what level of safety is appropriate for your portfolio's needs, but more safety is more expensive.",
"title": ""
},
{
"docid": "357324",
"text": "Cart's answer is basically correct, but I'd like to elaborate: A futures contract obligates both the buyer of a contract and the seller of a contract to conduct the underlying transaction (settle) at the agreed-upon future date and price written into the contract. Aside from settlement, the only other way either party can get out of the transaction is to initiate a closing transaction, which means: The party that sold the contract buys back another similar contract to close his position. The party that bought the contract can sell the contract on to somebody else. Whereas, an option contract provides the buyer of the option with the choice of completing the transaction. Because it's a choice, the buyer can choose to walk away from the transaction if the option exercise price is not attractive relative to the underlying stock price at the date written into the contract. When an option buyer walks away, the option is said to have expired. However – and this is the part I think needs elaboration – the original seller (writer) of the option contract doesn't have a choice. If a buyer chooses to exercise the option contract the seller wrote, the seller is obligated to conduct the transaction. In such a case, the seller's option contract is said to have been assigned. Only if the buyer chooses not to exercise does the seller's obligation go away. Before the option expires, the option seller can close their position by initiating a closing transaction. But, the seller can't simply walk away like the option buyer can.",
"title": ""
},
{
"docid": "310837",
"text": "\"I look for buying a call option only at the money, but first understand the background above: Let's suppose X stock is being traded by $10.00 and it's January The call option is being traded by $0.20 with strike $11.00 for February. (I always look for 2% prize or more) I buy 100 stocks by $10.00 each and sell the option, earning $0.20 for each X stock. I will have to deliver my stocks by $11.00 (strike value agreed). No problem for me here, I took the prize plus the gain of $1.00. (continuing from item 3) I still can sell the option for the next month with strike equal or higher than that I bought. For instance, I can sell a call option of strike $10.00 and it might be worth to deliver stocks by $10.00 and take the prize. (continuing from item 3) Probably, it won't be possible to sell a call option with strike at the price that I paid for the stock, but that's not a problem. At the end of the option life (in February), the strike was $11.00 but the stock's price is $8.00. I got the $0.20 as prize and my stocks are free for trade again. I'll sell the call option for March with strike $9.00 (taking around 2% of prize). Well, I don't want to sell my stocks by $9.00 and make loss, right? But I'm selling the call option anyway. Then I wait till the price of the stock gets near the strike value (almost ATM) and I \"\"re-buy\"\" the option sold (Example: [StockX]C9 where C means month = March) and sell again the call option with higher strike to April (Example [StockX]D10, where D means month = April) PS.: At item 9 there should be no loss between the action of \"\"re-buy\"\" and sell to roll-out to the next month. When re-buying it with the stock's price near the strike, option value for March (C9) will be lower than when selling it to April (D10). This isn't any rule to be followed, this is just a conservative (I think they call it hedge) way to handle options and stocks. Few free to make money according to your goals and your style. The perfect rule is the one that meet your expectation, don't take the generalized rules too serious.\"",
"title": ""
}
] |
159
|
BRCA 1 mutation carriers' risk of breast and ovarian cancer depends on where the mutation is located.
|
[
{
"docid": "9394119",
"text": "IMPORTANCE Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES Breast and ovarian cancer risks. RESULTS Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.",
"title": "Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer."
}
] |
[
{
"docid": "2015126",
"text": "The management of women who have a genetic predisposition for breast cancer requires careful planning. Women who have BRCA 1 and BRCA 2 mutations are at increased risk for breast cancer and for other cancers as well, particularly ovarian cancer. Screening, prophlyactic surgery, and chemoprevention are commonly utilized strategies in the management of these patients, and women may choose more than one of these strategies. No randomized prospective trials have assessed the impact of these strategies specifically in mutation carriers. All patients should be informed that screening, prophylactic surgery, and chemoprevention have the potential for harm as well as benefit.",
"title": "Management of women who have a genetic predisposition for breast cancer."
},
{
"docid": "3285322",
"text": "PURPOSE Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations. PATIENTS AND METHODS Tumor pathologic features and clinical characteristics were examined in 491 women with breast cancer who underwent genetic testing for BRCA mutations between 1997 and 2006. A retrospective review of medical records was conducted to determine clinical characteristics including ethnicity, age and clinical stage at diagnosis, age at parity, number of full-term pregnancies, use of oral contraceptives and hormone replacement therapy, and BRCA mutation status. Tumor pathology was reviewed to determine histologic type, tumor grade, and estrogen receptor, progesterone receptor, and HER-2/neu status. RESULTS Of the 491 patients with identified breast cancers, 391 patients were BRCA negative, and 86 patients were BRCA positive. Triple-negative breast cancer (ie, those with negative estrogen receptor, progesterone receptor, and HER-2/neu status) was diagnosed in 57.1% of the BRCA1-positive patients, 23.3% of the BRCA2-positive patients, and 13.8% of the BRCA-negative patients. BRCA1 mutation carriers had higher nuclear grade tumors than the other two groups (P < .001). Of the triple-negative cancer patients, BRCA2 mutation carriers were older when diagnosed than BRCA1 mutation carriers and noncarriers (P < .01). CONCLUSION These results suggest that tumors associated with BRCA1 mutations may be divided into two distinct groups, triple-negative and non-triple-negative groups. Future studies should seek to determine whether patients with BRCA1 mutations and triple-negative breast cancer respond to treatment better than BRCA-negative patients with similar tumor pathology.",
"title": "Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer."
},
{
"docid": "22975806",
"text": "For individuals genetically predisposed to breast and ovarian cancer through inheritance of a mutant BRCA allele, somatic loss of heterozygosity affecting the wild-type allele is considered obligatory for cancer initiation and/or progression. However, several lines of evidence suggest that phenotypic effects may result from BRCA haploinsufficiency. Archival fixed and embedded tissue specimens from women with germ line deleterious mutations in BRCA1 or BRCA2 were identified. After pathologic review, focal areas of normal breast epithelium, atypical ductal hyperplasia, ductal carcinoma-in-situ, and invasive ductal carcinoma were identified from 14 BRCA1-linked and 9 BRCA2-linked breast cancers. Ten BRCA-linked prophylactic mastectomy specimens and 12 BRCA-linked invasive ovarian carcinomas were also studied. Laser catapult microdissection was used to isolate cells from the various pathologic lesions and corresponding normal tissues. After DNA isolation, real-time polymerase chain reaction assays were used to quantitate the proportion of wild-type to mutant BRCA alleles in each tissue sample. Quantitative allelotyping of microdissected cells revealed a high level of heterogeneity in loss of heterozygosity within and between preinvasive lesions and invasive cancers from BRCA1 and BRCA2 heterozygotes with breast cancer. In contrast, all BRCA-associated ovarian cancers displayed complete loss of the wild-type BRCA allele. These data suggest that loss of the wild-type BRCA allele is not required for BRCA-linked breast tumorigenesis, which would have important implications for the genetic mechanism of BRCA tumor suppression and for the clinical management of this patient population.",
"title": "Heterogenic Loss of the Wild-Type BRCA Allele in Human Breast Tumorigenesis"
},
{
"docid": "4414547",
"text": "Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case–control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10−5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10−4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10−9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.",
"title": "Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer"
},
{
"docid": "17088791",
"text": "Most multiple case families of young onset breast cancer and ovarian cancer are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. However, these mutations are uncommon in the population and they probably account for only a few percent of all breast cancer incidence. A much larger fraction of breast cancer might, in principle, be due to common variants which confer more modest individual risks. There are several common polymorphisms in the BRCA1 gene which generate amino acid substitutions. We have examined the frequency of four of these polymorphisms: Gln356Arg, Pro871Leu, Glu1038Gly and Ser1613Gly in large series of breast and ovarian cancer cases and matched controls. Due to strong linkage disequilibrium, these four sites generate only three haplotypes with a frequency > 1.3%. The most common haplotypes, defined by the alleles Gln356Pro871Glu1038Ser1613 and Gln356Leu871Gly1038Gly1613, have frequencies of 0.57 and 0.32 respectively, and these frequencies do not differ significantly between patient and control groups. Thus the most common polymorphisms of the BRCA1 gene do not make a significant contribution to breast or ovarian cancer risk. However, our data suggest that the Arg356 allele may have a different genotype distribution in breast cancer patients from that in controls (Arg356 homozygotes are more frequent in the control groups, P = 0.01), indicating that it may be protective against breast cancer. If this finding can be confirmed, it may provide an insight into the structural features of the BRCA1 protein that are important for its function.",
"title": "Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population."
},
{
"docid": "20280410",
"text": "Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07–1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner.",
"title": "A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability"
},
{
"docid": "24144677",
"text": "Homozygous mutation in the ATM gene causes ataxia telangiectasia and heterozygous mutation carriers may be at increased risk of breast cancer. We studied a total of 22 ATM variants; 18 variants were analyzed in one of two large population-based studies from the U.S. and Poland, and four variants were analyzed in all 2,856 breast cancer cases and 3,344 controls from the two studies. The missense mutation Ser49Cys (c.146C>G, p. S49C), carried by approximately 2% of subjects, was more common in cases than controls in both study populations, combined odds ratio (OR) 1.69 (95% CI, 1.19-2.40; P=0.004). Another missense mutation at approximately 2% frequency, Phe858Leu (c.2572T>C, p. F858L), was associated with a significant increased risk in the U.S. study but not in Poland, and had a combined OR of 1.44 (95% CI, 0.98-2.11; P=0.06). These analyses provide the most convincing evidence thus far that missense mutations in ATM, particularly p. S49C, may be breast cancer susceptibility alleles. Because of their low frequency, even larger sample sizes are required to more firmly establish these associations.",
"title": "The ATM missense mutation p.Ser49Cys (c.146C>G) and the risk of breast cancer."
},
{
"docid": "13519661",
"text": "Background Checkpoint kinase 2 (CHEK2) averts cancer development by promoting cell cycle arrest and activating DNA repair in genetically damaged cells. Previous investigation has established a role for the CHEK2 gene in breast cancer aetiology, but studies have largely been limited to the rare 1100delC mutation. Whether common polymorphisms in this gene influence breast cancer risk remains unknown. In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs). Methods and Findings We analyzed 14 common SNPs spanning 52 kilobases (kb) of the CHEK2 gene in 92 Swedish women. Coverage evaluation indicated that these typed SNPs would efficiently convey association signal also from untyped SNPs in the same region. Six of the 14 SNPs predicted well both the haplotypic and single SNP variations within CHEK2. We genotyped these six tagSNPs in 1,577 postmenopausal breast cancer cases and 1,513 population controls, but found no convincing association between any common CHEK2 haplotype and breast cancer risk. The 1100delC mutation was rare in our Swedish population—0.7% in cases and 0.4% in controls— with a corresponding odds ratio for carriers versus noncarriers of 2.26 (95% confidence interval, 0.99–5.15). Estimates of the population frequency and the odds ratio of 1100delC indicate that our sample is representative of a Northern European population.",
"title": "Linkage Disequilibrium Mapping of CHEK2: Common Variation and Breast Cancer Risk "
},
{
"docid": "1387104",
"text": "CONTEXT Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life. OBJECTIVE To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations. DESIGN, SETTING, AND PATIENTS A large population-based, case-control (Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis) study of 3220 consecutive patients aged 18 to 70 years, with a first deep venous thrombosis of the leg or pulmonary embolism, between March 1, 1999, and May 31, 2002, at 6 anticoagulation clinics in the Netherlands, and separate 2131 control participants (partners of the patients) reported via a questionnaire on acquired risk factors for venous thrombosis. Three months after discontinuation of the anticoagulant therapy, all patients and controls were interviewed, a blood sample was taken, and DNA was isolated to ascertain the factor V Leiden and prothrombin 20210A mutations. MAIN OUTCOME MEASURE Risk of venous thrombosis. RESULTS The overall risk of venous thrombosis was increased 7-fold in patients with a malignancy (odds ratio [OR], 6.7; 95% confidence interval [CI], 5.2-8.6) vs persons without malignancy. Patients with hematological malignancies had the highest risk of venous thrombosis, adjusted for age and sex (adjusted OR, 28.0; 95% CI, 4.0-199.7), followed by lung cancer and gastrointestinal cancer. The risk of venous thrombosis was highest in the first few months after the diagnosis of malignancy (adjusted OR, 53.5; 95% CI, 8.6-334.3). Patients with cancer with distant metastases had a higher risk vs patients without distant metastases (adjusted OR, 19.8; 95% CI, 2.6-149.1). Carriers of the factor V Leiden mutation who also had cancer had a 12-fold increased risk vs individuals without cancer and factor V Leiden (adjusted OR, 12.1; 95% CI, 1.6-88.1). Similar results were indirectly calculated for the prothrombin 20210A mutation in patients with cancer. CONCLUSIONS Patients with cancer have a highly increased risk of venous thrombosis especially in the first few months after diagnosis and in the presence of distant metastases. Carriers of the factor V Leiden and prothrombin 20210A mutations appear to have an even higher risk.",
"title": "Malignancies, prothrombotic mutations, and the risk of venous thrombosis."
},
{
"docid": "1866911",
"text": "Basal-like breast cancers arising in women carrying mutations in the BRCA1 gene, encoding the tumor suppressor protein BRCA1, are thought to develop from the mammary stem cell. To explore early cellular changes that occur in BRCA1 mutation carriers, we have prospectively isolated distinct epithelial subpopulations from normal mammary tissue and preneoplastic specimens from individuals heterozygous for a BRCA1 mutation. We describe three epithelial subsets including basal stem/progenitor, luminal progenitor and mature luminal cells. Unexpectedly, we found that breast tissue from BRCA1 mutation carriers harbors an expanded luminal progenitor population that shows factor-independent growth in vitro. Moreover, gene expression profiling revealed that breast tissue heterozygous for a BRCA1 mutation and basal breast tumors were more similar to normal luminal progenitor cells than any other subset, including the stem cell–enriched population. The c-KIT tyrosine kinase receptor (encoded by KIT) emerged as a key marker of luminal progenitor cells and was more highly expressed in BRCA1-associated preneoplastic tissue and tumors. Our findings suggest that an aberrant luminal progenitor population is a target for transformation in BRCA1-associated basal tumors .",
"title": "Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers"
},
{
"docid": "27270151",
"text": "In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are \"KRAS equal\"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents. Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer.",
"title": "Changing the course of pancreatic cancer--Focus on recent translational advances."
},
{
"docid": "5468807",
"text": "ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with this genetic characteristic remain to be explored. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours. This correlated with the suppression of growth and dissemination of ARID1A-mutated, but not wild-type, tumours. The dependence on HDAC6 activity in ARID1A-mutated cells correlated with a direct transcriptional repression of HDAC6 by ARID1A. HDAC6 inhibition selectively promoted apoptosis of ARID1A-mutated cells. HDAC6 directly deacetylates Lys120 of p53, a pro-apoptotic post-translational modification. Thus, ARID1A mutation inactivates the apoptosis-promoting function of p53 by upregulating HDAC6. Together, these results indicate that pharmacological inhibition of HDAC6 is a therapeutic strategy for ARID1A-mutated cancers.",
"title": "ARID1A-mutated ovarian cancers depend on HDAC6 activity"
},
{
"docid": "9211173",
"text": "BACKGROUND Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. METHODS We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. RESULTS ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. CONCLUSIONS These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.).",
"title": "ARID1A mutations in endometriosis-associated ovarian carcinomas."
},
{
"docid": "25576204",
"text": "Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.",
"title": "Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene."
},
{
"docid": "5864770",
"text": "Epidemiologic studies suggest that ovarian hormones contribute to the development of breast cancer at all stages. Early menopause and premenopausal obesity reduces the risk while postmenopausal obesity and menopausal estrogen replacement therapy increases the risk. Combined oral contraceptives and Depo-Provera do not reduce the risk. It appears that estrogens and progestogens act through and with proto-oncogenes and growth factors to affect breast cell proliferation and breast cancer etiology. Animal studies suggest that estrogen causes interlobular ductal cell division and progesterone causes increased terminal duct lobular unit cell division in the luteal phase. Most breast carcinomas originate from terminal duct lobular unit cells. During pregnancy, these cells fully multiply. Their reproduction is also increased during the luteal phase. Yet, there is considerable interpersonal variation. No studies examining breast cell division have compared cell division rates with serum hormone concentrations, however. The peak of mitosis occurs about 3 days before breast cell death in the late luteal and very early follicular phases. Other research suggests that breast stem cell proliferation is linked to breast cancer development. Endocrine therapy reduces mitotic activity, indicating the estrogen and progesterone receptor content of breast cancers. Hormone-dependent breast cancer cell lines are all estrogen-dependent. Progesterone can block the estrogen-dependent cell lines which act like endometrial cells. The results of the various breast cell proliferation studies in relation to breast cancer are unclear and research identifying a molecular explanation would help in understanding the different findings.",
"title": "Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk."
},
{
"docid": "3360428",
"text": "Kras mutation is a common phenomenon in many human neoplasms. We aimed to assess the Kras mutational status along the histological continuum from normal ovaries to the development of benign, borderline and malignant ovarian mucinous neoplasms. We analyzed 41 cases of malignant, 10 cases of borderline, 7 cases of benign mucinous ovarian tumors and 7 cases of normal ovarian tissue. The prevalence of Kras mutations in the normal ovary was 0.00% (n=0/7), while the prevalence in benign, borderline and malignant mucinous neoplasms was 57.14% (n=4/7), 90.00% (n=9/10) and 75.61% (n=31/41), respectively. Multiple Kras mutations were detected in 6 cases of mucinous carcinoma, including 5 double mutations with G13D/V14I (n=1), G12V/G13S (n=1), G12D/G13S (n=3) and one triple mutation with A11V/G13N/V14I (n=1). We identified six cases with 3 novel Kras mutations not previously described in the COSMIC database, which included A11V (n=3) and V14I (n=2) in mucinous carcinomas, and A11T (n=1) in a mucinous borderline tumor. In conclusion, Kras mutation appears to be one of the imperative events in the ovarian mucinous adenoma-borderline tumor-carcinoma sequence, as increased numbers of Kras mutations have been shown to be the strongest predictor of unequivocal malignancy in ovarian mucinous neoplasms.",
"title": "Multipoint Kras oncogene mutations potentially indicate mucinous carcinoma on the entire spectrum of mucinous ovarian neoplasms"
},
{
"docid": "23557241",
"text": "BACKGROUND Emerging evidence suggests an association between female prenatal experience and her subsequent risk of developing breast cancer. Potential underlying mechanisms include variation in amounts of maternal endogenous sex hormones and growth hormones, germ-cell mutations, formation of cancer stem-cells, and other genetic or epigenetic events. We reviewed and summarised quantitatively the available data on intrauterine exposures and risk of breast cancer. METHODS We systematically searched for studies that assessed association between perinatal factors and risk of breast cancer. We reviewed separately each of the perinatal factors, including birthweight, birth length, parental age at delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin membership, maternal pre-eclampsia or eclampsia, and other factors. FINDINGS We identified 57 studies published between Oct 1, 1980, and June 21, 2007. Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]). Decreased risk of breast cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and twin membership (0.93 [0.87-1.00]). No association was noted between risk of breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal diethylstilbestrol treatment (1.40 [0.86-2.28]). INTERPRETATION The intrauterine environment contributes to the predisposition of women to breast cancer in adulthood. The in-utero mechanisms responsible for such predisposition need to be elucidated.",
"title": "Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence."
},
{
"docid": "3524352",
"text": "High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors.",
"title": "Breast cancer clusters in the northeast United States: a geographic analysis."
},
{
"docid": "18340282",
"text": "BACKGROUND Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. METHODS We tested gene-environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). FINDINGS After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162.4 cm [95% CI 162.1-162.7] vs 163.1 cm [162.9-163.2]; p=0.01 after allowance for multiple testing). INTERPRETATION Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. FUNDING Cancer Research UK and the UK Medical Research Council.",
"title": "Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study"
},
{
"docid": "15600979",
"text": "EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario wherein: (a) EMSY amplification may mimic BRCA2 deficiency, at least by overriding RPA and PALB2, crippling the BRCA2/RAD51 complex at DNA-damage and replication/transcription sites; and (b) BRCA2/RAD51 may coordinate these processes by employing at least EMSY, PALB2 and RPA. We extensively discuss the molecular details of how this can happen to ascertain its implications for a novel recombination mechanism apparently conceived as checkpoint rather than a DNA repair system for cell division, survival, death, and human diseases, including the tissue specificity of cancer predisposition, which may renew our thinking about targeted therapy and prevention.",
"title": "EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases"
},
{
"docid": "18078750",
"text": "Mechanisms that are responsible for sorting newly synthesized proteins for traffic to the cell surface from the Golgi are poorly understood. Here, we show that the potassium channel Kir2.1, mutations in which are associated with Andersen-Tawil syndrome, is selected as cargo into Golgi export carriers in an unusual signal-dependent manner. Unlike conventional trafficking signals, which are typically comprised of short linear peptide sequences, Golgi exit of Kir2.1 is dictated by residues that are embedded within the confluence of two separate domains. This signal patch forms a recognition site for interaction with the AP1 adaptor complex, thereby marking Kir2.1 for incorporation into clathrin-coated vesicles at the trans-Golgi. The identification of a trafficking signal in the tertiary structure of Kir2.1 reveals a quality control step that couples protein conformation to Golgi export and provides molecular insight into how mutations in Kir2.1 arrest the channels at the Golgi.",
"title": "Golgi Export of the Kir2.1 Channel Is Driven by a Trafficking Signal Located within Its Tertiary Structure"
},
{
"docid": "4828631",
"text": "BACKGROUND High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING National Institute for Health Research, Wellcome Trust, and Medical Research Council.",
"title": "Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults"
},
{
"docid": "20886584",
"text": "Taxanes have resulted in improved survival for breast cancer patients, but often cause neurological toxicities. Identification of biomarkers related to toxicities could be important for dictating treatment regimen. We evaluated single nucleotide polymorphisms (SNPs) in the Fanconi Anemia (FA)/BRCA pathway in relation to grade 3/4 neurotoxicities in patients (n = 888) from SWOG0221, a phase III adjuvant trial for breast cancer of 4 dose/schedules of cyclophosphamide (C), doxorubicin (A), and paclitaxel (T). In a separate cohort, we measured the correlation of significant FANCD2 SNPs with corresponding gene expression. For FANCD2, permutation testing revealed that 4 (out of 20) SNPs were significantly associated with an almost two-fold increased risk of toxicity. Two FANCD2 haplotypes were also associated with neurological toxicity, with odds ratios (OR) in the overall population of 1.8 (95% confidence interval (CI) 1.3, 2.5) and 1.7 (95% CI, 1.2, 2.4). Although numbers were small, an African-American-specific haplotype was associated with an almost 3-fold increase in risk of neurologic toxicity (OR = 2.84, 95% CI = 1.2, 6.9). Expression analyses revealed that significant FANCD2 SNPs were associated with FANCD2 expression levels (P = 0.03). There were no associations between SNPs in BRCA1 and neurotoxicities. In this trial of CA+T for breast cancer, SNPs in FANCD2, but not in BRCA1, were associated with a 70–80% increase in the odds of grade 3/4 neurological toxicities and increased expression of the gene. If replicated, women with these genotypes should be closely monitored for toxicities and could be targeted for preventive measures or alternative therapeutic approaches.",
"title": "Genetic predictors of taxane-induced neurotoxicity in a SWOG phase III intergroup adjuvant breast cancer treatment trial (S0221)"
},
{
"docid": "27123743",
"text": "Breast cancer may originate in utero. We reviewed the available evidence on the association between birthweight and the risk of breast cancer. To date, 26 research papers addressing this issue have been published. The majority of studies identified a positive link between birthweight and premenopausal, but not postmenopausal, breast cancer. The relative risk estimate for breast cancer comparing women with high birthweight to women with low birthweight combining all studies including both pre- and postmenopausal breast cancer was 1.23 (95% confidence interval 1.13-1.34). The mechanisms underlying this association likely include elevated levels of growth factors that may increase the number of susceptible stem cells in the mammary gland or initiate tumors through DNA mutations. Loss of imprinting (LOI) of growth hormone genes relevant for intrauterine growth, such as insulin-like growth factor 2 (IGF2), leads to abnormally high levels of these hormones evidenced by high birthweight. LOI of IGF2 has also been found in mammary tumor tissue. The role of environmental factors that stimulate such epigenetic regulation of gene expression remains to be elucidated.",
"title": "Role of birthweight in the etiology of breast cancer."
},
{
"docid": "8963413",
"text": "PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial. Blocking antibodies that target PD-1 and PD-L1 have achieved remarkable response rates in cancer patients who have PD-L1-overexpressing tumors. However, using PD-L1 as an exclusive predictive biomarker for cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. Factors that affect the accuracy of PD-L1 immunohistochemistry staining are as follows. First, antibodies used in different studies have different sensitivity. Second, in different studies, the cut-off value of PD-L1 staining positivity is different. Third, PD-L1 expression in tumors is not uniform, and sampling time and location may affect the results of PD-L1 staining. Therefore, better understanding of tumor microenvironment and use of other biomarkers such as gene marker and combined index are necessary to better identify patients who will benefit from PD-1/PD-L1 checkpoint blockade therapy.",
"title": "PD-L1 expression in human cancers and its association with clinical outcomes"
},
{
"docid": "17648235",
"text": "De-regulation of the wingless and integration site growth factor (WNT) signaling pathway via mutations in APC and Axin, proteins that target β-catenin for destruction, have been linked to various types of human cancer. These genetic alterations rarely, if ever, are observed in breast tumors. However, various lines of evidence suggest that WNT signaling may also be de-regulated in breast cancer. Most breast tumors show hypermethylation of the promoter region of secreted Frizzled-related protein 1 (sFRP1), a negative WNT pathway regulator, leading to downregulation of its expression. As a consequence, WNT signaling is enhanced and may contribute to proliferation of human breast tumor cells. We previously demonstrated that, in addition to the canonical WNT/β-catenin pathway, WNT signaling activates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in mouse mammary epithelial cells via epidermal growth factor receptor (EGFR) transactivation. Using the WNT modulator sFRP1 and short interfering RNA-mediated Dishevelled (DVL) knockdown, we interfered with autocrine WNT signaling at the ligand-receptor level. The impact on proliferation was measured by cell counting, YOPRO, and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay; β-catenin, EGFR, ERK1/2 activation, and PARP (poly [ADP-ribose]polymerase) cleavages were assessed by Western blotting after treatment of human breast cancer cell lines with conditioned media, purified proteins, small-molecule inhibitors, or blocking antibodies. Phospho-DVL and stabilized β-catenin are present in many breast tumor cell lines, indicating autocrine WNT signaling activity. Interfering with this loop decreases active β-catenin levels, lowers ERK1/2 activity, blocks proliferation, and induces apoptosis in MDA-MB-231, BT474, SkBr3, JIMT-1, and MCF-7 cells. The effects of WNT signaling are mediated partly by EGFR transactivation in human breast cancer cells in a metalloprotease- and Src-dependent manner. Furthermore, Wnt1 rescues estrogen receptor-positive (ER+) breast cancer cells from the anti-proliferative effects of 4-hydroxytamoxifen (4-HT) and this activity can be blocked by an EGFR tyrosine kinase inhibitor. Our data show that interference with autocrine WNT signaling in human breast cancer reduces proliferation and survival of human breast cancer cells and rescues ER+ tumor cells from 4-HT by activation of the canonical WNT pathway and EGFR transactivation. These findings suggest that interference with WNT signaling at the ligand-receptor level in combination with other targeted therapies may improve the efficiency of breast cancer treatments.",
"title": "Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation"
},
{
"docid": "8892905",
"text": "Alzheimer's disease (AD) is hypothesized to be caused by an overproduction or reduced clearance of amyloid-β (Aβ) peptide. Autosomal dominant AD (ADAD) caused by mutations in the presenilin (PSEN) gene have been postulated to result from increased production of Aβ42 compared to Aβ40 in the central nervous system (CNS). This has been demonstrated in rodent models of ADAD but not in human mutation carriers. We used compartmental modeling of stable isotope labeling kinetic (SILK) studies in human carriers of PSEN mutations and related noncarriers to evaluate the pathophysiological effects of PSEN1 and PSEN2 mutations on the production and turnover of Aβ isoforms. We compared these findings by mutation status and amount of fibrillar amyloid deposition as measured by positron emission tomography (PET) using the amyloid tracer Pittsburgh compound B (PIB). CNS Aβ42 to Aβ40 production rates were 24% higher in mutation carriers compared to noncarriers, and this was independent of fibrillar amyloid deposits quantified by PET PIB imaging. The fractional turnover rate of soluble Aβ42 relative to Aβ40 was 65% faster in mutation carriers and correlated with amyloid deposition, consistent with increased deposition of Aβ42 into plaques, leading to reduced recovery of Aβ42 in cerebrospinal fluid (CSF). Reversible exchange of Aβ42 peptides with preexisting unlabeled peptide was observed in the presence of plaques. These findings support the hypothesis that Aβ42 is overproduced in the CNS of humans with PSEN mutations that cause AD, and demonstrate that soluble Aβ42 turnover and exchange processes are altered in the presence of amyloid plaques, causing a reduction in Aβ42 concentrations in the CSF.",
"title": "Increased in vivo amyloid-β42 production, exchange, and loss in presenilin mutation carriers."
},
{
"docid": "857189",
"text": "The protein cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of immune responses, and its loss causes fatal autoimmunity in mice. We studied a large family in which five individuals presented with a complex, autosomal dominant immune dysregulation syndrome characterized by hypogammaglobulinemia, recurrent infections and multiple autoimmune clinical features. We identified a heterozygous nonsense mutation in exon 1 of CTLA4. Screening of 71 unrelated patients with comparable clinical phenotypes identified five additional families (nine individuals) with previously undescribed splice site and missense mutations in CTLA4. Clinical penetrance was incomplete (eight adults of a total of 19 genetically proven CTLA4 mutation carriers were considered unaffected). However, CTLA-4 protein expression was decreased in regulatory T cells (Treg cells) in both patients and carriers with CTLA4 mutations. Whereas Treg cells were generally present at elevated numbers in these individuals, their suppressive function, CTLA-4 ligand binding and transendocytosis of CD80 were impaired. Mutations in CTLA4 were also associated with decreased circulating B cell numbers. Taken together, mutations in CTLA4 resulting in CTLA-4 haploinsufficiency or impaired ligand binding result in disrupted T and B cell homeostasis and a complex immune dysregulation syndrome.",
"title": "Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations"
},
{
"docid": "14241418",
"text": "Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is a common event in human cancer, either through inactivation of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 or activating mutations of p110-alpha. These hotspot mutations result in oncogenic activity of the enzyme and contribute to therapeutic resistance to the anti-HER2 antibody trastuzumab. The PI3K pathway is, therefore, an attractive target for cancer therapy. We have studied NVP-BEZ235, a dual inhibitor of the PI3K and the downstream mammalian target of rapamycin (mTOR). NVP-BEZ235 inhibited the activation of the downstream effectors Akt, S6 ribosomal protein, and 4EBP1 in breast cancer cells. The antiproliferative activity of NVP-BEZ235 was superior to the allosteric selective mTOR complex inhibitor everolimus in a panel of 21 cancer cell lines of different origin and mutation status. The described Akt activation due to mTOR inhibition was prevented by higher doses of NVP-BEZ235. NVP-BEZ235 reversed the hyperactivation of the PI3K/mTOR pathway caused by the oncogenic mutations of p110-alpha, E545K, and H1047R, and inhibited the proliferation of HER2-amplified BT474 cells exogenously expressing these mutations that render them resistant to trastuzumab. In trastuzumab-resistant BT474 H1047R breast cancer xenografts, NVP-BEZ235 inhibited PI3K signaling and had potent antitumor activity. In treated animals, there was complete inhibition of PI3K signaling in the skin at pharmacologically active doses, suggesting that skin may serve as surrogate tissue for pharmacodynamic studies. In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-alpha.",
"title": "NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations."
},
{
"docid": "8524891",
"text": "OBJECTIVE White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. METHODS The study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first-degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed-effects piece-wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. RESULTS Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. INTERPRETATION Autosomal-dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929-939.",
"title": "White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network."
}
] |
1940
|
Shares in Chinese startup company
|
[
{
"docid": "183247",
"text": "Setting up an entity that is partially foreign owned is not that difficult. It takes an additional 1-1.5 months in total, and in this particular case, you guys would be formed as a Joint Venture. It will cost a bit more (about 3-5000). If you're serious about owning a part of a business in China, you should carefully examine what he means by 'more complicated'. From my point of view, I have set up my own WOFE in China, and examined the possibilities of a JV and even considered using a friend to set up the company under their personal name as a domestic company (which is what your supervisor is doing), any difference between the three are not really a big deal anymore, and comes down to the competency of the agencies you are using and the business partner themselves. It cost me 11,000 for a WOFE including the agency and government registration fees (only Chinese speaking). You should also consider the other shareholders who may be part of this venture as well. If there are other shareholders, and you are not providing further tangible contribution, you will end up replaced and penniless (unless of course you trust them too...), because they are actually paying money to be part of the business and you are not. They will not part with equity for you. I'm not a lawyer, but think you should not rely on any promises other than what it says on a company registration paper. Good luck!",
"title": ""
}
] |
[
{
"docid": "239656",
"text": "Is it just me, or does it seem like Jia Yueting is the stupidest self-made billionaire of all time? The guy just seems like an unprecedentedly financially naive and arrogant moron. He's Chinese Reed Hastings throwing money at the idea of being Chinese Elon Musk too. Starting not one but TWO ambitious car companies competing with fucking Tesla as a division of a company whose business has nothing to do with automobiles, risking bringing down a cash cow with two absurdly ambitious (and even cannibalizing!) startups? What the fuck is he thinking? How the hell did this illiterate hack start a company and make billions in the first place?",
"title": ""
},
{
"docid": "466673",
"text": "It is a highly competitive market with many local competitors who already understand the shopping habits of the Chinese, which are very different to those of consumers in the Western world. Chinese platforms such as Taobao and Tmall dominate the shopping world in China, so it is crucial to understand exactly how these platforms run in order to successfully market your own brand. One of the biggest problems that you will initially face when entering the Chinese market is that, as a business entering from the outside, you are essentially invisible to the Chinese market. You have no existing reputation within China, and any existing reputation you have is not guaranteed to help you. As China is cut off from the rest of the world by the ‘great firewall’ (no access to Facebook, Twitter, Instagram, Google, etc), there is no way in which Chinese consumers will be able to research your company on it’s existing platforms and therefore gain an idea of any previous reputation your business may have. So what is the solution? Start by building your reputation and visibility on Chinese platforms in order to ultimately drive leads and sales. Below are some essential tips on how to start doing this successfully. BAIDU DOMINATES ONLINE Currently, there are an estimated 900 million internet users across China, with most users spending 1.5 hours a day just browsing. Baidu is the most popular search engine across China. Think of it as ‘the Google of China’. This site is where 70% of all online research is carried out, so it is important to become visible in the search results through SEO (search engine optimisation), you need to build backlinks, produce quality content and audit the site for Chinese keyword searches to rank highly in the results over time. Baidu also brings the opportunity of paid advert links and banner ads, both very effective ways of reaching a wider audience. SOCIAL MEDIA IS A NECESSITY OF LIFE As the most popular social media app across China, it is imperative that your company becomes familiar with the inner workings of Wechat. Wechat is fundamentally a social media app, which allows the user to chat to friends, post photos and make free calls, however, it allows so much more than that. Booking cinema tickets, taxis, flights, topping up mobile phone credit, paying bills and even paying in store through Wechat pay are all possible. Many local and foreign companies already successful in China have official accounts on Wechat. An official account acts like a mini site, or an E store. You can personalise it to reflect the vibe of your brand, so an eye catching, professional looking account is key. An official account also allows the user to shop. Shopping in this way is becoming increasingly popular with the Chinese, as it is so quick and straightforward with payment being taken straight from your Wechat wallet. Many companies now also offer customer service through Wechat. Again, this is highly advisable as this is a service many Chinese consumers will now look for as it is quick and direct. Weibo is another popular social media app used across China. Think of Weibo as ‘the Twitter of China’. Weibo is an open network site so users can see posts from anyone without being their friend or following them. Similar to Twitter, Weibo can be an excellent way to market your company by sharing the latest updates, offers, promotions etc. Your followers can also start to share your content helping your company’s reputation spread by word of mouth. [Read more](https://marketingtochina.com/market-new-business-china)",
"title": ""
},
{
"docid": "121622",
"text": "\"BigCo is selling new shares and receives the money from Venturo. If Venturo is offering $250k for 25% of the company, then the valuation that they are agreeing on is a value of $1m for the company after the new investment is made. If Jack is the sole owner of one million shares before the new investment, then BigCo sells 333,333 shares to Venturo for $250k. The new total number of shares of BigCo is 1,333,333; Venturo holds 25%, and Jack holds 75%. The amount that Jack originally invested in the company is irrelevant. At the moment of the sale, the Venturo and Jack agree that Jack's stake is worth $750k. The value of Jack's stake may have gone up, but he owes no capital gains tax, because he hasn't realized any of his gains yet. Jack hasn't sold any of his stake. You might think that he has, because he used to hold 100% and now he holds 75%. However, the difference is that the company is worth more than was before the sale. So the value of his stake was unchanged immediately before and after the sale. Jack agrees to this because the company needs this additional capital in order to meet its potential. (See \"\"Why is stock dilution legal?\"\") For further explanation and another example of this, see the question \"\"If a startup receives investment money, does the startup founder/owner actually gain anything?\"\" Your other scenario, where Venturo purchases existing shares directly from Jack, is not practical in this situation. If Jack sells his existing shares, you are correct that the company does not gain any additional capital. An investor would not want to invest in the company this way, because the company is struggling and needs new capital.\"",
"title": ""
},
{
"docid": "22207",
"text": "\"I agree with all the people cautioning against working for free, but I'll also have a go at answering the question: When do I see money related to that 5%? Is it only when they get bought, or is there some sort of quarterly payout of profits? It's up to the shareholders of the company whether and when it pays dividends. A new startup will typically have a small number of people, perhaps 1-3, who between them control any shareholder vote (the founder(s) and an investor). If they're offering you 5%, chances are they've made sure your vote will not matter, but some companies (an equity partnership springs to mind) might be structured such that control is genuinely distributed. You would want to check what the particular situation is in this company. Assuming the founders/main investors have control, those people (or that person) will decide whether to pay dividends, so you can ask them their plans to realise money from the company. It is very rare for startups to pay any dividends. This is firstly because they're rarely profitable, but even when they are profitable the whole point of a startup is to grow, so there are plenty of things to spend cash on other than payouts to shareholders. Paying anything out to shareholders is the opposite of receiving investment. So unless you're in the very unusual position of a startup that will quickly make so much money that it doesn't need investment, and is planning to pay out to shareholders rather than spend on growth, then no, it will not pay out. One way for a shareholder to exit is to be bought out by other shareholders. For example if they want to get rid of you then they might make you an offer for your 5%. This can be any amount they think you'll take, given the situation at the time. If you don't take it, there may be things they can do in future to reduce its value to you (see below). If you do take it then your 5% would pay you once, when you leave. If the company succeeds, commonly it will be wholly or partly sold (either privately or by IPO). At this point, if it's wholly sold then the soon-to-be-ex-shareholders at the time will receive the proceeds of the sale. If it's partly sold then as with an investment round it's up for negotiation what happens. For example I believe the cash from an IPO of X% of the company could be taken into the company, leaving the shareholders with no immediate direct payout but (100-X)% of shares in their names that they're more-or-less free to sell, or retain and receive future dividends. Alternatively, if the company settles down as a small private business that's no longer in startup mode, it might start paying out without a sale. If the company fails, as most startups do, it will never pay anything. It's very important to remember that it's the shareholders at the time who receive money in proportion to their holding (or as defined by the company articles, if there are different classes of share). Just because you have 5% now doesn't mean you'll have 5% by that time, because any new investment into the company in the mean time will \"\"dilute\"\" your shareholding. It works like this: Note that I've assumed for simplicity that the new investment comes in at equal value to the old investment. This isn't necessarily the case, it can be more or less according to the terms of the new investment voted for by the shareholders, so the first line really is \"\"nominal value\"\", not necessarily the actual cash the founders put in. Therefore, you should not think of your 5% as 5% of what you imagine a company like yours might eventually exit for. At best, think of it as 5% of what a company like yours might exit for, if it receives no further investment whatsoever. Ah, but won't the founders also have their holdings diluted and lose control of the company, so they wouldn't do that? Well, not necessarily. Look carefully at whether you're being offered the same class of shares as the founders. If not consider whether they can dilute your shares without diluting their own. Look also at whether a new investor could use the founders' executive positions to give them new equity in the same way they gave you old equity, without giving you any new equity. Look at whether the founders will themselves participate in future investment rounds using sacks of cash that they own from other ventures, when you can't afford to keep up. Look at whether new investors will receive a priority class of share that's guaranteed at exit to pay out a certain multiple of the money invested before the older, inferior classes of shares receive anything (VCs like to do this, at least in the UK). Look at any other tricks they can legally pull: even if the founders aren't inclined to be tricky, they may eventually be forced to consider pulling them by a future new investor. And when I say \"\"look\"\", I mean get your lawyer to look. If your shareholding survives until exit, then it will pay out at exit. But repeated dilutions and investors with priority classes of shares could mean that your holding doesn't survive to exit even if the company does. Your 5% could turn into a nominal holding that hasn't really \"\"survived\"\", that entitles you to 0.5% of any sale value over $100 million. Then if the company sells for $50 million you get $0, while other investors are getting a good return. All of this is why you should not work for equity unless you can afford to work for free. And even then you need to lawyer up, now and during any future investment, so your lawyer can explain to you what your investment actually is, which almost certainly is different from what it looks like at a casual uninformed glance.\"",
"title": ""
},
{
"docid": "154841",
"text": "The short answer, probably not much. Unless you have a controlling interest in the company. If at least 50%+1 of the shareholder votes are in favor of the dilution then it can be done. There are some SEC rules that should protect against corporate looting and theft like what the Severin side is trying to make it appear as happened. However it would appear that Severin did something stupid. He signed away all of his voting right to someone who would use them to make his rights basically worthless. Had he kept his head in the game he could probably have saved himself. But he didn't. If your average startup started issuing lots of stock and devaluing existing shares significantly then I would expect it would be harder to find investors willing to watch as their investment dwindled. But if you are issuing a limited amount stock to get leverage to grow bigger then it is worth it. In the .com bubble there were quite a few companies that just issued stock to buy other companies. Eventually most of these companies got delisted because they diluted them selves to much when they were overvalued. Any company not just a startup can dilute its shares. Many if not most major companies issue stock to raise capital. This capital is then generally used to build the business further and increase the value of all shares. Most of the time this dilution is very minor (<.1%) and has little if any impact on the stock. There are rules that have to be followed as listed companies are regulated by the SEC. There are less regulations with private corporations. It looks like the dilution was combined with the buyout of the Florida company which probably contributed to the legality of the dilution. With options they are generally issued at a set price. This may be higher or lower than the reported sell price of the stock when the option is issued. The idea is over time the stock will increase in value so that those people who hold on to their options can buy the stock for the price listed on the option. I worked at an ISP start up in the 90's that made it pretty well. I left before the options were issued but I had friends still there that were issued an option at $16 a share the value of the stock at the time of the issue of the option was about 12. Well the company diluted the shares and used them to acquire more ISP's unfortunately this was about the time that DSL And cable internet took off so the dial up market tanked. The value eventually fell to .10 they did a reverse split and when they did the called in all options. The options did not have a positive cash value at any time. Had RMI ever made it big then the options could have been worth millions. There are some people from MS and Yahoo that were in early that made millions off of their options. This became a popular way for startups to attract great talent paying peanuts. They invested their time in the business hoping to strike gold. A lot of IT people got burned so this is less popular among top talent as the primary compensation anymore.",
"title": ""
},
{
"docid": "580542",
"text": "> Google would be forced to actually compete with companies vs. Giving everything away free. That creates employment opportunities for other startups to compete in a fair environment vs. Trying to acquire millions of users on no revenue. TL;DR Don't blame business, blame the politics that let bad business happen. Business doesn't work like that, specially for a publicly traded company. 'Free' goods or services are used as a loss leader to drive their profits in other sectors of the company. Whether it's for PR, marketing, or sales, no company drives their business at a loss. Somewhere, somehow the free things they do are driving their business towards higher profitability. Money isn't being lost on the economy by providing these things as free, it's just being used in different ways. Sure it could be used to pay for the wages of an employee at a startup which provides the same service... but if Google is providing it at or below the most efficient market price then it would be *wasting* money to have less efficient companies providing essentially the same product or service. That money could instead be used in more profitable sectors of the economy, which could in turn generate a healthier and/or faster growing economy overall. Working smarter, not harder. Secondly, startups aren't designed for profitability in the first few years of their operations. They're designed to capture users and information (or as patent holders but that's largely unrelated to my main point) that can later be acquired by larger companies who are looking to target those users. Why else would any company pay for a startup while they're operating at a loss? The revenue for startups comes much later on as they're bought out by bigger companies or they find a way to monetize their user base/generate stable sources of revenue. If your argument is that employment by start ups drives the economy at large, I have to ask, if the economy is operating less efficiently (by supporting start ups in replacing the market share currently held by much more efficiently operating large companies ~) by employing more people, how is this healthier for the economy as a whole? Supporting start ups is good but it has to be done in such a way that it doesn't hurt existing business just for the sake of making jobs. The size of a company doesn't make them bad as long as they compete fairly with everyone else in the market. ~ caveat being where large companies do not form an oligopoly (ie Comcast, TWC, etc...) which is obviously inefficient to begin with which is largely a product of bad politics rather than market forces",
"title": ""
},
{
"docid": "417838",
"text": "\"The main thing is the percentage of the company represented by the shares. Number of shares is meaningless without total shares. If you compute percentage and total company value you can estimate the value of the grant. Or perhaps more useful for a startup is to multiple the percentage by some plausible \"\"exit\"\" value, such as how much the company might sell for or IPO for. Many grants expire when or soon after you leave the company if you don't \"\"cash out\"\" vested shares when you leave, this is standard, but do remember it when you leave. The other major thing is vesting. In the tech industry, vesting 1/4 after a year and then the rest quarterly over 3 more years is most common.\"",
"title": ""
},
{
"docid": "285041",
"text": "\"Companies normally do not give you X% of shares, but in effect give you a fixed \"\"N\"\" number of shares. The \"\"N\"\" may translate initially to X%, but this can go down. If say we began with 100 shares, A holding 50 shares and B holding 50 shares. As the startup grows, there is need for more money. Create 50 more shares and sell it at an arranged price to investor C. Now the percentage of each investor is 33.33%. The money that comes in will go to the company and not to A & B. From here on, A & C together can decide to slowly cut out B by, for example: After any of the above the % of shares held by B would definitely go down.\"",
"title": ""
},
{
"docid": "381568",
"text": "I started a company that's in the process of trying to become an SEC approved funding portal as defined by this Act. That being said, I obviously think it was a good thing overall. It's going to be much easier for companies to raise money. However, I think it's also going to be much more difficult find good investments. There's a chance that it might fuel a bubble similar to the Dotcom bubble in the late 90's/early 00's. That's *if* it takes off. I have some doubts that it will really change the landscape a whole lot. Even though it's now legal, you still don't see startups, hedge funds, etc. soliciting investments. At least I don't. Some of the relaxing of SOX requirements is interesting, but I don't think that really does anything but just defer the inevitable. There are quite a few private companies that are already SOX compliant simply because if they go public or get purchased by a public company, that can be a big advantage. The increasing of shareholders of record from 500 to 2,000 is irrelevant really. One shareholder of record can sell portions of their interest to as many people as they want (See: Goldman Sachs and Facebook). Making equity investments in startups available to regular Joe's is a good thing overall. It allows the possibility that someone making $50k per year to invest in a company that could, in the long run, boost them up a tax bracket or two. The flipside of that is that I still believe most of the US to be financially illiterate. There's a possibility of abuse. The SEC is currently writing rules to try and stem that, but there will still be people who do it. Hopefully it's not too bad. Lifting the ban on general solicitation is, in general, a good thing. For startups I think this might be advantageous, but won't be used very much. Part of the reason startups choose the investors they do (if they're smart) is for what value that person or people bring to the table besides cash. If I'm a startup and I need some money, I'm giving up a portion of my baby to someone. I want to make sure that person is smart and on the same page with me. I'm not going to settle for just anyone. It's important to remember that even if that person has one share, they still get a vote and a say in how I run my company. **TL;DR** - Overall I think it's going to be good. It's not going to be quite as radical as most people think. There will be some abuses of the new laws and regs, but that comes with the territory.",
"title": ""
},
{
"docid": "76556",
"text": "Stuff I wish I had known, based on having done the following: Obtained employment at a startup that grants Incentive Stock Options (ISOs); Early-exercised a portion of my options when fair market value was very close to my strike price to minimize AMT; made a section 83b) election and paid my AMT up front for that tax year. All this (the exercise and the AMT) was done out of pocket. I've never see EquityZen or Equidate mention anything about loans for your exercise. My understanding is they help you sell your shares once you actually own them. Stayed at said startup long enough to have my exercised portion of these ISOs vest and count as long term capital gains; Tried to sell them on both EquityZen and Equidate with no success, due to not meeting their transaction minimums. Initial contact with EquityZen was very friendly and helpful, and I even got a notice about a potential sale, but then they hired an intern to answer emails and I remember his responses being particularly dismissive, as if I was wasting their time by trying to sell such a small amount of stock. So that didn't go anywhere. Equidate was a little more friendly and was open to the option of pooling shares with other employees to make a sale in order to meet their minimum, but that never happened either. My advice, if you're thinking about exercising and you're worried about liquidity on the secondary markets, would be to find out what the minimums would be for your specific company on these platforms before you plunk any cash down. Eventually brought my request for liquidity back to the company who helped connect me with an interested external buyer, and we completed the transaction that way. As for employer approval - there's really no reason or basis that your company wouldn't allow it (if you paid to exercise then the shares are yours to sell, though the company may have a right of first refusal). It's not really in the company's best interest to have their shares be illiquid on the secondary markets, since that sends a bad signal to potential investors and future employees.",
"title": ""
},
{
"docid": "277645",
"text": "If the company is non-public, your hands are tied. Most startups have a Stock Option Plan with specific rules on the shares. In almost all cases, they have a Transferability clause preventing transfers of options and shares unless approved by the company (who would almost always say no). Additionally, they usually have a Right of First Refusal (ROFR), which states that if shares are going to be transferred, the company gets the chance to buy it first. In your case, the company may argue your friend would sell you the shares for free and the company would exercise their ROFR and buy back the shares for free. There is not much you can do in this case. You may be able to write up a contract between your friend and you, but it would be costly and possibly not worth the effort. You may be better off asking for a lump sum or some other sort of compensation. Additionally, your friend might want to be careful with this idea. You could potentially gain access to sensitive company tools/documents which could get them in a lot of trouble.",
"title": ""
},
{
"docid": "106249",
"text": "For one, the startup doesn't exist yet, so until March I will get nothing on hand, though I have enough reserves to bridge that time. I would not take this deal unless the start-up exists in some form. If it's just not yet profitable, then there's a risk/reward to consider. If it doesn't exist at all, then it cannot make a legal obligation to you and it's not worth taking the deal yet. If everything else is an acceptable risk to you, then you should be asking the other party to create the company and formalize the agreement with you. As regards reserves, if you're really getting paid in shares instead of cash, then you may need them later. Shares in a start-up likely are not easy to sell (if you're allowed to sell them at all), so it may be a while before a paycheck given what you've described. For a second, who pays the tax? This is my first non-university job so I don't exactly know, but usually the employer has to/does pay my taxes and some other stuff from my brutto-income (that's what I understood). If brutto=netto, where is the tax? This I cannot answer for Germany. In the U.S. it would depend in part on how the company is organized. It's likely that some or all of the tax will be deferred until you monetize your shares, but you should get some professional advice on that before you move forward. As an example, it's likely that you'd get taxed (in part or in whole) on what we'd call capital gains (maybe Abgeltungsteuer in German?) that would only be assessed when you sell the shares. For third, shares are a risk. If I or any other in the startup screw really, my pay might be a lot less than expected. Of course, if it works out I'm rich(er). This is the inherent risk of a start-up, so there's no getting around the fact that there's a chance that the business may fail and your shares become worthless. Up to you if you think the risk is acceptable. Where you can mitigate risk is in ensuring that there's a well-written and enforceable set of documents that define what rights go with the shares, who controls the company, how profits will be distributed, etc. Don't do this by spoken agreement only. Get it all written down, and then get it checked by a lawyer representing your interests.",
"title": ""
},
{
"docid": "365092",
"text": "\"they are entirely free to do whatever they want with the shares. In particular, they can sell them to whomever they choose No. Restrictions on who can sell when and to whom are a common thing with startups. \"\"Publicly traded\"\" companies are regulated in a much stricter way than private companies, so until the IPO the sales are limited to the OTC markets. But even that can be restricted by bylaws - for example ownership can only be limited to a group of investors approved by the board. As an employee - your grant was approved by the board, but when you come to sell, the buyer was not and the company may not agree to vet them. Bottom line is that it is not illegal to impose all kinds of restrictions on what the employees can do with their shares, as long as the shares are not listed on a public stock exchange (even after the company goes IPO with one class, other classes may remain restricted).\"",
"title": ""
},
{
"docid": "421892",
"text": "As it stands equity contracts in startups are by default structured differently. The standard equity is shares or convertible notes. Having equity that's structured in the way you propose is a bad idea for both sides. VC don't like equity that's not done with standard equity contracts. If the lawyer of the VC has to review your equity document and understand how the exact terms work that makes it more complicated to invest money into the startup. On your end it might not be fair because a company doesn't need to make any income to be successful. Various companies manage to reduce their tax burden to next to nothing by clever accounting that results in having no taxable income. Uber brought the uber.com domain name with 2% equity at the beginning, so there are certainly deals that get made with equity. There are also other kinds of deals where domain names don't get sold for a one-time payment but with regular payment for 8 years where the domain names goes back to the seller if the company folds or otherwise doesn't want to pay anyone.",
"title": ""
},
{
"docid": "267266",
"text": "\"It's called \"\"dilution\"\". Usually it is done to attract more investors, and yes - the existing share holders will get diluted and their share of ownership shrinks. As a shareholder you can affect the board decisions (depends on your stake of ownership), but usually you'll want to attract more investors to keep the company running, so not much you can do to avoid it. The initial investors/employees in a startup company are almost always diluted out. Look at what happened to Steve Jobs at Apple, as an example.\"",
"title": ""
},
{
"docid": "181582",
"text": "\"There are two different companies named \"\"Volvo.\"\" The publicly-traded company with ticker symbol VOLV-B is called Volvo Group, or AB Volvo. They primarily build trucks, buses, and construction equipment. The company that makes the Volvo branded cars is called Volvo Cars. It is a privately-held company currently owned by the Chinese Geely Holding Group. It was all one company until 1999, when AB Volvo sold off its car brand to Ford. Because of the history, the two companies share the same logo.\"",
"title": ""
},
{
"docid": "156747",
"text": "\"Equity could mean stock options. If that's the case if the company makes it big, you'll have the option to buy stocks cheap (which can then be sold at a huge profit) How are you going to buy those without income? 5% equity is laughable. I'd be looking for 30-40% if not better without salary. Or even better, a salary. To elaborate, 5% is fine, and even normal for an early employee taking a mild pay cut in exchange for a chance at return. That chance of any return on the equity is only about 1/20 (94% of startups fail) There is no reason for an employee to work for no pay. An argument could be made for a cofounder, with direct control and influence in the company to work for equity only, but it would be a /lot/ more (that 30-40%), or an advisory role (5% is reasonable) I also just noticed you mentioned \"\"investing\"\" in the startup with cash. As an angel investor, I'd still expect far more than 5%, and preferred shares at that. More like 16-20%. Read this for more info on how equity is usually split.\"",
"title": ""
},
{
"docid": "36366",
"text": "\"This is such a common question here and elsewhere that I will attempt to write the world's most canonical answer to this question. Hopefully in the future when someone on answers.onstartups asks how to split up the ownership of their new company, you can simply point to this answer. The most important principle: Fairness, and the perception of fairness, is much more valuable than owning a large stake. Almost everything that can go wrong in a startup will go wrong, and one of the biggest things that can go wrong is huge, angry, shouting matches between the founders as to who worked harder, who owns more, whose idea was it anyway, etc. That is why I would always rather split a new company 50-50 with a friend than insist on owning 60% because \"\"it was my idea,\"\" or because \"\"I was more experienced\"\" or anything else. Why? Because if I split the company 60-40, the company is going to fail when we argue ourselves to death. And if you just say, \"\"to heck with it, we can NEVER figure out what the correct split is, so let's just be pals and go 50-50,\"\" you'll stay friends and the company will survive. Thus, I present you with Joel's Totally Fair Method to Divide Up The Ownership of Any Startup. For simplicity sake, I'm going to start by assuming that you are not going to raise venture capital and you are not going to have outside investors. Later, I'll explain how to deal with venture capital, but for now assume no investors. Also for simplicity sake, let's temporarily assume that the founders all quit their jobs and start working on the new company full time at the same time. Later, I'll explain how to deal with founders who do not start at the same time. Here's the principle. As your company grows, you tend to add people in \"\"layers\"\". The top layer is the first founder or founders. There may be 1, 2, 3, or more of you, but you all start working about the same time, and you all take the same risk... quitting your jobs to go work for a new and unproven company. The second layer is the first real employees. By the time you hire this layer, you've got cash coming in from somewhere (investors or customers--doesn't matter). These people didn't take as much risk because they got a salary from day one, and honestly, they didn't start the company, they joined it as a job. The third layer are later employees. By the time they joined the company, it was going pretty well. For many companies, each \"\"layer\"\" will be approximately one year long. By the time your company is big enough to sell to Google or go public or whatever, you probably have about 6 layers: the founders and roughly five layers of employees. Each successive layer is larger. There might be two founders, five early employees in layer 2, 25 employees in layer 3, and 200 employees in layer 4. The later layers took less risk. OK, now here's how you use that information: The founders should end up with about 50% of the company, total. Each of the next five layers should end up with about 10% of the company, split equally among everyone in the layer. Example: Two founders start the company. They each take 2500 shares. There are 5000 shares outstanding, so each founder owns half. They hire four employees in year one. These four employees each take 250 shares. There are 6000 shares outstanding. They hire another 20 employees in year two. Each one takes 50 shares. They get fewer shares because they took less risk, and they get 50 shares because we're giving each layer 1000 shares to divide up. By the time the company has six layers, you have given out 10,000 shares. Each founder ends up owning 25%. Each employee layer owns 10% collectively. The earliest employees who took the most risk own the most shares. Make sense? You don't have to follow this exact formula but the basic idea is that you set up \"\"stripes\"\" of seniority, where the top stripe took the most risk and the bottom stripe took the least, and each \"\"stripe\"\" shares an equal number of shares, which magically gives employees more shares for joining early. A slightly different way to use the stripes is for seniority. Your top stripe is the founders, below that you reserve a whole stripe for the fancy CEO that you recruited who insisted on owning 10%, the stripe below that is for the early employees and also the top managers, etc. However you organize the stripes, it should be simple and clear and easy to understand and not prone to arguments. Now that we have a fair system set out, there is one important principle. You must have vesting. Preferably 4 or 5 years. Nobody earns their shares until they've stayed with the company for a year. A good vesting schedule is 25% in the first year, 2% each additional month. Otherwise your co-founder is going to quit after three weeks and show up, 7 years later, claiming he owns 25% of the company. It never makes sense to give anyone equity without vesting. This is an extremely common mistake and it's terrible when it happens. You have these companies where 3 cofounders have been working day and night for five years, and then you discover there's some jerk that quit after two weeks and he still thinks he owns 25% of the company for his two weeks of work. Now, let me clear up some little things that often complicate the picture. What happens if you raise an investment? The investment can come from anywhere... an angel, a VC, or someone's dad. Basically, the answer is simple: the investment just dilutes everyone. Using the example from above... we're two founders, we gave ourselves 2500 shares each, so we each own 50%, and now we go to a VC and he offers to give us a million dollars in exchange for 1/3rd of the company. 1/3rd of the company is 2500 shares. So you make another 2500 shares and give them to the VC. He owns 1/3rd and you each own 1/3rd. That's all there is to it. What happens if not all the early employees need to take a salary? A lot of times you have one founder who has a little bit of money saved up, so she decides to go without a salary for a while, while the other founder, who needs the money, takes a salary. It is tempting just to give the founder who went without pay more shares to make up for it. The trouble is that you can never figure out the right amount of shares to give. This is just going to cause conflicts. Don't resolve these problems with shares. Instead, just keep a ledger of how much you paid each of the founders, and if someone goes without salary, give them an IOU. Later, when you have money, you'll pay them back in cash. In a few years when the money comes rolling in, or even after the first VC investment, you can pay back each founder so that each founder has taken exactly the same amount of salary from the company. Shouldn't I get more equity because it was my idea? No. Ideas are pretty much worthless. It is not worth the arguments it would cause to pay someone in equity for an idea. If one of you had the idea but you both quit your jobs and started working at the same time, you should both get the same amount of equity. Working on the company is what causes value, not thinking up some crazy invention in the shower. What if one of the founders doesn't work full time on the company? Then they're not a founder. In my book nobody who is not working full time counts as a founder. Anyone who holds on to their day job gets a salary or IOUs, but not equity. If they hang onto that day job until the VC puts in funding and then comes to work for the company full time, they didn't take nearly as much risk and they deserve to receive equity along with the first layer of employees. What if someone contributes equipment or other valuable goods (patents, domain names, etc) to the company? Great. Pay for that in cash or IOUs, not shares. Figure out the right price for that computer they brought with them, or their clever word-processing patent, and give them an IOU to be paid off when you're doing well. Trying to buy things with equity at this early stage just creates inequality, arguments, and unfairness. How much should the investors own vs. the founders and employees? That depends on market conditions. Realistically, if the investors end up owning more than 50%, the founders are going to feel like sharecroppers and lose motivation, so good investors don't get greedy that way. If the company can bootstrap without investors, the founders and employees might end up owning 100% of the company. Interestingly enough, the pressure is pretty strong to keep things balanced between investors and founders/employees; an old rule of thumb was that at IPO time (when you had hired all the employees and raised as much money as you were going to raise) the investors would have 50% and the founders/employees would have 50%, but with hot Internet companies in 2011, investors may end up owning a lot less than 50%. Conclusion There is no one-size-fits-all solution to this problem, but anything you can do to make it simple, transparent, straightforward, and, above-all, fair, will make your company much more likely to be successful. The above awesome answer came from the Stack Exchange beta site for startups, which has now closed. I expect that this equity distribution question (which is strongly tied to personal finance) will come up more times in the future so I have copied the content originally posted. All credit for this excellent answer is due to Joel Spolsky, a moderator for the Startups SE beta site, and co-founder of Stack Exchange.\"",
"title": ""
},
{
"docid": "394952",
"text": "Thank you for sharing. I had a feeling it be a legal but soulless job. Unfortunately I have mouths to feed so I'll do what it takes. I just don't want to be fucked over from a startup company since I never worked for one.",
"title": ""
},
{
"docid": "480119",
"text": "As a start-up, the initial shares can be given at various price points. So essentially they can give someone a larger percentage based on the same amount earlier, and lesser percentage to someone else for the same amount. As its a start-up the valuations can be very tricy and what matters is that whether you believe the percentage you got for the amount is right or not. It is very important to note that when you have been given an ownership in the company, how that is designated. Is it in absolute number of shares or is it in terms of percentage based on the existing shares. For example you maybe given 100 shares, without any qualification. Or you maybe given a 5% stake in the paid-up capital, that translates to 100 shares. It is always better to hold the shares in % of the total shares. Also read the contract, any dilution should require your approval. Normally start-ups once the valuation starts to go up, start creating more shares and sell these to private equity or create more shares and give it as a bonus to promoters. Hence in both cases your holding will keep getting diluted. There is a related quesiton If a startup can always issue new shares, what value is there to stocks/options?",
"title": ""
},
{
"docid": "467081",
"text": "\"Different stocks balance dividend versus growth differently. Some have relatively flat value but pay a strong dividend -- utility stocks used to be examples of that model, and bonds are in some sense an extreme version of this. Some, especially startups, pay virtually no dividends and aim for growth in the value of the stock. And you can probably find a stock that hits any point between these. This is the \"\"growth versus income\"\" spectrum you may have heard mentioned. In the past, investors took more of their return on investment as dividends -- conceptually, a share of the company's net profits for the year reflecting the share's status as partial ownership. If you wanted to do so, you could use the dividend to purchase more shares (via a dividend reinvestment plan or not), but that was up to you. These days, with growth having been strongly hyped, many companies have shifted much more to the growth model and dividends are often relatively wimpy. Essentially, this assumes that everyone wants the money reinvested and will take their profit by having that increase the value of their shares. Of course that's partly because some percentage of stockholders have been demanding growth at all costs, not always realistically. To address your specific case: No, you probably aren't buying Microsoft because you like its dividend rate; you're buying it in the hope it continues to grow in stock value. But the dividend is a bit of additional return on your investment. And with other companies the tradeoff will be different. That's one of the things, along with how much you believe in the company, that would affect your decision when buying shares in specific companies. (Personally I mostly ignore the whole issue, since I'm in index funds rather than individual stocks. Picking the fund sets my overall preference in terms of growth versus income; after that it's their problem to maintain that balance.)\"",
"title": ""
},
{
"docid": "282538",
"text": "Alot of these answers have focused on the dilution aspect, but from a purely legal aspect, there are usually corporate bylaws that spell out what kind of vote and percentage of votes is needed to take this type of action. If all other holders of stock voted to do this, so 90% for, and you didn't, so 10% against, it's still legal if that vote meets the threshold for taking the action. As an example of this, I known of a startup where employees got $0/share for their vested shares when the company was sold because the voting stock holders agreed to it. Effectively the purchase amount was just enough to cover debts and preferred stock.",
"title": ""
},
{
"docid": "15272",
"text": "\"Buying shares back is an indication that the company has nothing better to do with their money. True. However, buying the shares back is essentially moving money around, the firms (or individuals) they buy from, will invest their money differently. Mergers and acquisitions are productive though. The idea is that you combine things to work more efficiently. For example, a small startup might have a great product but not a lot of infrastructure or cash. So the big guys with both buy em up. Or, big companies might have redundant expenditures in infrastructure or employees, and by merging they can produce more efficiently. The term you keep using \"\"real economy\"\" is a strange one. The above parties are part of the real economy. Really. What, may I ask, is your education in economics? What books have you read on the subject, classes taken, jobs worked, podcasts listened to, etcetera, that are giving you these ideas?\"",
"title": ""
},
{
"docid": "370976",
"text": "Everything in life is a combination of luck and skill. Startups are no different. The risks are higher and most sensible people know and understand that. You know why we worship the successes? Because against all odds, those startups stood up to your salaried buddies who work for faceless large corporations and have tons of people and kicked their asses. At some point, they deserve it. You see startups as gambling, others see it as betting on yourself. Especially founding or joining an early stage startup. It's also taking on huge responsibility. In a mega-corp your failures and shortcomings will be covered and almost certainly won't tank the company. Your creativity probably won't flourish and their is an incentive to do just well enough. Why should you work your ass off for a company that you're not invested in other than a paycheck? Startups aren't for everyone. Hell, startups probably aren't for most people. But there are some people, those select few, who simply can't imagine not working for themselves, creating things, tinkering, trying to change the world. It's not even gambling to them, it's a way of life.",
"title": ""
},
{
"docid": "331664",
"text": "\"This is the best tl;dr I could make, [original](https://www.theguardian.com/technology/2017/oct/20/tech-startups-facebook-amazon-google-apple) reduced by 91%. (I'm a bot) ***** > Startups drive job creation and innovation, but the number of new business launches is at a 30-year low and some economists, investors and entrepreneurs are pointing their fingers at big tech. > For one thing, the deep pockets and resources of companies like Facebook, Google, Amazon and Apple - with a combined value of almost $2.5tn - make it increasingly difficult for startups to compete or attract investment. > Even multibillion-dollar startups like Snap, Snapchat&#039;s parent company, struggle to compete against these tech titans. ***** [**Extended Summary**](http://np.reddit.com/r/autotldr/comments/781c68/as_tech_companies_get_richer_is_it_game_over_for/) | [FAQ](http://np.reddit.com/r/autotldr/comments/31b9fm/faq_autotldr_bot/ \"\"Version 1.65, ~233105 tl;drs so far.\"\") | [Feedback](http://np.reddit.com/message/compose?to=%23autotldr \"\"PM's and comments are monitored, constructive feedback is welcome.\"\") | *Top* *keywords*: **startup**^#1 **Amazon**^#2 **Facebook**^#3 **company**^#4 **launch**^#5\"",
"title": ""
},
{
"docid": "87696",
"text": "Source, see if you have access to it Convertible notes are often used by angel investors who wish to fund businesses without establishing an explicit valuation of the company in which they are investing. When an investor purchases equity in a startup, the purchase price of the equity implies a company valuation. For example, if an investor purchases a 10 per cent ownership stake in a company, and pay $1m for that stake, this implies that the company is worth $10m. Some early stage investors may wish to avoid placing a value on the company in this way, because this in turn will affect the terms under which later-stage investors will invest in the company. Convertible notes are structured as loans at the time the investment is made. The outstanding balance of the loan is automatically converted to equity when a later equity investor appears, under terms that are governed by the terms set by the later-stage equity investor. An equity investor is someone who purchases equity in a company. Example:- Suppose an angel investor invests $100,000 using a convertible note. Later, an equity investor invests $1m and receives 10% of the company's shares. In the simplest possible case, the initial angel investor's convertible note would convert to 1/10th of the equity investor's claim. Depending on the exact structure of the convertible note, however, the angel investor may also receive extra shares to compensate them for the additional risk associated with being an earlier investor The worst-case scenario would be if the issuing company initially performed well, meaning that the debt would be converted into shares, and subsequently went bankrupt. The converted shares would become worthless, but the holder of the note would no longer have any recourse. Will twitter have to sell their offices and liquidate staff to close this debt? This depends on the seniority(priority) of the debt. Debt is serviced according to seniority. The higher seniority debts will be paid off first and then only the lower seniority debts be serviced. This will all be in the agreements when you enter into a transaction. When you say liquidate staff you mean sell off their assets and not sell their staff into slavery.",
"title": ""
},
{
"docid": "586984",
"text": "Similar premise, yes. It's an investment so you're definitely hoping it grows so you can sell it for a profit/gain. Public (stock market) vs. private (shark tank) are a little different though in terms of how much money you get and the form of income. With stocks, if you buy X number of shares at a certain price, you definitely want to sell them when they are worth more. However, you don't get, say 0.001% (or whatever percentage you own, it would be trivial) of the profits. They just pay a dividend to you based on a pre-determined amount and multiply it by the number of shares you own and that would be your income. Unless you're like Warren Buffet and Berkshire who can buy significant stakes of companies through the stock market, then they can likely put the investment on the balance sheet of his company, but that's a different discussion. It would also be expensive as hell to do that. With shark tank investors, the main benefit they get is significant ownership of a company for a cheap price, however the risk can be greater too as these companies don't have a strong foundation of sales and are just beginning. Investing in Apple vs. a small business is pretty significant difference haha. These companies are so small and in such a weak financial position which is why they're seeking money to grow, so they have almost no leverage. Mark Cuban could swoop in and offer $50k for 25% and that's almost worth it relative to what $50k in Apple shares would get him. It's all about the return. Apple and other big public companies are mature and most of the growth has already happened so there is little upside. With these startups, if they ever take off then and you own 25% of the company, it can be worth billions.",
"title": ""
},
{
"docid": "319817",
"text": "Summarized article: Huawei and ZTE, China's two largest telecommunications companies, disputed the findings of a report by the House Intelligence Committee which determined that both companies pose a national security threat. The report determined that using equipment from Huawei and ZTE could provide opportunities for Chinese intelligence services to tamper or spy on US telecommunications networks. Huawei and ZTE failed to cooperate with a year-long investigation and to fully explain their relationship with the Chinese government, according to the report. Additionally, the report noted Huawei's pattern of illegal behavior in the US, including intellectual property violations, immigration violations and bribery and corruption. Committee officials intend to refer their findings to federal law enforcement agencies. In response to the report, both Huawei and ZTE said they fully cooperated with the congressional investigation and called the findings baseless. They also deny they are controlled by the Chinese government. Additionally, Huawei said it believes the congressional findings were predetermined in order to impede competition and block Chinese telecommunications companies from entering the US market. Although Huawei often refers to its business operations in the United Kingdom to show the company's integrity, Huawei has been consistently passed over for contracts in the US. Huawei was also blocked from bidding on an Australian national contract in March. * For more summarized news, subscribe to the [/r/SkimThat](http://www.reddit.com/r/SkimThat) subreddit",
"title": ""
},
{
"docid": "412037",
"text": "By the by, I'm 27. I've been living on my own since I was 15. I've worked at startup-style companies with a rich founder and no investment (Limewire), worked for funded startups companies as a consultant (ex: Ning), personally know the founders and/or very early stage employees of many famous startups (Gowalla, Twitter, GitHub, Shopify, etc), and I've also consulted for companies like Bear Stearns, Pepsico, Ford… But you could already tell all that from my picture, I'm sure.",
"title": ""
},
{
"docid": "232388",
"text": "\"Previous answers have done a great job with the \"\"Should I invest?\"\" question. One thing you may be overlooking is the question \"\"Am I allowed to invest?\"\" For most offerings of stock in a startup, investors are required to be accredited by the SEC's definition. See this helpful quora post for more information on requirements to invest in startups. To be honest, if a startup is looking for investors to put in \"\"a few thousand dollars\"\" each, this would raise my alarm bells. The cost and hassle of the paperwork to (legitimately) issue shares in that small of number would lead me just to use a credit card to keep me going until I was able to raise a larger amount of capital.\"",
"title": ""
}
] |
6537
|
Can you sell on the settlement date?
|
[
{
"docid": "124188",
"text": "Yes, on the settlement the stock is yours to sell with no risk of freeride or day trading applying.",
"title": ""
}
] |
[
{
"docid": "226984",
"text": "\"The settlement date for any trade is the date on which the seller gets the buyer's money and the buyer gets the seller's product. In US equities markets the settlement date is (almost universally) three trading days after the trade date. This settlement period gives the exchanges, the clearing houses, and the brokers time to figure out how many shares and how many dollars need to actually be moved around in order to give everyone what they're owed (and then to actually do all that moving around). So, \"\"settling\"\" a short trade is the same thing as settling any other trade. It has nothing to do with \"\"closing\"\" (or covering) the seller's short position. Q: Is this referring to when a short is initiated, or closed? A: Initiated. If you initiate a short position by selling borrowed shares on day 1, then settlement occurs on day 4. (Regardless of whether your short position is still open or has been closed.) Q: All open shorts which are still open by the settlement date have to be reported by the due date. A: Not exactly. The requirement is that all short positions evaluated based on their settlement dates (rather than their trade dates) still open on the deadline have to be reported by the due date. You sell short 100 AAPL on day 1. You then cover that short by buying 100 AAPL on day 2. As far as the clearing houses and brokers are concerned, however, you don't even get into the short position until your sell settles at the end of day 4, and you finally get out of your short position (in their eyes) when your buy settles at the end of day 5. So imagine the following scenarios: The NASDAQ deadline happens to be the end of day 2. Since your (FINRA member) broker has been told to report based on settlement date, it would report no open position for you in AAPL even though you executed a trade to sell on day 1. The NASDAQ deadline happens to be the end of day 3. Your sell still has not settled, so there's still no open position to report for you. The NASDAQ deadline happens to be the end of day 4. Your sell has settled but your buy has not, so the broker reports a 100 share open short position for you. The NASDAQ deadline happens to be the end of day 5. Your sell and buy have both settled, so the broker once again has no open position to report for you. So, the point is that when dealing with settlement dates you just pretend the world is 3 days behind where it actually is.\"",
"title": ""
},
{
"docid": "340815",
"text": "When you buy a futures contract you are entering into an agreement to buy gold, in the future (usually a 3 month settlement date). this is not an OPTION, but a contract, so each party is taking risk, the seller that the price will rise, the buyer that the price will fall. Unlike an option which you can simply choose not to exercise if the price goes down, with futures you are obligated to follow through. (or sell the contract to someone else, or buy it back) The price you pay depends on the margin, which is related to how far away the settlement date is, but you can expect around 5% , so the minimum you could get into is 100 troy ounces, at todays price, times 5%. Since we're talking about 100 troy ounces, that means the margin required to buy the smallest sized future contract would be about the same as buying 5 ounces of gold. roughly $9K at current prices. If you are working through a broker they will generally require you to sell or buy back the contract before the settlement date as they don't want to deal with actually following through on the purchase and having to take delivery of the gold. How much do you make or lose? Lets deal with a smaller change in the price, to be a bit more realistic since we are talking typically about a settlement date that is 3 months out. And to make the math easy lets bump the price of gold to $2000/ounce. That means the price of a futures contract is going to be $10K Lets say the price goes up 10%, Well you have basically a 20:1 leverage since you only paid 5%, so you stand to gain $20,000. Sounds great right? WRONG.. because as good as the upside is, the downside is just as bad. If the price went down 10% you would be down $20000, which means you would not only have to cough up the 10K you committed but you would be expected to 'top up the margin' and throw in ANOTHER $10,000 as well. And if you can't pay that up your broker might close out your position for you. oh and if the price hasn't changed, you are mostly just out the fees and commissions you paid to buy and sell the contract. With futures contracts you can lose MORE than your original investment. NOT for the faint of heart or the casual investor. NOT for folks without large reserves who can afford to take big losses if things go against them. I'll close this answer with a quote from the site I'm linking below The large majority of people who trade futures lose their money. That's a fact. They lose even when they are right in the medium term, because futures are fatal to your wealth on an unpredicted and temporary price blip. Now consider that, especially the bit about 'price blip' and then look at the current volatility of most markets right now, and I think you can see how futures trading can be as they say 'Fatal to your Wealth' (man, I love that phrase, what a great way of putting it) This Site has a pretty decent primer on the whole thing. their view is perhaps a bit biased due to the nature of their business, but on the whole their description of how things work is pretty decent. Investopedia has a more detailed (and perhaps more objective) tutorial on the futures thing. Well worth your time if you think you want to do anything related to the futures market.",
"title": ""
},
{
"docid": "467463",
"text": "Typically the settlement price for a financial instrument (such as AAPL stock) underlying a derivative contract is determined from the average price of trading in that instrument during some short time window specified by the exchange offering the derivative. (Read the fine print on your contract to learn the exact date and time of that settlement period.) Because it's in an exchange's best interest to appear as fair as possible, the exchange will in general pick a high-volume period of time -- such as the close of trading on the expiry date -- in which to determine the settlement price. Now, the expiry date/time may be different from the last time at which the option can be traded, which may be different from the underlying settlement time. For example, most US equity options currently expire on the Saturday following the third Friday of the month, whereas they can last be traded at end-of-day on the third Friday of the month, and the settlement period may be at a slightly different time on the third Friday of the month. (Again, read the contract to know for sure.) Moreover, your broker may demand to know whether you plan to exercise the option at an even earlier date/time. So, to answer your question: After-hours trading can only affect the settlement price of an underlying instrument if the exchange in question decides that the settlement period should happen during after-hours trading. But since no exchange that wants to stay in business would possibly do that, the answer is no. Contract expiry time, contract exercise time, final contract trading time, and underlying settlement time may all fall at different dates/times. The important one for your question is settlement time.",
"title": ""
},
{
"docid": "124630",
"text": "In the United States taxes on the sale of a principal residence are based on the difference between the sale price and the cost of the home. Assuming you meet the requirements you can shelter 250,000 or 500,000 of gains from the sale of your principal residence. This calculation is not related to the loan balance. The basic equation is sales price minus purchase price. It get a little more complex because some costs to purchase and sell the home are included in the calculation, or if you made renovations to the house that will increase your costs and decrease your gains. Trying to decrease the loan balance just before selling the house would just be paying yourself that money at the settlement table. It could save you some money on interest between now and settlement but emptying your bank account to save a few bucks doesn't seem worth it. I would also prefer to have the money in the bank to pay for some expenses that will popup getting the house sold, you moving, and the settlement date.",
"title": ""
},
{
"docid": "493012",
"text": "\"Well, futures don't have a \"\"strike\"\" like an option - the price represents how much you're obligated to buy/sell the index for at a specified date in the future. You are correct that there's no cost to enter a contract (though there may be broker fees and margin payments). Any difference between the contract price and the price of the index at settlement is what is exchanged at settlement. It's analogous to the bid/ask on a stock - the bid price represents the price at which someone is willing to \"\"buy\"\" a futures contract (meaning enter into a long position) and the ask is how much someone is willing to \"\"sell\"\" a contract. So if you want to take a long position on S&P500 mini futures you'd have to enter in at the \"\"ask\"\" price. If the index is above your contract price on the future expiry date you'll make a profit; if it is below the contract price you'll take a loss.\"",
"title": ""
},
{
"docid": "182272",
"text": "Here's a simple example for a put, from both sides. Assume XYZ stock trades at $200 right now. Let's say John writes a $190 out of the money put on XYZ stock and sells this put to Abby for the premium, which is say $5. Assume the strike date, or date of settlement, is 6 months from now. Thus Abby is long one put option and John is short one put option (the writer of the option is short the option). On settlement date, let's assume two different scenarios: (1) If the price of the stock decreases by $50, then the put that Abby bought is 'in the money'. Abby's profit can be calculated as being strike price 190 - current stock price 150 - premium paid 5 = $35 So not including any transaction fees, that is a $35 dollar return on a $5 investment. (2) If the price of the stock increases by $50, then the put that Abby bought is worthless and her loss was 100%, or her entire $5 premium. For John, he made $5 in 6 months (in reality you need collateral and good credit to be able to write sizable option positions).",
"title": ""
},
{
"docid": "36193",
"text": "At the bottom of the page you linked to, NASDAQ provides a link to this page on nasdaqtrader.com, which states Each FINRA member firm is required to report its “total” short interest positions in all customer and proprietary accounts in NASDAQ-listed securities twice a month. These reports are used to calculate short interest in NASDAQ stocks. FINRA member firms are required to report their short positions as of settlement on (1) the 15th of each month, or the preceding business day if the 15th is not a business day, and (2) as of settlement on the last business day of the month.* The reports must be filed by the second business day after the reporting settlement date. FINRA compiles the short interest data and provides it for publication on the 8th business day after the reporting settlement date. The dates you are seeing are the dates the member firms settled their trades. In general (also from nasdaq.com), the settlement date is The date on which payment is made to settle a trade. For stocks traded on US exchanges, settlement is currently three business days after the trade.",
"title": ""
},
{
"docid": "14461",
"text": "For a company listed on NASDAQ, the numbers are published on NASDAQ's site. The most recent settlement date was 4/30/2013, and you can see that it lists 27.5 million shares as held short. NASDAQ gets these numbers from FINRA member firms, which are required to submit them to the exchange twice a month: Each FINRA member firm is required to report its “total” short interest positions in all customer and proprietary accounts in NASDAQ-listed securities twice a month. These reports are used to calculate short interest in NASDAQ stocks. FINRA member firms are required to report their short positions as of settlement on (1) the 15th of each month, or the preceding business day if the 15th is not a business day, and (2) as of settlement on the last business day of the month.* The reports must be filed by the second business day after the reporting settlement date. FINRA compiles the short interest data and provides it for publication on the 8th business day after the reporting settlement date.",
"title": ""
},
{
"docid": "246586",
"text": "Brokerage firms are required to report the number of shares being shorted. This information is reported to the exchange (NYSE of NASDAQ) and is made public. Most financial sites indicate the number of shares being shorted for a particular stock. The image below from Yahoo finance shows 3.29 million shares of CMG were being shorted at the close of 9-28-2012. This is over 12% of the total outstanding shares of CMG. For naked short selling additional information is tracked. If the brokerage is unable to borrow shares to deliver before the settlement date of a short sale then the transaction is recorded as fails-to-deliver. No money or shares are exchanged since the brokerage is unable to deliver the shares that were agreed upon. A large amount of fails-to-deliver transactions for a stock usually indicates an excessive amount of naked shorting. When investors and brokerage firms start to aggressively short a stock they will do so without having borrowed the shares to sell. This will result in a large amount of naked short selling. When there are a large number of naked short sellers not all the sellers will be able to borrow the necessary shares before the settlement date and many fails-to-deliver transactions will be recorded. The SEC records the number of fails-to-deliver transactions. The table below summarizes the fails-to-deliver transactions from 1-1-2012 through 9-14-2012 (data obtained from here). The “Ext Amount” column shows the total dollar value of the transactions that failed ( i.e. Fail Qty * Share price ). The “Volume” column is the total number of shares traded in the same time period. The “% Volume” shows the percentage of shares that failed to deliver as a percentage of the total market volume. The table orders the data in descending order by the quantity of shares that were not delivered. Most of the companies at the top of the list no longer exist. For many of these companies, the quantity of shares that failed to deliver where many multiples of the number of shares traded during the same time period. This indicates massive naked short selling as many brokerages where unable to find shares to borrow before the settlement date. More information here.",
"title": ""
},
{
"docid": "121465",
"text": "\"Securities clearing and settlement is a complex topic - you can start by browsing relevant Wikipedia articles, and (given sufficient quantities of masochism and strong coffee) progress to entire technical books. You're correct - modern trade settlement systems are electronic and heavily streamlined. However, you're never going to see people hand over assets until they're sure that payment has cleared - given current payment systems, that means the fastest settlement time is going to be the next business day (so-called T+1 settlement), which is what's seen for heavily standardized instruments like standard options and government debt securities. Stocks present bigger obstacles. First, the seller has to locate the asset being sold & make sure they have clear title to it... which is tougher than it might seem, given the layers of abstraction/virtualization involved in the chain of ownership & custody, complicated in particular by \"\"rehypothecation\"\" involved in stock borrowing/lending for short sales... especially since stock borrow/lending record-keeping tends to be somewhat slipshod (cf. periodic uproar about \"\"naked shorting\"\" and \"\"failure to deliver\"\"). Second, the seller has to determine what exactly it is that they have sold... which, again, can be tougher than it might seem. You see, stocks are subject to all kinds of corporate actions (e.g. cash distributions, spin-offs, splits, liquidations, delistings...) A particular topic of keen interest is who exactly is entitled to large cash distributions - the buyer or the seller? Depending on the cutoff date (the \"\"ex-dividend date\"\"), the seller may need to deliver to the buyer just the shares of stock, or the shares plus a big chunk of cash - a significant difference in settlement. Determining the precise ex-dividend date (and so what exactly are the assets to be settled) can sometimes be very difficult... it's usually T-2, except in the case of large distributions, which are usually T+1, unless the regulatory authority has neglected to declare an ex-dividend date, in which case it defaults to standard DTC payment policy (i.e. T-2)... I've been involved in a few situations where the brokers involved were clueless, and full settlement of \"\"due bills\"\" for cash distributions to the buyer took several months of hard arguing. So yeah, the brokers want a little time to get their records in order and settle the trade correctly.\"",
"title": ""
},
{
"docid": "565007",
"text": "\"In this scenario the date of income is the date on which the contract has been signed, even if you received the actual money (settlement) later. Regardless of the NY special law for residency termination - that is the standard rule for recognition of income during a cash (not installments) sale. The fact that you got the actual money later doesn't matter, which is similar to selling stocks on a public exchange. When you sell stocks through your broker on a public exchange - you still recognize the income on the day of the sale, not on the day of the settlement. This is called \"\"the Constructive Receipt doctrine\"\". The IRS publication 538 has this to say about the constructive receipt: Constructive receipt. Income is constructively received when an amount is credited to your account or made available to you without restriction. You need not have possession of it. If you authorize someone to be your agent and receive income for you, you are considered to have received it when your agent receives it. Income is not constructively received if your control of its receipt is subject to substantial restrictions or limitations. Once you signed the contract, the money has essentially been credited to your account with the counter-party, and unless they're bankrupt or otherwise insolvent - you have no restrictions over it. And also (more specifically for your case): You cannot hold checks or postpone taking possession of similar property from one tax year to another to postpone paying tax on the income. You must report the income in the year the property is received or made available to you without restriction. Timing wire transfer is akin to holding and not depositing a check, from this perspective. So unless there was a restriction that was lifted after you moved out of New York, I doubt you can claim that you couldn't have received it before moving out, i.e.: you have, in fact, constructively received it.\"",
"title": ""
},
{
"docid": "327080",
"text": "The T+3 settlement date only affects cash accounts. In a cash account, you need to wait until the T+3 settlement date for your funds to be available to make your next trade. But if you convert your cash account into a margin account, then you do not need to wait until the T+3 settlement date for your next trade - your broker will allow you to make another trade immediately.",
"title": ""
},
{
"docid": "525337",
"text": "Purchases and sales from the same trade date will both settle on the same settlement date. They don't have to pay for their purchases until later either. Because HFT typically make many offsetting trades -- buying, selling, buying, selling, buying, selling, etc -- when the purchases and sales settle, the amount they pay for their purchases will roughly cancel with the amount they receive for their sales (the difference being their profit or loss). Margin accounts and just having extra cash around can increase their ability to have trades that do not perfectly offset. In practice, the HFT's broker will take a smaller amount of cash (e.g. $1 million) as a deposit of capital, and will then allow the HFT to trade a larger amount of stock value long or short (e.g. $10 million, for 10:1 leverage). That $1 million needs to be enough to cover the net profit/loss when the trades settle, and the broker will monitor this to ensure that deposit will be enough.",
"title": ""
},
{
"docid": "474384",
"text": "From 26 CFR 1.1012(c)(1)i): ... if a taxpayer sells or transfers shares of stock in a corporation that the taxpayer purchased or acquired on different dates or at different prices and the taxpayer does not adequately identify the lot from which the stock is sold or transferred, the stock sold or transferred is charged against the earliest lot the taxpayer purchased or acquired to determine the basis and holding period of the stock. From 26 CFR 1.1012(c)(3): (i) Where the stock is left in the custody of a broker or other agent, an adequate identification is made if— (a) At the time of the sale or transfer, the taxpayer specifies to such broker or other agent having custody of the stock the particular stock to be sold or transferred, and ... So if you don't specify, the first share bought (for $100) is the one sold, and you have a capital gain of $800. But you can specify to the broker if you would rather sell the stock bought later (and thus have a lower gain). This can either be done for the individual sale (no later than the settlement date of the trade), or via standing order: 26 CFR 1.1012(c)(8) ... A standing order or instruction for the specific identification of stock is treated as an adequate identification made at the time of sale, transfer, delivery, or distribution.",
"title": ""
},
{
"docid": "164001",
"text": "\"Ignoring the complexities of a standardised and regulated market, a futures contract is simply a contract that requires party A to buy a given amount of a commodity from party B at a specified price. The future can be over something tangible like pork bellies or oil, in which case there is a physical transfer of \"\"stuff\"\" or it can be over something intangible like shares. The purpose of the contract is to allow the seller to \"\"lock-in\"\" a price so that they are not subject to price fluctuations between the date the contract is entered and the date it is complete; this risk is transferred to the seller who will therefore generally pay a discounted rate from the spot price on the original day. In many cases, the buyer actually wants the \"\"stuff\"\"; futures contracts between farmers and manufacturers being one example. The farmer who is growing, say, wool will enter a contract to supply 3000kg at $10 per kg (of a given quality etc. there are generally price adjustments detailed for varying quality) with a textile manufacturer to be delivered in 6 months. The spot price today may be $11 - the farmer gives up $1 now to shift the risk of price fluctuations to the manufacturer. When the strike date rolls around the farmer delivers the 3000kg and takes the money - if he has failed to grow at least 3000kg then he must buy it from someone or trigger whatever the penalty clauses in the contract are. For futures over shares and other securities the principle is exactly the same. Say the contract is for 1000 shares of XYZ stock. Party A agrees to sell these for $10 each on a given day to party B. When that day rolls around party A transfers the shares and gets the money. Party A may have owned the shares all along, may have bought them before the settlement day or, if push comes to shove, must buy them on the day of settlement. Notwithstanding when they bought them, if they paid less than $10 they make a profit if they pay more they make a loss. Generally speaking, you can't settle a futures contract with another futures contract - you have to deliver up what you promised - be it wool or shares.\"",
"title": ""
},
{
"docid": "41214",
"text": "The short float ratio and percent change are all calculated based on the short interest (the total number of shares shorted). The short interest data for Nasdaq and NYSE stocks is published every two weeks. NasdaqTrader.com shows the exact dates for when short interest is published for Nasdaq stocks, and also says the following: FINRA member firms are required to report their short positions as of settlement on (1) the 15th of each month, or the preceding business day if the 15th is not a business day, and (2) as of settlement on the last business day of the month.* The reports must be filed by the second business day after the reporting settlement date. FINRA compiles the short interest data and provides it for publication on the 8th business day after the reporting settlement date. The NYSE also shows the exact dates for when short interest is published for NYSE stocks, and those dates are exactly the same as for Nasdaq stocks. Since the short interest is only updated once every 2 weeks, there is no way to see real-time updating of the short float and percent change. That information only gets updated once every 2 weeks - after each publication of the short interest.",
"title": ""
},
{
"docid": "288289",
"text": "As other answers state, selling the options contracts to the market is a definite way out, and probably the best in most cases. If you're determined to exercise your options (or there's not enough liquidity to reasonably sell your contracts to the market), then you could plan ahead and exercise smaller number of contracts at a time and sell the resulting position in the underlying, which will give you funds to exercise some more contracts and sell the underlying. If you think you're going down this path, however, make sure that you take into account your broker's rules for settlement. You may need to start the exercise / sell cycle before the option's expiration date.",
"title": ""
},
{
"docid": "367873",
"text": "According to Regulation T, you can make as many day trade (round trip) stock purchases using a cash account as long as you have the funds to cover each and every round trip sale. However, the funds generated from the sales cannot be used again to purchase new stocks until the settlement period (T-2 or T-3) is over. For example, say you have $10000 dollars in your cash account and no securities. You buy 1000 shares of XYZ stock in the morning at one dollar per share and you sell the stock 30 minutes later because it went up say by 50 cents. According to Regulation T, you cannot use the money generated from the sale of your 1000 shares until after the settlement date. However, you can use the remaining $9000 dollars in your account to execute other trades just as the first trade. You can do this as many times as you want as long as you have funds available to pay for the transaction the same day it's executed. The only thing to worry about and that isn't clear, is, what happens if you perform this action more than 3 times in a week? Does it mean that your cash account now becomes a margin account subject to margin account rules because you executed more than three round trip trades in a five day rolling period?",
"title": ""
},
{
"docid": "115553",
"text": "No, the dividends can't be exploited like that. Dividends settlement are tied to an ex-dividend date. The ex-dividend, is the day that allows you to get a dividend if you own the stock. Since a buyer of the stock after this date won't get the dividend, the price usually drop by the amount of the dividend. In your case the price of a share would lose $2.65 and you will be credited by $2.65 in cash such that your portfolio won't change in value due to the dividend. Also, you can't exploit the drop in price by short-selling, as you would be owing the dividend to the person lending you the stock for the short sale. Finally, the price of the stock at the ex-dividend will also be affected by the supply and demand, such that you can't be precisely sure of the drop in price of the security.",
"title": ""
},
{
"docid": "342903",
"text": "Here is the technical guidance from the accounting standard FRS 23 (IAS 21) 'The Effects of Changes in Foreign Exchange Rates' which states: Exchange differences arising on the settlement of monetary items or on translating monetary items at rates different from those at which they were translated on initial recognition during the period or in previous financial statements shall be recognised in profit or loss in the period in which they arise. An example: You agree to sell a product for $100 to a customer at a certain date. You would record the sale of this product on that date at $100, converted at the current FX rate (lets say £1:$1 for ease) in your profit loss account as £100. The customer then pays you several $100 days later, at which point the FX rate has fallen to £0.5:$1 and you only receive £50. You would then have a realised loss of £50 due to exchange differences, and this is charged to your profit and loss account as a cost. Due to double entry bookkeeping the profit/loss on the FX difference is needed to balance the journals of the transaction. I think there is a little confusion as to what constitutes a (realised) profit/loss on exchange difference. In the example in your question, you are not making any loss when you convert the bitcoins to dollars, as there is no difference in the exchange rate between the point you convert them. Therefore you have not made either a profit or a loss. In terms of how this effects your tax position; you only pay tax on your profit and loss account. The example I give above is an instance where an exchange difference is recorded to the P&L. In your example, the value of your cash held is reflected in your balance sheet, as an asset, whatever its value is at the balance sheet date. Unfortunately, the value of the asset can rise/fall, but the only time where you will record a profit/loss on this (and therefore have an impact on tax) is if you sell the asset.",
"title": ""
},
{
"docid": "338563",
"text": "You will need to check the language of your sales contract. Most of the time, it will be written that the pro-rated property taxes will be part of closing costs. In general, If you've already paid taxes, then the buyer will pay you the pro-rated portion of that, from the closing date through the end of the year. If you haven't, then you would usually be charged the pro-rated amount to be held in the buyer's mortgage company escrow account, with the remainder being collected from the buyer at a later date. For your income tax purposes, you can deduct that tiny amount of the paid property taxes from your income (assuming itemized deductions). Doing some research on property tax for the state of Georgia brings up this interesting note: If you owned property on January 1, you are responsible for the ad valorem tax for the entire year even if you sell the property on January 2. Georgia law does not allow a refund for partial year residents. This leads me to believe that your sales contract would have it written in that the buyer paid you almost the entire year's property taxes in anticipation that you would be responsible for the property taxes, as you owned the property on January 1st. Again, you should consult with the settlement attorney and review your contract.",
"title": ""
},
{
"docid": "519781",
"text": "\"When the buyout happens, the $30 strike is worth $10, as it's in the money, you get $10 ($1000 per contract). Yes, the $40 strike is pretty worthless, it actually dropped in value today. Some deals are worded as an offer or intention, so a new offer can come in. This appears to be a done deal. From Chapter 8 of CHARACTERISTICS AND RISKS OF STANDARDIZED OPTIONS - FEB 1994 with supplemental updates 1997 through 2012; \"\"In certain unusual circumstances, it might not be possible for uncovered call writers of physical delivery stock and stock index options to obtain the underlying equity securities in order to meet their settlement obligations following exercise. This could happen, for example, in the event of a successful tender offer for all or substantially all of the outstanding shares of an underlying security or if trading in an underlying security were enjoined or suspended. In situations of that type, OCC may impose special exercise settlement procedures. These special procedures, applicable only to calls and only when an assigned writer is unable to obtain the underlying security, may involve the suspension of the settlement obligations of the holder and writer and/or the fixing of cash settlement prices in lieu of delivery of the underlying security. In such circumstances, OCC might also prohibit the exercise of puts by holders who would be unable to deliver the underlying security on the exercise settlement date. When special exercise settlement procedures are imposed, OCC will announce to its Clearing Members how settlements are to be handled. Investors may obtain that information from their brokerage firms.\"\" I believe this confirms my observation. Happy to discuss if a reader feels otherwise.\"",
"title": ""
},
{
"docid": "357324",
"text": "Cart's answer is basically correct, but I'd like to elaborate: A futures contract obligates both the buyer of a contract and the seller of a contract to conduct the underlying transaction (settle) at the agreed-upon future date and price written into the contract. Aside from settlement, the only other way either party can get out of the transaction is to initiate a closing transaction, which means: The party that sold the contract buys back another similar contract to close his position. The party that bought the contract can sell the contract on to somebody else. Whereas, an option contract provides the buyer of the option with the choice of completing the transaction. Because it's a choice, the buyer can choose to walk away from the transaction if the option exercise price is not attractive relative to the underlying stock price at the date written into the contract. When an option buyer walks away, the option is said to have expired. However – and this is the part I think needs elaboration – the original seller (writer) of the option contract doesn't have a choice. If a buyer chooses to exercise the option contract the seller wrote, the seller is obligated to conduct the transaction. In such a case, the seller's option contract is said to have been assigned. Only if the buyer chooses not to exercise does the seller's obligation go away. Before the option expires, the option seller can close their position by initiating a closing transaction. But, the seller can't simply walk away like the option buyer can.",
"title": ""
},
{
"docid": "420551",
"text": "The easiest route for you to go down will be to consult wikipedia, which will provide a comprehensive list of all US stock exchanges (there are plenty more than the ones you list!). Then visit the websites for those that are of interest to you, where you will find a list of holiday dates along with the trading schedule for specific products and the settlement dates where relevant. In answer to the other part of your question, yes, a stock can trade on multiple exchanges. Typically (unless you instruct otherwise), your broker will route your order to the exchange where it can be matched at the most favorable price to you at that time.",
"title": ""
},
{
"docid": "77016",
"text": "Here is the definition of Ex-dividend date from the SEC: Once the company sets the record date, the stock exchanges or the National Association of Securities Dealers, Inc. fix the ex-dividend date. The ex-dividend date is normally set for stocks two business days before the record date. If you purchase a stock on its ex-dividend date or after, you will not receive the next dividend payment. Instead, the seller gets the dividend. If you purchase before the ex-dividend date, you get the dividend. The linked document discusses weekend, and holidays involved in the calculation. The difference between the record date and the ex-dividend is to allow for the three days of settlement.",
"title": ""
},
{
"docid": "186869",
"text": "A lot may depend on the nature of a buyout, sometimes it's is for stock and cash, sometimes just stock, or in the case of this google deal, all cash. Since that deal was used, we'll discuss what happens in a cash buyout. If the stock price goes high enough before the buyout date to put you in the money, pull the trigger before the settlement date (in some cases, it might be pulled for you, see below). Otherwise, once the buyout occurs you will either be done or may receive adjusted options in the stock of the company that did the buyout (not applicable in a cash buyout). Typically the price will approach but not exceed the buyout price as the time gets close to the buyout date. If the buyout price is above your option strike price, then you have some hope of being in the money at some point before the buyout; just be sure to exercise in time. You need to check the fine print on the option contract itself to see if it had some provision that determines what happens in the event of a buyout. That will tell you what happens with your particular options. For example Joe Taxpayer just amended his answer to include the standard language from CBOE on it's options, which if I read it right means if you have options via them you need to check with your broker to see what if any special exercise settlement procedures are being imposed by CBOE in this case.",
"title": ""
},
{
"docid": "279151",
"text": "\"What you're looking for are either FX Forwards or FX Futures. These products are traded differently but they are basically the same thing -- agreements to deliver currency at a defined exchange rate at a future time. Almost every large venue or bank will transact forwards, when the counterparty (you or your broker) has sufficient trust and credit for the settlement risk, but the typical duration is less than a year though some will do a single-digit multi-year forward on a custom basis. Then again, all forwards are considered custom contracts. You'll also need to know that forwards are done on currency pairs, so you'll need to pick the currency to pair your NOK against. Most likely you'll want EUR/NOK simply for the larger liquidity of that pair over other possible pairs. A quote on a forward will usually just be known by the standard currency pair ticker with a settlement date different from spot. E.g. \"\"EUR/NOK 12M\"\" for the 12 month settlement. Futures, on the other hand, are exchange traded and more standardized. The vast majority through the CME (Chicago Mercantile Exchange). Your broker will need access to one of these exchanges and you simply need to \"\"qualify\"\" for futures trading (process depends on your broker). Futures generally have highest liquidity for the next \"\"IMM\"\" expiration (quarterly expiration on well known standard dates), but I believe they're defined for more years out than forwards. At one FX desk I've knowledge of, they had 6 years worth of quarterly expirations in their system at any one time. Futures are generally known by a ticker composed of a \"\"globex\"\" or \"\"cme\"\" code for the currency concatenated with another code representing the expiration. For example, \"\"NOKH6\"\" is 'NOK' for Norwegian Krone, 'H' for March, and '6' for the nearest future date's year that ends in '6' (i.e. 2016). Note that you'll be legally liable to deliver the contracted size of Krone if you hold through expiration! So the common trade is to hold the future, and net out just before expiration when the price more accurately reflects the current spot market.\"",
"title": ""
},
{
"docid": "11927",
"text": "You set it based on liquidity management. Cash drag is one of the reasons actively managed funds underperform. The longer your settlement date, the less cash you have to hold because you can take three days to liquidate positions to redeem. So it's a convenience vs performance question.",
"title": ""
},
{
"docid": "576976",
"text": "\"Am I getting it right that in India in terms of short selling in F&O market its what in the rest of the world is called naked short and you actually make promise to depositary that you will deliver that security you sold on settlement without actually owning the security or going through SLB mechanism? In Future and Options; there is no concept of short selling. You buy a future for a security / index. On the settlement day; the exchange determines the settlement price. The trade is closed in cash. i.e. Based on the settlement price, you [and the other party] will either get money [other party looses money] or you loose money [other party gets the money]. Similarly for Options; on expiry, the all \"\"In Money\"\" [or At Money] Options are settled in cash and you are credit with funds [the option writer is debited with funds]. If the option is \"\"out of money\"\" it expires and you loose the premium you paid to exercise the option.\"",
"title": ""
},
{
"docid": "292159",
"text": "\"Scenario 1 - When you sell the shares in a margin account, you will see your buying power go up, but your \"\"amount available to withdraw\"\" stays the same until settlement. Yes, you can reallocate the same day, no need to wait until settlement. There is no margin interest for this scenario. Scenario 2 - If that stock is marginable to 50%, and all you have is $10,000 in that stock, you can buy another $10,000. Once done, you are at 50% margin, exactly.\"",
"title": ""
}
] |
PLAIN-607
|
arthritis
|
[
{
"docid": "MED-3302",
"text": "In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.",
"title": "A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States."
},
{
"docid": "MED-3952",
"text": "Endothelial anti-inflammatory effects of açaí (Ac) and red muscadine grape (Gp) polyphenolics have not been extensively investigated. It was hypothesized that polyphenolics from Ac and Gp exert comparable protective effects in human vascular endothelial cells (HUVEC) upon inflammatory stress. Furthermore, this study investigated whether microRNAs relevant to endothelial function might be regulated by Ac and Gp. Results showed that Ac and Gp (5-20 mg gallic acid equivalent/L) protected HUVEC against glucose-induced oxidative stress and inflammation. Glucose-induced expression of interleukin-6 and -8 was down-regulated by Ac and Gp at mRNA and protein levels. Upon lipopolysaccharide (LPS; 1 μg/L)-induced inflammation, Ac and Gp inhibited gene expression of adhesion molecules and NF-κB activation to similar extents, although Gp was more effective in decreasing PECAM-1 and ICAM-1 protein. Of the screened microRNAs, only microRNA-126 expression was found to be modulated by Ac and Gp as the underlying mechanism to inhibit gene and protein expression of VCAM-1.",
"title": "Polyphenolics from açaí ( Euterpe oleracea Mart.) and red muscadine grape (Vitis rotundifolia ) protect human umbilical vascular Endothelial cell..."
},
{
"docid": "MED-1441",
"text": "Most ethnic foods and cooking practices have incorporated the use of spices and other food additives. Many common spices have crossed cultural boundaries and appear in multiple ethnic cuisines. Recent studies have demonstrated that many of these ingredients possess antimicrobial properties against common food spoilage microorganisms. We developed a laboratory exercise that promotes the use of scientific methodology to evaluate the effectiveness of salsa components at inhibiting the growth of undesirable microorganisms. Tomato, onion, garlic, cilantro, and jalapeño were tested for antimicrobial properties against a representative fungus, Saccharomyces cerevisiae, and the common food spoilage bacteria Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Each component was ethanol extracted and a modification of the Kirby-Bauer method of antimicrobial sensitivity was employed. Garlic demonstrated the greatest inhibitory effects against all organisms tested. Onion demonstrated a slight inhibition of all four organisms, while cilantro showed some inhibition of all three bacteria but no effect against the fungus. Jalapeño may have slightly inhibited E. coli and S. aureus, as evidenced by a consistently measured increase in the zone of inhibition that was not statistically significant when compared to that of the control. Following the initial exercise, students were given the opportunity to repeat the exercise using other spices such as cinnamon, clove, nutmeg, and coriander. Student learning outcomes were evaluated using preliminary and secondary surveys, mainly focusing on definitions of science and hypothesis as well as the process of science. Students enjoyed this exercise and met the learning goals of understanding the process and methodology of science, as well as the interdisciplinarity inherent in the sciences. Student learning was evidenced by an increase in the number of correct responses on the secondary survey in comparison to the preliminary.",
"title": "The Science of Salsa: Antimicrobial Properties of Salsa Components to Learn Scientific Methodology"
},
{
"docid": "MED-5327",
"text": "OBJECTIVE: To investigate the associations between dietary patterns and mental health in early adolescence. METHOD: The Western Australian Pregnancy Cohort (Raine) Study is a prospective study of 2900 pregnancies recruited from 1989-1992. At 14 years of age (2003-2006; n=1324), the Child Behaviour Checklist (CBCL) was used to assess behaviour (characterising mental health status), with higher scores representing poorer behaviour. Two dietary patterns (Western and Healthy) were identified using factor analysis and food group intakes estimated by a 212-item food frequency questionnaire. Relationships between dietary patterns, food group intakes and behaviour were examined using general linear modelling following adjustment for potential confounding factors at age 14: total energy intake, body mass index, physical activity, screen use, family structure, income and functioning, gender and maternal education at pregnancy. RESULTS: Higher total (b=2.20, 95% CI=1.06, 3.35), internalizing (withdrawn/depressed) (b=1.25, 95% CI=0.15, 2.35) and externalizing (delinquent/aggressive) (b=2.60, 95% CI=1.51, 3.68) CBCL scores were significantly associated with the Western dietary pattern, with increased intakes of takeaway foods, confectionary and red meat. Improved behavioural scores were significantly associated with higher intakes of leafy green vegetables and fresh fruit (components of the Healthy pattern). CONCLUSION: These findings implicate a Western dietary pattern in poorer behavioural outcomes for adolescents. Better behavioural outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.",
"title": "The association between dietary patterns and mental health in early adolescence."
},
{
"docid": "MED-4853",
"text": "OBJECTIVE: To demonstrate the effects of a very low-fat, vegan diet on patients with rheumatoid arthritis (RA). DESIGN: Single-blind dietary intervention study. SUBJECTS AND STUDY INTERVENTIONS: This study evaluated the influence of a 4-week, very low-fat (approximately 10%), vegan diet on 24 free-living subjects with RA, average age, 56 +/- 11 years old. OUTCOME MEASUREMENTS: Prestudy and poststudy assessment of RA symptomatology was performed by a rheumatologist blind to the study design. Biochemical measures and 4-day diet data were also collected. Subjects met weekly for diet instruction, compliance monitoring, and progress assessments. RESULTS: There were significant (p < 0.001) decreases in fat (69%), protein (24%), and energy (22%), and a significant increase in carbohydrate (55%) intake. All measures of RA symptomatology decreased significantly (p < 0.05), except for duration of morning stiffness (p > 0.05). Weight also decreased significantly (p < 0.001). At 4 weeks, C-reactive protein decreased 16% (ns, p > 0.05), RA factor decreased 10% (ns, p > 0.05), while erythrocyte sedimentation rate was unchanged (p > 0.05). CONCLUSION: This study showed that patients with moderate-to-severe RA, who switch to a very low-fat, vegan diet can experience significant reductions in RA symptoms.",
"title": "Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis."
},
{
"docid": "MED-2819",
"text": "OBJECTIVES: Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literature with the use of a text-mining tool. We highlight both the potential benefits and drawbacks of using this chemopreventive agent for treating osteoarthritis (OA). We also explore the recent literature on the molecular mechanisms of curcumin mediated alterations in gene expression mediated via activator protein 1 (AP-1)/nuclear factor-kappa B (NF-kappaB) signalling in chondrocytes, osteoblasts and synovial fibroblasts. METHODS: A computer-aided search of the PubMed/Medline database aided by a text-mining tool to interrogate the ResNet Mammalian database 6.0. RESULTS: Recent work has shown that curcumin protects human chondrocytes from the catabolic actions of interleukin-1 beta (IL-1beta) including matrix metalloproteinase (MMP)-3 up-regulation, inhibition of collagen type II and down-regulation of beta1-integrin expression. Curcumin blocks IL-1beta-induced proteoglycan degradation, AP-1/NF-kappaB signalling, chondrocyte apoptosis and activation of caspase-3. CONCLUSIONS: The available data from published in vitro and in vivo studies suggest that curcumin may be a beneficial complementary treatment for OA in humans and companion animals. Nevertheless, before initiating extensive clinical trials, more basic research is required to improve its solubility, absorption and bioavailability and gain additional information about its safety and efficacy in different species. Once these obstacles have been overcome, curcumin and structurally related biochemicals may become safer and more suitable nutraceutical alternatives to the non-steroidal anti-inflammatory drugs that are currently used for the treatment of OA. Copyright 2009 Osteoarthritis Research Society International. All rights reserved.",
"title": "Biological actions of curcumin on articular chondrocytes."
},
{
"docid": "MED-2825",
"text": "Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric."
},
{
"docid": "MED-2812",
"text": "Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Molecular mechanisms of curcumin action: gene expression."
},
{
"docid": "MED-1990",
"text": "BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.) 2009 Massachusetts Medical Society",
"title": "Intensive versus conventional glucose control in critically ill patients."
},
{
"docid": "MED-3308",
"text": "An occupational health survey conducted in a workshop in which asbestos cement was used showed initial atmospheric asbestos levels ranging from 1.9 to 27.5 fibres per millilitre of air. Radiological changes suggestive of asbestos-related pleural disease were found in 2 workers (2.5%), while 3 (3.8%) had borderline features of asbestosis. The survey confirmed that uncontrolled and hazardous use of asbestos continues in industry despite public awareness of its dangers and the Asbestos Regulations of 1987.",
"title": "Third wave of asbestos-related disease from secondary use of asbestos. A case report from industry."
},
{
"docid": "MED-3294",
"text": "In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (PToV) and porcine lymphotropic herpesviruses (PLHV), are mostly subclinical in swine herds. Although some emerging swine viruses such as swine hepatitis E virus (swine HEV), porcine endogenous retrovirus (PERV) and porcine sapovirus (porcine SaV) may have a limited clinical implication in swine health, they do pose a potential public health concern in humans due to zoonotic (swine HEV) or potential zoonotic (porcine SaV) and xenozoonotic (PERV, PLHV) risks. Other emerging viruses such as Nipah virus, Bungowannah virus and Menangle virus not only cause diseases in pigs but some also pose important zoonotic threat to humans. This article focuses on emerging and re-emerging swine viruses that have a limited or uncertain clinical and economic impact on pig health. The transmission, epidemiology and pathogenic potential of these viruses are discussed. In addition, the two economically important emerging viruses, PRRSV and PCV2, are also briefly discussed to identify important knowledge gaps. © 2012 Blackwell Verlag GmbH.",
"title": "Emerging and re-emerging swine viruses."
},
{
"docid": "MED-4631",
"text": "BACKGROUND: Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA. METHODS: Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period. RESULTS: Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01). Compared to baseline levels, higher enrichment of eicosapentaenoic acid in erythrocyte lipids (244% vs 217%) and lower formation of leukotriene B(4) (34% vs 8%, P>0.01), 11-dehydro-thromboxane B(2) (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6-8 of the experiment. CONCLUSION: A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.",
"title": "Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis."
},
{
"docid": "MED-3288",
"text": "In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.",
"title": "Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue."
},
{
"docid": "MED-4855",
"text": "OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs)--of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS: The three studies (287 patients and a median trial-duration of 3 months)--all supported by the manufacturer (Hyben-Vital International)--showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients. CONCLUSIONS: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.",
"title": "Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?--a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-2364",
"text": "We have recently demonstrated that both antibodies to Gal alpha(1,3)Gal, and the Gal alpha(1,3)Gal binding lectin (IB4), bind a synthetic peptide (DAHWESWL), there being a similar recognition of carbohydrate and peptide structures. We now report that the anti-Gal alpha(1,3)Gal antibodies and IB4 lectin also react with peptides encoded by mucin genes (MUC 1, 3, 4)-sequences known to be rich in serine, threonine and proline. This activity was demonstrated (1) by the ability of mucin derived peptides to block the reaction of anti-Gal alpha(1,3)Gal antibodies and IB4 lectin with a Gal alpha(1,3)Gal+ pig endothelial cell line; the reactions were specific and did not occur with a random peptide containing the same sequences or with other mucin peptides; (2) by the fact that anti-mucin1 antibodies could react with the Gal alpha(1,3)Gal expressed after transfection of COS cells (Gal alpha(1,3)Gal-,Muc1-) with cDNA encoding the pig alpha, 3galactosyltransferase; and (3) that the IB4 lectin and anti-Gal alpha(1,3)Gal antibodies could react with mucin 1 found on the surface of human breast cancer cells. Thus natural occurring anti-Gal alpha(1,3)Gal antibodies found in all human serum can react with self (Muc1) peptides expressed in large amounts on the surface of tumour cells but not on normal cells. The findings are of interest and serve to explain the previously reported findings that human cells can, at times, express Gal alpha(1,3)Gal; such expression is an artefact, the reaction is due to the phenomenon described herein, i.e. that anti-Gal alpha(1,3)Gal antibodies react with mucin peptides.",
"title": "Natural human anti-Gal alpha(1,3)Gal antibodies react with human mucin peptides."
},
{
"docid": "MED-2814",
"text": "Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin in various cancers."
},
{
"docid": "MED-4854",
"text": "In a controlled clinical trial we have recently shown that patients with rheumatoid arthritis (RA) improved after fasting for 7-10 d and that the improvement could be sustained through 3.5 months with a vegan diet and 9 months with a lactovegetarian diet. Other studies have indicated that the inflammatory process in RA can be reduced through manipulation of dietary fatty acids. A switch to a vegetarian diet significantly alters the intake of fatty acids. Therefore, we have analysed the changes in fatty acid profiles of the plasma phospholipid fraction and related these changes to disease activity. The concentrations of the fatty acids 20:3n-6 and 20:4n-6 were significantly reduced after 3.5 months with a vegan diet (P < 0.0001 and P < 0.01 respectively), but the concentration increased to baseline values with a lactovegetarian diet. The concentration of 20:5n-3 was significantly reduced after the vegan diet (P < 0.0001) and the lactovegetarian diet periods (P < 0.01). There was no significant difference in fatty acid concentrations between diet responders and diet non-responders after the vegan or lactovegetarian diet periods. Our results indicate that the changes in the fatty acid profiles cannot explain the clinical improvement.",
"title": "Changes in plasma phospholipid fatty acids and their relationship to disease activity in rheumatoid arthritis patients treated with a vegetarian diet."
},
{
"docid": "MED-2273",
"text": "Objective To examine and quantify the relation between purine intake and the risk of recurrent gout attacks among gout patients. Methods The authors conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for 1 year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, clinical symptoms and signs, medications (including antigout medications), and presence of potential risk factors (including daily intake of various purine-containing food items) during the 2-day period prior to the gout attack. The same exposure information was also assessed over 2-day control periods. Results This study included 633 participants with gout. Compared with the lowest quintile of total purine intake over a 2-day period, OR of recurrent gout attacks were 1.17, 1.38, 2.21 and 4.76, respectively, with each increasing quintile (p for trend <0.001). The corresponding OR were 1.42, 1.34, 1.77 and 2.41 for increasing quintiles of purine intake from animal sources (p for trend <0.001), and 1.12, 0.99, 1.32 and 1.39 from plant sources (p=0.04), respectively. The effect of purine intake persisted across subgroups by sex, use of alcohol, diuretics, allopurinol, NSAIDs and colchicine. Conclusions The study findings suggest that acute purine intake increases the risk of recurrent gout attacks by almost fivefold among gout patients. Avoiding or reducing amount of purine-rich foods intake, especially of animal origin, may help reduce the risk of gout attacks.",
"title": "Purine-rich foods intake and recurrent gout attacks"
},
{
"docid": "MED-1443",
"text": "SUMMARY BACKGROUND: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti-inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo. METHODS: 40 volunteers were enrolled in this monocentric,randomized,placebo-controlled double-blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV-B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place-bo.The effect of the test substances on the UV-induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non-irradiated skin. RESULTS: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV-induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent. CONCLUSIONS: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.",
"title": "Anti-inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test."
},
{
"docid": "MED-4088",
"text": "The influence of a 3-week vegetarian diet and fasting on serum concentration of peroxides, lipids, apolipoproteins, and plasma fibrinogen was studied in ten middle-aged fibromyalgia/fibrositis patients (eight women, two men). Mean serum peroxide concentration (estimated as thiobarbituric acid reacting substances) was reduced from 3.60 +/- 0.14 to 2.82 +/- 0.15 umol/l (p = 0.01) and plasma fibrinogen from 3.33 +/- 0.25 to 2.74 +/- 0.15 g/l (p = 0.02). Serum total cholesterol fell from 6.61 +/- 0.50 to 4.83 +/- 0.35 mmol/l (p < 0.0001), apolipoprotein B from 1.77 +/- 0.14 to 1.31 +/- 0.11 g/l (p < 0.0001), and apolipoprotein A from 1.41 +/- 0.09 to 1.23 +/- 0.05 g/l (p = 0.03). High density lipoprotein cholesterol concentration also decreased somewhat (from 1.26 +/- 0.09 to 1.07 +/- 0.04 mmol/l, p = 0.03) An atherogenic index, reflecting the balance between low and high density lipoproteins, was reduced by 31% (from 5.74 +/- 0.79 to 3.97 +/- 0.60, p = 0.02). The results suggest that vegetarian diet/fasting may have a beneficial influence on the concentration of serum peroxides and plasma fibrinogen concentration, and on the serum level of several lipoprotein-related coronary risk factors.",
"title": "Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3-week vegetarian diet."
},
{
"docid": "MED-3944",
"text": "Dietary interventions involving antioxidants are of interest for reducing inflammation, improving joint motion, and altering pain perception. We evaluated the effect of oral consumption of a fruit and berry blend on pain and range of motion (ROM). This open-label clinical pilot study involved 14 study participants with limitations in ROM that was associated with pain and affected daily living. Participants included but were not limited to those with age-related osteoarthritis. Study participants consumed 120 mL MonaVie Active® fruit juice, predominantly containing açai pulp (Euterpe oleracea Mart.) and other fruit concentrates, daily for 12 weeks. Study participants were assessed at baseline and 2, 4, 8, and 12 weeks by structured nurse interviews, pain and activities of daily living (ADL) questionnaires, blood samples, and ROM assessment. Pain was scored by using a visual analogue scale. ROM was assessed by using dual digital inclinometry as recommended by American Medical Association guidelines. Consumption of the juice resulted in significant pain reduction, improved ROM measures, and improvement in ADLs. Serum antioxidant status, as monitored by the cell-based antioxidant protection in erythrocytes (CAP-e) assay, was improved within 2 weeks and continued to improve throughout the 12 weeks of study participation (P<.01). The inflammatory marker C-reactive protein was reduced at 12 weeks, but this change did not reach statistical significance. Lipid peroxidation decreased mildly at 12 weeks. The antioxidant status, as measured by the CAP-e bioassay, showed the best correlation with improvements in physical well-being (pain, ROM, and ADL). The significant association among increased antioxidant status, improved ROM, and pain reduction warrants further study.",
"title": "Pain Reduction and Improvement in Range of Motion After Daily Consumption of an Açai (Euterpe oleracea Mart.) Pulp–Fortified Polyphenolic-Rich Fruit and Berry Juice Blend"
},
{
"docid": "MED-2363",
"text": "We have previously shown that an antibody pool present in normal human serum binds cytokine receptors in vitro and may therefore interfere with assays that capture cytokines using their receptors. Here we show that this antibody pool is the same as the natural antibody termed anti-gal, that binds to the alpha-galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle to xenotransplantation. We report that there are high levels of IgD anti alpha-gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin isotypes against alpha-gal previously described. To determine if anti-gal may interfere with assays that depend on capture of cytokine with its receptor, we measured levels of several anti-carbohydrate antibodies in a cohort of patients with advanced atherosclerosis that had previously been used to measure levels of active TGF-beta using such an assay. For many isotype / carbohydrate combinations, there is a large and significant difference between the levels of anti-carbohydrate antibodies in patients with atherosclerosis and controls, after adjustment for age, sex and blood group. These results are similar to the previous data obtained for active TGF-beta, and therefore we cannot discount the possibility that anti-gal contributed to the previous data. Following further adjustment for several risk factors associated with cardiovascular disease, several anti-carbohydrate antibodies were still significantly different between patients and controls. Therefore, anti-carbohydrate antibodies may represent a new class of risk factors that may be associated with presence of advanced atherosclerosis, although larger studies will be required to confirm this hypothesis.",
"title": "A pattern of anti-carbohydrate antibody responses present in patients with advanced atherosclerosis."
},
{
"docid": "MED-5322",
"text": "BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel.",
"title": "Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting."
},
{
"docid": "MED-2810",
"text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".",
"title": "Curcumin as \"Curecumin\": from kitchen to clinic."
},
{
"docid": "MED-5324",
"text": "Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.",
"title": "Effects of a high-fat meal on pulmonary function in healthy subjects."
},
{
"docid": "MED-5011",
"text": "AV119 is a patented blend of two sugars from avocado that can induce human beta-defensin-2 production by normal human keratinocytes. In this study, we analysed the effect of AV119 on growth and invasiveness of Malassezia furfur, a dimorphic, lipid-dependent yeast that is part of the normal human cutaneous commensal flora. The ability to modulate the expression of the proinflammatory and immunomodulatory cytokines in normal human keratinocytes was also investigated. Microbiological assay demonstrated that this sugar induced the aggregation of yeast cells and inhibited the invasiveness of M. furfur, without affecting its growth. Real-time PCR analysis demonstrated that AV119 was able to modulate the HBD-2 response in treated keratinocytes, reaching a maximum after 48-h treatment, and to induce the recovery of a satisfactory proinflammatory response in human keratinocytes. As AV119 can induce aggregation of yeast cells, thus inhibiting their penetration into the keratinocytes, the sugar could be used in the preparation of cosmetics or pharmacological drugs to inhibit colonization of the skin by pathogenic strains of M. furfur.",
"title": "Effects of AV119, a natural sugar from avocado, on Malassezia furfur invasiveness and on the expression of HBD-2 and cytokines in human keratinocytes."
},
{
"docid": "MED-2079",
"text": "Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (-8.78%, -13.72% and -20.80%, respectively; P<.05) compared with baseline period, while high-density lipoprotein cholesterol remained unchanged. Strawberry supplementation also significant decreased serum malondialdehyde, urinary 8-OHdG and isoprostanes levels (-31.40%, -29.67%, -27.90%, respectively; P<.05). All the parameters returned to baseline values after the washout period. A significant increase in plasma total antioxidant capacity measured by both ferric reducing ability of plasma and oxygen radical absorbance capacity assays and vitamin C levels (+24.97%, +41.18%, +41.36%, respectively; P<.05) was observed after strawberry consumption. Moreover, the spontaneous and oxidative hemolysis were significant reduced (-31.7% and -39.03%, respectively; P<.05), compared to the baseline point, which remained stable after the washout period. Finally, strawberry intake significant decrease (P<.05) the number of activated platelets, compared to both baseline and washout values. Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk. Copyright © 2014 Elsevier Inc. All rights reserved.",
"title": "One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans."
},
{
"docid": "MED-4856",
"text": "OBJECTIVE: To investigate if standardised powder made from rose-hip (Rosa canina) can reduce the symptom score in patients with rheumatoid arthritis. METHODS: In a double-blind placebo-controlled trial, patients with rheumatoid arthritis (RA) according to ARA/ACR criteria were randomised to treatment with capsulated rose-hip powder 5g daily or matching placebo for 6 months at two outpatient clinics in Berlin and Copenhagen. Primary outcome variable was Health Assessment Questionnaire (HAQ) at 6 months, secondary outcome included DAS-28, physician's global evaluation of disease activity, RAQoL, SF-12 and concomitant pain medication. RESULTS: In a total of 89 patients (90% female, mean age 56.6+11.3 years, mean disease duration 12.8+9.6 years) HAQ-DI in the rose-hip group improved by 0.105+/-0.346, whereas in the placebo group it worsened by 0.039+/-0.253 (p adjusted=0.032). In the HAQ Patient Pain Scale no significant differences were observed between both groups. In the HAQ Patient Global Scale a trend was seen favouring rose-hip (p=0.078). The DAS-28 score yielded improvement in the rose-hip group of 0.89+/-1.32 and in the placebo group of 0.34+/-1.27 (p=0.056) indicating moderate clinical relevance. The Physicians Global Scale demonstrated more improvement in the rose-hip compared to the placebo group (p=0.012). RAQoL and SF-12 physical score improved significantly in the rose-hip group compared to placebo, whereas SF-12 mental score remained unchanged. Intake of pain medication was not different between the groups. Per-protocol analysis confirmed these results. CONCLUSION: The results indicate that patients with RA may benefit from additional treatment with rose hip powder. Copyright 2009 Elsevier GmbH. All rights reserved.",
"title": "Rose hip herbal remedy in patients with rheumatoid arthritis - a randomised controlled trial."
},
{
"docid": "MED-5337",
"text": "PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.",
"title": "Intensive lifestyle changes may affect the progression of prostate cancer."
},
{
"docid": "MED-2805",
"text": "Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.",
"title": "Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation"
},
{
"docid": "MED-2815",
"text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin, a component of turmeric: from farm to pharmacy."
},
{
"docid": "MED-2802",
"text": "OBJECTIVE: The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis. STUDY DESIGN AND SETTING: The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand. METHODS: One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded. RESULTS: Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively). CONCLUSIONS: C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.",
"title": "Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis."
},
{
"docid": "MED-4103",
"text": "Patients with rheumatoid arthritis (RA) have been described as having significantly low serum potassium concentrations than that in healthy subjects. We assessed the therapeutic efficacy and tolerability of oral potassium supplement dissolved in grape juice in female hypokalemic patients with active RA. Thirty-two hypokalemic patients with active RA were investigated in a parallel, randomized design. In addition to their usual medication, the control group received placebo and the intervention group received 6000 mg chloride potassium dissolved in grape juice on 28 consecutive days. The primary outcome parameter was the change of pain on a visual analog scale (VAS). The American College of Rheumatology (ACR) percent response criteria and Disease Activity Score 28 (DAS28, 28-joint count) and the European League Against Rheumatism (EULAR) moderate response were assessed. Mean age was 48.6 +/- 6 years. In the potassium group, 43.75% (7/16) of the patients met the criteria of 33% lower pain intensity compared with 6.25% (1/16) in the placebo group (P < .02) at day 28. Also, 31.25% (5/16) of the patients in the intervention group achieved moderate responses, according to the EULAR criteria. The corresponding percentage for patients receiving placebo was 6.25% (1/16) (P < .05). Potassium supplements appeared to decrease pain intensity. PERSPECTIVE: This article reports a trial evaluating the effect of potassium supplementation in the treatment of pain in hypokalemic patients with rheumatoid arthritis. The elevated serum cortisol and potassium values in the treatment group correlate negatively with patient's assessment of pain intensity, reflecting an anti-pain effect for potassium supplementation.",
"title": "A pilot study of potassium supplementation in the treatment of hypokalemic patients with rheumatoid arthritis: a randomized, double-blinded, placeb..."
},
{
"docid": "MED-1116",
"text": "Molecular mimicry is one of the pathological mechanisms proposed to explain the association between microorganisms and autoimmune diseases. This review deals with the association between bacteria and rheumatic diseases with a special emphasis on rheumatoid arthritis where upper urinary tract infection by Proteus mirabilis is the possible cause of this severe, arthritic condition. Prospective trials involving anti-Proteus therapy should be carried out.",
"title": "Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity."
},
{
"docid": "MED-2813",
"text": "The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to \"get back to our roots.\"",
"title": "Curcumin: getting back to the roots."
},
{
"docid": "MED-4852",
"text": "OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.",
"title": "Self-reported food intolerance and mucosal reactivity after rectal food protein challenge in patients with rheumatoid arthritis."
},
{
"docid": "MED-4844",
"text": "Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r(2) 0.877, P<0.001 for eight countries). The statistical correlations for meat and offal were almost as high as those for their fat. Similar correlations were found for temporal changes in indices of effects of RA in several European countries between 1968 and 1978 as more meat was added to the national diets, although the correlations were higher for meat than for fat. It is hypothesized that meat and offal may be a major factor contributing to the inflammation in RA. In the present short review, the author examines some of the data that associate meat consumption with RA and the possible factors, e.g. fat, Fe and nitrite, which may contribute to the inflammation.",
"title": "The role of meat in the expression of rheumatoid arthritis."
},
{
"docid": "MED-1442",
"text": "We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h2 from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype–phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.",
"title": "Genetic Analysis of Chemosensory Traits in Human Twins"
},
{
"docid": "MED-1127",
"text": "Rheumatoid arthritis is a crippling and disabling joint disease affecting over 20 million people. It occurs predominantly in women and smokers, and affects the HLA-DR1/4 individuals who carry the \"shared epitope\" of amino acids EQRRAA. The cause of this disease was investigated by the methods of the philosopher of science Karl Popper who suggested that scientific research should be based on bold conjectures and critical refutations. The \"Popper sequences\" generate new facts which then change or alter the original problem. The new facts must then be explained by any new theory. Using the \"molecular mimicry\" model, it was found that Proteus bacteria possess an amino acid sequence ESRRAL in haemolysin which resembles the, shared epitope, and another sequence in urease which resembles type XI collagen. Antibodies to Proteus bacteria have been found in 14 different countries. It would appear that rheumatoid arthritis is caused by an upper urinary tract infection by Proteus bacteria. Anti-Proteus therapy should be assessed in the management of this disease separately or in conjunction with existing modalities of therapy.",
"title": "Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper."
},
{
"docid": "MED-1996",
"text": "Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.",
"title": "Childhood obesity and type 2 diabetes mellitus."
},
{
"docid": "MED-3318",
"text": "Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.",
"title": "Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium"
},
{
"docid": "MED-4139",
"text": "Pigs are the major animal reservoir for Yersinia enterocolitica strains, which are potentially pathogenic for humans. The goals of this study were (i) to estimate the individual animal and on-farm prevalences of Y. enterocolitica in hogs based on tonsil samples collected during National Animal Health Monitoring System Swine 2002 study and (ii) to use these data with data previously published for fecal samples to determine on-farm risk factors for Y. enterocolitica. Tonsil swabs (1,218) and fecal samples (2,847) were collected on 124 farms located in the top 17 pork-producing states. Ten percent of tonsils (122 of 1,218 samples) were positive in irgasan-tiracillin-chlorate (ITC) enrichment broth by real-time PCR, but only 5.6% of samples (68 of 1,218) were positive after subculture on the more selective cefsulodin-irgasan-novobiocin (CIN) agar. For tonsils, the on-farm prevalence based on real-time PCR detection of the ail gene in ITC enrichment broth cultures was 32% (32 of 100 premises sampled); the prevalence based on subculture in CIN agar was 19.6% (20 of 102 premises). Results of bacteriological isolation and real-time PCR analysis of tonsils and feces were combined to estimate prevalence (individual animal and farm), which was subsequently correlated with 40 farm management practices. Four factors and their accompanying odds ratios (ORs) were identified in the final regression model: location in a central state (OR = 0.3), vaccination for Escherichia coli (OR = 3.0), percentage of deaths due to scours (OR = 3.5), and presence of meat or bone meal in grower-finisher diet (OR = 4.1).",
"title": "Prevalence of Yersinia enterocolitica in market weight hogs in the United States."
},
{
"docid": "MED-3317",
"text": "Twenty-four patients, all of whom were exposed to aerosolized porcine brain tissue through work-place environment (abattoir), developed a syndrome of immune-mediated polyradiculoneuropathy; three also had central nervous system manifestations (transverse myelitis, meningoencephalitis, and aseptic meningitis). Patients had characteristic electrophysiological findings of very distal and proximal conduction slowing (prolonged distal and F-wave latencies, regions where the blood-nerve barrier is the most permeable) and all patients' serum contained a novel IgG immunofluorescence pattern. Nerve pathology, when available, showed mild changes of segmental demyelination, axonal degeneration, and inflammatory changes. Patients had meaningful improvement of symptoms and electrophysiologic findings with immune therapy and with removal of exposure to aerosolized brain tissue. We postulate that this outbreak is an auto-immune polyradiculoneuropathy triggered by occupational exposure to multiple aerosolized porcine neural tissue antigens that result in neural damage where the blood-nerve barrier is the least robust. © 2011 Peripheral Nerve Society.",
"title": "Auto-immune polyradiculoneuropathy and a novel IgG biomarker in workers exposed to aerosolized porcine brain."
},
{
"docid": "MED-4134",
"text": "Yersinia enterocolitica is considered an important food-borne pathogen impacting the pork production and processing industry in the United States. Since this bacterium is a commensal of swine, the primary goal of this study was to determine the prevalence of pathogenic Y. enterocolitica in pigs in the United Sates using feces as the sample source. A total of 2,793 fecal samples were tested for its presence in swine. Fecal samples were collected from late finisher pigs from 77 production sites in the 15 eastern and midwestern pork-producing states over a period of 27 weeks (6 September 2000 to 20 March 2001). The prevalence of ail-positive Y. enterocolitica was determined in samples using both a fluorogenic 5′ nuclease PCR assay and a culture method. The mean prevalence was 13.10% (366 of 2,793 fecal samples tested) when both PCR- and culture-positive results were combined. Forty-one of 77 premises (53.25%) contained at least one fecal sample positive for the ail sequence. The PCR assay indicated a contamination rate of 12.35% (345/2,793) compared to 4.08% (114/2,793) by the culture method. Of the 345 PCR-positive samples, 252 were culture negative, while of the 114 culture-positive samples, 21 were PCR negative. Among 77 premises, the PCR assay revealed a significantly (P < 0.05) higher percentage (46.75%, n = 36 sites) of samples positive for the pathogen (ail sequence) than the culture method (22.08%, n = 17 sites). Thus, higher sensitivity, with respect to number of samples and sites identified as positive for the PCR method compared with the culture method for detecting pathogenic Y. enterocolitica, was demonstrated in this study. The results support the hypothesis that swine are a reservoir for Y. enterocolitica strains potentially pathogenic for humans.",
"title": "Prevalence of Pathogenic Yersinia enterocolitica Strains in Pigs in the United States"
},
{
"docid": "MED-2809",
"text": "Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.",
"title": "Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials"
},
{
"docid": "MED-2822",
"text": "Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.",
"title": "A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis."
},
{
"docid": "MED-2354",
"text": "A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.",
"title": "A unique natural human IgG antibody with anti-alpha-galactosyl specificity"
},
{
"docid": "MED-1121",
"text": "Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age. Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies. Patients with RA especially during the early stages of the disease could benefit from Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments.",
"title": "Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection"
},
{
"docid": "MED-2221",
"text": "Context: In 1954 the tobacco industry paid to publish the “Frank Statement to Cigarette Smokers” in hundreds of U.S. newspapers. It stated that the public's health was the industry's concern above all others and promised a variety of good-faith changes. What followed were decades of deceit and actions that cost millions of lives. In the hope that the food history will be written differently, this article both highlights important lessons that can be learned from the tobacco experience and recommends actions for the food industry. Methods: A review and analysis of empirical and historical evidence pertaining to tobacco and food industry practices, messages, and strategies to influence public opinion, legislation and regulation, litigation, and the conduct of science. Findings: The tobacco industry had a playbook, a script, that emphasized personal responsibility, paying scientists who delivered research that instilled doubt, criticizing the “junk” science that found harms associated with smoking, making self-regulatory pledges, lobbying with massive resources to stifle government action, introducing “safer” products, and simultaneously manipulating and denying both the addictive nature of their products and their marketing to children. The script of the food industry is both similar to and different from the tobacco industry script. Conclusions: Food is obviously different from tobacco, and the food industry differs from tobacco companies in important ways, but there also are significant similarities in the actions that these industries have taken in response to concern that their products cause harm. Because obesity is now a major global problem, the world cannot afford a repeat of the tobacco history, in which industry talks about the moral high ground but does not occupy it.",
"title": "The Perils of Ignoring History: Big Tobacco Played Dirty and Millions Died. How Similar Is Big Food?"
},
{
"docid": "MED-2353",
"text": "Summary Anti-Gal is the most abundant natural antibody in humans, constituting ∼ 1% of immunoglobulins. Anti-Gal is naturally produced also in apes and Old World monkeys. The ligand of anti-Gal is a carbohydrate antigen called the ‘α-gal epitope’ with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is present as a major carbohydrate antigen in non-primate mammals, prosimians and New World monkeys. Anti-Gal can contributes to several immunological pathogeneses. Anti-Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α-gal epitopes. Aberrant expression of the α-gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α-Gal epitopes produced by Trypanosoma cruzi interact with anti-Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti-Gal IgM and IgG further mediate rejection of xenografts expressing α-gal epitopes. Because of its abundance, anti-Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α-gal epitopes by targeting them for effective uptake by antigen-presenting cells. Tumour lesions are converted into vaccines against autologous tumour-associated antigens by intra-tumoral injection of α-gal glycolipids, which insert into tumour cell membranes. Anti-Gal binding to α-gal epitopes on tumour cells targets them for uptake by antigen-presenting cells. Accelerated wound healing is achieved by application of α-gal nanoparticles, which bind anti-Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.",
"title": "Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits"
},
{
"docid": "MED-2080",
"text": "Beyond obvious functions in haemostasis and thrombosis, platelets are considered to be essential in proinflammatory surroundings such as atherosclerosis, allergy, rheumatoid arthritis and even cancer. In atherosclerosis, platelets facilitate the recruitment of inflammatory cells towards the lesion sites and release a plethora of inflammatory mediators, thereby enriching and boosting the inflammatory milieu. Platelets do so by interacting with endothelial cells, circulating leukocytes (monocytes, neutrophils, dendritic cells, T-cells) and progenitor cells. This cross-talk enforces leukocyte activation, adhesion and transmigration. Furthermore, platelets are known to function in innate host defense through the release of antimicrobial peptides and the expression of pattern recognition receptors. In severe sepsis, platelets are able to trigger the formation of neutrophil extracellular traps (NETs), which bind and clear pathogens. The present antiplatelet therapies that target key pathways of platelet activation and aggregation therefore hold the potential to modulate platelet-derived immune functions by reducing cellular interactions of platelets with other immune components and by reducing the secretion of inflammatory proteins into the milieu. The objective of this review is to update and discuss the current perceptions of the platelet immune constituents and their prospect as therapeutic targets in an atherosclerotic setting.",
"title": "Platelets in atherosclerosis."
},
{
"docid": "MED-1993",
"text": "Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice. Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities, even if the prevalence of obesity is not increasing any more. The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American, Hispanic, Asian/Pacific Islanders and American Indians. Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood. Therefore, a screening seems meaningful especially in high risk groups such as children and adolescents with obesity, relatives with type 2 diabetes mellitus, and clinical features of insulin resistance (hypertension, dyslipidemia, polycystic ovarian syndrome, or acanthosis nigricans). Treatment of choice is lifestyle intervention followed by pharmacological treatment (e.g., metformin). New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type 2 diabetes mellitus. However, recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type 2 diabetes mellitus requires some remodeling of current healthcare practices.",
"title": "Type 2 diabetes mellitus in children and adolescents"
},
{
"docid": "MED-2820",
"text": "Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.",
"title": "Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis"
},
{
"docid": "MED-4131",
"text": "In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.",
"title": "Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens."
},
{
"docid": "MED-4142",
"text": "Swine confinement buildings in eastern Canada are enclosed and equipped with modern production systems to manage waste. Bioaerosols of these swine confinement buildings could be contaminated by human pathogens and antimicrobial resistant bacteria which could colonize exposed workers. We therefore wanted to analyze bioaerosols of swine confinement buildings and nasal flora of Canadian hog producers to evaluate possible colonization with human pathogens and tetracycline-resistant bacteria. Culturable and non-culturable human pathogens and tet genes were investigated in the bioaerosols of 18 barns. The nasal passages of 35 hog producers were sampled and total DNA was extracted from the calcium-alginate swabs to detect, by PCR, Campylobacter, C. perfringens, Enterococcus, E. coli, Y. enterocolitica, tetA/tetC, tetG and ribosomal protection protein genes. Airborne culturable C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were present in the bioaerosols of 16, 17, 11 and 6 of the 18 facilities. Aerosolized total (culturable/non culturable) Campylobacter, C. perfringens, Enterococcus, E. coli and Y. enterocolitica were detected in 10, 6, 15, 18 and 2 barns, respectively. Tet genes were found in isolates of culturable human pathogens. TetA/tetC, tetG and ribosomal protection protein genes were detected in the bioaerosols of all 18 studied buildings. Campylobacter, C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were found respectively in 4, 9, 17, 14 and one nasal flora of workers. One and 10 workers were positive for tetA/tetC and tetG genes, respectively. In swine confinement buildings, hog producers are exposed to aerosolized human pathogens and tetracycline-resistant bacteria that can contaminate the nasal flora. Copyright © 2010 Elsevier GmbH. All rights reserved.",
"title": "Human pathogens and tetracycline-resistant bacteria in bioaerosols of swine confinement buildings and in nasal flora of hog producers."
},
{
"docid": "MED-4845",
"text": "Fasting is an effective treatment for rheumatoid arthritis, but most patients relapse on reintroduction of food. The effect of fasting followed by one year of a vegetarian diet was assessed in a randomised, single-blind controlled trial. 27 patients were allocated to a four-week stay at a health farm. After an initial 7-10 day subtotal fast, they were put on an individually adjusted gluten-free vegan diet for 3.5 months. The food was then gradually changed to a lactovegetarian diet for the remainder of the study. A control group of 26 patients stayed for four weeks at a convalescent home, but ate an ordinary diet throughout the whole study period. After four weeks at the health farm the diet group showed a significant improvement in number of tender joints, Ritchie's articular index, number of swollen joints, pain score, duration of morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and a health assessment questionnaire score. In the control group, only pain score improved score. In the control group, only pain score improved significantly. The benefits in the diet group were still present after one year, and evaluation of the whole course showed significant advantages for the diet group in all measured indices. This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis.",
"title": "Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis."
},
{
"docid": "MED-5090",
"text": "OBJECTIVE: To examine associations between the prevalence of degenerative arthritis and soft tissue disorders and consumption of meat and other foods among participants in the Adventist Health Study. METHODS: Unconditional logistic regression analysis is used to examine cross-sectional associations, adjusting for the effects of age, smoking, alcohol consumption, body mass index, use of sex hormones and parity. RESULTS: The prevalence of degenerative arthritis and soft tissue disorders was 22.60 percent. Women had a higher prevalence than men and prevalence increased greatly with age. Smoking, higher body mass index, never use of contraceptive pills, and current hormone replacement therapy are associated with a higher prevalence of these disorders on multivariate analysis. Multivariate OR's comparing consumption of meat < 1/week; >or= 1/week; with the reference being no meat, were 1.31(95% CI: 1.21,1.43) and 1.49(1.31, 1.70) in women; and 1.19 (95% CI: 1.05,1.34) and 1.43(1.20, 1.70) in men. Dairy fat and fruit consumption were weakly associated with increased risk. There were protective associations with nut and salad consumption. CONCLUSIONS: Greater meat consumption is associated with a higher prevalence of degenerative arthritis and soft tissue disorders in both male and female subjects of this population, as is hormone replacement therapy in women.",
"title": "Associations between meat consumption and the prevalence of degenerative arthritis and soft tissue disorders in the adventist health study, Califor..."
},
{
"docid": "MED-4422",
"text": "OBJECTIVES: To test the efficacy and safety of oral L-citrulline supplementation in improving erection hardness in patients with mild erectile dysfunction (ED). L-arginine supplementation improves nitric oxide-mediated vasodilation and endothelial function; however, oral administration has been hampered by extensive presystemic metabolism. In contrast, L-citrulline escapes presystemic metabolism and is converted to L-arginine, thus setting the rationale for oral L-citrulline supplementation as a donor for the L-arginine/nitric oxide pathway of penile erection. METHODS: In the present single-blind study, men with mild ED (erection hardness score of 3) received a placebo for 1 month and L-citrulline, 1.5 g/d, for another month. The erection hardness score, number of intercourses per month, treatment satisfaction, and adverse events were recorded. RESULTS: A total of 24 patients, mean age 56.5 ± 9.8 years, were entered and concluded the study without adverse events. The improvement in the erection hardness score from 3 (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01). The mean number of intercourses per month increased from 1.37 ± 0.93 at baseline to 1.53 ± 1.00 at the end of the placebo phase (P = .57) and 2.3 ± 1.37 at the end of the treatment phase (P < .01). All patients reporting an erection hardness score improvement from 3 to 4 reported being very satisfied. CONCLUSIONS: Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychologically fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction."
},
{
"docid": "MED-1118",
"text": "OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.",
"title": "Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet."
},
{
"docid": "MED-2360",
"text": "Lyme-like illness (also known as southern tick-associated rash illness [STARI] or Masters disease) is vectored by the Lone Star tick (Amblyomma americanum). Lyme-like illness lesions, which are similar to the erythema migrans rash of Lyme disease, tend to have lymphocytic dermal infiltrates. With the exception of Borrelia lonestari, the possible causative agent or agents of Lyme-like illness have not been cultured. More research is needed to fully understand this newly recognized zoonosis. Clinicians are encouraged to increase their knowledge and awareness of this Lyme disease mimic.",
"title": "STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness."
},
{
"docid": "MED-1123",
"text": "OBJECTIVES: To provide a state of the art of economic analyses applied to rheumatoid arthritis (RA). METHODS: A systematic literature review on economic consequences and pharmacoeconomic issues of RA was performed. RESULTS: 127 valid articles were examined in this review. Generally, the financial impact of RA is substantial for health-care systems and society worldwide, although differences exist among national economies. Both direct and indirect (i.e. loss of productivity) costs contribute to economic burden of RA and must be taken into account when estimating overall impact to society. Disease severity, disease activity, age and socioeconomic status have been found to be the most relevant predictors of cost increase in RA. Moreover, introduction of biological anti-rheumatic agents has significantly raised direct medical costs in certain patients, but has also led to marked improvements in reducing disease activity, joint damage, and productivity loss in many of these patients. RA has also a significant impact on all aspects of quality of life; recent publications on health utility scores showed RA to be one of the diseases associated with poorest quality of life. CONCLUSIONS: RA represents a clinical and economic burden for healthcare systems. Although attributable RA costs have been extensively evaluated over the last decades, several issues, especially concerning the use of expensive therapies, must be addressed and frequently updated. Future research should also provide health economic evidence from usual practice settings, and on the economic impact of different therapeutic approaches to pursue specific clinical targets in individual patients.",
"title": "Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis."
},
{
"docid": "MED-4349",
"text": "Inflammation is a pathological condition underlying a number of diseases including cardiovascular diseases, cancer, and chronic inflammatory diseases. In addition, healthy, obese subjects also express markers of inflammation in their blood. Diet provides a variety of nutrients as well as non-nutritive bioactive constituents which modulate immunomodulatory and inflammatory processes. Epidemiological data suggest that dietary patterns strongly affect inflammatory processes. Primarily the intake of fruit and vegetables as well as of whole wheat is inversely associated with the risk of inflammation. In addition to observational studies there are also data from human intervention studies suggesting an anti-inflammatory potential of these plant foods. At the level of bioactive compounds occurring in plant foods, primarily carotenoids and flavonoids seem to modulate inflammatory as well as immunological processes. In conclusion, there is convincing evidence that plant foods and non-nutritive constituents associated with these foods modulate immunological and inflammatory processes. By means of anti-inflammatory activities a plant-based diet may contribute to the lower risk of cardiovascular diseases and cancer. A high intake of vegetables, fruit, and whole wheat as recommended by all international nutrition authorities provides a wide spectrum of bioactive compounds at health-promoting concentrations.",
"title": "Anti-inflammatory effects of plant-based foods and of their constituents."
},
{
"docid": "MED-5339",
"text": "Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.",
"title": "Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat."
},
{
"docid": "MED-4140",
"text": "A survey of 788 pigs from 120 farms was conducted to determine the within-farm prevalence of pathogenic Yersinia enterocolitica and a questionnaire of management conditions was mailed to the farms afterwards. A univariate statistical analysis with carriage and shedding as outcomes was conducted with random-effects logistic regression with farm as a clustering factor. Variables with a P value <0·15 were included into the respective multivariate random-effects logistic regression model. The use of municipal water was discovered to be a protective factor against carriage and faecal shedding of the pathogen. Organic production and buying feed from a certain feed manufacturer were also protective against total carriage. Tonsillar carriage, a different feed manufacturer, fasting pigs before transport to the slaughterhouse, higher-level farm health classification, and snout contacts between pigs were risk factors for faecal shedding. We concluded that differences in management can explain different prevalences of Y. enterocolitica between farms.",
"title": "Factors related to the prevalence of pathogenic Yersinia enterocolitica on pig farms."
},
{
"docid": "MED-2272",
"text": "To assess the physiologic effects of cherry consumption, we measured plasma urate, antioxidant and inflammatory markers in 10 healthy women who consumed Bing sweet cherries. The women, age 22-40 y, consumed two servings (280 g) of cherries after an overnight fast. Blood and urine samples were taken before the cherry dose, and at 1.5, 3 and 5 h postdose. Plasma urate decreased 5 h postdose, mean +/- SEM = 183 +/- 15 micro mol/L compared with predose baseline of 214 +/- 13 micro mol/L (P < 0.05). Urinary urate increased postdose, with peak excretion of 350 +/- 33 micro mol/mmol creatinine 3 h postdose compared with 202 +/- 13 at baseline (P < 0.01). Plasma C-reactive protein (CRP) and nitric oxide (NO) concentrations had decreased marginally 3 h postdose (P < 0.1), whereas plasma albumin and tumor necrosis factor-alpha were unchanged. The vitamin C content of the cherries was solely as dehydroascorbic acid, but postdose increases in plasma ascorbic acid indicated that dehydroascorbic acid in fruits is bioavailable as vitamin C. The decrease in plasma urate after cherry consumption supports the reputed anti-gout efficacy of cherries. The trend toward decreased inflammatory indices (CRP and NO) adds to the in vitro evidence that compounds in cherries may inhibit inflammatory pathways.",
"title": "Consumption of cherries lowers plasma urate in healthy women."
},
{
"docid": "MED-3943",
"text": "The health benefits associated with pomegranate juice have led to the development of pomegranate extracts as botanical dietary supplements. Pomegranates contain hydrolyzable tannins in the form of punicalagins and punicalin as well as tannin-based complex oligomers that account for much of the antioxidant activity in juice. The content of ellagic acid has been used to standardize most pomegranate extract dietary supplements marketed. However, supplements can be adulterated with ellagic acid from less expensive plant sources and undercut this method of standardization. To compare the phytochemical contents and antioxidant activities of commercially available pomegranate extract dietary supplements beyond their content of ellagic acid, a total of 27 different supplements in the form of capsules, tablets, and soft gels were studied. Total phenolics were measured using both gallic acid equivalent (GAE) and ellagic acid equivalent (EAE) assays. Punicalagins, punicalin, and ellagic acid contents were determined by HPLC, whereas antioxidant capacity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay. Of the 27 supplements tested, only 5 had the typical pomegranate tannin profile by HPLC, 17 had ellagic acid as the predominant chemical with minor or no detectable pomegranate tannins, and 5 had no detectable tannins or ellagic acid. Therefore, standardization of pomegranate extract supplements based on their ellagic acid content does not guarantee pomegranate supplement authenticity. Future research is needed to assess the health impact of substituting ellagic acid for the complex mix of phytochemicals in a pomegranate extract dietary supplement.",
"title": "Absence of pomegranate ellagitannins in the majority of commercial Pomegranate extracts: implications for standardization and quality control."
},
{
"docid": "MED-2082",
"text": "BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.",
"title": "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease S..."
},
{
"docid": "MED-3949",
"text": "In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.",
"title": "Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia."
},
{
"docid": "MED-5335",
"text": "Three recent case-control studies conclude that diets high in animal fat or cholesterol are associated with a substantial increase in risk for Parkinson's disease (PD); in contrast, fat of plant origin does not appear to increase risk. Whereas reported age-adjusted prevalence rates of PD tend to be relatively uniform throughout Europe and the Americas, sub-Saharan black Africans, rural Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear to enjoy substantially lower rates. Since current PD prevalence in African-Americans is little different from that in whites, environmental factors are likely to be responsible for the low PD risk in black Africans. In aggregate, these findings suggest that vegan diets may be notably protective with respect to PD. However, they offer no insight into whether saturated fat, compounds associated with animal fat, animal protein, or the integrated impact of the components of animal products mediates the risk associated with animal fat consumption. Caloric restriction has recently been shown to protect the central dopaminergic neurons of mice from neurotoxins, at least in part by induction of heat-shock proteins; conceivably, the protection afforded by vegan diets reflects a similar mechanism. The possibility that vegan diets could be therapeutically beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus retarding progression of the syndrome, may merit examination. Vegan diets could also be helpful to PD patients by promoting vascular health and aiding blood-brain barrier transport of L-dopa. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Does a vegan diet reduce risk for Parkinson's disease?"
},
{
"docid": "MED-1444",
"text": "Coriander (Coriandrum sativum L.), a herbal plant, belonging to the family Apiceae, is valued for its culinary and medicinal uses. All parts of this herb are in use as flavoring agent and/or as traditional remedies for the treatment of different disorders in the folk medicine systems of different civilizations. The plant is a potential source of lipids (rich in petroselinic acid) and an essential oil (high in linalool) isolated from the seeds and the aerial parts. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb, which include anti-microbial, anti-oxidant, anti-diabetic, anxiolytic, anti-epileptic, anti-depressant, anti-mutagenic, anti-inflammatory, anti-dyslipidemic, anti-hypertensive, neuro-protective and diuretic. Interestingly, coriander also possessed lead-detoxifying potential. This review focuses on the medicinal uses, detailed phytochemistry, and the biological activities of this valuable herb to explore its potential uses as a functional food for the nutraceutical industry. Copyright © 2012 John Wiley & Sons, Ltd.",
"title": "Coriander (Coriandrum sativum L.): a potential source of high-value components for functional foods and nutraceuticals--a review."
},
{
"docid": "MED-2085",
"text": "A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.",
"title": "Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables."
},
{
"docid": "MED-2076",
"text": "BACKGROUND: Berries are a particularly rich source of polyphenols. They also contain other bioactive substances, such as vitamin C. Previous studies indicated that the consumption of polyphenol-rich foods (eg, cocoa, tea, and red wine) may induce beneficial changes in pathways related to cardiovascular health. Whether the consumption of berries has similar effects is unknown. OBJECTIVE: We aimed to investigate the effects of berry consumption on hemostatic function, serum lipids, and blood pressure (BP). DESIGN: Middle-aged unmedicated subjects (n = 72) with cardiovascular risk factors consumed moderate amounts of berry or control products for 8 wk in a single-blind, randomized, placebo-controlled intervention trial. RESULTS: Berry consumption inhibited platelet function as measured with a platelet function analyzer (using collagen and ADP as platelet activator) [changes: 11% and -1.4% in the berry and control groups, respectively; P = 0.018, analysis of covariance (ANCOVA)]. Plasma biomarkers of platelet activation, coagulation, and fibrinolysis did not change during the intervention. Serum HDL-cholesterol concentrations increased significantly more (P = 0.006, ANCOVA) in the berry than in the control group (5.2% and 0.6%, respectively), but total cholesterol and triacylglycerol remained unchanged. Systolic BP decreased significantly (P = 0.050, ANCOVA); the decrease mostly occurred in subjects with high baseline BP (7.3 mm Hg in highest tertile; P = 0.024, ANCOVA). Polyphenol and vitamin C concentrations in plasma increased, whereas other nutritional biomarkers (ie, folate, tocopherols, sodium, and potassium) were unaffected. CONCLUSION: The consumption of moderate amounts of berries resulted in favorable changes in platelet function, HDL cholesterol, and BP. The results indicate that regular consumption of berries may play a role in the prevention of cardiovascular disease.",
"title": "Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol."
},
{
"docid": "MED-2352",
"text": "BACKGROUND: Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. METHODS: Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. RESULTS: Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. CONCLUSIONS: Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.",
"title": "Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose."
},
{
"docid": "MED-2356",
"text": "Background In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001). Conclusion The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.",
"title": "The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose"
},
{
"docid": "MED-3307",
"text": "OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.",
"title": "Mortality in workers employed in pig abattoirs and processing plants."
},
{
"docid": "MED-2365",
"text": "Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).",
"title": "An association between tick bite reactions and red meat allergy in humans."
},
{
"docid": "MED-2816",
"text": "Plants contain numerous polyphenols, which have been shown to reduce inflammation and hereby to increase resistance to disease. Examples of such polyphenols are isothiocyanates in cabbage and broccoli, epigallocatechin in green tee, capsaicin in chili peppers, chalones, rutin and naringenin in apples, resveratrol in red wine and fresh peanuts and curcumin/curcuminoids in turmeric. Most diseases are maintained by a sustained discreet but obvious increased systemic inflammation. Many studies suggest that the effect of treatment can be improved by a combination of restriction in intake of proinflammatory molecules such as advanced glycation end products (AGE), advanced lipoperoxidation end products (ALE), and rich supply of antiinflammatory molecules such as plant polyphenols. To the polyphenols with a bulk of experimental documentation belong the curcuminoid family and especially its main ingredient, curcumin. This review summarizes the present knowledge about these turmericderived ingredients, which have proven to be strong antioxidants and inhibitors of cyclooxigenase-2 (COX-2), lipoxygenase (LOX) and nuclear factor kappa B (NF-kappaB) but also AGE. A plethora of clinical effects are reported in various experimental diseases, but clinical studies in humans are few. It is suggested that supply of polyphenols and particularly curcuminoids might be value as complement to pharmaceutical treatment, but also prebiotic treatment, in conditions proven to be rather therapy-resistant such as Crohn's, long-stayed patients in intensive care units, but also in conditions such as cancer, liver cirrhosis, chronic renal disease, chronic obstructive lung disease, diabetes and Alzheimer's disease.",
"title": "Plant-derived health: the effects of turmeric and curcuminoids."
},
{
"docid": "MED-5330",
"text": "Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.",
"title": "Effect of a single high-fat meal on endothelial function in healthy subjects."
},
{
"docid": "MED-2800",
"text": "The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.",
"title": "Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management"
},
{
"docid": "MED-5363",
"text": "OBJECTIVE: Although several studies have reported associations of depressive state with specific nutrients and foods, few studies examined the association with dietary patterns in adults. We investigated the association between major dietary patterns and depressive symptoms in Japanese. METHODS: Subjects were 521 municipal employees (309 men and 212 women), aged 21-67 years, who participated in a health survey at the time of periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Dietary patterns were derived by using principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief diet history questionnaire. Logistic regression analysis was used to estimate odds ratios of depressive symptoms (CES-D >or=16) with adjustment for potential confounding variables. RESULTS: We identified three dietary patterns. A healthy Japanese dietary pattern characterized by high intakes of vegetables, fruit, mushrooms and soy products was associated with fewer depressive symptoms. The multivariate-adjusted odds ratios (95% confidence intervals) of having depressive symptoms for the lowest through highest tertiles of the healthy Japanese dietary pattern score were 1.00 (reference), 0.99 (0.62-1.59) and 0.44 (0.25-0.78), respectively (P for trend=0.006). Other dietary patterns were not appreciably associated with depressive symptoms. CONCLUSIONS: Our findings suggest that a healthy Japanese dietary pattern may be related to decreased prevalence of depressive status.",
"title": "Dietary patterns and depressive symptoms among Japanese men and women."
},
{
"docid": "MED-4133",
"text": "BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.",
"title": "Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study."
},
{
"docid": "MED-1986",
"text": "BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up.",
"title": "Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935."
},
{
"docid": "MED-3464",
"text": "The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.",
"title": "Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women."
},
{
"docid": "MED-3947",
"text": "Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.",
"title": "Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells."
},
{
"docid": "MED-2362",
"text": "The study of the expression of Gal alpha 1----3Gal beta 1----4GlcNAc residues on mammalian glycoconjugates is of particular interest since as many as 1% of circulating IgG antibodies in man (the natural anti-Gal antibody) interact specifically with this carbohydrate residue. In recent studies, we have found that Gal alpha 1----3Gal beta 1----4GlcNAc residues are abundant on red cells and nucleated cells of nonprimate mammals, prosimians, and New World monkeys, but their expression is diminished in Old World monkeys, apes, and humans. In the present work, we have analyzed the expression of these residues on secreted mammalian glycoproteins. For this purpose, we have developed a radioimmunoassay (RIA) which enables the quantification of Gal alpha 1----3Gal beta 1----4GlcNAc residues on the secreted glycoproteins. Purified biotinylated anti-Gal was used as the antibody in the RIA, and bovine thyroglobulin enriched for Gal alpha 1----3Gal beta 1----4GlcNAc residues served as a solid-phase antigen. In this study, it is reported for the first time that the evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells. Thyroglobulin, fibrinogen, or IgG molecules from nonprimate mammals and from New World monkeys express varying amounts of Gal alpha 1----3Gal beta 1----4GlcNAc residues ranging between 0.01 and 11 residues per molecule, whereas no such residues are present on any of these glycoproteins of human or Old World monkey origin.(ABSTRACT TRUNCATED AT 250 WORDS)",
"title": "Distribution of Gal alpha 1----3Gal beta 1----4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G..."
},
{
"docid": "MED-4407",
"text": "Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects. Copyright © 2010 Elsevier Ltd. All rights reserved.",
"title": "Addition of açaí (Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice."
},
{
"docid": "MED-5334",
"text": "Until recently, intact protein that is rich in tryptophan was not seen as an alternative to pharmaceutical-grade tryptophan because protein also contains large neutral amino acids (LNAAs) that compete for transport sites across the blood-brain barrier. Recent evidence indicates that when deoiled gourd seed (a rich source of tryptophan with approximately 22 mg/g protein) is combined with glucose (a carbohydrate that reduces serum levels of competing LNAAs) a clinical effect similar to that of pharmaceutical-grade tryptophan is achieved. Objective and subjective measures of anxiety in those suffering from social phobia (also known as social anxiety disorder) were employed to measure changes in anxiety in response to a stimulus as part of a double-blind, placebo-controlled, crossover study with a wash-out period of 1 week between study sessions. Subjects were randomly assigned to start with either (i) protein-source tryptophan (deoiled gourd seed) in combination with carbohydrate or (ii) carbohydrate alone. One week after the initial session, subjects returned for a follow-up session and received the opposite treatment of that received at the first session. All 7 subjects who began the study completed the 2-week protocol. Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement on an objective measure of anxiety. Protein-source tryptophan combined with a high glycemic carbohydrate is a potential anxiolytic to those suffering from social phobia.",
"title": "Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study."
},
{
"docid": "MED-4520",
"text": "Evidence suggests that endothelial dysfunction is on the causal pathway for both atherogenesis and destabilization of established plaques. In this review, the role of flow-mediated dilatation (FMD) as a non-invasive method to assess endothelial function is discussed. Technical modifications and development of analysis software have significantly improved the variability of the method. Following a strict standardized protocol enables reproducible measurements to be achieved and export of the technique from specialized laboratories to population studies and multicentre settings. Endothelial function assessed by FMD has been shown to be affected by cardiovascular risk factors, to be related to structural arterial disease and to cardiovascular outcome, validating its use for studying the pathophysiology of arterial disease. Numerous studies have also demonstrated that it is responsive to physiological and pharmacological interventions. Flow-mediated dilatation provides unique opportunities in drug development programmes to assess an early rapidly responsive signal of risk or benefit, complementing endpoints of structural arterial disease and cardiovascular outcomes that take much longer and are more expensive.",
"title": "Assessment of atherosclerosis: the role of flow-mediated dilatation."
},
{
"docid": "MED-4087",
"text": "Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.",
"title": "Fibromyalgia and nutrition, what do we know?"
},
{
"docid": "MED-4141",
"text": "To study the origin and spread of Yersinia enterocolitica among pigs, fecal and blood samples were repeatedly taken on a fattening farm. A few piglets were found to be already infected on breeding farms. After the piglets were mixed, the infection spread through the whole unit. Eventually, all the pigs excreted the pathogen.",
"title": "Piglets Are a Source of Pathogenic Yersinia enterocolitica on Fattening-Pig Farms"
},
{
"docid": "MED-4843",
"text": "We have previously reported that significant improvement may be obtained in rheumatoid arthritis patients by fasting followed by a vegetarian diet for one year. The present study was carried out to examine to what extent biochemical and immunological variables changed during the clinical trial of fasting and vegetarian diet. For the patients who were randomised to the vegetarian diet there was a significant decrease in platelet count, leukocyte count, calprotectin, total IgG, IgM rheumatoid factor (RF), C3-activation products, and the complement components C3 and C4 after one month of treatment. None of the measured parameters changed significantly during this period in the group of omnivores. The course of 14 of 15 measured variables favored the vegetarians compared with the omnivores, but the difference was only significant for leukocyte count, IgM RF, and the complement components C3 and C4. Most of the laboratory variables declined considerably in the vegetarians who improved according to clinical variables, indicating a substantial reduction in inflammatory activity. The leukocyte count, however, decreased in the vegetarians irrespective of the clinical results. Thus, the decline in leukocyte count may be attributed to vegetarian diet per se and not to the reduction in disease activity. The results of the present study are in accordance with the findings from the clinical trial, namely that dietary treatment can reduce the disease activity in some patients with rheumatoid arthritis.",
"title": "Changes in laboratory variables in rheumatoid arthritis patients during a trial of fasting and one-year vegetarian diet."
},
{
"docid": "MED-4132",
"text": "Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.",
"title": "Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic..."
},
{
"docid": "MED-2804",
"text": "Osteoarthritis (OA) is the most common form of arthritis in the US, and a leading cause of disability. It is typically defined in epidemiologic studies on the basis of radiographic findings and consideration of symptoms. Its incidence and prevalence are rising, likely related to the aging of the population and increasing obesity. Risk factors for OA include a number of person-level factors, such as age, sex, obesity, and genetics, as well as joint-specific factors that are likely reflective of abnormal loading of the joints. A number of methodologic challenges exist in studying OA that can hamper our ability to identify pertinent relationships.",
"title": "Epidemiology of OA"
},
{
"docid": "MED-2807",
"text": "In a previous three-month study of Meriva, a proprietary curcumin-phosphatidylcholine phytosome complex, decreased joint pain and improvement in joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a chronic condition requiring prolonged treatment, the long-term efficacy and safety of Meriva were investigated in a longer (eight months) study involving 100 OA patients. The clinical end points (Western Ontario and McMaster Universities [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking performance) were complemented by the evaluation of a series of inflammatory markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate [ESR]). This represents the most ambitious attempt, to date, to evaluate the clinical efficacy and safety of curcumin as an anti-inflammatory agent. Significant improvements of both the clinical and biochemical end points were observed for Meriva compared to the control group. This, coupled with an excellent tolerability, suggests that Meriva is worth considering for the long-term complementary management of osteoarthritis.",
"title": "Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients."
},
{
"docid": "MED-4104",
"text": "BACKGROUND: Although vegan diets improve diabetes management, little is known about the nutrient profiles or diet quality of individuals with type 2 diabetes who adopt a vegan diet. OBJECTIVE: To assess the changes in nutrient intake and dietary quality among participants following a low-fat vegan diet or the 2003 American Diabetes Association dietary recommendations. DESIGN: A 22-week randomized, controlled clinical trial examining changes in nutrient intake and diet quality. SUBJECTS/SETTING: Participants with type 2 diabetes (n=99) in a free-living setting. RESEARCH DESIGN AND METHODS: Participants were randomly assigned to a low-fat vegan diet or a 2003 American Diabetes Association recommended diet. MAIN OUTCOME MEASURES: Nutrient intake and Alternate Healthy Eating Index (AHEI) scores were collected at baseline and 22 weeks. STATISTICAL ANALYSES PERFORMED: Between-group t tests were calculated for changes between groups and paired comparison t tests were calculated for changes within-group. Pearson's correlation assessed relationship of AHEI score to hemoglobin A1c and body weight changes. RESULTS: Both groups reported significant decreases in energy, protein, fat, cholesterol, vitamin D, selenium, and sodium intakes. The vegan group also significantly reduced reported intakes of vitamin B-12 and calcium, and significantly increased carbohydrate, fiber, total vitamin A activity, beta carotene, vitamins K and C, folate, magnesium, and potassium. The American Diabetes Association recommended diet group also reported significant decreases in carbohydrate and iron, but reported no significant increases. The vegan group significantly improved its AHEI score (P<0.0001), while the American Diabetes Association recommended diet group did not (P=0.7218). The difference in AHEI score at 22 weeks between groups was significant (P<0.0001). With both groups combined, AHEI score was negatively correlated with both changes in hemoglobin A1c value (r=-0.24, P=0.016) and weight (r=-0.27, P=0.007). CONCLUSIONS: Vegan diets increase intakes of carbohydrate, fiber, and several micronutrients, in contrast with the American Diabetes Association recommended diet. The vegan group improved its AHEI score whereas the American Diabetes Association recommended diet group's AHEI score remained unchanged.",
"title": "Changes in nutrient intake and dietary quality among participants with type 2 diabetes following a low-fat vegan diet or a conventional diabetes di..."
},
{
"docid": "MED-4138",
"text": "Yersinia enterocolitica is a zoonotic agent that causes gastrointestinal disease in humans, as well as reactive arthritis and erythema nodosum. Enteropathogenic Yersinia are the etiological agents for yersiniosis, which can be acquired through the consumption of contaminated foods. As porcine animals are the main carriers of Y. enterocolitica, food safety measures to minimize human infection are of increasing interest to the scientific and medical community. In this review, we examine why it is imperative that information on the reservoirs, prevalence, virulence, and ability of this pathogen to survive in different environments is further investigated to provide rational measures to prevent or decrease associated disease risks.",
"title": "Yersinia enterocolitica: a brief review of the issues relating to the zoonotic pathogen, public health challenges, and the pork production chain."
},
{
"docid": "MED-2797",
"text": "Osteoarthritis (OA) has long been considered a \"wear and tear\" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an \"inflammatory\" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.",
"title": "Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)."
},
{
"docid": "MED-4130",
"text": "We investigated characteristics of Yersinia enterocolitica infection in Ontario finisher pig herds. Our specific objectives were to estimate or test: prevalence of Y. enterocolitica shedding in finisher pigs, bioserotype distribution, agreement between the herd-level tests based on sampling pig and pooled fecal samples, whether bioserotypes cluster by farms, and whether Y. enterocolitica-positive herds cluster spatially. In total, 3747 fecal samples were collected from 100 farms over the years 2001, 2002, and 2004 (250 total herd visits). Fecal samples were tested by culture and positive isolates were biotyped and serotyped. Apparent pig-level prevalence of Y. enterocolitica was 1.8%, 3.2%, and 12.5% in 2001, 2002, and 2004, respectively. Estimated true pig-level prevalence of Y. enterocolitica was 5.1%, 9.1%, and 35.1% in 2001, 2002, and 2004, respectively. Herd-level prevalence was 16.3%, 17.9%, and 37.5% in 2001, 2002, and 2004, respectively. In all years, the most common bioserotype was 4, O:3, followed by bioserotype 2, O:5,27. Kappa between herd-level status based on pig and pooled samples ranged between 0.51 and 0.68 for biotype 1A and bioserotype 4, O:3, respectively. For 4, O:3, a significant bias in discordant pairs was detected, indicating that pig samples were more sensitive than pooled samples in declaring a herd as positive. Farms tended to be repeatedly positive with the same bioserotype, but positive study farms did not cluster spatially (suggesting lack of between herd transmission and lack of a common geographic risk factor). Copyright 2009 Elsevier B.V. All rights reserved.",
"title": "Prevalence of Yersinia enterocolitica shedding and bioserotype distribution in Ontario finisher pig herds in 2001, 2002, and 2004."
},
{
"docid": "MED-2278",
"text": "OBJECTIVES: To investigate the anti-inflammatory and anti-oxidative effects of anthocyanins from cherries on Freund's adjuvant-induced arthritis (AIA) in rats. METHODS: Arthritis was induced intradermally by injection with 0.1 mL of complete Freund's adjuvant (CFA) into the right hind footpad of male Sprague Dawley (SD) rats. Anthocyanins at 40, 20 and 10 mg/kg (body weight) were administered orally to the treated rats for 28 days after the injection. Tumour necrosis factor-alpha (TNFalpha) in serum and prostaglandin E2 (PGE2) in paws were assayed by radioimmunoassay (RIA), and anti-oxidative effects was assayed by measuring total anti-oxidative capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. RESULTS: Anthocyanins at 40 mg/kg significantly decreased the levels of TNFalpha in serum and PGE2 in paws, simultaneously improving the anti-oxidative status of AIA. We found that at this dosage T-AOC was potentized, the activity of SOD increased and the level of MDA in serum decreased. However, anthocyanins at 20 and 10 mg/kg had less effect on the inflammatory factors and anti-oxidative capacity of AIA. CONCLUSIONS: Anthocyanins have potential anti-inflammatory and anti-oxidative effects on AIA.",
"title": "Anti-inflammatory and anti-oxidative effects of cherries on Freund's adjuvant-induced arthritis in rats."
},
{
"docid": "MED-4630",
"text": "Arachidonic acid (AA)-derived eicosanoids belong to a complex family of lipid mediators that regulate a wide variety of physiological responses and pathological processes. They are produced by various cell types through distinct enzymatic pathways and act on target cells via specific G-protein-coupled receptors. Although originally recognized for their capacity to elicit biological responses such as vascular homeostasis, protection of the gastric mucosa and platelet aggregation, eicosanoids are now understood to regulate immunopathological processes ranging from inflammatory responses to chronic tissue remodelling, cancer, asthma, rheumatoid arthritis and autoimmune disorders. Here, we review the major properties of eicosanoids and their expanding roles in biology and medicine.",
"title": "Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology."
},
{
"docid": "MED-3852",
"text": "Recently two groups of compounds with diphenolic structure, the lignans and the isoflavonic phytoestrogens, were detected and identified in human urine and other biological fluids. These compounds are of great biological interest because they exhibit both in vitro and in vivo weak estrogenic and sometimes also antiestrogenic activities and many plant lignans have been shown to have anticarcinogenic, antiviral, antifungal and other interesting biological effects. The compounds found in relatively large amounts (10-1000 times more than estrogens) in urine are modified by intestinal bacteria from plant lignans and phytoestrogens, which are present in fiber-rich food such as grain and beans. They bind with low affinity to estrogen receptors and preliminary results suggest that they may induce production of sex hormone binding globulin (SHBG) in the liver and in this way may influence sex hormone metabolism and biological effects. Five compounds, the lignans enterolactone (Enl), enterodiol (End) and the isoflavonic phytoestrogen metabolites daidzein (Da), equol (Eq) and O-desmethylangolensin (O-Dma) were measured in urine by gas chromatography-mass spectrometry (selected ion monitoring) using deuterated internal standards in 5 groups of women (total number 53). The members of three dietary groups (omnivores, lactovegetarians and macrobiotics) were living in Boston and of two groups in Helsinki (omnivores and lactovegetarians). Until now measurements have been carried out in 94 72-h samples. The highest mean excretion of the most abundant compound, enterolactone, was found in the macrobiotic group and the lowest in the omnivoric groups. Total mean 24-h excretion of enterolactone was 17,680 nmol in the macrobiotics, 4,170 nmol in the Boston lactovegetarians, 3,650 nmol in the Helsinki lactovegetarians, 2,460 nmol in the Helsinki omnivores and 2,050 nmol in the Boston omnivores. The other diphenols followed approximately the same pattern. In an earlier study the lowest excretion of enterolactone (1,040 nmol/24 h) was found in a group of postmenopausal apparently healthy breast cancer patients living in Boston. It is concluded that further studies are necessary to elucidate the possible role of these compounds in cancer and other diseases. However, the evidence obtained until now seems to justify the conclusion that these compounds may be among the dietary factors affording protection against hormone-dependent cancers in vegetarians and semivegetarians.",
"title": "Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual ..."
},
{
"docid": "MED-3314",
"text": "OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.",
"title": "Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC)."
},
{
"docid": "MED-1126",
"text": "Lignans are a class of secondary plant metabolites produced by oxidative dimerization of two phenylpropanoid units. Although their molecular backbone consists only of two phenylpropane (C6-C3) units, lignans show an enormous structural diversity. There is a growing interest in lignans and their synthetic derivatives due to applications in cancer chemotherapy and various other pharmacological effects. This review deals with lignans possessing anticancer, antioxidant, antimicrobial, anti-inflammatory and immunosuppressive activities, and comprises the data reported in more than 100 peer-reviewed articles, so as to highlight the recently reported bioactive lignans that could be a first step towards the development of potential new therapeutic agents.",
"title": "An update on bioactive plant lignans."
},
{
"docid": "MED-1987",
"text": "OBJECTIVE: Over the last 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. This technical report describes, in detail, the procedures undertaken to develop the recommendations given in the accompanying clinical practice guideline, \"Management of Type 2 Diabetes Mellitus in Children and Adolescents,\" and provides in-depth information about the rationale for the recommendations and the studies used to make the clinical practice guideline's recommendations. METHODS: A primary literature search was conducted relating to the treatment of T2DM in children and adolescents, and a secondary literature search was conducted relating to the screening and treatment of T2DM's comorbidities in children and adolescents. Inclusion criteria were prospectively and unanimously agreed on by members of the committee. An article was eligible for inclusion if it addressed treatment (primary search) or 1 of 4 comorbidities (secondary search) of T2DM, was published in 1990 or later, was written in English, and included an abstract. Only primary research inquiries were considered; review articles were considered if they included primary data or opinion. The research population had to constitute children and/or adolescents with an existing diagnosis of T2DM; studies of adult patients were considered if at least 10% of the study population was younger than 35 years. All retrieved titles, abstracts, and articles were reviewed by the consulting epidemiologist. RESULTS: Thousands of articles were retrieved and considered in both searches on the basis of the aforementioned criteria. From those, in the primary search, 199 abstracts were identified for possible inclusion, 58 of which were retained for systematic review. Five of these studies were classified as grade A studies, 1 as grade B, 20 as grade C, and 32 as grade D. Articles regarding treatment of T2DM selected for inclusion were divided into 4 major subcategories on the basis of type of treatment being discussed: (1) medical treatments (32 studies); (2) nonmedical treatments (9 studies); (3) provider behaviors (8 studies); and (4) social issues (9 studies). From the secondary search, an additional 336 abstracts relating to comorbidities were identified for possible inclusion, of which 26 were retained for systematic review. These articles included the following: 1 systematic review of literature regarding comorbidities of T2DM in adolescents; 5 expert opinions presenting global recommendations not based on evidence; 5 cohort studies reporting natural history of disease and comorbidities; 3 with specific attention to comorbidity patterns in specific ethnic groups (case-control, cohort, and clinical report using adult literature); 3 reporting an association between microalbuminuria and retinopathy (2 case-control, 1 cohort); 3 reporting the prevalence of nephropathy (cohort); 1 reporting peripheral vascular disease (case series); 2 discussing retinopathy (1 case-control, 1 position statement); and 3 addressing hyperlipidemia (American Heart Association position statement on cardiovascular risks; American Diabetes Association consensus statement; case series). A breakdown of grade of recommendation shows no grade A studies, 10 grade B studies, 6 grade C studies, and 10 grade D studies. With regard to screening and treatment recommendations for comorbidities, data in children are scarce, and the available literature is conflicting. Therapeutic recommendations for hypertension, dyslipidemia, retinopathy, microalbuminuria, and depression were summarized from expert guideline documents and are presented in detail in the guideline. The references are provided, but the committee did not independently assess the supporting evidence. Screening tools are provided in the Supplemental Information.",
"title": "Management of type 2 diabetes mellitus in children and adolescents."
},
{
"docid": "MED-4846",
"text": "The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.",
"title": "Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis."
},
{
"docid": "MED-3313",
"text": "INTRODUCTION: Asbestos is banned in most Western countries but related malignancies are still of clinical concern because of their long latencies. This review identifies and addresses some controversial occupational and clinical aspects of asbestos-related malignancies. METHODS: Papers published in English from 1980 to 2009 were retrieved from PubMed. A total of 307 original articles were identified and 159 were included. ASSESSMENT OF EXPOSURE: The retrospective assessment of exposure is usually performed by using questionnaires and job exposure matrices and by careful collection of medical history. In this way crucial information about manufacturing processes and specific jobs can be obtained. In addition, fibers and asbestos bodies are counted in lung tissue, broncho-alveolar lavage, and sputum, but different techniques and interlaboratory variability hamper the interpretation of reported measurements. SCREENING FOR MALIGNANCIES: The effectiveness of low-dose chest CT screening in exposed workers is debatable. Several biomarkers have also been considered to screen individuals at risk for lung cancer and mesothelioma but reliable signatures are still missing. ATTRIBUTION OF LUNG CANCER: Exposures correlating with lung cancer are high and in the same range where asbestosis occurs. However, the unresolved question is whether the presence of fibrosis is a requirement for the attribution of lung cancer to asbestos. The etiology of lung cancer is difficult to define in cases of low-level asbestos exposure and concurrent smoking habits. MESOTHELIOMA: The diagnosis of malignant mesothelioma may also be difficult, because of procedures in sampling, fixation, and processing, and uses of immunohistochemical probes. CONCLUSIONS: Assessment of exposure is crucial and requires accurate medical and occupational histories. Quantitative analysis of asbestos body burden is better performed in digested lung tissues by counting asbestos bodies by light microscopy and/or uncoated fibers by transmission electron microscopy. The benefits of screenings for asbestos-related malignancies are equivocal. The attribution of lung cancer to asbestos exposure is difficult in a clinical setting because of the need to assess asbestos body burden and the fact that virtually all these patients are also tobacco smokers or former smokers. Given the premise that asbestosis is necessary to causally link lung cancer to asbestos, it follows that the assessment of both lung fibrosis and asbestos body burden is necessary.",
"title": "Occupational toxicology of asbestos-related malignancies."
},
{
"docid": "MED-5341",
"text": "The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.",
"title": "Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro."
},
{
"docid": "MED-2366",
"text": "Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.",
"title": "A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis."
},
{
"docid": "MED-3292",
"text": "The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.",
"title": "The Restriction of Zoonotic PERV Transmission by Human APOBEC3G"
},
{
"docid": "MED-4137",
"text": "Swine have been identified as the primary reservoir of pathogenic Yersinia enterocolitica (YE), but little research has focused on the epidemiology of YE at the farm level. The objective of this study was to describe the prevalence of YE in different production phases on swine farms. In this cross-sectional study, individual pigs on eight swine operations were sampled for the presence of YE. On each farm, both feces and oral-pharyngeal swabs were collected from pigs in five different production phases: gestating, farrowing, suckling, nursery, and finishing. A pig was considered positive if either sample tested positive. Samples were cultured with cold enrichment followed by isolation on selective media plates. Presumptive isolates were confirmed as YE and assayed for the presence of ail with a multiplex PCR. Of the 2,349 pigs sampled, 120 (5.1%) tested positive, and of those, 51 were ail positive (42.5% of YE isolates). On all farms, there was a trend of increasing prevalence as pigs mature. Less than 1% of suckling piglets tested positive for YE. Only 1.4% (44.4% of which were ail positive) of nursery pigs tested positive, but 10.7% (48.1% of which were ail positive) of finishing pigs harbored YE. Interestingly, gestating sows had the second highest prevalence of YE at 9.1% (26.7% of which were ail positive), yet YE was never detected from the farrowing sows. These results represent the first on-farm description of YE in U.S. herds and provide the initial step for designing future studies of YE.",
"title": "Prevalence of Yersinia enterocolitica in different phases of production on swine farms."
},
{
"docid": "MED-2083",
"text": "Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. This study evaluated whether commercial grape, orange and grapefruit juices, taken daily, reduce ex vivo platelet activity. In a randomized cross-over design, ten healthy human subjects (ages 26-58 y, five of each gender) drank 5-7.5 mL/(kg. d) of purple grape juice, orange juice or grapefruit juice for 7-10 d each. Platelet aggregation (whole blood impedance aggregometry, Chronolog Model #590) at baseline was compared to results after consumption of each juice. Drinking purple grape juice for one week reduced the whole blood platelet aggregation response to 1 mg/L of collagen by 77% (from 17.9 +/- 2.3 to 4.0 +/- 6.8 ohms, P = 0.0002). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.",
"title": "Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation."
},
{
"docid": "MED-5010",
"text": "Phytochemicals are recognized as playing an important role in cancer prevention by fruits and vegetables. The avocado is a widely grown and consumed fruit that is high in nutrients and low in calories, sodium, and fats. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with chloroform from avocado fruits target multiple signaling pathways and increase intracellular reactive oxygen leading to apoptosis. This review summarizes the reported phytochemicals in avocado fruit and discusses their molecular mechanisms and targets. These studies suggest that individual and combinations of phytochemicals from the avocado fruit may offer an advantageous dietary strategy in cancer prevention.",
"title": "Chemopreventive characteristics of avocado fruit."
},
{
"docid": "MED-3310",
"text": "We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.",
"title": "A new type of Hypersensitivity Pneumonitis: salami brusher's disease."
},
{
"docid": "MED-4317",
"text": "Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.",
"title": "Intestinal iron absorption: regulation by dietary & systemic factors."
},
{
"docid": "MED-3951",
"text": "INTRODUCTION: This case report describes a patient who developed rhabdomyolysis temporally associated with the use of a mislabeled acai berry dietary supplement. METHODS AND RESULTS: The authors describe a 22-year-old man presenting with rhabdomyolysis approximately 2 weeks after starting a weight-loss dietary supplement. His medical history was significant only for hypertension treated with amlodipine. The diagnosis of rhabdomyolysis was confirmed (creatine kinase, 84,000 IU/L, positive urine myoglobin) with other potential causes ruled out. The signs and symptoms of the patient gradually resolved and he was discharged on hospital day 5. Assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 3, indicating a possible relationship between the supplement and rhabdomyolysis. Although the product was labeled and promoted as containing acai berry and additional ingredients, there was no acai berry found on analysis. CONCLUSION: Clinicians should be aware that all dietary supplements may vary in uniformity and contain unknown contaminants.",
"title": "Rhabdomyolysis associated with the use of a mislabeled \"acai berry\" dietary supplement."
},
{
"docid": "MED-2359",
"text": "INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Anti-Gal titers in healthy adults and inflammatory bowel disease patients."
},
{
"docid": "MED-1988",
"text": "PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.",
"title": "Pediatrician's role in screening and treatment: bullying, prediabetes, oral health."
},
{
"docid": "MED-4628",
"text": "BACKGROUND & AIMS: Dietary arachidonic acid, an n-6 polyunsaturated fatty acid (n-6 PUFA), might be involved in the etiology of ulcerative colitis (UC). We performed a prospective cohort study to determine whether high levels of arachidonic acid in adipose tissue samples (which reflects dietary intake) are associated with UC. METHODS: We analyzed data collected from 57,053 men and women in the EPIC-Denmark Prospective Cohort Study from 1993 to 1997. Adipose tissue biopsy samples were collected from gluteal regions at the beginning of the study, the cohort was monitored over subsequent years, and participants who developed UC were identified. A subcohort of 2510 randomly selected participants were used as controls. Concentrations of arachidonic acid were measured in adipose tissue samples. In the analysis, arachidonic acid levels were divided into quartiles; relative risks (RR) were calculated and adjusted for smoking, use of aspirin and nonsteroidal anti-inflammatory drugs, and levels of n-3 PUFAs. RESULTS: A total of 34 subjects (56% men) developed incident UC at a median age of 58.8 years (range, 50.0-69.0 years). Those in the highest quartile for arachidonic acid concentrations in adipose tissue had an RR for UC of 4.16 (95% confidence interval [CI]: 1.56-11.04); a trend per 0.1% increase in arachidonic acid of 1.77 in RR was observed (95% CI: 1.38-2.27). The fraction attributed the highest levels of arachidonic acid was 40.3%. CONCLUSIONS: Individuals with the highest relative concentrations of arachidonic acid in adipose tissue have a significantly greater risk of developing UC. Dietary modifications might therefore prevent UC or reduce disease symptoms. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.",
"title": "An association between dietary arachidonic acid, measured in adipose tissue, and ulcerative colitis."
},
{
"docid": "MED-2817",
"text": "Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin in inflammatory diseases."
},
{
"docid": "MED-4135",
"text": "Yersinia enterocolitica are ubiquitous, being isolated frequently from soil, water, animals, and a variety of foods. They comprise a biochemically heterogeneous group that can survive and grow at refrigeration temperatures. The ability to propagate at refrigeration temperatures is of considerable significance in food hygiene. Virulent strains of Yersinia invade mammalian cells such as HeLa cells in tissue culture. Two chromosomal genes, inv and ail, were identified for cell invasion of mammalian. The pathogen can cause diarrhoea, appendicitis and post-infection arthritis may occur in a small proportion of cases. The most common transmission route of pathogenic Y. enterocolitica is thought to be fecal-oral via contaminated food. Direct person-to-person contact is rare. Occasionally, pathogenic Y. enterocolitica has been detected in vegetables and environmental water; thus, vegetables and untreated water are also potential sources of human yersiniosis. However, the isolation rates of pathogenic Y. enterocolitica have been low, which may be due to the limited sensitivity of the detection methods. To identify other possible transmission vehicles, different food items should be studied more extensively. Many factors related to the epidemiology of Y. enterocolitica, such as sources, transmission routes, and predominating genotypes remain obscure because of the low sensitivity of detection methods.",
"title": "Behavior of Yersinia enterocolitica in Foods"
},
{
"docid": "MED-4851",
"text": "The notion that dietary factors may influence rheumatoid arthritis (RA) has been a part of the folklore of the disease, but scientific support for this has been sparse. In a controlled, single-blind trial we tested the effect of fasting for 7-10 d, then consuming an individually adjusted, gluten-free, vegan diet for 3.5 mo, and then consuming an individually adjusted lactovegetarian diet for 9 mo on patients with RA. For all clinical variables and most laboratory variables measured, the 27 patients in the fasting and vegetarian diet groups improved significantly compared with the 26 patients in the control group who followed their usual omnivorous diet throughout the study period. One year after the patients completed the trial, they were reexamined. Compared with baseline, the improvements measured were significantly greater in the vegetarians who previously benefited from the diet (diet responders) than in diet nonresponders and omnivores. The beneficial effect could not be explained by patients' psychologic characteristics, antibody activity against food antigens, or changes in concentrations of prostaglandin and leukotriene precursors. However, the fecal flora differed significantly between samples collected at time points at which there was substantial clinical improvement and time points at which there were no or only minor improvements. In summary, the results show that some patients with RA can benefit from a fasting period followed by a vegetarian diet. Thus, dietary treatment may be a valuable adjunct to the ordinary therapeutic armamentarium for RA.",
"title": "Rheumatoid arthritis treated with vegetarian diets."
},
{
"docid": "MED-2077",
"text": "Cardiovascular diseases are one of the leading causes of morbidity and mortality in industrialized countries, and although many processes play a role in the development of vascular disease, thrombosis is the primary event that precipitates stroke and acute coronary syndromes. The blood platelets are of significant importance in medicine. These cells are involved in many physiological processes, particularly haemostasis through their ability to aggregate and form clots in response to activation. In addition, these dynamic cells display activities that extend beyond thrombosis, including an important role in initiating and sustaining vascular inflammation. The expansion of knowledge from basic and clinical research has highlighted the critical position of platelets in several inflammatory diseases such as arthritis and atherosclerosis. Platelets are emerging as important mediators of inflammation and provide important signals to mediate phenotype of other blood and vascular cells. The important role of platelets in arterial thrombosis and the onset of acute myocardial infarction after atherosclerotic plaque rupture make inhibition of platelet aggregation a critical step in preventing thrombotic events associated with stroke, heart attack, and peripheral arterial thrombosis. However, the use of platelet inhibitors for thrombosis prevention must seek a delicate balance between inhibiting platelet activation and an associated increased bleeding risk. The aim of this review is to up-date the knowledge on platelets physiology and dysfunction in pathologies, such as diabetes mellitus, hypercholesterolemia, and hypertension, emphasizing the link between platelets and the inflammation-related atherosclerosis. The review evaluates the opportunities offered by the novel platelet inhibitors to efficiently alleviate the thrombotic events. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Platelet dysfunction in vascular pathologies and how can it be treated."
},
{
"docid": "MED-4629",
"text": "In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.",
"title": "Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?"
},
{
"docid": "MED-5342",
"text": "Background The physical health status of vegetarians has been extensively reported, but there is limited research regarding the mental health status of vegetarians, particularly with regard to mood. Vegetarian diets exclude fish, the major dietary source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), critical regulators of brain cell structure and function. Omnivorous diets low in EPA and DHA are linked to impaired mood states in observational and experimental studies. Methods We examined associations between mood state and polyunsaturated fatty acid intake as a result of adherence to a vegetarian or omnivorous diet in a cross-sectional study of 138 healthy Seventh Day Adventist men and women residing in the Southwest. Participants completed a quantitative food frequency questionnaire, Depression Anxiety Stress Scale (DASS), and Profile of Mood States (POMS) questionnaires. Results Vegetarians (VEG:n = 60) reported significantly less negative emotion than omnivores (OMN:n = 78) as measured by both mean total DASS and POMS scores (8.32 ± 0.88 vs 17.51 ± 1.88, p = .000 and 0.10 ± 1.99 vs 15.33 ± 3.10, p = .007, respectively). VEG reported significantly lower mean intakes of EPA (p < .001), DHA (p < .001), as well as the omega-6 fatty acid, arachidonic acid (AA; p < .001), and reported higher mean intakes of shorter-chain α-linolenic acid (p < .001) and linoleic acid (p < .001) than OMN. Mean total DASS and POMS scores were positively related to mean intakes of EPA (p < 0.05), DHA (p < 0.05), and AA (p < 0.05), and inversely related to intakes of ALA (p < 0.05), and LA (p < 0.05), indicating that participants with low intakes of EPA, DHA, and AA and high intakes of ALA and LA had better mood. Conclusions The vegetarian diet profile does not appear to adversely affect mood despite low intake of long-chain omega-3 fatty acids.",
"title": "Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults"
},
{
"docid": "MED-2355",
"text": "Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: (1) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and (2) delayed onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g., beef and pork). The results of our studies strongly suggest that tick bites are a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the southern, eastern and central United States. Patients with IgE Ab to alpha-gal continue to emerge and, increasingly, these cases involve children. This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations.",
"title": "Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal)"
},
{
"docid": "MED-1120",
"text": "Molecular mimicry is a hallmark of the pathogenesis of rheumatic fever where the streptococcal group A carbohydrate epitope, N-acetyl glucosamine, and the a-helical coiled-coil streptococcal M protein structurally mimic cardiac myosin in the human disease, rheumatic carditis, and in animal models immunized with streptococcal M protein and cardiac myosin. Recent studies have unraveled the potential pathogenic mechanisms by which the immune response against the group A streptococcus attacks the rheumatic valve leading to chronic rheumatic heart disease. Both B- and T-cell responses are involved in the process, and evidence for the hypotheses of molecular mimicry and epitope spreading are reviewed.",
"title": "Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease."
},
{
"docid": "MED-1130",
"text": "The beneficial effect of a 1-yr vegetarian diet in RA has recently been demonstrated in a clinical trial. We have analysed stool samples of the 53 RA patients by using direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. Based on repeated clinical assessments disease improvement indices were constructed for the patients. At each time point during the intervention period the patients in the diet group were then assigned either to a group with a high improvement index (HI) or a group with a low improvement index (LI). Significant alteration in the intestinal flora was observed when the patients changed from omnivorous to vegan diet. There was also a significant difference between the periods with vegan and lactovegetarian diets. The faecal flora from patients with HI and LI differed significantly from each other at 1 and 13 months during the diet. This finding of an association between intestinal flora and disease activity may have implications for our understanding of how diet can affect RA.",
"title": "Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet."
},
{
"docid": "MED-5325",
"text": "Objective Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design Data are analysed from a calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort who attended clinics and provided validated FFQ. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Clinics were conducted at churches across the USA and Canada. Dietary data were gathered by mailed questionnaire. Subjects Five hundred white subjects representing the AHS-2 cohort. Results Covariate-adjusted regression analyses demonstrated that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Adventists (β =−6·8, P<0·05 and β = −6·9, P<0·001). Findings for lacto-ovo vegetarians (β = −9·1, P<0·001 and β = −5·8, P<0·001) were similar. The vegetarians (mainly the vegans) were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or use of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0·37 (95 % CI 0·19, 0·74), 0·57 (95 % CI 0·36, 0·92) and 0·92 (95 % CI 0·50, 1·70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Effects were reduced after adjustment for BMI. Conclusions We conclude from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. This is only partly due to their lower body mass.",
"title": "Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2)"
},
{
"docid": "MED-1128",
"text": "Rheumatoid arthritis (RA) is a chronic inflammatory arthritic and potentially disabling condition, mainly affecting women of middle age and having characteristic clinical features. Various microbial agents were implicated in the causation of RA. Extensive literature based on the results of various genetic, microbiological, molecular, and immunological studies carried out by independent research groups supports the role of Proteus mirabilis bacteria in the etiopathogenesis of RA. New diagnostic markers and criteria and the use of a novel therapeutic protocol in the form of antibiotic and dietary measures are suggested to be used together with current treatments in the management of RA. Prospective longitudinal studies with the use of antimicrobial measures in patients with RA are required to establish the therapeutic benefit of this microbe-disease association.",
"title": "Rheumatoid arthritis is linked to Proteus--the evidence."
},
{
"docid": "MED-5328",
"text": "Aim To evaluate the relationship of diet to incident diabetes among non-Black and Black participants in the Adventist Health Study-2. Methods and Results Participants were 15,200 men and 26,187 women (17.3% Blacks) across the U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data. Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian (reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semi-vegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364; 95% confidence interval [CI], 1.093–1.702). In multiple logistic regression analysis controlling for age, gender, education, income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.236–0.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503–0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312–0.755) had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were protective against diabetes (OR 0.429, 95% CI 0.249–0.740; OR 0.684, 95% CI 0.542–0.862; OR 0.501, 95% CI 0.303–0.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110–0.842; OR 0.472, 95% CI 0.270–0.825). These associations were strengthened when BMI was removed from the analyses. Conclusion Vegetarian diets (vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black ethnicity.",
"title": "Vegetarian diets and incidence of diabetes in the Adventist Health Study-2"
},
{
"docid": "MED-1129",
"text": "Molecular mimicry between streptococci and heart components has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). In this review, we present data from cellular autoimmune responses, focusing on the interactions between HLA class II molecules, streptococcal peptides and heart tissue proteins and T-cell receptor (TCR) usage. HLA-DR7DR53 associated with DQ molecules seem to be related with the development of valvular lesions in severe RHD patients. DR7DR53 molecules were also involved in the recognition of an immunodominant M5 peptide in these patients. T cells infiltrating RHD hearts displayed several oligoclonal expansions. Intralesional T-cell clones presenting identical TCR-BVBJ AVAJ and -CDR3 sequences were able to recognize several antigens with little or low homology, showing an intramolecular degenerate pattern of antigen recognition. Peripheral blood mononuclear cells of rheumatic fever (RF) patients produced proinflammatory cytokines, and intralesional mononuclear cells from severe RHD patients produced predominantly Th1-type cytokines. These results illustrate the complex mechanisms leading to heart tissue damage in RF/RHD patients. Copyright 2004 S. Karger AG, Basel",
"title": "Rheumatic fever: from sore throat to autoimmune heart lesions."
},
{
"docid": "MED-5323",
"text": "This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans. The results depended on the type of chemical, exposure level, timing of exposure and gender. Nearly all the studies investigating dichlorodiphenyldichloroethylene (DDE) found that exposure was associated with an increase in body size, whereas the results of the studies investigating polychlorinated biphenyl (PCB) exposure were depending on dose, timing and gender. Hexachlorobenzene, polybrominated biphenyls, beta-hexachlorocyclohexane, oxychlordane and phthalates were likewise generally associated with an increase in body size. Studies investigating polychlorinated dibenzodioxins and polychlorinated dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes predisposing to later weight gain. The study findings suggest that some endocrine disruptors may play a role for the development of the obesity epidemic, in addition to the more commonly perceived putative contributors. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.",
"title": "Endocrine-disrupting chemicals and obesity development in humans: a review."
},
{
"docid": "MED-5340",
"text": "In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non-vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level.",
"title": "Renal function parameters of Thai vegans compared with non-vegans."
},
{
"docid": "MED-2803",
"text": "Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.",
"title": "Dietary polyphenols and mechanisms of osteoarthritis."
},
{
"docid": "MED-2276",
"text": "A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.",
"title": "Sweet bing cherries lower circulating concentrations of markers for chronic inflammatory diseases in healthy humans."
},
{
"docid": "MED-5333",
"text": "BACKGROUND/AIM: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. METHODS: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. RESULTS: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (-10%). CONCLUSION: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process. Copyright 2008 S. Karger AG, Basel.",
"title": "Vegetarian diet affects genes of oxidative metabolism and collagen synthesis."
},
{
"docid": "MED-3305",
"text": "BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.",
"title": "Non-occupational malignant pleural mesothelioma due to asbestos and non-asbestos fibres."
},
{
"docid": "MED-2368",
"text": "BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human atherosclerosis, but no detailed information is available on their composition. METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP proteins were identified by tandem mass spectrometry, metabolite profiles were determined by high-resolution nuclear magnetic resonance spectroscopy, and antibody reactivity was assessed against combinatorial antigen libraries. Plaque MPs expressed surface antigens consistent with their leukocyte origin, including major histocompatibility complex classes I and II, and induced a dose-dependent stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling of proteins on the MP surface suggested immunoglobulins to be trapped inside, which was confirmed by flow cytometry analysis on permeabilized and nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin. Screening against an antigen library revealed that the immunologic profiles of antibodies in MPs were similar to those found in plaques but differed profoundly from antibodies in plasma and unexpectedly, showed strong reactions with oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This study provides the first evidence that immunoglobulins are present within MPs derived from plaque macrophages, that the portfolio of plaque antibodies is different from circulating antibodies in plasma, and that anticarbohydrate antibodies are retained in human atherosclerotic lesions.",
"title": "Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques."
},
{
"docid": "MED-1991",
"text": "The objective of this article is to review the epidemiologic literature examining the role of plant foods and plant-based diets in the prevention of childhood obesity. Available data suggest a protective effect of ready-to-eat cereal on risk of obesity, although prospective studies are still needed. Studies on fruit and vegetables; grains other than cereal; high-protein foods, including beans, legumes, and soy; fiber; and plant-based dietary patterns are inconsistent or generally null. The evidence base is limited, and most studies are fraught with methodologic limitations, including cross-sectional design, inadequate adjustment for potential confounders, and lack of consideration of reporting errors, stage of growth, and genetic influences. Well-designed prospective studies are needed. The lack of evidence showing an association between plant-based diets and childhood obesity does not mean that such diets should not be encouraged. Plant foods are highlighted in the Dietary Guidelines for Americans, and children do not meet the current recommendations for most plant foods. Although the advice to consume a plant-based, low-energy-dense diet is sound, ethical questions arise concerning the relatively high price of these diets in the United States and the way in which such diets are perceived in other parts of the world. Reducing the burden of childhood obesity, eliminating health disparities, and preventing the further spread of the disease around the globe will require not only policy interventions to ensure that plant foods are affordable and accessible to children of all income levels but also awareness of sociocultural norms that affect consumption.",
"title": "Plant foods and plant-based diets: protective against childhood obesity?"
},
{
"docid": "MED-2369",
"text": "Background Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-α-1,3-galactose (α-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective We sought to determine whether IgE antibodies to α-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results Twenty-four patients with IgE antibodies to α-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow’s milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for α-gal. Conclusion We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope α-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb.",
"title": "Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose"
},
{
"docid": "MED-2821",
"text": "The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment.",
"title": "Turmeric (curcumin) remedies gastroprotective action"
},
{
"docid": "MED-1131",
"text": "To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.",
"title": "Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet."
},
{
"docid": "MED-2808",
"text": "Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumours. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. Mechanistically, resistance phenomena may be explained by (i) overexpression of drug efflux pumps, (ii) enhanced drug detoxification, (iii) rapid DNA repair efficiency, (iv) defects in apoptosis regulation, and (v) active cell survival signals. Several adverse effects associated with multidrug resistance and the need for safe multi-targeted anticancer drugs instigated the use of the phytochemical, curcumin, the yellow pigment of the spice turmeric, which has pleotropic activities. We performed a structured literature review using PubMed and Medline searches with secondary review of cited publications, identifying studies on the role of curcumin in conquering drug resistance in cancer. This review describes how curcumin sensitizes cancer cells through regulation of multiple multidrug resistance pathways, thus employing one drug for multiple targets. Curcumin helps the cancer cells to regain their 'forgotten' apoptosis, modulates drug-target interaction at different levels, restrains survival pathways when their proteins are overexpressed, and finds an alternate way to carry forward the process of sensitization of different resistant tumours. Additionally, the review dissects the role of curcumin, if any, in targeting the major culprit of drug resistance, cancer stem cells (CSC), thereby circumventing resistance. Taken together, this review strongly suggests that curcumin is a promising chemosensitizing agent and that the unique properties of curcumin may be exploited for successful management of resistant tumours.",
"title": "Death by design: where curcumin sensitizes drug-resistant tumours."
},
{
"docid": "MED-4848",
"text": "We have previously reported that a significant improvement can be obtained in rheumatoid arthritis patients by fasting followed by an individually adjusted vegetarian diet for one year. The patients who changed their diet could be divided into diet responders and diet nonresponders. After the clinical trial the patients were free to change diet or medication and after approximately one year they were asked to attend a new clinical examination. We compared the change from baseline (i.e. at the time of study entry) to the time of the follow-up examination for diet responders, diet nonresponders and controls who ate an omnivorous diet. The following variables favoured diet responders: pain score, duration of morning stiffness, Stanford Health Assessment Questionnaire index, number of tender joints, Ritchie's articular index, number of swollen joints, ESR and platelet count [corrected]. The difference between the three groups were significant for all the clinical variables, except for grip strength. There was no significant difference between the groups with regard to laboratory or anthropometric variables. At the time of the follow-up examination all diet responders but only half of the diet nonresponders still followed a diet. Our findings indicate that a group of patients with rheumatoid arthritis benefit from dietary manipulations and that the improvement can be sustained through a two-year period.",
"title": "Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet."
},
{
"docid": "MED-4318",
"text": "Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.",
"title": "Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal."
},
{
"docid": "MED-5329",
"text": "OBJECTIVE: This study was conducted to demonstrate the effectiveness of a strictly vegetarian, very low-fat diet on cardiac risk factor modification. METHODS: Five hundred men and women, participants in an intensive 12-day live-in program, were studied. The program focused on dietary modification, moderate exercise, and stress management at a hospital-based health-center. RESULTS: During this short time period, cardiac risk factors improved: there was an average reduction of total serum cholesterol of 11% (p < 0.001), of blood pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for women. Serum triglycerides did not increase except for two subgroups: females age > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64 years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A strict, very low-fat vegetarian diet free from all animal products combined with lifestyle changes that include exercise and weight loss is an effective way to lower serum cholesterol and blood pressure.",
"title": "Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low fat, strictly vegetarian diet."
},
{
"docid": "MED-3311",
"text": "OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.",
"title": "Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants."
},
{
"docid": "MED-3941",
"text": "The effects of açai polyphenolics on the antiproliferation and induction of apoptosis in HL-60 human leukemia cells were investigated. Interactions between anthocyanins and non-anthocyanin-polyphenolics in both their glycosidic and their aglycone forms were also investigated to determine additive or nonadditive responses. Polyphenolic fractions at 0.17-10.7 microM were found to reduce cell proliferation from 56 to 86% likely due to caspase-3 activation (apoptosis). Anthocyanin and polyphenolic fractions were nonadditive in their contribution to the cell antiproliferation activity. At equimolar concentrations, the glycosidic forms of phenolic acids and flavonoids induced a higher magnitude of change in cell parameters (proliferation and apoptosis) than their respective aglycone forms, while the opposite trend was observed for anthocyanin aglycones. This study demonstrated that açai offers a rich source of bioactive polyphenolics and confirmed the importance of investigating whole food systems when evaluating the potential health benefits of individual phytochemical compounds.",
"title": "Açai (Euterpe oleracea Mart.) polyphenolics in their glycoside and aglycone forms induce apoptosis of HL-60 leukemia cells."
},
{
"docid": "MED-2357",
"text": "Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.",
"title": "Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression"
},
{
"docid": "MED-4847",
"text": "Clinical experience suggests that fasting followed by vegetarian diet may help patients with rheumatoid arthritis (RA). We reviewed the available scientific evidence, because patients frequently ask for dietary advice, and exclusive pharmacological treatment of RA is often not satisfying. Fasting studies in RA were searched in MEDLINE and by checking references in relevant reports. The results of the controlled studies which reported follow-up data for at least three months after fasting were quantitatively pooled. Thirty-one reports of fasting studies in patients with RA were found. Only four controlled studies investigated the effects of fasting and subsequent diets for at least three months. The pooling of these studies showed a statistically and clinically significant beneficial long-term effect. Thus, available evidence suggests that fasting followed by vegetarian diets might be useful in the treatment of RA. More randomised long-term studies are needed to confirm this view by methodologically convincing data.",
"title": "Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review."
},
{
"docid": "MED-1994",
"text": "PURPOSE OF REVIEW: The prevalence of obesity in youth is increasing alarmingly among children and adolescents in the United States. The problem falls disproportionately on African-American and Hispanic children. Many of the metabolic and cardiovascular complications associated with obesity are already present during childhood and are closely linked to the concomitant insulin resistance/hyperinsulinemia and degree of obesity. Moreover, these co-morbidities persist into adulthood. RECENT FINDINGS: The progression from normal glucose tolerance to type 2 diabetes mellitus involves an intermediate stage known as prediabetes or impaired glucose regulation. Prediabetes is characterized by peripheral insulin-resistance and impaired glucose sensitivity of first-phase insulin secretion. On the other hand, in overt type 2 diabetes mellitus beta-cell failure becomes fully manifested. Progression from prediabetes to type 2 diabetes mellitus in youth is characterized by marked weight gain and further reduction in insulin secretion and insulin resistance. SUMMARY: Reverting obesity through lifestyle modification, that involves nutrition education, behavior modification and exercise, is an important step to prevent the progression to diabetes.",
"title": "Prediabetes and type 2 diabetes in youth: an emerging epidemic disease?"
},
{
"docid": "MED-1998",
"text": "The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.",
"title": "The early treatment of type 2 diabetes."
},
{
"docid": "MED-4084",
"text": "Experiences with food intake, diet manipulations and fast were registered in rheumatic patients. The study was a questionnaire-based survey in which 742 patients participated. It comprised 290 patients with rheumatoid arthritis, 51 patients with juvenile rheumatoid arthritis, 87 patients with ankylosing spondylitis, 51 patients with psoriatic arthropathy, 65 patients with primary fibromyalgia and 34 patients with osteoarthritis. One third of the patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthropathy reported aggravation of disease symptoms after intake of certain foods while 43% of the patients with juvenile rheumatoid arthritis and 42% of the patients with primary fibromyalgia stated the same. Twenty-six percent of the patients with juvenile rheumatoid arthritis and 23% of the patients with rheumatoid arthritis, ankylosing spondylitis and primary fibromyalgia had previously tried certain diets in the attempt to alleviate disease symptoms, whereas 13% of the patients with psoriatic arthropathy and 10% with osteoarthritis had tried diet therapy. Less pain and stiffness were reported by 46% of the patients and 36% reported reduced joint swelling. Similar beneficial effects of diet were also reported in other rheumatic disease groups. Fifteen percent of the patients with rheumatoid arthritis and ankylosing spondylitis had been through a fasting period. Less pain and stiffness were reported by 2/3 of the patients in both groups and half of the patients in both groups reported a reduced number of swollen joints.",
"title": "Diet and disease symptoms in rheumatic diseases--results of a questionnaire based survey."
},
{
"docid": "MED-4128",
"text": "Various methods have been described in the literature for the detection of virulent Yersinia enterocolitica in pigs. The risk factors for pig herd contamination have yet to be determined. The objective of this study was to validate a sensitive method for the detection of Y. enterocolitica and to describe the distribution of the bacteria in pigs at slaughter from conventional and alternative (\"organic\") housing systems. First, samples were collected from tonsils, caecum with caecal contents, and the caecal lymph nodes of 60 slaughter pigs. These samples were used to compare the sensitivity of six different laboratory culture methods either in common use or described in the literature with that of a polymerase chain reaction with two primer pairs (multiplex PCR). Then, only PCR was used to examine tonsils, caecum and caecal lymph nodes from two groups of slaughter pigs: 210 from six conventional fattening farms and 200 from three with alternative housing. The results of the multiplex PCR were positive in 28 cases. All culture methods proved inferior to PCR in sensitivity. In the second part of the study, PCR detected 36 (18%) positive pigs from alternative housing and 60 (29%) from conventional housing (p<0.05). The highest rate of Y. enterocolitica contamination was found in tonsils (11% alternative, 22% conventional; p<0.05), followed by caecum (5%, 11%) and lymph nodes (2%, 7%). The housing system appears to be one important factor in the prevalence of this common pathogen in pig herds, as we found important differences between the two systems studied here. In the conventional system, the main risk factors appeared to be sourcing pigs from different pig suppliers, use of commercial feed and transportation to slaughter.",
"title": "Validation of a method for the detection of virulent Yersinia enterocolitica and their distribution in slaughter pigs from conventional and alterna..."
},
{
"docid": "MED-4433",
"text": "BACKGROUND: The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. OBJECTIVE: To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. METHODS: Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. RESULTS: Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. CONCLUSION: This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures. Copyright 2010 Elsevier Inc. All rights reserved.",
"title": "Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund."
},
{
"docid": "MED-1124",
"text": "The effect of an uncooked extreme vegan diet on fecal microflora was studied by direct stool sample gas-liquid chromatography (GLC) of bacterial cellular fatty acids and by quantitative bacterial culture by using classical microbiological techniques of isolation, identification, and enumeration of different bacterial species. Eighteen volunteers were divided randomly into two groups. The test group received an uncooked vegan diet for 1 month and a conventional diet of mixed Western type for the other month of the study. The control group consumed a conventional diet throughout the study period. Stool samples were collected. Bacterial cellular fatty acids were extracted directly from the stool samples and measured by GLC. Computerized analysis of the resulting fatty acid profiles was performed. Such a profile represents all bacterial cellular fatty acids in a sample and thus reflects its microflora and can be used to detect changes, differences, or similarities of bacterial flora between individual samples or sample groups. GLC profiles changed significantly in the test group after the induction and discontinuation of the vegan diet but not in the control group at any time, whereas quantitative bacterial culture did not detect any significant change in fecal bacteriology in either of the groups. The results suggest that an uncooked extreme vegan diet alters the fecal bacterial flora significantly when it is measured by direct stool sample GLC of bacterial fatty acids.",
"title": "An uncooked vegan diet shifts the profile of human fecal microflora: computerized analysis of direct stool sample gas-liquid chromatography profiles of bacterial cellular fatty acids."
},
{
"docid": "MED-3535",
"text": "Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.",
"title": "Cherries and health: a review."
},
{
"docid": "MED-2823",
"text": "Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.",
"title": "Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies"
},
{
"docid": "MED-3295",
"text": "Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.",
"title": "Cancer and Noncancer Mortality Among American Seafood Workers"
},
{
"docid": "MED-3321",
"text": "Avian leukosis/sarcoma viruses (ALSV) infect and cause cancers in chickens. Poultry workers are exposed to ALSV and other infectious agents in the workplace. This study examines if industrial hygiene assessment of antibody levels in poultry workers can identify risky job tasks at the higher exposure risk to an infectious agent, i.e., ALSV. We compared ALSV antibody levels in poultry workers and control subjects. Occupational and demographical factors were examined for an association with the exposure risk in poultry workers. We found that the antibody levels were significantly higher in poultry workers than in control subjects. Job category and age together were significantly associated with the antibody levels in workers. Certain job tasks were identified with significantly higher antibody levels as compared to others, implying that recommendations should be made to protect workers at these jobs. The findings of this study indicate that the measurement of antibody levels in workers can be useful for industrial hygiene assessment of exposure to infectious agents.",
"title": "Occupational exposure assessment using antibody levels: exposure to avian leukosis/sarcoma viruses in the poultry industry."
},
{
"docid": "MED-5009",
"text": "OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.",
"title": "Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials."
},
{
"docid": "MED-5303",
"text": "IMPORTANCE: Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN: We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS: US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE: From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.",
"title": "The state of US health, 1990-2010: burden of diseases, injuries, and risk factors."
},
{
"docid": "MED-4850",
"text": "Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.",
"title": "Antioxidants in vegan diet and rheumatic disorders."
},
{
"docid": "MED-1997",
"text": "The increased prevalence of childhood overweight and obesity is not unique to industrialized societies; dramatic increases are occurring in urbanized areas of developing countries. In light of the consensus that obesity is a significant public health concern and that many weight-loss interventions have been unsuccessful in the long term, an exploration of food patterns that are beneficial in the primary prevention of obesity is warranted. The focus of this article is to review the relation between vegetarian diets and obesity, particularly as they relate to childhood obesity. Epidemiologic studies indicate that vegetarian diets are associated with a lower body mass index (BMI) and a lower prevalence of obesity in adults and children. A meta-analysis of adult vegetarian diet studies estimated a reduced weight difference of 7.6 kg for men and 3.3 kg for women, which resulted in a 2-point lower BMI (in kg/m(2)). Similarly, compared with nonvegetarians, vegetarian children are leaner, and their BMI difference becomes greater during adolescence. Studies exploring the risk of overweight and food groups and dietary patterns indicate that a plant-based diet seems to be a sensible approach for the prevention of obesity in children. Plant-based diets are low in energy density and high in complex carbohydrate, fiber, and water, which may increase satiety and resting energy expenditure. Plant-based dietary patterns should be encouraged for optimal health and environmental benefits. Food policies are warranted to support social marketing messages and to reduce the cultural and economic forces that make it difficult to promote plant-based dietary patterns.",
"title": "Vegetarian diets and childhood obesity prevention."
},
{
"docid": "MED-4136",
"text": "BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.",
"title": "Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10..."
},
{
"docid": "MED-2799",
"text": "Objective: To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA). Methods: Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-κB activation, expression of tumour necrosis factor α (TNFα) and interleukin 1ß (IL1ß), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2) Results: Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFα and IL1ß were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-κB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups. Conclusion: Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.",
"title": "Synovial tissue inflammation in early and late osteoarthritis"
},
{
"docid": "MED-3306",
"text": "OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.",
"title": "Farming, growing up on a farm, and haematological cancer mortality."
},
{
"docid": "MED-1999",
"text": "Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.",
"title": "Strategies for preventing type 2 diabetes: an update for clinicians"
},
{
"docid": "MED-3950",
"text": "The Açaí (Acai) fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.",
"title": "Polysaccharides Isolated from Açaí Fruit Induce Innate Immune Responses"
},
{
"docid": "MED-2078",
"text": "Platelet hyperactivity is one of the most important factors responsible for the incidence of cardiovascular disease. There are many nutritive and non-nutritive compounds present in the diet which may affect platelet function in various ways. Recent discovery of anti-platelet factors in plants, vegetables and fruits provides a new dietary means for a long-term strategy to favorably modify human blood platelet activity. This review summarises the effects of these dietary components on human platelet function both in vitro and in vivo.",
"title": "Dietary components and human platelet activity."
},
{
"docid": "MED-2811",
"text": "Inflammatory bowel disease (IBD) comprising of ulcerative colitis (UC) and Crohn's disease (CD) is a major ailment affecting the small and large bowel. In clinics, IBD is treated using 5-amninosalicylates, antibiotics, the steroids and immunomodulators. Unfortunately, the long term usages of these agents are associated with undue side effects and compromise the therapeutic advantage. Accordingly, there is a need for novel agents that are effective, acceptable and non toxic to humans. Preclinical studies in experimental animals have shown that curcumin, an active principle of the Indian spice turmeric (Curcuma longa Linn) is effective in preventing or ameliorating UC and inflammation. Over the last few decades there has been increasing interest in the possible role of curcumin in IBD and several studies with various experimental models of IBD have shown it to be effective in mediating the inhibitory effects by scavenging free radicals, increasing antioxidants, influencing multiple signaling pathways, especially the kinases (MAPK, ERK), inhibiting myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-γ, iNOS; inhibiting the transcription factor NF-κB. Clinical studies have also shown that co-administration of curcumin with conventional drugs was effective, to be well-tolerated and treated as a safe medication for maintaining remission, to prevent relapse and improve clinical activity index. Large randomized controlled clinical investigations are required to fully understand the potential of oral curcumin for treating IBD.",
"title": "Curcumin, an active component of turmeric in the prevention and treatment of ulcerative colitis: preclinical and clinical observations."
},
{
"docid": "MED-1985",
"text": "The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age-adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat.",
"title": "Attained height of lacto-ovo vegetarian children and adolescents."
},
{
"docid": "MED-2351",
"text": "Anti-Gal is a natural Ab abundantly produced in humans. It interacts specifically with the carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). This epitope is expressed in large amounts on thyrocytes of nonprimate mammals, but not of humans. We have previously found that binding of anti-Gal to alpha-galactosyl epitopes on porcine thyrocytes results in stimulatory effects similar to those exerted by thyroid-stimulating hormone (thyrotropin). In the present study, we tested the hypothesis that anti-Gal may contribute to Graves' disease (GD) pathogenesis by stimulation of the thyrocytes of patients with this autoimmune disorder. Anti-Gal binding and stimulatory effects were assessed in primary thyrocyte cultures. Anti-Gal specifically bound to GD thyrocytes and induced an increase in cAMP synthesis, 125I uptake, and DNA synthesis in these cells. Furthermore, the stimulatory effects of autologous sera on GD thyrocytes were greatly reduced after specific depletion of anti-Gal from these sera. No binding and no stimulatory effects of anti-Gal were observed, however, with normal human thyrocytes and with thyrocytes from thyrotoxic patients who lack thyroid-stimulating Igs or thyrotropin binding inhibiting Igs. These in vitro stimulatory effects of anti-Gal on GD thyrocytes suggest that this natural Ab may contribute to the in vivo continuous stimulation of thyrocytes in GD patients. The possibility that anti-Gal may stimulate GD thyrocytes via interaction with aberrantly expressed alpha-galactosyl epitopes on the thyroid-stimulating hormone receptor is discussed.",
"title": "Specific stimulation of Graves' disease thyrocytes by the natural anti-Gal antibody from normal and autologous serum."
},
{
"docid": "MED-2818",
"text": "Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.",
"title": "Curcumin: the story so far."
},
{
"docid": "MED-3315",
"text": "PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupationally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2-10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR = 4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "A pilot case-cohort study of liver and pancreatic cancers in poultry workers."
},
{
"docid": "MED-3942",
"text": "Background The purpose of this study was to evaluate the effect of açai fruit pulp on risk factors for metabolic disorders in overweight subjects. The açaí palm (Euterpe oleracea Mart.), which is native to South America, produces a small, black-purple fruit which is edible. The fruit has recently become popular as a functional food due to its antioxidant potential. Although several studies have been conducted in vitro and with animals, little is known about the potential health benefits in humans aside from an increase in plasma anti-oxidant capacity. Metabolic syndrome is a condition which is defined by a cluster of risk factors for cardiovascular disease and/or type-2 diabetes. Preliminary studies indicate that a reduction in reactive oxygen species can assist in the normalization of the metabolic pathways involved in this syndrome. Methods This was an open label pilot study conducted with 10 overweight adults (BMI ≥ 25 kg/m2 and ≤ 30 kg/m2) who took 100 g açai pulp twice daily for 1 month. The study endpoints included levels of fasting plasma glucose, insulin, cholesterol, triglycerides, exhaled (breath) nitric oxide metabolites (eNO) and plasma levels of high sensitivity C-reactive protein (hs-CRP). The response of blood glucose, blood pressure and eNO to a standardized meal was determined at baseline and following the 30 day treatment. Results Compared to baseline, there were reductions in fasting glucose and insulin levels following the 30 day treatment (both p < 0.02). There was also a reduction in total cholesterol (p = 0.03), as well as borderline significant reductions in LDL-cholesterol and the ratio of total cholesterol to HDL-cholesterol (both p = 0.051). Compared to baseline, treatment with açai ameliorated the post-prandial increase in plasma glucose following the standardized meal, measured as the area under the curve (p = 0.047). There was no effect on blood pressure, hs-CRP or eNO. Conclusion In this uncontrolled pilot study, consumption of açai fruit pulp reduced levels of selected markers of metabolic disease risk in overweight adults, indicating that further studies are warranted.",
"title": "Effects of Açai (Euterpe oleracea Mart.) berry preparation on metabolic parameters in a healthy overweight population: A pilot study"
},
{
"docid": "MED-4849",
"text": "We tested the effects of an uncooked vegan diet, rich in lactobacilli, in rheumatoid patients randomized into diet and control groups. The intervention group experienced subjective relief of rheumatic symptoms during intervention. A return to an omnivorous diet aggravated symptoms. Half of the patients experienced adverse effects (nausea, diarrhoea) during the diet and stopped the experiment prematurely. Indicators of rheumatic disease activity did not differ statistically between groups. The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and pain on movement). However, a composite index showed a higher number of patients with 3-5 improved disease activity measures in the intervention group. Stepwise regression analysis associated a decrease in the disease activity (measured as change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll-rich drinks, increase in fibre intake, and no need for gold, methotrexate or steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid arthritis. Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis.",
"title": "Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis."
},
{
"docid": "MED-4316",
"text": "The intestinal absorption of the essential trace element iron and its mobilization from storage sites in the body are controlled by systemic signals that reflect tissue iron requirements. Recent advances have indicated that the liver-derived peptide hepcidin plays a central role in this process by repressing iron release from intestinal enterocytes, macrophages and other body cells. When iron requirements are increased, hepcidin levels decline and more iron enters the plasma. It has been proposed that the level of circulating diferric transferrin, which reflects tissue iron levels, acts as a signal to alter hepcidin expression. In the liver, the proteins HFE, transferrin receptor 2 and hemojuvelin may be involved in mediating this signal as disruption of each of these molecules decreases hepcidin expression. Patients carrying mutations in these molecules or in hepcidin itself develop systemic iron loading (or hemochromatosis) due to their inability to down regulate iron absorption. Hepcidin is also responsible for the decreased plasma iron or hypoferremia that accompanies inflammation and various chronic diseases as its expression is stimulated by pro-inflammatory cytokines such as interleukin 6. The mechanisms underlying the regulation of hepcidin expression and how it acts on cells to control iron release are key areas of ongoing research. IUBMB Life, 57: 499-503, 2005.",
"title": "Systemic regulation of intestinal iron absorption."
},
{
"docid": "MED-3946",
"text": "The fruit of Euterpe oleraceae, commonly known as acai, has been demonstrated to exhibit significantly high antioxidant capacity in vitro, especially for superoxide and peroxyl scavenging, and, therefore, may have possible health benefits. In this study, the antioxidant capacities of freeze-dried acai fruit pulp/skin powder (OptiAcai) were evaluated by different assays with various free radical sources. It was found to have exceptional activity against superoxide in the superoxide scavenging (SOD) assay, the highest of any food reported to date against the peroxyl radical as measured by the oxygen radical absorbance capacity assay with fluorescein as the fluorescent probe (ORACFL), and mild activity against both the peroxynitrite and hydroxyl radical by the peroxynitrite averting capacity (NORAC) and hydroxyl radical averting capacity (HORAC) assays, respectively. The SOD of acai was 1614 units/g, an extremely high scavenging capacity for O2*-, by far the highest of any fruit or vegetable tested to date. Total phenolics were also tested as comparison. In the total antioxidant (TAO) assay, antioxidants in acai were differentiated into \"slow-acting\" and \"fast-acting\" components. An assay measuring inhibition of reactive oxygen species (ROS) formation in freshly purified human neutrophils showed that antioxidants in acai are able to enter human cells in a fully functional form and to perform an oxygen quenching function at very low doses. Furthermore, other bioactivities related to anti-inflammation and immune functions were also investigated. Acai was found to be a potential cyclooxygenase (COX)-1 and COX-2 inhibitor. It also showed a weak effect on lipopolysaccharide (LPS)-induced nitric oxide but no effect on either lymphocyte proliferation and phagocytic capacity.",
"title": "Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (acai)."
},
{
"docid": "MED-5331",
"text": "A global health transition is currently underway. The burden of non-communicable diseases (NCDs) is increasing rapidly in the developing world, very much as a result of changes in lifestyles. In addition to changes in tobacco use and physical activity, major changes are taking place in diets, contributing greatly to the growing epidemic of NCD. Thus, a huge global public health challenge is how to influence the trends in diet and nutrition for effective global NCD prevention. The health transition took place rapidly in Finland after World War II and mortality from cardiovascular disease (CVD) was exceptionally high. The North Karelia Project was launched in 1972 as a community-based, and later as a national, programme to influence diet and other lifestyles that are crucial in the prevention of CVD. The intervention had a strong theory base and it employed comprehensive strategies. Broad community organisation and the strong participation of people were the key elements. Evaluation has shown how the diet (particularly fat consumption) has changed and how these changes have led to a major reduction in population serum cholesterol and blood pressure levels. It has also shown how ischaemic heart disease mortality in a working-age population has declined by 73% in North Karelia and by 65% in the whole country from 1971 to 1995. Although Finland is an industrialised country, North Karelia was rural, of rather low socio-economic level and with many social problems in the 1970s and 1980s. The project was based on low-cost intervention activities, where people's participation and community organisations played a key role. Comprehensive interventions in the community were eventually supported by national activities--from expert guidelines and media activities to industry collaboration and policy. Similar principles for nutrition intervention programmes could be used in developing countries, obviously tailored to the local conditions. This paper discusses the experiences of the North Karelia Project in the light of needs from the less-industrialised countries and makes some general recommendations.",
"title": "Influencing public nutrition for non-communicable disease prevention: from community intervention to national programme--experiences from Finland."
},
{
"docid": "MED-4085",
"text": "The effect of a strict, low-salt, uncooked vegan diet rich in lactobacteria on symptoms in 18 fibromyalgia patients during and after a 3-month intervention period in an open, non-randomized controlled study was evaluated. As control 15 patients continued their omnivorous diet. The groups did not differ significantly from each other in the beginning of the study in any other parameters except in pain and urine sodium. The results revealed significant improvements in Visual analogue scale of pain (VAS) (p=0.005), joint stiffness (p=0.001), quality of sleep (p=0.0001), Health assessment questionnaire (HAQ) (p=0.031), General health questionnaire (GHQ) (p=0.021), and a rheumatologist's own questionnaire (p=0.038). The majority of patients were overweight to some extent at the beginning of the study and shifting to a vegan food caused a significant reduction in body mass index (BMI) (p=0.0001). Total serum cholesterol showed a statistically significant lowering (p=0.003). Urine sodium dropped to 1/3 of the beginning values (p=0.0001) indicating good diet compliance. It can be concluded that vegan diet had beneficial effects on fibromyalgia symptoms at least in the short run.",
"title": "Vegan diet alleviates fibromyalgia symptoms."
},
{
"docid": "MED-1125",
"text": "Genetic, molecular and biological studies indicate that rheumatoid arthritis (RA), a severe arthritic disorder affecting approximately 1% of the population in developed countries, is caused by an upper urinary tract infection by the microbe, Proteus mirabilis. Elevated levels of specific antibodies against Proteus bacteria have been reported from 16 different countries. The pathogenetic mechanism involves six stages triggered by cross-reactive autoantibodies evoked by Proteus infection. The causative amino acid sequences of Proteus namely, ESRRAL and IRRET, contain arginine doublets which can be acted upon by peptidyl arginine deiminase thereby explaining the early appearance of anti-citrullinated protein antibodies in patients with RA. Consequently, RA patients should be treated early with anti-Proteus antibiotics as well as biological agents to avoid irreversible joint damages. © 2013 APMIS. Published by John Wiley & Sons Ltd.",
"title": "Rheumatoid arthritis is caused by a Proteus urinary tract infection."
},
{
"docid": "MED-1992",
"text": "Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.",
"title": "Prediabetes: A high-risk state for developing diabetes"
},
{
"docid": "MED-4129",
"text": "Pigs are considered as a major reservoir of human pathogenic Yersinia enterocolitica and a source of human yersiniosis. However, the transmission route of Y. enterocolitica from farm to pork is still unclear. The transmission of pathogenic Y. enterocolitica from pigs to carcasses and pluck sets was investigated by collecting samples from 364 individual ear-tagged pigs on the farm and at the slaughterhouse. In addition, isolated strains were analyzed, using pulsed-field gel electrophoresis. Isolation of similar genotypes of pathogenic Y. enterocolitica 4/O:3 in animals on the farm and at the slaughterhouse and in carcasses shows that carcass contamination originates from the strains a pig carries during the fattening period. Direct contamination from the carrier pig to its subsequent pluck set is also the primary contamination route for pluck sets, but cross-contamination appears to have a larger impact on pluck set contamination than on carcasses. In this study, the within-farm prevalence of pathogenic Y. enterocolitica varied from 0% to 100%, indicating specific farm factors affect the prevalence of Y. enterocolitica in pigs. The association of farm factors with the high prevalence of pathogenic Y. enterocolitica on farms was studied for the first time, using correlation and two-level logistic regression analyses. Specific farm factors, i.e. drinking from a nipple, absence of coarse feed or bedding for slaughter pigs, and no access of pest animals to pig house, were associated with a high prevalence of pathogenic Y. enterocolitica 4/O:3.",
"title": "Contamination of carcasses with human pathogenic Yersinia enterocolitica 4/O:3 originates from pigs infected on farms."
},
{
"docid": "MED-2824",
"text": "Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called \"curry powder\") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an \"old-age\" disease such as cancer requires an \"age-old\" treatment.",
"title": "Curcumin and cancer: an \"old-age\" disease with an \"age-old\" solution."
},
{
"docid": "MED-2367",
"text": "Naturally developing xenospecific Abs are well-documented barriers to xenograft transplantation in humans, but whether analogous xenoreactive T cell immunity develops is not known. We used an enzyme-linked immunospot assay to determine the frequency and cytokine profiles of xenoreactive PBLs from a panel of human volunteers. Because naive T cells produce only IL-2 in short term culture, IFN-gamma production by this approach is a measure of a memory immune response. Stimulation of human PBLs or purified T lymphocytes with stimulator cells from inbred swine revealed a high frequency of IFN-gamma producers with 5-fold fewer IL-2 producers. In contrast, lymphocytes obtained from neonatal umbilical cord blood contained swine-specific IL-2 producers but few IFN-gamma producers, which is what one would expect to find with a naive phenotype. Moreover, PBLs from adults with a history of abstention from pork consumption responded to swine cells with a significantly lower frequency of IFN-gamma producers than PBLs from adults with unrestricted diets did, suggesting that pork consumption may result in priming of swine-specific T cell immunity. Our findings provide the first evidence for naturally occurring xenospecific T cell immunity in humans. The detected strength of this memory response suggests that it will present a formidable barrier to transplantation of swine organs.",
"title": "Naturally developing memory T cell xenoreactivity to swine antigens in human peripheral blood lymphocytes."
},
{
"docid": "MED-3945",
"text": "The pomegranate fruit ( Punica granatum ) has become an international high-value crop for the production of commercial pomegranate juice (PJ). The perceived consumer value of PJ is due in large part to its potential health benefits based on a significant body of medical research conducted with authentic PJ. To establish criteria for authenticating PJ, a new International Multidimensional Authenticity Specifications (IMAS) algorithm was developed through consideration of existing databases and comprehensive chemical characterization of 45 commercial juice samples from 23 different manufacturers in the United States. In addition to analysis of commercial juice samples obtained in the United States, data from other analyses of pomegranate juice and fruits including samples from Iran, Turkey, Azerbaijan, Syria, India, and China were considered in developing this protocol. There is universal agreement that the presence of a highly constant group of six anthocyanins together with punicalagins characterizes polyphenols in PJ. At a total sugar concentration of 16 degrees Brix, PJ contains characteristic sugars including mannitol at >0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.",
"title": "International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration."
},
{
"docid": "MED-3953",
"text": "An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.",
"title": "An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration."
},
{
"docid": "MED-4143",
"text": "In this study, we hoped to provide valuable clinical information on yersiniosis for clinicians. Two thousand six hundred stool samples were collected from in- and outpatients with diarrhea, which were tested with both culture method and real-time polymerase chain reaction (RT-PCR). In total, 188 positive samples were detected by RT-PCR (178) and culture method (160), while the incidence was about 7.23%. The detection rate of RT-PCR was significantly higher than culture method and a higher incidence in autumn-winter was also noticeably identified than in spring-summer. Infection sources mostly focused on unboiled foods (101) and pets (45), while clinical manifestation mainly presented as gastroenteritis (156), pseudoappendicitis (32), and extraintestinal complications (46). The morbidity of extraintestinal complications in adults was significantly higher than in children and it was the same for high-risk patients between adults over the age of 60 years (4.7%) and children under the age of 3 years (1.4%), whereas the constituent ratio of children versus adults with yersiniosis in different systems was not significant. Of 160 isolates tested for antimicrobial susceptibility, the majority were susceptible to third-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, whereas only a small portion was susceptible to the first-generation cephalosporins and penicillins. During autumn-winter months, clinicians should pay more attention to clinical manifestation, early diagnosis, and treatment with susceptible antibiotics of yersiniosis and its complications, targeting high-risk patients.",
"title": "Yersinia enterocolitica infection in diarrheal patients."
},
{
"docid": "MED-3316",
"text": "BACKGROUND: Between November, 2006, and May, 2008, a subacute neurological syndrome affected workers from two swine abattoirs in Minnesota and Indiana who had occupational exposure to aerosolised porcine brain. We aimed to describe the pathogenic and immunological characteristics of this illness. METHODS: All patients from two abattoirs who presented or were referred to the Mayo Clinic (Rochester, MN, USA) with neurological symptoms were included. We recorded details of exposure to aerosolised brain tissue and did comprehensive neurological, laboratory, neuroimaging, electrophysiological, pathological, and autoimmune serological assessments. Healthy controls were recruited from the community and from workers at the plant in Minnesota. FINDINGS: 24 patients were identified (21 from Minnesota, three from Indiana). The shortest duration from first exposure to symptom onset was 4 weeks. No infectious agent that could trigger disease was identified. All patients developed polyradiculoneuropathy, which was usually sensory predominant and painful. Two patients had initial CNS manifestations: transverse myelitis and meningoencephalitis. Nerve conduction studies localised abnormalities to the most proximal and distal nerve segments. Quantitative sensory and autonomic testing revealed involvement of large and small sensory fibres and sweat fibres. MRI showed prominent abnormalities of roots and ganglia. Nerve biopsies identified mild demyelination, axonal degeneration, and perivascular inflammation. Protein concentrations were high in the CSF of 18 (86%) of 21 patients. Sera from all patients and 29 (34%) of 85 unaffected workplace controls (but none of 178 community controls) had a distinctive neural-reactive IgG; 75% of patients' sera contained an IgG specific to myelin basic protein. Seropositivity correlated directly with exposure risk in patients and controls. 17 patients required immunomodulatory therapies, six improved spontaneously, and one was lost to follow-up after exposure stopped. INTERPRETATION: The neurological disorder described is autoimmune in origin and is related to occupational exposure to multiple aerosolised porcine brain tissue antigens. The pattern of nerve involvement suggests vulnerability of nerve roots and terminals where the blood-nerve barrier is most permeable. FUNDING: Mayo Clinic Foundation; Minnesota Department of Health; Centers for Disease Control and Prevention. Copyright 2010 Elsevier Ltd. All rights reserved.",
"title": "An outbreak of neurological autoimmunity with polyradiculoneuropathy in workers exposed to aerosolised porcine neural tissue: a descriptive study."
},
{
"docid": "MED-3320",
"text": "OBJECTIVES: Reticuloendotheliosis viruses (REV) are a group of retroviruses like avian leukosis/sarcoma viruses (ALSV) that naturally infect and cause cancers in chickens. We recently found that ALSV antibody levels were associated with job tasks in the poultry industry. The objectives of this study are to examine whether a similar association can be found with REV antibody levels and to examine the correlation between REV and ALSV antibody levels. METHODS: Relative risk was estimated comparing REV antibody levels of 45 poultry workers with those of 44 controls. The expected mean antibody level was predicted for the association with employment by a generalized linear model. Correlation coefficient was measured between ALSV and REV antibody levels. RESULTS: REV antibody levels were significantly higher in poultry workers than in control subjects and were associated with gender and employment conditions, especially employment duration. The relative risk was significantly higher for some job categories. A significant correlation was observed between REV and ALSV antibody levels, which was strong among poultry workers, but weak among the control subjects. CONCLUSION: Antibody levels can be validly used to identify certain job tasks associated with high risk of exposure to REV in the workplace, and the practical implication is recommendations for protection at these job tasks. Importantly, in situations where there is exposure to multiple pathogens in the workplace, the analysis of antibody levels of one pathogen may sufficiently represent exposure to the other correlated pathogens. This suggested exposure assessment may hold true for pathogens with a similar route of transmission.",
"title": "Industrial hygiene assessment of reticuloendotheliosis viruses exposure in the poultry industry."
},
{
"docid": "MED-2274",
"text": "Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.",
"title": "Cherry Consumption and the Risk of Recurrent Gout Attacks"
},
{
"docid": "MED-2801",
"text": "Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin and obesity."
},
{
"docid": "MED-5293",
"text": "Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. Funding Bill & Melinda Gates Foundation.",
"title": "A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010"
},
{
"docid": "MED-5326",
"text": "The effect of meat consumption on cancer risk is a controversial issue. However, recent meta-analyses show that high consumers of cured meats and red meat are at increased risk of colorectal cancer. This increase is significant but modest (20-30%). Current WCRF-AICR recommendations are to eat no more than 500 g per week of red meat, and to avoid processed meat. Moreover, our studies show that beef meat and cured pork meat promote colon carcinogenesis in rats. The major promoter in meat is heme iron, via N-nitrosation or fat peroxidation. Dietary additives can suppress the toxic effects of heme iron. For instance, promotion of colon carcinogenesis in rats by cooked, nitrite-treated and oxidized high-heme cured meat was suppressed by dietary calcium and by α-tocopherol, and a study in volunteers supported these protective effects in humans. These additives, and others still under study, could provide an acceptable way to prevent colorectal cancer. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Red meat and colon cancer: should we become vegetarians, or can we make meat safer?"
},
{
"docid": "MED-5332",
"text": "The gastrointestinal microbiota produces short-chain fatty acids, especially butyrate, which affect colonic health, immune function and epigenetic regulation. To assess the effects of nutrition and aging on the production of butyrate, the butyryl-CoA:acetate CoA-transferase gene and population shifts of Clostridium clusters lV and XlVa, the main butyrate producers, were analysed. Faecal samples of young healthy omnivores (24 ± 2.5 years), vegetarians (26 ± 5 years) and elderly (86 ± 8 years) omnivores were evaluated. Diet and lifestyle were assessed in questionnaire-based interviews. The elderly had significantly fewer copies of the butyryl-CoA:acetate CoA-transferase gene than young omnivores (P=0.014), while vegetarians showed the highest number of copies (P=0.048). The thermal denaturation of the butyryl-CoA:acetate CoA-transferase gene variant melting curve related to Roseburia/Eubacterium rectale spp. was significantly more variable in the vegetarians than in the elderly. The Clostridium cluster XIVa was more abundant in vegetarians (P=0.049) and in omnivores (P<0.01) than in the elderly group. Gastrointestinal microbiota of the elderly is characterized by decreased butyrate production capacity, reflecting increased risk of degenerative diseases. These results suggest that the butyryl-CoA:acetate CoA-transferase gene is a valuable marker for gastrointestinal microbiota function. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.",
"title": "Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age."
},
{
"docid": "MED-3312",
"text": "BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites. Copyright 2004 American Cancer Society.",
"title": "Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S."
},
{
"docid": "MED-5338",
"text": "Summary Background and objectives Patients with advanced chronic kidney disease (CKD) are in positive phosphorus balance, but phosphorus levels are maintained in the normal range through phosphaturia induced by increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for recommendations to restrict dietary phosphate intake to 800 mg/d. However, the protein source of the phosphate may also be important. Design, setting, participants, & measurements We conducted a crossover trial in nine patients with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat diets with equivalent nutrients prepared by clinical research staff. During the last 24 hours of each 7-day diet period, subjects were hospitalized in a research center and urine and blood were frequently monitored. Results The results indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal variation for blood phosphorus, calcium, PTH, and urine fractional excretion of phosphorus but significant differences between the vegetarian and meat diets. Finally, the 24-hour fractional excretion of phosphorus was highly correlated to a 2-hour fasting urine collection for the vegetarian diet but not the meat diet. Conclusions In summary, this study demonstrates that the source of protein has a significant effect on phosphorus homeostasis in patients with CKD. Therefore, dietary counseling of patients with CKD must include information on not only the amount of phosphate but also the source of protein from which the phosphate derives.",
"title": "Original Articles: Vegetarian Compared with Meat Dietary Protein Source and Phosphorus Homeostasis in Chronic Kidney Disease"
},
{
"docid": "MED-2361",
"text": "The most common clinical manifestation of Lyme disease is the characteristic rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in Missouri and other southeastern states. The EM-like eruptions, which were of unknown etiology, often followed the bite of the Lone Star tick (Amblyomma americanum) and the rash is called STARI (southern tick-associated rash illness). Although the Lone Star tick is found in the Lyme disease-endemic areas of New England and Mid-Atlantic regions of the United States, STARI has been reported only once from the Northeast and Mid-Atlantic regions. We report a child from Connecticut who visited Long Island, New York, and developed a rash that was thought to be EM. Because the patient failed to respond to antibiotics used to treat Lyme disease, an investigation ensued, and the diagnosis of STARI was established.",
"title": "Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a tick bite in Long Island, New York."
},
{
"docid": "MED-1122",
"text": "OBJECTIVES: patients with rheumatoid arthritis (RA) are reported to have in their sera raised levels of antibody specific to Proteus mirabilis. The aim of the study was to verify this and to determine an explanation for it by investigating the frequency of P. mirabilis urinary tract infection in RA patients and matched controls. METHODS: freshly voided urine was examined for the presence, number and identity of infecting bacteria. The levels of antibody in blood and in urine of the IgM, IgA and IgG classes to the common O serotypes of P. mirabilis and the antigens to which they reacted were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: analysis of urine from 76 patients with RA and 48 age- and gender-matched healthy controls showed that only two (4%) of the control urines but 25 (33%) of those from the RA patients were infected. The commonest infecting organism in the RA patients' urine was Proteus mirabilis which occurred twice as frequently as Escherichia coli. Proteus mirabilis was found in 52% of the infected urines of the RA patients and was always detected as a pure growth and usually in insignificant (< 10(4)/ml) numbers. It is highly improbable that this finding was the outcome of differences in age, physical ability or medication between the RA and control patient groups. Comparison of antibody levels to P. mirabilis by ELISA showed RA patients had raised (P < 0.0001, P = 0.001, P = 0.0063) levels of IgA, IgG and IgM respectively in their sera and raised (P < 0.0001, P < 0.0001, P = 0.0001) levels of IgG, IgM and IgA respectively in their urine compared with the control group. It was not possible to detect an antibody reacting to a P. mirabilis antigen that was specific to the RA patients. CONCLUSION: the results confirm that RA patients have raised levels of antibody to P. mirabilis not only in blood but also in urine and suggest that this arises because RA patients have an asymptomatic, non-significant P. mirabilis bacteriuria more frequently or more prolonged than control patients. This may be the trigger for their RA condition.",
"title": "Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Proteus mirabilis bacteriuria more frequently than healthy con..."
}
] |
[
{
"docid": "MED-933",
"text": "A case of occult coeliac disease (CD) presenting with recurrent monoarthritis in a boy aged 11 years is reported. The case is unique due to the association of occult untreated CD and arthritis in childhood. Peripheral or axial arthritis as a first manifestation of occult CD has been described in adult patients, with an interval between the arthritis and CD of up to 15 years. In our case the interval between the appearance of arthritis and the diagnosis of CD was 2 years. The boy was asymptomatic for bowel disease and his nutritional status was normal. The diagnosis of CD was established using anti-gliadin (AGA) and anti-endomysium (EMA) antibody tests and was confirmed by small bowel biopsy. The introduction of a gluten-free diet resulted in the persistent remission of arthritis. As the treatment of CD-associated arthritis is based on dietary therapy, physicians should be alert to the possibility of occult CD in any child with arthritis of unclear origin.",
"title": "Recurrent monoarthritis in an 11-year-old boy with occult coeliac disease. Successful and stable remission after gluten-free diet."
},
{
"docid": "MED-4080",
"text": "Background Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases. While microbiological fecal culture analysis is now increasingly used, little is known about the relationship of changes in intestinal flora, dietary patterns and clinical outcome in specific diseases. To clarify the role of microbiological culture analysis we aimed to evaluate whether in patients with rheumatoid arthritis (RA) or fibromyalgia (FM) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome. Methods During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA (n = 16) or FM (n = 35) were included in the study. According to predefined clinical criteria and the subjects' choice the patients received a mostly vegetarian Mediterranean diet (n = 21; mean age 50.9 +/-13.3 y) or participated in an intermittent modified 8-day fasting therapy (n = 30; mean age 53.7 +/- 9.4 y). Quantitative aerob and anaerob bacterial flora, stool pH and concentrations of secretory immunoglobulin A (sIgA) were analysed from stool samples at the beginning, at the end of the 2-week hospital stay and at a 3-months follow-up. Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients. Results We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups, nor were significant differences found in the analysis of sIgA and stool ph. Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA (p = 0.09). Clinical outcome was not related to alterations in the intestinal flora. Conclusion Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM. The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques. The potential benefit of fasting treatment in RA and FM should be further tested in randomised trials.",
"title": "Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study"
},
{
"docid": "MED-4114",
"text": "Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an..."
},
{
"docid": "MED-2788",
"text": "Turmeric root has been used medicinally in China and India for thousands of years. The active components are thought to be the curcuminoids, primarily curcumin, which is commonly available worldwide as a standardized extract. This article reviews the pharmacology of curcuminoids, their use and efficacy, potential adverse effects, and dosage and standardization. Preclinical studies point to mechanisms of action that are predominantly anti-inflammatory and antineoplastic, while early human clinical trials suggest beneficial effects for dyspepsia, peptic ulcer, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, uveitis, orbital pseudotumor, and pancreatic cancer. Curcumin is well-tolerated; the most common side effects are nausea and diarrhea. Theoretical interactions exist due to purported effects on metabolic enzymes and transport proteins, but clinical reports do not support any meaningful interactions. Nonetheless, caution, especially with chemotherapy agents, is advised. Late-phase clinical trials are still needed to confirm most beneficial effects.",
"title": "Clinical utility of curcumin extract."
},
{
"docid": "MED-2284",
"text": "In 1999, drug manufacturers introduced a class of NSAIDs called COX-2 inhibitors or coxibs. The drugs were avidly promoted directly to the consumers and became bestsellers from the start. Arthritis sufferers were eager to take medications that eased joint pain with less risk of causing gastrointestinal pain, bleeding and other side-effects. In the year after their introduction, doctors wrote over 100 million prescriptions for celecoxib (Celebrex) and rofecoxib (Vioxx). Celebrex is the sixth best-selling drug, with sales of more than US$ 4 billion since its debut in 1999. Vioxx had sales of US$ 2.6 billion in 2001. However, the coxibs increase the risk of heart attacks and strokes, and their price, in the USA, is obscene. The manufacturers faced a possibly complicit, toothless and bloodless FDA, and used every maneuvering to fleece the patients. We must now reflect on attitudes that we thought only belong to the tobacco industry. Fortunately, safe and active alternatives exist.",
"title": "COX-2 inhibitors: a story of greed, deception and death."
},
{
"docid": "MED-716",
"text": "Throughout evolution sunlight produced vitamin D in the skin has been critically important for health. Vitamin D, known as the sunshine vitamin, is actually a hormone. Once it is produced in the skin or ingested from the diet it is converted sequentially in the liver and kidneys to its biologically active form 1,25-dihydroxyvitamin D. This hormone interacts with its receptor in the small intestine to increase the efficiency of intestinal calcium and phosphate absorption for the maintenance of the skeleton throughout life. Vitamin D deficiency during the first few years of life results in a flattened pelvis making it difficult for childbirth. Vitamin D deficiency causes osteopenia and osteoporosis increasing risk of fracture. Essentially every tissue and cell in the body has a vitamin D receptor. Therefore vitamin D deficiency has been linked to increased risk for preeclampsia, requiring a Cesarean section for birthing, multiple sclerosis, rheumatoid arthritis, type I diabetes, type II diabetes, heart disease, dementia, deadly cancers and infectious diseases. Therefore sensible sun exposure along with vitamin D supplementation of at least 2000 IU/d for adults and 1000 IU/d for children is essential to maximize their health.",
"title": "VITAMIN D: A D-LIGHTFUL SOLUTION FOR HEALTH"
},
{
"docid": "MED-1730",
"text": "The United States (US) Environmental Protection Agency (EPA) and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. To examine potential health risks in humans, we searched and reviewed the literature to evaluate whether exposure to glyphosate is associated causally with non-cancer health risks in humans. We also reviewed biomonitoring studies of glyphosate to allow for a more comprehensive discussion of issues related to exposure assessment and misclassification. Cohort, case-control and cross-sectional studies on glyphosate and non-cancer outcomes evaluated a variety of endpoints, including non-cancer respiratory conditions, diabetes, myocardial infarction, reproductive and developmental outcomes, rheumatoid arthritis, thyroid disease, and Parkinson's disease. Our review found no evidence of a consistent pattern of positive associations indicating a causal relationship between any disease and exposure to glyphosate. Most reported associations were weak and not significantly different from 1.0. Because accurate exposure measurement is crucial for valid results, it is recommended that pesticide-specific exposure algorithms be developed and validated. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "Epidemiologic studies of glyphosate and non-cancer health outcomes: a review."
},
{
"docid": "MED-2791",
"text": "Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.",
"title": "Bioavailability of curcumin: problems and promises."
},
{
"docid": "MED-1167",
"text": "Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. Copyright © 2013 Elsevier Inc. All rights reserved.",
"title": "Pesticides and human chronic diseases: evidences, mechanisms, and perspectives."
},
{
"docid": "MED-2777",
"text": "BACKGROUND: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. METHODS: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. RESULTS: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). CONCLUSION: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. Copyright 2002 by the National Kidney Foundation, Inc.",
"title": "The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994."
},
{
"docid": "MED-2827",
"text": "Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.",
"title": "Soy protein may alleviate osteoarthritis symptoms."
},
{
"docid": "MED-4612",
"text": "Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.",
"title": "Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity."
},
{
"docid": "MED-3577",
"text": "PROBLEM/CONDITION: During the twenty first century, growth in the number of older adults (persons aged > or =65 years) in the United States will produce an unprecedented increase in the number of persons at risk for costly age-associated chronic diseases and other health conditions and injuries. REPORTING PERIOD: 1995-1996. DESCRIPTION OF SYSTEMS: This report uses data from CDC's National Center for Health Statistics (NCHS) to report on leading causes of death in 1996 (from the National Vital Statistics System), major causes of hospitalization (1996 National Hospital Discharge Survey [NHDSI), and major chronic conditions (1995 National Health Interview Survey [NHIS]). The National Vital Statistics System compiles information regarding all death certificates filed in the United States. NHDS is an annual probability sample of discharges from nonfederal, short-stay hospitals. NHIS is an ongoing annual cross-sectional household survey of the U.S. civilian, noninstitutionalized population. In addition, health-care expenditures for older adults are examined by using information obtained from published reports from the U.S. Health Care Financing Administration (HCFA) and health-services literature. RESULTS: The leading causes of death among adults aged > or =65 years were heart disease (1,808 deaths/100,000 population), malignant neoplasms (1,131/100,000), and cerebrovascular disease (415/100,000). Several leading causes of mortality among older adults differed by race, with deaths caused by Alzheimer's disease more frequent among whites and deaths caused by diabetes, kidney diseases, septicemia, and hypertension more frequent among blacks. Rates of hospitalization and length of hospital stays increased with age. Hospitalizations for heart disease represented the highest proportion of all discharges among older adults (23%). Discharge rates for malignant neoplasms, stroke, and pneumonia were similar for adults aged > or =65 years and, as with heart disease, were higher for men than for women. However, the rate of hospitalization for fractures among women exceeded the rate among men. Arthritis was the most prevalent chronic condition among adults aged > or =65 years (48.9/100 adults), followed by hypertension (40.3/100) and heart disease (28.6/100). In 1995, adults aged > or =65 years comprised 13% of the population but accounted for 35% of total personal health care dollars spent ($310 billion), and real per capita personal health-care expenditure for this age group increased at an average annual rate of 5.8% during 1985-1995. Projections for future medical expenditures for older adults vary; however, all project substantial increases after the year 2000. Hip fracture, dementia, and urinary incontinence are discussed as examples of prevalent and costly health conditions among older adults that differ in potential for prevention. These conditions were selected because they result in substantial medical and social costs and they differ in potential for prevention. INTERPRETATION: The higher prevalence of serious and costly health conditions among adults aged > or =65 years highlights the importance of implementing preventive health measures in this population. PUBLIC HEALTH ACTIONS: Data regarding causes of morbidity, mortality, and health-care expenditures among older adults provide information for measuring the effectiveness of public health efforts to reduce modifiable risk factors for morbidity and mortality in this population.",
"title": "Surveillance for morbidity and mortality among older adults--United States, 1995-1996."
},
{
"docid": "MED-957",
"text": "Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to \"negative\" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)",
"title": "Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powde..."
},
{
"docid": "MED-1394",
"text": "BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).",
"title": "Primary prevention of cardiovascular disease with a Mediterranean diet."
},
{
"docid": "MED-2123",
"text": "Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.",
"title": "Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth"
},
{
"docid": "MED-4679",
"text": "OBJECTIVES The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The κ statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage ≥2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage ≥2. The prime determinant of height velocity was pubertal status. CONCLUSIONS In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.",
"title": "Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls"
},
{
"docid": "MED-5025",
"text": "Gel filtration chromatography, ultra-filtration, and solid-phase extraction silica gel clean-up were evaluated for their ability to remove microcystins selectively from extracts of cyanobacteria Spirulina samples after using the reversed-phase octadecylsilyl ODS cartridge for subsequent analysis by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The reversed-phase ODS cartridge/silica gel combination were effective and the optimal wash and elution conditions were: H(2)O (wash), 20% methanol in water (wash), and 90% methanol in water (elution) for the reversed-phase ODS cartridge, followed by 80% methanol in water elution in the silica gel cartridge. The presence of microcystins in 36 kinds of cyanobacteria Spirulina health food samples obtained from various retail outlets in China were detected by LC-MS/MS, and 34 samples (94%) contained microcystins ranging from 2 to 163 ng g(-1) (mean = 14 +/- 27 ng g(-1)), which were significantly lower than microcystins present in blue green alga products previously reported. MC-RR - which contains two molecules of arginine (R) - (in 94.4% samples) was the predominant microcystin, followed by MC-LR - where L is leucine - (30.6%) and MC-YR - where Y is tyrose - (27.8%). The possible potential health risks from chronic exposure to microcystins from contaminated cyanobacteria Spirulina health food should not be ignored, even if the toxin concentrations were low. The method presented herein is proposed to detect microcystins present in commercial cyanobacteria Spirulina samples.",
"title": "Detection of the hepatotoxic microcystins in 36 kinds of cyanobacteria Spirulina food products in China."
},
{
"docid": "MED-818",
"text": "Lepidium meyenii (Maca) is a plant that grows at over 4000 meters above sea level in the central Peruvian Andes. The hypocotyls of this plant are traditionally consumed for their nutritional and medicinal properties. The aim of this study was to determine the health status based on a health related quality of life (HRQL) questionnaire (SF-20) and serum levels of interleukin 6 (IL-6) in subjects that are maca consumers. For this, a cross-sectional study was designed to be performed in 50 subjects from Junin (4100 m): 27 subjects were maca consumers and 23 were non-consumers. The SF-20 survey is used to obtain a summary measure of health status. The stand up from a chair and sit down (SUCSD) test (to assess lower-extremity function), hemoglobin measurement, blood pressure, sexual hormone levels, serum IL-6 levels and the score of chronic mountain sickness (CMS) were evaluated. Testosterone/estradiol ratio (P≪0.05), IL-6 (P<0.05) and CMS score were lower, whereas the health status score was higher, in maca consumers when compared to non-consumers (P<0.01). A greater proportion of maca consumers successfully completed the SUCSD test compared to non-consumers (P<0.01), showing a significant association with lower values of serum IL-6 (P<0.05). In conclusion, consumption of maca was associated with low serum IL-6 levels and in turn with better health status scores in the SF-20 survey and low chronic mountain sickness scores.",
"title": "Role of maca (Lepidium meyenii) consumption on serum interleukin-6 levels and health status in populations living in the Peruvian central Andes over 4000 m of altitude"
},
{
"docid": "MED-1606",
"text": "Background: Plant-based and fiber-rich diets high in vegetables, fruit, and whole grains are recommended to prevent cancer and chronic conditions associated with renal cell carcinoma (RCC), such as obesity, hypertension, and diabetes. Diet may play a role in the etiology of RCC directly and/or indirectly. Objective: In a large prospective cohort of US men and women, we comprehensively investigated dietary intake and food sources of fiber in relation to RCC risk. Design: Participants of the NIH-AARP Diet and Health Study (n = 491,841) completed a self-administered questionnaire of demographics, diet, lifestyle, and medical history. Over 9 (mean) years of follow-up we identified 1816 incident cases of RCC. HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Results: Total dietary fiber intake was associated with a significant 15–20% lower risk of RCC in the 2 highest quintiles compared with the lowest (P-trend = 0.005). Intakes of legumes, whole grains, and cruciferous vegetables were also associated with a 16–18% reduced risk of RCC. Conversely, refined grain intake was positively associated with RCC risk in a comparison of quintile 5 with quintile 1 (HR: 1.19; 95% CI: 1.02, 1.39; P-trend = 0.04). The inverse association between fiber intake and RCC was consistent among participants who never smoked, had a body mass index [BMI (in kg/m2)] <30, and did not report a history of diabetes or hypertension. Conclusions: Intake of fiber and fiber-rich plant foods was associated with a significantly lower risk of RCC in this large US cohort. This trial was registered at clinicaltrials.gov as NCT00340015.",
"title": "Intake of fiber and fiber-rich plant foods is associated with a lower risk of renal cell carcinoma in a large US cohort"
},
{
"docid": "MED-5276",
"text": "Background: Cellular changes lead to coronary artery endothelial dysfunction (ED) and precede plaque formation. Clinical events, such as unstable angina and acute coronary syndromes, are common consequences of ED. Coronary artery ED, as characterized by Rb-82 PE, is a perfusion abnormality at rest, which improves following stress. In risk factor modification studies, particularly in cholesterol-lowering trials, coronary artery ED has been demonstrated to be reversible. Other studies have correlated low fat diet modification with improvement in coronary artery disease.Purpose: This study evaluates changes in myocardial perfusion following meals with low versus high TG content, and its influence on post prandial serum TG.Methods: With a randomized, double blind placebo controlled, cross over design, we investigated 19 patients (10 with ED and 9 with normal perfusion) with Rb-82 PET for myocardial blood flow at rest and with adenosine stress. PET images and serum triglycerides were obtained before and after an olestra (OA) meal (2.7g TG, 44g olestra) and a high-fat meal (46.7g TG). Meals were matched for carbohydrate, protein, and cholesterol content.Results: Myocardial perfusion (uCi/cc) increased 11 - 12% following the OA meal compared to the high-fat meal in patients with ED. For all patients combined, serum TG increased significantly (p < 0.01) in the non-OA group with the median change from baseline to 170.0 mg/dl, compared to 21.5 mg/dl in the OA group during the 6 hours following the meal.Conclusions: A single olestra meal significantly diminishes post prandial serum TG levels and improves myocardial perfusion in patients with endothelial disease.",
"title": "8:45-90:00. The Influence of a High Fat Meal Compared to an Olestra Meal on Coronary Artery Endothelial Dysfunction by Rubidium (Rb)-82 Positron Em..."
},
{
"docid": "MED-5109",
"text": "The objective of this research was to evaluate the effects of 2 levels of raw milk somatic cell count (SCC) on the composition of Prato cheese and on the microbiological and sensory changes of Prato cheese throughout ripening. Two groups of dairy cows were selected to obtain low-SCC (<200,000 cells/mL) and high-SCC (>700,000 cells/mL) milks, which were used to manufacture 2 vats of cheese. The pasteurized milk was evaluated according to the pH, total solids, fat, total protein, lactose, standard plate count, coliforms at 45 degrees C, and Salmonella spp. The cheese composition was evaluated 2 d after manufacture. Lactic acid bacteria, psychrotrophic bacteria, and yeast and mold counts were carried out after 3, 9, 16, 32, and 51 d of storage. Salmonella spp., Listeria monocytogenes, and coagulase-positive Staphylococcus counts were carried out after 3, 32, and 51 d of storage. A 2 x 5 factorial design with 4 replications was performed. Sensory evaluation of the cheeses from low- and high-SCC milks was carried out for overall acceptance by using a 9-point hedonic scale after 8, 22, 35, 50, and 63 d of storage. The somatic cell levels used did not affect the total protein and salt:moisture contents of the cheeses. The pH and moisture content were higher and the clotting time was longer for cheeses from high-SCC milk. Both cheeses presented the absence of Salmonella spp. and L. monocytogenes, and the coagulase-positive Staphylococcus count was below 1 x 10(2) cfu/g throughout the storage time. The lactic acid bacteria count decreased significantly during the storage time for the cheeses from both low- and high-SCC milks, but at a faster rate for the cheese from high-SCC milk. Cheeses from high-SCC milk presented lower psychrotrophic bacteria counts and higher yeast and mold counts than cheeses from low-SCC milk. Cheeses from low-SCC milk showed better overall acceptance by the consumers. The lower overall acceptance of the cheeses from high-SCC milk may be associated with texture and flavor defects, probably caused by the higher proteolysis of these cheeses.",
"title": "Microbial and sensory changes throughout the ripening of Prato cheese made from milk with different levels of somatic cells."
},
{
"docid": "MED-3182",
"text": "OBJECTIVE: Review of human cysticercosis in Canada, to estimate the magnitude of the disease and to describe the pattern of disease expression in this country. METHODS: MEDLINE and manual search of case reports and case series of patients with cysticercosis diagnosed in Canada. ed data included year of diagnosis, citizenship status, clinical manifestations, and form of cysticercosis. FINDINGS: A total of 21 articles reporting 60 patients were found. Forty (67%) of these patients were diagnosed in the past two decades. Most cases came from Ontario (n=43) and Quebec (n=14). Immigrants accounted for 96% of the 28 cases in whom citizenship information was available. Neurocysticercosis was observed in 55 patients, and isolated compromise of striated muscles in the remaining five. Seizures was the primary or sole manifestation of the disease in 72% of patients, and most of them had parenchymal brain cysticerci (either viable cysts or calcifications). Two of seven patients were positive for Taenia eggs. In no case were household contacts of the patients investigated for taeniasis. CONCLUSIONS: An increasing number of patients with cysticercosis have been reported from Canada in the past two decades, suggesting that the prevalence of this parasitic disease may be on the rise. While most cases occur in immigrants, it is possible that at least some of these patients had acquired the disease in Canada.",
"title": "A review of cases of human cysticercosis in Canada."
},
{
"docid": "MED-1840",
"text": "OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.",
"title": "Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P."
},
{
"docid": "MED-1190",
"text": "The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.",
"title": "High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae."
},
{
"docid": "MED-334",
"text": "OBJECTIVE: Among plant foods, grain products, legumes, and seeds are important sources of phosphorus (P). Current data on P content and absorbability of P from these foods are lacking. Measurement of in vitro digestible P (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected foods and to compare the amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP content of 21 foods and drinks of plant origin were measured by inductively coupled plasma optical emission spectrometry. In DP analysis, samples were digested enzymatically in principle in the same way as in the alimentary canal before P analyses. The most popular national brands were chosen for analysis. RESULTS: The highest amount of TP (667 mg/100 g) was found in sesame seeds with hull, which also had the lowest percentage of DP (6%) to TP. Instead, in cola drinks and beer, the percentage of DP to TP was 87 to 100% (13 to 22 mg/100 g). In cereal products, the highest TP content (216 mg/100 g) and DP proportion (100%) were present in industrial muffins, which contain sodium phosphate as a leavening agent. Legumes contained an average DP content of 83 mg/100 g (38% of TP). CONCLUSION: Absorbability of P may differ substantially among different plant foods. Despite high TP content, legumes may be a relatively poor P source. In foods containing phosphate additives, the proportion of DP is high, which supports previous conclusions of the effective absorbability of P from P additives. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.",
"title": "Differences among total and in vitro digestible phosphorus content of plant foods and beverages."
},
{
"docid": "MED-1523",
"text": "Peppermint oil is easily available as a constituent of medicines. A near fatal case due to ingestion of toxic dose of oral peppermint oil is being reported. The patient came in a comatosed state and was in shock. She was managed with mechanical ventilation and ionotropes. Her vital parameters reached normal within 8 hours and became conscious by 24 hours. The side effects of peppermint oil are considered to be mild but this case report warns that ingestion of oral toxic doses of peppermint oil could be dangerous.",
"title": "A near fatal case of high dose peppermint oil ingestion- Lessons learnt"
},
{
"docid": "MED-1473",
"text": "To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.",
"title": "Mechanism of free fatty acid-induced insulin resistance in humans."
},
{
"docid": "MED-5057",
"text": "High fructose corn syrup (HFCS) has become an increasingly common food ingredient in the last 40 years. However, there is concern that HFCS consumption increases the risk for obesity and other adverse health outcomes compared to other caloric sweeteners. The most commonly used types of HFCS (HFCS-42 and HFCS-55) are similar in composition to sucrose (table sugar), consisting of roughly equal amounts of fructose and glucose. The primary difference is that these monosaccharides exist free in solution in HFCS, but in disaccharide form in sucrose. The disaccharide sucrose is easily cleaved in the small intestine, so free fructose and glucose are absorbed from both sucrose and HFCS. The advantage to food manufacturers is that the free monosaccharides in HFCS provide better flavor enhancement, stability, freshness, texture, color, pourability, and consistency in foods in comparison to sucrose. Because the composition of HFCS and sucrose is so similar, particularly on absorption by the body, it appears unlikely that HFCS contributes more to obesity or other conditions than sucrose does. Nevertheless, few studies have evaluated the potentially differential effect of various sweeteners, particularly as they relate to health conditions such as obesity, which develop over relatively long periods of time. Improved nutrient databases are needed to analyze food consumption in epidemiologic studies, as are more strongly designed experimental studies, including those on the mechanism of action and relationship between fructose dose and response. At the present time, there is insufficient evidence to ban or otherwise restrict use of HFCS or other fructose-containing sweeteners in the food supply or to require the use of warning labels on products containing HFCS. Nevertheless, dietary advice to limit consumption of all added caloric sweeteners, including HFCS, is warranted.",
"title": "The effects of high fructose syrup."
},
{
"docid": "MED-2740",
"text": "To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.",
"title": "FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States."
}
] |
PLAIN-3155
|
Avoiding Epilepsy Through Diet
|
[
{
"docid": "MED-1981",
"text": "The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Antibiotic resistance-the need for global solutions."
},
{
"docid": "MED-1980",
"text": "Enterobacterial strains producing clavulanic-acid-inhibited extended-spectrum β-lactamases (ESBLs) are increasingly reported worldwide. Conventional detection of ESBL production remains time-consuming (24 to 48 h). Therefore, the ESBL NDP (Nordmann/Dortet/Poirel) test was developed for a rapid identification of ESBLs in Enterobacteriaceae. This biochemical test was based on the in vitro detection of a cephalosporin (cefotaxime) hydrolysis that is inhibited by tazobactam addition. The ESBL activity was evidenced by a color change (red to yellow) of a pH indicator (red phenol) due to carboxyl-acid formation resulting from cefotaxime hydrolysis that was reversed by addition of tazobactam (positive test). The ESBL NDP test was applied to cultured strains (215 ESBL producers and 40 ESBL nonproducers). Its sensitivity and specificity were 92.6% and 100%, respectively. Its sensitivity (100%) was excellent for detection of CTX-M producers. A few ESBL producers (n = 16) that remained susceptible to cefotaxime were not detected. The test was also evaluated on spiked blood cultures and showed excellent sensitivity and specificity (100% for both). The test was rapid (less than 1 h) and cost-effective. It can be implemented in any health care facility and is well adapted for infection control purposes in particular.",
"title": "Rapid Detection of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae"
},
{
"docid": "MED-2748",
"text": "The consumption of fresh produce is frequently associated with outbreaks of human norovirus (hNoV) disease. To prevent the contamination of fresh produce with hNoV, knowledge of the possible introduction sources of the viruses, such as water, is needed to be able to implement appropriate and efficient preventive measures. Contaminated water used to reconstitute pesticides could be a relevant source of infectious hNoV, determined by the initial level of virus contamination and the persistence of these viruses in reconstituted pesticides. We studied the persistence of hNoV GI.4, hNoV GII.4 and murine norovirus (MNV-1), the only culturable norovirus, in eight different pesticides after 0 and 2h. Virus concentrations were determined by reverse transcriptase PCR, and infectivity of MNV-1 was determined by endpoint dilutions followed by maximum likelihood estimations. MNV-1 was found to remain infectious in seven of the eight tested pesticides at the highest concentration applied in practice. In the presence of the insecticide Vertimec, MNV-1 infectivity decreased rapidly with a 1.9 log(10)-unit reduction at timepoint T(0). Also, the concentration of NoV GI.4 RNA decreased considerably with a 1.7 log(10)-unit reduction; whereas the detected PCR fragment of hNoV GII.4 remained stable. Assuming a similar persistence of infectious MNV-1 and hNoV we can conclude that water containing hNoV used to dilute pesticides may be an important source of infectious hNoV in fresh produce chains. The application of pesticides may therefore not only be a chemical hazard, but also a microbiological hazard for public health. The inclusion of antiviral substances in reconstituted pesticides may be appropriate to reduce the virological health risk posed by the application of pesticides. Copyright © 2012 Elsevier B.V. All rights reserved.",
"title": "Persistence of human norovirus in reconstituted pesticides--pesticide application as a possible source of viruses in fresh produce chains."
},
{
"docid": "MED-4131",
"text": "In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.",
"title": "Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens."
},
{
"docid": "MED-2744",
"text": "Homicide disproportionately affects persons aged 10-24 years in the United States and consistently ranks in the top three leading causes of death in this age group, resulting in approximately 4,800 deaths and an estimated $9 billion in lost productivity and medical costs in 2010. To investigate trends in homicide among persons aged 10-24 years for the period 1981-2010, CDC analyzed National Vital Statistics System data on deaths caused by homicide of persons in this age group and examined trends by sex, age, race/ethnicity, and mechanism of injury. This report describes the results of that analysis, which indicated that homicide rates varied substantially during the study period, with a sharp rise from 1985 to 1993 followed by a decline that has slowed since 1999. During the period 2000-2010, rates declined for all groups, although the decline was significantly slower for males compared with females and for blacks compared with Hispanics and persons of other racial/ethnic groups. By mechanism of injury, the decline for firearm homicides from 2000 to 2010 was significantly slower than for nonfirearm homicides. The homicide rate among persons aged 10-24 years in 2010 was 7.5 per 100,000, the lowest in the 30-year study period. Primary prevention strategies remain critical, particularly among groups at increased risk for homicide.",
"title": "Homicide rates among persons aged 10-24 years - United States, 1981-2010."
},
{
"docid": "MED-2745",
"text": "The current study was undertaken to acquire data on contamination of chicken parts with Salmonella at retail and to acquire data on cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation. Whole raw chickens (n = 31) were obtained from local retail stores and cut into two wings, two breasts without skin or bones, two thighs, and two drumsticks. Data for cross-contamination were obtained by cutting up a sterile, cooked chicken breast with the same board and knife used to cut up the raw chicken. The board, knife, and latex gloves used by the food handler were not rinsed or washed before cutting up the sterile, cooked chicken breast, thus providing a worst-case scenario for cross-contamination. Standard curves for the concentration of Salmonella bacteria in 400 ml of buffered peptone water after 6 h of incubation of chicken parts as a function of the initial log number of Salmonella bacteria inoculated onto chicken parts were developed and used to enumerate Salmonella bacteria. Standard curves were not affected by the type of chicken part but did differ (P < 0.05) among the five isolates of Salmonella examined. Consequently, Salmonella bacteria were enumerated on naturally contaminated chicken parts using a standard curve developed with the serotype of Salmonella that was isolated from the original sample. The prevalence of contamination was 3 % (4 of 132), whereas the incidence of cross-contamination was 1.8 % (1 of 57). The positive chicken parts were a thigh from chicken 4, which contained 3 CFU of Salmonella enterica serotype Kentucky, and both wings, one thigh, and one cooked breast portion from chicken 15, which all contained 1 CFU of serotype 8,20:-:z(6). These results indicated that the poultry industry is providing consumers in the studied area with chicken that has a low prevalence and low number of Salmonella bacteria at retail and that has a low incidence and low level of cross-contamination of cooked chicken with Salmonella from raw chicken during meal preparation under a worst-case scenario.",
"title": "Initial contamination of chicken parts with Salmonella at retail and cross-contamination of cooked chicken with Salmonella from raw chicken during ..."
},
{
"docid": "MED-2736",
"text": "Campylobacter represents the leading cause of gastroenteritis in Europe. Campylobacteriosis is mainly due to C. jejuni and C. coli. Poultry meat is the main source of contamination, and cross-contaminations in the consumer's kitchen appear to be the important route for exposure. The aim of this study was to examine the transfer of Campylobacter from naturally contaminated raw poultry products to a cooked chicken product via the cutting board and to determine the characteristics of the involved isolates. This study showed that transfer occurred in nearly 30% of the assays and that both the C. jejuni and C. coli species were able to transfer. Transfer seems to be linked to specific isolates: some were able to transfer during separate trials while others were not. No correlation was found between transfer and adhesion to inert surfaces, but more than 90% of the isolates presented moderate or high adhesion ability. All tested isolates had the ability to adhere and invade Caco-2 cells, but presented high variability between isolates. Our results highlighted the occurrence of Campylobacter cross-contamination via the cutting board in the kitchen. Moreover, they provided new interesting data to be considered in risk assessment studies. Copyright © 2013 Elsevier B.V. All rights reserved.",
"title": "Characterization of Campylobacter spp. transferred from naturally contaminated chicken legs to cooked chicken slices via a cutting board."
},
{
"docid": "MED-2741",
"text": "Overcrowding stress is a reality in the poultry industry. Chickens exposed to long-term stressful situations present a reduction of welfare and immunosuppression. We designed this experiment to analyse the effects from overcrowding stress of 16 birds/m(2) on performance parameters, serum corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA and IgG levels, intestinal integrity, macrophage activity and experimental Salmonella Enteritidis invasion. The results of this study indicate that overcrowding stress decreased performance parameters, induced enteritis and decreased macrophage activity and the relative bursa weight in broiler chickens. When the chickens were similarly stressed and infected with Salmonella Enteritidis, there was an increase in feed conversion and a decrease in plasma IgG levels in the stressed and Salmonella-infected birds. We observed moderate enteritis throughout the duodenum of chickens stressed and infected with Salmonella. The overcrowding stress decreased the macrophage phagocytosis intensity and increased Salmonella Enteritidis counts in the livers of birds challenged with the pathogenic bacterium. Overcrowding stress via the hypothalamic-pituitary-adrenal axis that is associated with an increase in corticosterone and enteritis might influence the quality of the intestinal immune barrier and the integrity of the small intestine. This effect allowed pathogenic bacteria to migrate through the intestinal mucosa, resulting in inflammatory infiltration and decreased nutrient absorption. The data strengthen the hypothesis that control of the welfare of chickens and avoidance of stress from overcrowding in poultry production are relevant factors for the maintenance of intestinal integrity, performance and decreased susceptibility to Salmonella infection.",
"title": "Overcrowding stress decreases macrophage activity and increases Salmonella Enteritidis invasion in broiler chickens."
},
{
"docid": "MED-2742",
"text": "A national telephone survey was conducted of 1,620 randomly selected U.S. residents who spoke English, were at least 18 years old, and resided in households with kitchen facilities. Respondents were interviewed about their recognition of foodborne pathogens, foods at risk for transmitting infection, knowledge of safe food handling, and food-handling practices. One-third of the respondents who prepared meals reported unsafe food hygiene practices: e.g., they did not wash hands or take precautions to prevent cross-contamination from raw meat. Unsafe practices were reported more often by men, adults 18 to 29 years of age, and occasional food preparers than by women, persons 30 years old or older, and frequent food preparers. Respondents who identified a food vehicle for Salmonella spp. were more likely to report washing their hands and cleaning cutting boards after preparing raw meat and poultry. The results raise concerns about consumer food-handling practices. The influence of food safety training, food-handling experience, and age on food-handling practices should be studied further. Awareness of a food vehicle for Salmonella spp., for example, may indicate knowledge of the etiology of foodborne disease that promotes safe food handling. Understanding the factors associated with safe food handling will assist in development of effective safe-food instruction programs.",
"title": "Consumer knowledge of foodborne microbial hazards and food-handling practices."
},
{
"docid": "MED-4672",
"text": "Neurocysticercosis cases were identified in 1991 in an Orthodox Jewish community. Transmission was linked to tapeworm-infected immigrant housekeepers from countries where Taenia solium is endemic. To evaluate the extent of and risks for locally acquired cysticercosis, a seroprevalence survey was conducted in 9% of the households in this community. Cysticercosis antibodies were detected in 23 (1.3%) of 1,789 persons from 612 families. All 23 seropositive persons were asymptomatic, and no intracerebral lesions were found for the 21 seropositive persons who underwent brain imaging. Seropositivity was associated with female sex (relative risk [RR] = 2.45, P = 0.049), hiring a domestic worker for child care duties (RR = 3.79, P = 0.05), and with employees from Central America (RR = 2.70, P = 0.0001). Exposure to T. solium in this community is unexpectedly high. Widespread employment of domestic workers from endemic regions and high employee turnover contributes to exposure risk.",
"title": "Seroprevalence of cysticercosis in an Orthodox Jewish community."
},
{
"docid": "MED-2673",
"text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.",
"title": "Determination of microbial transglutaminase in meat and meat products."
},
{
"docid": "MED-2749",
"text": "Noroviruses are the leading cause of foodborne illness in the United States. To better guide interventions, we analyzed 2,922 foodborne disease outbreaks for which norovirus was the suspected or confirmed cause, which had been reported to the Foodborne Disease Outbreak Surveillance System of the Centers for Disease Control and Prevention during 2001–2008. On average, 365 foodborne norovirus outbreaks were reported annually, resulting in an estimated 10,324 illnesses, 1,247 health care provider visits, 156 hospitalizations, and 1 death. In 364 outbreaks attributed to a single commodity, leafy vegetables (33%), fruits/nuts (16%), and mollusks (13%) were implicated most commonly. Infected food handlers were the source of 53% of outbreaks and may have contributed to 82% of outbreaks. Most foods were likely contaminated during preparation and service, except for mollusks, and occasionally, produce was contaminated during production and processing. Interventions to reduce the frequency of foodborne norovirus outbreaks should focus on food workers and production of produce and shellfish.",
"title": "Epidemiology of Foodborne Norovirus Outbreaks, United States, 2001–2008"
},
{
"docid": "MED-4136",
"text": "BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.",
"title": "Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10..."
},
{
"docid": "MED-3884",
"text": "Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to beta-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen.",
"title": "The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective."
},
{
"docid": "MED-2746",
"text": "Foods prepared in the kitchen can become cross-contaminated with Campylobacter by contacting raw products, particularly skinned poultry. We measured the percent transfer rate from naturally contaminated poultry legs purchased in supermarkets. Transfer of Campylobacter from skin (n = 43) and from meat (n = 12) to high-density polyethylene cutting board surfaces was quantitatively assessed after contact times of 1 and 10 min. The percent transfer rate was defined as the ratio between the number of Campylobacter cells counted on the cutting board surface and the initial numbers of Campylobacter naturally present on the skin (i.e., the sum of Campylobacter cells on the skin and board). Qualitative transfer occurred in 60.5% (95% confidence interval, 45.5 to 75.4) of the naturally contaminated legs studied and reached 80.6% (95% confidence interval, 63.0 to 98.2) in the subpopulation of legs that were in contact with the surface for 10 min. The percent transfer rate varied from 5 x 10(-2)% to 35.7% and was observed as being significantly different (Kruskall-Wallis test, P < 0.025) and inversely related to the initial counts on poultry skin. This study provides quantitative data describing the evolution of the proportion of Campylobacter organisms transferred from naturally contaminated poultry under kitchen conditions. We emphasize the linear relationship between the initial load of Campylobacter on the skin and the value of the percent transfer rate. This work confirms the need for modeling transfer as a function of initial load of Campylobacter on leg skin, the weight of poultry pieces, and the duration of contact between the skin and surface.",
"title": "Campylobacter transfer from naturally contaminated chicken thighs to cutting boards is inversely related to initial load."
},
{
"docid": "MED-2743",
"text": "In June 2012, the Oregon Health Authority and the Washington State Department of Health noted an increase in the number of Salmonella enterica serotype Heidelberg clinical isolates sharing an identical pulsed-field gel electrophoresis (PFGE) pattern. In 2004, this pattern had been linked to chicken from Foster Farms by the Washington State Department of Health; preliminary 2012 interviews with infected persons also indicated exposure to Foster Farms chicken. On August 2, 2012, CDC's PulseNet* detected a cluster of 19 Salmonella Heidelberg clinical isolates matching the outbreak pattern. This report summarizes the investigation by CDC, state and local health departments, the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS), and the Food and Drug Administration (FDA) and reinforces the importance of safe food handling to prevent illness. A total of 134 cases from 13 states were identified, including 33 patients who were hospitalized. This multifaceted investigation used standard epidemiologic and laboratory data along with patient shopper card purchase information, and PFGE data from the retail meat component of the National Antimicrobial Resistance Monitoring System (NARMS)†, a relatively novel tool in outbreak investigation, to link the outbreak strain to chicken from Foster Farms.",
"title": "Outbreak of Salmonella Heidelberg infections linked to a single poultry producer -- 13 states, 2012-2013."
},
{
"docid": "MED-3889",
"text": "Contamination of retail chicken meat by Extended Spectrum Beta-Lactamase (ESBL) producing bacteria likely contributes to the increasing incidence of infections with these bacteria in humans. This study aimed to compare the prevalence and load of ESBL positive isolates between organic and conventional retail chicken meat samples, and to compare the distribution of ESBL genes, strain genotypes and co-resistance. In 2010, 98 raw chicken breasts (n=60 conventional; n=38 organic) were collected from 12 local stores in the Netherlands. Prevalence of ESBL producing micro-organisms was 100% on conventional and 84% on organic samples (p<0.001). Median loads of ESBL producing micro-organisms were 80 (range <20-1360) in conventional, and <20 (range 0-260) CFU/25 g in organic samples (p=0.001). The distribution of ESBL genes in conventional samples and organic samples was 42% versus 56%, respectively (N.S.), for CTX-M-1, 20% versus 42% (N.S.) for TEM-52, and 23% versus 3% (p<0.001) for SHV-12. CTX-M-2 (7%), SHV-2 (5%) and TEM-20 (3%) were exclusively found in conventional samples. Co-resistance rates of ESBL positive isolates were not different between conventional and organic samples (co-trimoxazole 56%, ciprofloxacin 14%, and tobramycin 2%), except for tetracycline, 73% and 46%, respectively, p<0.001). Six of 14 conventional meat samples harbored 4 MLST types also reported in humans and 5 of 10 organic samples harbored 3 MLST types also reported in humans (2 ST10, 2 ST23, ST354). In conclusion, the majority of organic chicken meat samples were also contaminated with ESBL producing E. coli, and the ESBL genes and strain types were largely the same as in conventional meat samples. Copyright © 2011 Elsevier B.V. All rights reserved.",
"title": "Comparison of ESBL contamination in organic and conventional retail chicken meat."
},
{
"docid": "MED-1983",
"text": "Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has developed resistance to beta-lactam antibiotics and has been isolated at low population numbers in retail meat products. The objectives of this study were to estimate the potential transfer of MRSA from contaminated retail pork products to food contact surfaces and to estimate the potential for human exposure to MRSA by contact with those contaminated surfaces. Pork loins, bacon, and fresh pork sausage were inoculated with a four-strain mixed MRSA culture over a range of populations from approximately 4 to 8 log, vacuum packaged, and stored for 2 weeks at 5°C to simulate normal packaging and distribution. Primary transfer was determined by placing inoculated products on knife blades, cutting boards, and a human skin model (pork skin) for 5 min. Secondary transfer was determined by placing an inoculated product on the contact surface, removing it, and then placing the secondary contact surface on the initial contact surface. A pork skin model was used to simulate transfer to human skin by placing it into contact with the contact surface. The percentages of transfer for primary transfer from the inoculated products to the cutting board ranged from 39 to 49%, while the percentages of transfer to the knife ranged from 17 to 42%. The percentages of transfer from the inoculated products to the pork skin ranged from 26 to 36%. The secondary transfer percentages ranged from 2.2 to 5.2% across all products and contact surfaces. Statistical analysis showed no significant differences in the amounts of transfer between transfer surfaces and across cell concentrations.",
"title": "Transfer of methicillin-resistant Staphylococcus aureus from retail pork products onto food contact surfaces and the potential for consumer exposure."
},
{
"docid": "MED-1979",
"text": "Methicillin-resistant Staphylococcus aureus (MRSA) is a major global public health concern and could be a food safety issue. Recurrent reports have documented that pig herds are an important reservoir for MRSA, specifically the livestock-associated sequence type 398. The high prevalence of MRSA in pig primary production facilities and the frequent detection of MRSA of the same types in pork and pig meat products raise the question of underlying mechanisms behind the introduction and transmission of MRSA along the pork production chain. A comprehensive review of current literature on the worldwide presence of livestock-associated MRSA in various steps of the pork production chain revealed that the slaughter process plays a decisive role in MRSA transmission from farm to fork. Superficial heat treatments such as scalding and flaming during the slaughter process can significantly reduce the burden of MRSA on the carcasses. However, recontamination with MRSA might occur via surface treating machinery, as a result of fecal contamination at evisceration, or via increased human handling during meat processing. By optimizing processes for carcass decontamination and avoiding recontamination by effective cleaning and personal hygiene management, transmission of MRSA from pig to pork can be minimized.",
"title": "From pig to pork: methicillin-resistant Staphylococcus aureus in the pork production chain."
},
{
"docid": "MED-5169",
"text": "Fourteen sites evenly divided between the household kitchen and bathroom were monitored on a weekly basis for numbers of faecal coliforms, total coliforms and heterotrophic plate count bacteria. The first 10 weeks comprised the control period, hypochlorite cleaning products were introduced into the household during the second 10 weeks, and a strict cleaning regimen using hypochlorite products was implemented during the last 10 weeks. The kitchen was more heavily contaminated than the bathroom, with the toilet seat being the least contaminated site. The highest concentrations of all three classes of bacteria were found on sites that were moist environments and/or were frequently touched; these included the sponge/dishcloth, the kitchen sink drain area, the bath sink drain area, and the kitchen faucet handle(s). The implementation of a cleaning regimen with common household hypochlorite products resulted in the significant reduction of all three classes of bacteria at these four sites and other household sites.",
"title": "Reduction of faecal coliform, coliform and heterotrophic plate count bacteria in the household kitchen and bathroom by disinfection with hypochlori..."
},
{
"docid": "MED-1982",
"text": "In a study of 40 methicillin-resistant Staphylococcus aureus (MRSA) carriers, hand contamination was equally likely after contact with commonly examined skin sites and commonly touched environmental surfaces in patient rooms (40% vs 45%). These findings suggest that contaminated surfaces may be an important source of MRSA transmission.",
"title": "Contamination of hands with methicillin-resistant Staphylococcus aureus after contact with environmental surfaces and after contact with the skin o..."
},
{
"docid": "MED-1978",
"text": "Context Nearly 80% of antibiotics in the United States are sold for use in livestock feeds. The manure produced by these livestock contains antibiotic-resistant bacteria, resistance genes, and antibiotics, and is subsequently applied to crop fields where it may put community members at risk for antibiotic-resistant infections. Objective To assess the association between individual exposure to swine and dairy/veal industrial agriculture and risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Design, Setting, and Participants A population-based, nested case-control study of Geisinger primary care patients in Pennsylvania from 2005–2010. Incident MRSA cases were identified using electronic health records, classified as community-associated or healthcare-associated, and frequency-matched to randomly selected controls and patients with skin and soft tissue infection. Nutrient management plans were used to create two exposure variables: seasonal crop field manure application and number of livestock at the operation. In a sub-study we collected 200 isolates from patients stratified by location of diagnosis and proximity to livestock operations. Main outcome measures Community-associated MRSA, healthcare associated-MRSA, and skin and soft tissue infection status (with no history of MRSA) compared to controls. Results From 446,480 patients, 1539 community-associated MRSA, 1335 healthcare-associated MRSA, 2895 skin and soft tissue infection cases, and 2914 controls were included. After adjustment for MRSA risk factors, the highest quartile of swine crop field exposure was significantly associated with community-associated MRSA, healthcare-associated MRSA, and skin and soft tissue infection case status (adjusted odds ratio, 1.38 [95% CI, 1.13–1.69], 1.30 [95% CI, 1.05–1.61], and 1.37 [95% CI, 1.18–1.60], respectively); and there was a trend of increasing odds across quartiles for each outcome (all P for trend ≤0.01). There were similar but weaker associations of swine operations with community-associated MRSA and skin and soft tissue infection. Molecular testing of 200 isolates identified 31 unique spa types, none of which corresponded to CC398, but some have been previously found in swine. Conclusion Proximity to swine manure application to crop fields and livestock operations each was associated with MRSA and skin and soft tissue infection. These findings contribute to the growing concern about the potential public health impacts of high-density livestock production.",
"title": "High-density livestock operations, crop field application of manure, and risk of community-associated methicillin-resistant Staphylococcus aureus infection, Pennsylvania, USA"
},
{
"docid": "MED-1977",
"text": "Reports have documented colonization of swine in Europe, North America and more recently in China with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA). Contamination of pig farmers, veterinarians and abattoir workers with these strains has been observed. However, although contamination levels of 10% of retail pork were reported from the Netherlands and Canada, there are limited data of contamination rates of workers handling raw meat. We investigated the rates of MRSA contamination of local butchers working in wet markets, where recently slaughtered pigs are cut up. Nasal swabs collected from 300 pork butchers at markets throughout Hong Kong were enriched in brain heart infusion broth with 5% salt and cultured on MRSASelect(®) . Isolates were confirmed as Staphylococcus aureus and susceptibility testing performed. The presence of mecA was confirmed, SCCmec and spa type determined and relatedness investigated by PFGE. Subjects completed a questionnaire on MRSA carriage risk factors. Seventeen samples (5.6%) yielded MRSA, 15 harbouring SCCmec IVb. Ten strains were t899 (CC9), previously reported from local pig carcasses. Five strains were healthcare associated: SCCmec type II, t701(CC6), colonizing two subjects at the same establishment, and single isolates of t008 (CC8), t002 (CC5) and t123 (CC45). The remaining isolates were t359 (CC97), previously reported from buffaloes, and t375 (CC5), reported from bovine milk. None of these butchers reported recent hospitalization or a healthcare worker in the family. Two had recently received antibiotics, one for a skin infection. Four reported wound infections within the last year. All were exposed to meat for >9 h per day. Carriage of MRSA was higher in butchers than in the general community. Although five strains were probably of healthcare origin, the high incidence of t899 (CC9) suggests that cross-contamination from pork occurs frequently. Washing of hands after touching raw pork is advised. © 2012 Blackwell Verlag GmbH.",
"title": "Colonization of butchers with livestock-associated methicillin-resistant Staphylococcus aureus."
},
{
"docid": "MED-2747",
"text": "Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998–2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.",
"title": "Attribution of Foodborne Illnesses, Hospitalizations, and Deaths to Food Commodities by using Outbreak Data, United States, 1998–2008"
},
{
"docid": "MED-3880",
"text": "A common approach to reducing microbial contamination has been the implementation of a Hazard Analysis and Critical Control Point (HACCP) program to prevent or reduce contamination during production. One example is the Pathogen Reduction HACCP program implemented by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). This program consisted of a staged implementation between 1996 and 2000 to reduce microbial contamination on meat and poultry products. Of the commodities regulated by FSIS, one of the largest observed reductions was for Salmonella contamination on broiler chicken carcasses. Nevertheless, how this reduction might have influenced the total number of salmonellosis cases in the United States has not been assessed. This study incorporates information from public health surveillance and surveys of the poultry slaughter industry into a model that estimates the number of broiler-related salmonellosis cases through time. The model estimates that-following the 56% reduction in the proportion of contaminated broiler carcasses observed between 1995 and 2000-approximately 190,000 fewer annual salmonellosis cases (attributed to broilers) occurred in 2000 compared with 1995. The uncertainty bounds for this estimate range from approximately 37,000 to 500,000 illnesses. Estimated illnesses prevented, due to the more modest reduction in contamination of 13% between 2000 and 2007, were not statistically significant. An analysis relating the necessary magnitude of change in contamination required for detection via human surveillance also is provided.",
"title": "Estimating changes in public health following implementation of hazard analysis and critical control point in the United States broiler slaughter i..."
},
{
"docid": "MED-2740",
"text": "To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.",
"title": "FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States."
},
{
"docid": "MED-2672",
"text": "To quantify objectionable levels of connective tissues, restructured beef products were made with 2·5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2·5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. Copyright © 1990. Published by Elsevier Ltd.",
"title": "Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks."
},
{
"docid": "MED-3886",
"text": "The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.",
"title": "Mechanisms of antimicrobial resistance in bacteria."
},
{
"docid": "MED-3887",
"text": "Summary: Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the “precautionary principle.” Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans—directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.",
"title": "Food Animals and Antimicrobials: Impacts on Human Health"
},
{
"docid": "MED-3888",
"text": "BACKGROUND: Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices. METHODS: We analyzed the incidence of human SE infection during 1996-2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with rates of SE isolation from processed chickens and egg products; shell eggs are not routinely tested. We also compared molecular subtyping patterns of SE isolated from humans and chickens. RESULTS: Since the period 1996-1999, the incidence of human SE infection in FoodNet has increased by 44%. This change is mirrored in passive national surveillance data. The greatest relative increases were in young children, older adults, and FoodNet sites in the southern United States. The proportion of patients with SE infection who reported recent international travel has decreased in recent years, whereas the proportion of chickens from which SE was isolated has increased. Similar molecular subtypes of SE are commonly isolated from humans and chickens. CONCLUSIONS: Most SE infections in the United States are acquired from domestic sources, and the problem is growing. Chicken and eggs are likely major sources of SE. Continued close attention to surveillance data is needed to monitor the impact of recent regulatory control measures.",
"title": "Salmonella enterica serotype Enteritidis: increasing incidence of domestically acquired infections."
},
{
"docid": "MED-2671",
"text": "Microbiology of meats has been a subject of great concern in food science and public health in recent years. Although many articles have been devoted to the microbiology of beef, pork, and poultry meats, much less has been written about microbiology of lamb meat and even less on restructured lamb meat. This article presents data on microbiology and shelf-life of fresh lamb meat; restructured meat products, restructured lamb meat products, bacteriology of restructured meat products, and important foodborne pathogens such as Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes in meats and lamb meats. Also, the potential use of sodium and potassium lactates to control foodborne pathogens in meats and restructured lamb meat is reviewed This article should be of interest to all meat scientists, food scientists, and public health microbiologists who are concerned with the safety of meats in general and lamb meat in particular.",
"title": "Microbiology of fresh and restructured lamb meat: a review."
},
{
"docid": "MED-2738",
"text": "Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers.",
"title": "Trends in U.S. consumers' safe handling and consumption of food and their risk perceptions, 1988 through 2010."
},
{
"docid": "MED-3882",
"text": "Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) β-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n=18), food animals at slaughter (n=16), and retail meats (n=13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion.",
"title": "Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and h..."
},
{
"docid": "MED-4132",
"text": "Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.",
"title": "Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic..."
},
{
"docid": "MED-3891",
"text": "Escherichia coli isolates were recovered from the National Antimicrobial Resistance Monitoring System retail meat program and examined for antimicrobial susceptibility. Retail meat samples (n = 11,921) from four U.S. states collected during 2002 to 2008, consisting of 2,988 chicken breast, 2,942 ground turkey, 2,991 ground beef, and 3,000 pork chop samples, were analyzed. A total of 8,286 E. coli isolates were recovered. The greatest numbers of samples contaminated with the organism were chicken (83.5%) and turkey (82.0%), followed by beef (68.9%) and pork (44.0%). Resistance was most common to tetracycline (50.3%), followed by streptomycin (34.6%), sulfamethoxazole-sulfisoxazole (31.6%), ampicillin (22.5%), gentamicin (18.6%), kanamycin (8.4%), amoxicillin-clavulanic acid (6.4%), and cefoxitin (5.2%). Less than 5% of the isolates had resistance to trimethoprim, ceftriaxone, ceftiofur, nalidixic acid, chloramphenicol, and ciprofloxacin. All isolates were susceptible to amikacin. Compared to beef and pork isolates, the poultry meat isolates had a greater percentage of resistance to all tested drugs, with the exception of chloramphenicol, to which pork isolates had the most resistance. More than half of the turkey isolates (56%) were resistant to multidrugs (≥3 classes) compared to 38.9% of chicken, 17.3% of pork, and 9.3% of beef isolates. The blaCMY gene was present in all ceftriaxone- and ceftiofur-resistant isolates. The cmlA, flo, and catI genes were present in 45%, 43%, and 40% of chloramphenicol-resistant isolates, respectively. Most nalidixic acid-resistant isolates (98.5%) had a gyrA mutation in S83 or D87 or both, whereas only 6.7% had a parC mutation in either S80 or E84. The results showed that E. coli was commonly present in the retail meats, and antimicrobial resistance profiles differed according to the animal origin of the isolates.",
"title": "Comparison of the Prevalences and Antimicrobial Resistances of Escherichia coli Isolates from Different Retail Meats in the United States, 2002 to 2008"
},
{
"docid": "MED-3892",
"text": "Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country.",
"title": "Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model"
}
] |
[
{
"docid": "MED-5251",
"text": "Dietary habits have been rarely associated with seizure frequency in patients with epilepsy. We report a case of a man with a partial symptomatic epilepsy whose daily habit of heavy coffee drinking was associated with an increased seizure frequency. This patient witnessed a dramatic decrease in the frequency of his seizures after stopping coffee ingestion. Caffeine is a global stimulant and the reduction of its intake may help in the treatment of epilepsy.",
"title": "Heavy coffee drinking and epilepsy."
},
{
"docid": "MED-3178",
"text": "Neurocysticercosis (NCC) is the most frequent parasitic disease of the human brain. Modern imaging studies, CT and MRI, have defined the diagnosis and characterization of the disease. Through these studies the therapeutic approach for each case may be individualized with the aid of antihelmintics, steroids, symptomatic medicines, or surgery. The use of one or various therapeutic measures largely depends on the peculiar combination of number, location, and biological stage of lesions as well as the degree of inflammatory response to the parasites. Although there is not a typical clinical picture of NCC, epilepsy is the most frequent manifestation of parenchymal NCC, whereas hydrocephalus is the most frequent manifestation of meningeal NCC. Eradication of cysticercosis is an attainable goal by public education and sanitary improvement in endemic areas.",
"title": "Clinical manifestations, diagnosis, and treatment of neurocysticercosis."
},
{
"docid": "MED-301",
"text": "Epilepsy or seizure disorder is one of the most common neurological diseases in humans. Although genetic mutations in ion channels and receptors and some other risk factors such as brain injury are linked to epileptogenesis, the underlying cause for the majority of epilepsy cases remains unknown. Gene-environment interactions are thought to play a critical role in the etiology of epilepsy. Exposure to environmental chemicals is an important risk factor. Methylmercury (MeHg) is a prominent environmental neurotoxicant, which targets primarily the central nervous system (CNS). Patients or animals with acute or chronic MeHg poisoning often display epileptic seizures or show increased susceptibility to seizures, suggesting that MeHg exposure may be associated with epileptogenesis. This mini-review highlights the effects of MeHg exposure, especially developmental exposure, on the susceptibility of humans and animals to seizures, and discusses the potential role of low level MeHg exposure in epileptogenesis. This review also proposes that a preferential effect of MeHg on the inhibitory GABAergic system, leading to disinhibition of excitatory glutamatergic function, may be one of the potential mechanisms underlying MeHg-induced changes in seizure susceptibility.",
"title": "Methylmercury: A Potential Environmental Risk Factor Contributing to Epileptogenesis"
},
{
"docid": "MED-3170",
"text": "Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. Author Summary Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome.",
"title": "Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study"
},
{
"docid": "MED-4391",
"text": "Cancer is a leading cause of death worldwide. There are a lot of cancer causing agents which are divided as physical carcinogens, chemical carcinogens and biological carcinogens. But most of the carcinogens or causes of cancer are related to our lifestyle like diet, habit, occupation, radiation and some infection, etc. Chemoprevention is highly necessary to prevent cancer related preterm death. For this besides avoiding the causes of cancer we should concentrate ourselves on our diet. Because, numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents and recently attention has been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals. In this study, we tried to describe lifestyle related causes of cancer and the molecular basis of cancer prevention through the phytochemicals.",
"title": "Lifestyle related causes of cancer and chemoprevention through phytonutrients."
},
{
"docid": "MED-3527",
"text": "BACKGROUND: : Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. REVIEWER'S CONCLUSIONS: : Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.",
"title": "Melatonin for the prevention and treatment of jet lag."
},
{
"docid": "MED-3204",
"text": "Grapefruit is a healthy addition to a well-balanced diet. However, the fruit has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse effects. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 system, low bioavailability, and a narrow therapeutic index. Prominent medications known to interact with grapefruit include statins, antiarrhythmic agents, immunosuppressive agents, and calcium channel blockers. There are equally effective alternatives to these drug classes that do not have the potential to interact with grapefruit. These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. Patients also may choose to exclude grapefruit from their diets and consume other fruits, including other types of citrus, to avoid an interaction.",
"title": "Management of grapefruit-drug interactions."
},
{
"docid": "MED-1679",
"text": "BACKGROUND: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia. METHODS AND RESULTS: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986. Lifestyle factors were updated through self-reported questionnaires. Low risk was defined as (1) absence of smoking, (2) body mass index <25 kg/m2, (3) moderate-to-vigorous activity > or = 30 min/d, (4) moderate alcohol consumption (5 to 30 g/d), and (5) the top 40% of the distribution for a healthy diet score. Over 16 years, we documented 2183 incident cases of CHD (nonfatal myocardial infarction and fatal CHD). In multivariate-adjusted Cox proportional hazards models, men who were at low risk for 5 lifestyle factors had a lower risk of CHD (relative risk: 0.13; 95% confidence interval [CI]: 0.09, 0.19) compared with men who were at low risk for no lifestyle factors. Sixty-two percent (95% CI: 49%, 74%) of coronary events in this cohort may have been prevented with better adherence to these 5 healthy lifestyle practices. Among men taking medication for hypertension or hypercholesterolemia, 57% (95% CI: 32%, 79%) of all coronary events may have been prevented with a low-risk lifestyle. Compared with men who did not make lifestyle changes during follow-up, those who adopted > or = 2 additional low-risk lifestyle factors had a 27% (95% CI: 7%, 43%) lower risk of CHD. CONCLUSIONS: A majority of CHD events among US men may be preventable through adherence to healthy lifestyle practices, even among those taking medications for hypertension or hypercholesterolemia.",
"title": "Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and an..."
},
{
"docid": "MED-2437",
"text": "BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women in the United States. Extensive research has been completed to evaluate the relationship between dietary factors and breast cancer risk and survival after breast cancer; however, a summary report with clinical inference is needed. Materials and METHODS: This review summarizes the current epidemiological and clinical trial evidence relating diet to breast cancer incidence, recurrence, survival, and mortality. The review includes emerging epidemiological studies that assess risk within breast cancer subtypes as well as a summary of previous and ongoing dietary intervention trials designed to modify breast cancer risk. RESULTS: The available literature suggests that both low-fat and high-fiber diets may be weakly protective against breast cancer, whereas total energy intake and alcohol appear to be positively associated. Fiber may be weakly protective possibly through modulation of estrogen, whereas fruit and vegetable intake is not clearly associated with risk. Obesity is a risk factor for postmenopausal disease, and adult weight gain should be avoided to reduce risk. In survivors, diet has the greatest potential influence on overall mortality rather than breast cancer-specific events. CONCLUSION: Diet is modestly associated with breast cancer risk; associations appear more pronounced for postmenopausal disease, and healthy choices after diagnosis and treatment likely support longevity more so than reduced risk for recurrent disease.",
"title": "Diet and breast cancer: understanding risks and benefits."
},
{
"docid": "MED-2527",
"text": "BACKGROUND: One of the major issues in controlling serum cholesterol through dietetic intervention appears to be the need to improve patient adherence. AIMS: To explore the many questions regarding barriers to, and motivators for, cholesterol-lowering diet adherence. METHODS: We surveyed French general practitioners' dietetic practices for patients with hypercholesterolaemia, and looked at their patients' attitudes towards such an approach. RESULTS: We analysed 234 doctors' personal questionnaires and 356 patient self-survey questionnaires. Patients' reasons for not complying with the prescribed diet included: 'already having satisfactory food habits' (34.7%), 'unwillingness to suffer nutritional deprivation' (33.3%), 'difficulties to conciliate a diet with family life' (27.8%) and 'taking cholesterol-lowering drugs' (22.2%). Despite a generally good understanding by patients of doctors' recommendations, some discrepancies were seen between their respective declarations. While doctors largely thought that patients needed more explanation on why and how a diet can lower cholesterol (and avoid taking drugs), only 39.4% of patients declared needing this kind of information. Other discrepancies were observed concerning barriers to, and motivators for, patient adherence. Moreover, some dietetic rules appeared to be more difficult to comply with than others, e.g. 82.6% patients remembered they should 'eat more fish' but only 51.3% actually did so. Finally, physicians, as well as patients, displayed a lack of confidence in lipid-lowering diet efficiency. CONCLUSION: Improving patient education, especially concerning their perception of risk, as well as increasing the involvement of dieticians, are motivators to explore in order to improve adherence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.",
"title": "Cross-analysis of dietary prescriptions and adherence in 356 hypercholesterolaemic patients."
},
{
"docid": "MED-4451",
"text": "Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.",
"title": "Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish."
},
{
"docid": "MED-1748",
"text": "Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly precise log-normal distribution in the plasma samples while non-plasma (cord blood) control sample was found to be free of plant DNA.",
"title": "Complete Genes May Pass from Food to Human Blood"
},
{
"docid": "MED-3545",
"text": "Background Omnivorous diets are high in arachidonic acid (AA) compared to vegetarian diets. Research shows that high intakes of AA promote changes in brain that can disturb mood. Omnivores who eat fish regularly increase their intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fats that oppose the negative effects of AA in vivo. In a recent cross-sectional study, omnivores reported significantly worse mood than vegetarians despite higher intakes of EPA and DHA. This study investigated the impact of restricting meat, fish, and poultry on mood. Findings Thirty-nine omnivores were randomly assigned to a control group consuming meat, fish, and poultry daily (OMN); a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or a vegetarian group avoiding meat, fish, and poultry (VEG). At baseline and after two weeks, participants completed a food frequency questionnaire, the Profile of Mood States questionnaire and the Depression Anxiety and Stress Scales. After the diet intervention, VEG participants reduced their EPA, DHA, and AA intakes, while FISH participants increased their EPA and DHA intakes. Mood scores were unchanged for OMN or FISH participants, but several mood scores for VEG participants improved significantly after two weeks. Conclusions Restricting meat, fish, and poultry improved some domains of short-term mood state in modern omnivores. To our knowledge, this is the first trial to examine the impact of restricting meat, fish, and poultry on mood state in omnivores.",
"title": "Restriction of meat, fish, and poultry in omnivores improves mood: A pilot randomized controlled trial"
},
{
"docid": "MED-1552",
"text": "OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.",
"title": "Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies."
},
{
"docid": "MED-5134",
"text": "This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (>or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.",
"title": "Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition."
},
{
"docid": "MED-3181",
"text": "OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.",
"title": "Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil."
},
{
"docid": "MED-2014",
"text": "BACKGROUND: Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. SPECIFIC AIM: We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). METHODS: This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. RESULTS: Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. CONCLUSION: While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.",
"title": "Characteristics of patients who avoid wheat and/or gluten in the absence of Celiac disease."
},
{
"docid": "MED-1595",
"text": "Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.",
"title": "Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels."
},
{
"docid": "MED-3154",
"text": "Anecdotal, survey, and epidemiological data suggest that endurance athletes are at an increased risk for upper respiratory tract infection (URTI) during periods of heavy training and the 1 - to 2-wk period after race events. The majority of athletes, however, who participate in endurance race events do not experience illness. Of greater public health importance is the consistent finding of a reduction in URTI risk reported by fitness enthusiasts and athletes who engage in regular exercise training while avoiding overreaching/overtraining. Although it naturally follows that infection risk should in some way be linked to acute and chronic exercise-induced alterations in immunity, attempts thus far to measure this association have been unsuccessful. There is growing evidence that for several hours subsequent to heavy exertion, several components of both the innate and adaptive immune system exhibit suppressed function. The immune response to heavy exertion is transient, however, and further research on the mechanisms underlying the immune response to prolonged and intensive endurance exercise is necessary before meaningful clinical applications can be drawn. Some attempts have been made through chemical or nutritional means (e.g., indomethacin, glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune changes after intensive exercise to lower the risk of infection. No consistent relationship between nutritional interventions, exercise immunology, and alteration in URTI risk has yet been established.",
"title": "Is infection risk linked to exercise workload?"
},
{
"docid": "MED-3179",
"text": "OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.",
"title": "Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study."
},
{
"docid": "MED-4972",
"text": "Heterocyclic amines (HCAs), compounds formed when meat is cooked at high temperatures particularly through pan frying, grilling, or barbequing, pose a potential carcinogenic risk to the public. It is unclear whether there is any level at which consumption of HCAs can be considered safe. Efforts to measure these compounds mainly include cooking studies under laboratory conditions and some measurement of home-cooked foods, but analysis of commercially cooked foods has been minimal. Attempts to estimate exposure of the public to these compounds must take into consideration dining outside the home, which could result in significant exposure for some individuals. We surveyed at least 9 locations each of 7 popular chain restaurants (McDonald's, Burger King, Chick-fil-A, Chili's, TGI Friday's, Outback Steakhouse, and Applebee's) in California, collecting one or two entrees from each location. Entrees were analyzed for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using high-performance liquid chromatography tandem mass spectrometry. All 100 samples contained PhIP. Concentrations were variable within and between entrees and ranged from 0.08 to 43.2 ng/g. When factoring in the weight of the entrees, absolute levels of PhIP reached over 1,000 ng for some entrees. Potential strategies for reducing exposure include the avoidance of meats cooked using methods that are known to form PhIP.",
"title": "Detection of PhIP in grilled chicken entrées at popular chain restaurants throughout California."
},
{
"docid": "MED-5133",
"text": "We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.",
"title": "[Floppy baby with macrocytic anemia and vegan mother]."
},
{
"docid": "MED-1851",
"text": "The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.",
"title": "Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link?"
},
{
"docid": "MED-3523",
"text": "Melatonin, which is contained in certain vegetables, may have an influence on circulatory melatonin concentrations. This study examined the effects of the consumption of vegetables on 6-sulfatoxymelatonin concentrations in morning urine. Ninety-four healthy women aged 24-55 were recruited through a city public health center in Japan. The women randomly allocated to the intervention group were requested to consume high amounts of six selected vegetables, with a target of 350 g/day for 65 days, while those in the control group were asked to avoid the same six vegetables during the same period. First-void morning urine was collected before and at the end of the intervention period, and creatinine-adjusted 6-sulfatoxymelatonin concentrations were measured. At the end of the intervention period, daily mean intake of melatonin from the six vegetables was 1288.0 ng in the intervention group and 5.3 ng in the control group. In the intervention group, the mean concentration of 6-sulfatoxymelatonin changed from 48.1 [95% confidence interval (CI): 40.4-57.2] ng/mg creatinine to 49.6 (95% CI: 42.8-57.3) ng/mg creatinine across the intervention period. In the control group, the mean concentration of 6-sulfatoxymelatonin changed from 55.5 (95% CI: 48.7-63.2) ng/mg creatinine to 50.8 (95% CI: 44.0-58.7) ng/mg creatinine across the intervention period. A comparison of the two groups with regard to the changes in the 6-sulfatoxymelatonin concentrations across the intervention period showed a significant difference (P = 0.03). The results indicate that increased consumption of vegetables raises circulatory melatonin concentrations.",
"title": "Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration."
},
{
"docid": "MED-4511",
"text": "BACKGROUND: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. METHODS: Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. RESULTS: 49 subjects were tested. Most subjects (10th to 90th percentile) had followed this diet 23-49 months. 6 subjects had serum B12 concentrations <147 pmol/l (200 pg/ml). 37 subjects (76%) had serum B12 concentrations <221 pmol/l (300 pg/ml). 23 subjects (47%) had abnormal urinary MMA concentrations above or equal to 4.0 microg/mg creatinine. Sublingual cyanocobalamin and nutritional yeast, but not probiotic supplements, significantly reduced group mean MMA concentrations (tablet p < 0.01; yeast p < 0.05, probiotic > 0.20). CONCLUSIONS: The urinary MMA assay is effective for identifying early metabolic cobalamin deficiency. People following the Hallelujah diet and other raw-food vegetarian diets should regularly monitor their urinary MMA levels, consume a sublingual cobalamin supplement, or consume cobalamin in their food.",
"title": "Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements."
},
{
"docid": "MED-5272",
"text": "Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.",
"title": "Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial..."
},
{
"docid": "MED-1333",
"text": "New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.",
"title": "Insulin secretion as a determinant of pancreatic cancer risk."
},
{
"docid": "MED-3177",
"text": "Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.",
"title": "Neurocysticercosis: the enigmatic disease."
},
{
"docid": "MED-1540",
"text": "A number of studies have evaluated the health of vegetarians. Others have studied the health effects of foods that are preferred or avoided by vegetarians. The purpose of this review is to look critically at the evidence on the health effects of vegetarian diets and to seek possible explanations where results appear to conflict. There is convincing evidence that vegetarians have lower rates of coronary heart disease, largely explained by low LDL cholesterol, probable lower rates of hypertension and diabetes mellitus, and lower prevalence of obesity. Overall, their cancer rates appear to be moderately lower than others living in the same communities, and life expectancy appears to be greater. However, results for specific cancers are much less convincing and require more study. There is evidence that risk of colorectal cancer is lower in vegetarians and in those who eat less meat; however, results from British vegetarians presently disagree, and this needs explanation. It is probable that using the label “vegetarian” as a dietary category is too broad and that our understanding will be served well by dividing vegetarians into more descriptive subtypes. Although vegetarian diets are healthful and are associated with lower risk of several chronic diseases, different types of vegetarians may not experience the same effects on health.",
"title": "Vegetarian diets: what do we know of their effects on common chronic diseases?"
},
{
"docid": "MED-4327",
"text": "Hyperphosphatemia and hyperparathyroidism, frequently observed in patients with endstage renal disease, are associated with renal osteodystrophy, organ calcification, cardiovascular disease and sudden death. Restriction of dietary protein and phosphorus is beneficial in slowing the progression of renal failure. Dietary phosphorus restriction must be prescribed at all stages of renal failure in adults. It may be achieved by decreasing protein intake and avoiding foods rich in phosphorus. An average of 60-80% of the phosphorus intake is absorbed in the gut in dialysis patients. If phosphate binders are employed, the phosphorus absorbed from the diet may be reduced to 40%. Conventional hemodialysis with a high-flux, high-efficiency dialyzer removes approximately 30 mmol (900 mg) phosphorus during each dialysis performed three times weekly. Therefore, 750 mg of phosphorus intake should be the critical value above which a positive balance of phosphorus may occur. This value corresponds to a protein diet of 45-50 g/day or 0.8 g/kg body weight/day for a 60 kg patient. Target levels should become 9.2-9.6 mg/dl for calcium, 2.5-5.5 mg/dl for phosphorus, <55 mg2/dl2 for the calcium-phosphorus product, and 100-200 pg/ml for intact parathyroid hormone.",
"title": "Phosphate restriction in diet therapy."
}
] |
41001
|
Abraham Lincoln lost a Senate race to Stephen A. Douglas.
|
[
{
"docid": "Abraham_Lincoln",
"text": "Abraham Lincoln ( -LSB- ˈeɪbrəhæm_ˈlIŋkən -RSB- February 12 , 1809 -- April 15 , 1865 ) was an American politician and lawyer who served as the 16th President of the United States from March 1861 until his assassination in April 1865 . Lincoln led the United States through its Civil War -- its bloodiest war and perhaps its greatest moral , constitutional , and political crisis . In doing so , he preserved the Union , paved the way to the abolition of slavery , strengthened the federal government , and modernized the economy . Born in Hodgenville , Kentucky , Lincoln grew up on the western frontier in Kentucky and Indiana . Largely self-educated , he became a lawyer in Illinois , a Whig Party leader , and was elected to the Illinois House of Representatives , in which he served for eight years . Elected to the United States House of Representatives in 1846 , Lincoln promoted rapid modernization of the economy through banks , tariffs , and railroads . Because he had originally agreed not to run for a second term in Congress , and because his opposition to the Mexican -- American War was unpopular among Illinois voters , Lincoln returned to Springfield and resumed his successful law practice . Reentering politics in 1854 , he became a leader in building the new Republican Party , which had a statewide majority in Illinois . In 1858 , while taking part in a series of highly publicized debates with his opponent and rival , Democrat Stephen A. Douglas , Lincoln spoke out against the expansion of slavery , but lost the U.S. Senate race to Douglas . In 1860 , Lincoln secured the Republican Party presidential nomination as a moderate from a swing state . Though he gained very little support in the slaveholding states of the South , he swept the North and was elected president in 1860 . Lincoln 's victory prompted seven southern slave states to form the Confederate States of America before he moved into the White House -- no compromise or reconciliation was found regarding slavery and secession . Subsequently , on April 12 , 1861 , a Confederate attack on Fort Sumter inspired the North to enthusiastically rally behind the Union . As the leader of the moderate faction of the Republican Party , Lincoln confronted Radical Republicans , who demanded harsher treatment of the South , War Democrats , who called for more compromise , anti-war Democrats ( called Copperheads ) , who despised him , and irreconcilable secessionists , who plotted his assassination . Politically , Lincoln fought back by pitting his opponents against each other , by carefully planned political patronage , and by appealing to the American people with his powers of oratory . His Gettysburg Address became an iconic endorsement of the principles of nationalism , republicanism , equal rights , liberty , and democracy . Lincoln initially concentrated on the military and political dimensions of the war . His primary goal was to reunite the nation . He suspended habeas corpus , leading to the controversial ex parte Merryman decision , and he averted potential British intervention in the war by defusing the Trent Affair in late 1861 . Lincoln closely supervised the war effort , especially the selection of top generals , including his most successful general , Ulysses S. Grant . He also made major decisions on Union war strategy , including a naval blockade that shut down the South 's normal trade , moves to take control of Kentucky and Tennessee , and using gunboats to gain control of the southern river system . Lincoln tried repeatedly to capture the Confederate capital at Richmond ; each time a general failed , Lincoln substituted another , until finally Grant succeeded . As the war progressed , his complex moves toward ending slavery included the Emancipation Proclamation of 1863 ; Lincoln used the U.S. Army to protect escaped slaves , encouraged the border states to outlaw slavery , and pushed through Congress the Thirteenth Amendment to the United States Constitution , which permanently outlawed slavery . An exceptionally astute politician deeply involved with power issues in each state , Lincoln reached out to the War Democrats and managed his own re-election campaign in the 1864 presidential election . Anticipating the war 's conclusion , Lincoln pushed a moderate view of Reconstruction , seeking to reunite the nation speedily through a policy of generous reconciliation in the face of lingering and bitter divisiveness . On April 14 , 1865 , five days after the surrender of Confederate commanding general Robert E. Lee , Lincoln was assassinated by John Wilkes Booth , a Confederate sympathizer . Lincoln has been consistently ranked both by scholars and the public as among the greatest U.S. presidents .",
"title": ""
}
] |
[
{
"docid": "L/D",
"text": "L/D may refer to : Learning and development , in human resource management Lift-to-drag ratio , in aerodynamics Lincoln -- Douglas debates , a series of seven debates in 1858 between Abraham Lincoln , the Republican candidate for the Senate in Illinois , and Senator Stephen Douglas , the Democratic Party candidate",
"title": ""
},
{
"docid": "United_States_Senate_elections,_1858_and_1859",
"text": "The United States Senate elections of 1858 and 1859 were elections which had the Republican Party gain five additional seats in the United States Senate , but the Democrats retained their majority . That majority would erode in 1860 with the secession of the southern states leading up to the Civil War . In Illinois , incumbent Stephen A. Douglas ( D ) and challenger Abraham Lincoln held a series of seven debates , known as the `` Lincoln -- Douglas debates . '' As this election was prior to ratification of the seventeenth amendment , Senators were chosen by State legislatures .",
"title": ""
},
{
"docid": "Abraham_Lincoln's_Peoria_speech",
"text": "Abraham Lincoln 's Peoria speech was made in Peoria , Illinois on October 16 , 1854 . The speech , with its specific arguments against slavery , was an important step in Abraham Lincoln 's political ascension . The 1854 Kansas-Nebraska Act , written to form the territories of Kansas and Nebraska , was designed by Stephen A. Douglas , then the chairman of the Senate Committee on Territories . The Act included language that allowed settlers to decide whether they would or would not accept slavery in their region . Lincoln saw this as a repeal of the 1820 Missouri Compromise which had outlawed slavery above the 36 ° 30 ' parallel .",
"title": ""
},
{
"docid": "Pardon_Tillinghast",
"text": "Pardon Tillinghast ( 1625 -- 1718 ) was an early settler of Providence , Rhode Island , a public official there , and a pastor of the Baptist Church of Providence . A cooper by profession , he immigrated to New England about 1645 , and became a successful merchant . Later in life he became a clergyman , serving without compensation for nearly four decades . He died in 1718 aged about 96 , and was buried in a family cemetery on Benefit Street in Providence that remains extant . Among his thousands of descendants are many of great prominence , including Continental Congress delegate Samuel Ward ; Julia Ward Howe who wrote the Battle Hymn of the Republic ; and Stephen Arnold Douglas who was involved in a series of famed debates with Abraham Lincoln in 1858 , prior to a Senate race , and later lost to him in the 1860 presidential election .",
"title": ""
},
{
"docid": "The_Lincoln–Douglas_Debates_(1994_reenactments)",
"text": "The 1994 reenactments of the Lincoln -- Douglas Debates took place between August 20 and October 15 , 1994 and were facilitated and aired by C-SPAN . They featured historical reenactors presenting , in their entireties , the series of seven debates between Abraham Lincoln and Stephen A. Douglas that took place during the 1858 U.S. Senate campaign in Illinois . The debate reenactments were held in the same seven cities as were the 1858 debates , and were performed on dates very close to the anniversaries of the original debates . They were broadcast live on C-SPAN , and have been rebroadcast periodically ever since .",
"title": ""
},
{
"docid": "1860_Republican_National_Convention",
"text": "The 1860 Republican National Convention , also known as the 2nd Republican National Convention , was a nominating convention of the Republican Party of the United States , held in Chicago , Illinois , from May 16 to 18 , 1860 . The gathering nominated former U.S. Representative Abraham Lincoln of Illinois for President of the United States and Senator Hannibal Hamlin of Maine for Vice President . Lincoln 's nomination was a surprise , as the favorite before the convention had been former Governor of New York and U.S. Senator William H. Seward . Lincoln 's campaign manager , David Davis , is credited for Lincoln 's victory over Thurlow Weed , Seward 's campaign manager . Lincoln-Hamlin went on to defeat three other major tickets that year , including Democratic nominee Stephen A. Douglas , U.S. Senator from Illinois .",
"title": ""
},
{
"docid": "Stephen_A._Douglas",
"text": "Stephen Arnold Douglas ( April 23 , 1813 -- June 3 , 1861 ) was an American politician from Illinois and the designer of the Kansas -- Nebraska Act . He was a U.S. representative , a U.S. senator , and the Democratic Party nominee for president in the 1860 election , losing to Republican Abraham Lincoln . Douglas had previously defeated Lincoln in a Senate contest , noted for the famous Lincoln-Douglas debates of 1858 . He was nicknamed the `` Little Giant '' because he was short in physical stature , but a forceful and dominant figure in politics . ( His height is given in various sources as being in the range of 5 ft to 5 ft ; five feet four is reported most often . ) Douglas was well known as a resourceful party leader , and an adroit , ready , skillful tactician in debate and passage of legislation . He was a champion of the Young America movement which sought to modernize politics and replace the agrarian and strict constructionist orthodoxies of the past . Douglas was a leading proponent of democracy , and believed in the principle of popular sovereignty : that the majority of citizens should decide contentious issues such as slavery and territorial expansion . As chairman of the Committee on Territories , Douglas dominated the Senate from 1850 to 1859 . He was largely responsible for the Compromise of 1850 that apparently settled slavery issues ; however , in 1854 he reopened the slavery question with the Kansas -- Nebraska Act , which opened some previously prohibited territories to slavery under popular sovereignty . Opposition to this led to the formation of the Republican Party . Douglas initially endorsed the Dred Scott decision of 1857 . But during the 1858 Senate campaign , he argued its effect could be negated by popular sovereignty . He also opposed the efforts of President James Buchanan and his Southern allies to enact a Federal slave code and impose the Lecompton Constitution on Kansas . In 1860 , the conflict over slavery led to the split in the Democratic Party in the 1860 Convention . Hardline pro-slavery Southerners rejected Douglas , and nominated their own candidate , Vice President John C. Breckinridge , while the Northern Democrats nominated Douglas . Douglas deeply believed in democracy , arguing the will of the people should always be decisive . When civil war came in April 1861 , he rallied his supporters to the Union cause with all his energies , but he died of typhoid fever a few weeks later .",
"title": ""
},
{
"docid": "Archibald_Williams_(judge)",
"text": "Archibald Williams ( June 10 , 1801 -- September 21 , 1863 ) was a United States federal judge . Born in Montgomery County , Kentucky , Williams read law to enter the bar in 1828 . He was in private practice in Quincy , Illinois beginning in 1829 . He was the United States Attorney for the District of Illinois from 1849 to 1853 . He served in both the Illinois House of Representatives and the Illinois State Senate . On March 8 , 1861 , Williams was nominated by President Abraham Lincoln to a new seat on the United States District Court for the District of Kansas created by 12 Stat . 126 . He was confirmed by the United States Senate on March 12 , 1861 , and received his commission the same day . Williams served in that capacity until his death , in 1863 , in Quincy , Illinois . Archibald Williams 's historical significance was based on his close friendship with Abraham Lincoln , the 16th President of the United States , who issued the Emancipation Proclamation freeing the slaves . Lincoln was from Springfield , Illinois , and Williams was from Quincy , Illinois , a port city on the Mississippi River along the western border of the state . The two men were close political allies in the Whig Party and , later on , in the newly founded Republican Party . They first met when serving in the Illinois state legislature in the early 1830 's . They were compatriots for 29 years . Archibald Williams led the life of a political party workhorse , first for the Whig Party and then the Republicans . He served in the Illinois state legislature , made two unsuccessful runs for the U.S. Senate as a Whig , played a leading role at the Illinois state Constitutional Convention of 1847 , chaired many important political meetings in Quincy , Illinois , attended many state political party conventions , made an unsuccessful run for the U.S. House of Representatives , and in 1858 campaigned in Illinois for his friend Abraham Lincoln . In all recorded instances , Archibald Williams gave Abraham Lincoln his true and unwavering support . Archibald Williams died in 1863 . By that time , Abraham Lincoln was President of the United States and the leader of the Northern states during the American Civil War . Birth and Early Life Archibald Williams was born in Montgomery County , Kentucky , on June 10 , 1801 . He was the son of John Williams and Amelia Gill Williams . He grew up in Kentucky , qualified to be a lawyer in the neighboring state of Tennessee , and then moved west with some of his brothers and sisters to Quincy , Illinois . As a young attorney , he rode circuit , going from county court to county court arguing legal cases . He was particularly noted for taking cases on appeal , and he argued many cases before the Illinois state Supreme Court . He married Nancy Kemp , who also had come from Kentucky , on July 28 , 1831 . They had nine children , but only five grew up to be adults . For several months in early 1832 he served as a volunteer in the Black Hawk War against Native Americans . In the fall of 1832 he strongly supported Henry Clay for President of the United States . At the Illinois State Legislature Archibald Williams was elected to the Illinois state Senate in 1832 . He studied and reported on School Financing to the state Senate , arguing for local control of schools rather than establishing a statewide system . Later in his legislative career , he labeled the Illinois Internal Improvements program `` Infernal Improvements '' due to its financial difficulties leading to bankruptcy . Abraham Lincoln was elected to the state legislature in 1834 . Archibald Williams and Lincoln became good friends and both subsequently joined the Whig Party . Lincoln was said to have seen Archibald Williams as a great `` reasoner . '' The two men were described as `` sitting next to each other in the southeast corner of the statehouse . '' It was noted : `` Lincoln did not hesitate to consult Williams at all times , and the two men were often associated in legal work . '' Twice the Whig Candidate for U.S. Senator Archibald Williams ran for the United States Senate as a Whig in 1836 and in 1842 . At those times the selection of U.S. senators was made by both houses of the state legislature . Lincoln voted for Archibald Williams the first time he ran for U.S. Senator in 1836 . The second time Archibald Williams ran , in 1842 , Lincoln was no longer in the state legislature and thus could not vote for his friend . In both instances , Archibald Williams was not elected . Witnessed Abraham Lincoln 's Admission to U.S. Courts Abraham Lincoln was admitted to practice law in the United States Circuit Court on December 3 , 1839 . U.S Court Judge Nathaniel Pope presided over the ceremony . A Quincy , Illinois , newspaper noted that Archibald Williams was present at the ceremony . Presided Over Whig Party State Conventions in Illinois Archibald Williams presided over a Whig Party state convention meeting in Springfield , Illinois , in 1843 . Abraham Lincoln attended the convention and was elected a Whig Party presidential elector for the 1844 presidential election . Unfortunately for the Whigs , Democrat James K. Polk of Tennessee won the presidential election . In June of 1844 , Archibald Williams was elected president of an Illinois state Whig Party convention in Peoria , Illinois . Abraham Lincoln spoke to the convention in support of the United States charging higher tariffs on imported goods , a major Whig position at the time . Supported African Colonization of Freed Slaves Along with Abraham Lincoln , Archibald Williams in the 1840 's supported the African colonization of freed slaves by joining the Illinois colonization society . Although opposed to slavery , both men believed Southerners should be allowed to keep their slaves but also should be urged to free their slaves voluntarily and return them to Africa . This was thought to be a reasonable and non-coercive solution to the slavery problem . The Mormon Problem in Illinois Joining with his friend and fellow Quincy lawyer Orville Browning , Archibald Williams in 1840 helped to defend Mormon leader Joseph Smith from being extradited to Missouri to face possible execution for alleged crimes . Joseph Smith was the founder of the Church of Latter Day Saints ( Mormons ) , and he and his church were unpopular because of the voting power of his supporters and their belief in men having multiple wives . Thanks to Browning 's and Williams 's arguments in court , Smith was not extradited to Missouri but remained in Illinois and founded a Mormon colony at Nauvoo , Illinois . Four years later , in 1844 , Smith and his brother Hyrum were murdered by a mob while incarcerated in the jail at Carthage , Illinois . Williams and Browning switched sides and helped to defend in court the accused murderers of Joseph and Hyrum Smith . The murderers were all found not-guilty . Shortly afterward , Archibald Williams chaired a meeting in Quincy , Illinois , that sought to arrange for a peaceful departure of the Mormons from Illinois to the far western state of Utah . Archibald Williams appointed a delegation of Quincy citizens that traveled to Nauvoo and convinced the new Mormon leader , Brigham Young , to leave Illinois for Utah in an orderly manner . Brigham Young said the Mormons could not leave immediately , but when `` grass grows and water runs , '' both signs of spring . The following spring the Mormons peacefully left Illinois for Utah , traveling mainly by wagon train . The Illinois Constitutional Convention of 1847 Archibald Williams was elected to the Illinois state Constitutional Convention of 1847 as a Whig . The convention met in the state capitol in Springfield , Illinois , and proceeded to write an improved state constitution . Williams was elected in a Democratic district against a Democratic candidate . Although the Democrats had a majority of the delegates to the convention , the Whigs could break away Democratic votes when they needed them and ended up dominating the convention . A historian noted : `` James W. Singleton of Mount Sterling , Archibald Williams of Quincy , and David M. Woodson of Carrollton aggressively upheld the Whig cause against the attacks of various capable Democratic opponents . '' At the constitutional convention , Archibald Williams and the Whig Party supported the rights of property , strict voting requirements in state elections , and allowing the state legislature to override the governor 's veto by a majority vote rather than a two-thirds vote . Two issues were sent to the state 's voters - one calling for the creation of an Illinois state bank and the other limiting the immigration into Illinois of freed slaves from the slave states . The voters of Illinois rejected the idea of an Illinois state bank but approved limiting the immigration of freed slaves . Archibald Williams gave a major speech at the constitutional convention opposing the idea that the Illinois Supreme Court should meet at various locations throughout the state rather than only in the state capital of Springfield . After the constitutional convention adjourned , the voters of Illinois approved the new constitution by a ratio of almost 4 to 1 . The Constitutional Convention of 1847 was a landmark in the legal and political career of Archibald Williams . He succeeded in furthering the ideals and policies of the Whig Party against stiff Democratic Party opposition . He was three months in Springfield , the state capital , meeting and working with many of the leading politicians and government officials from throughout the state . It helped to make him a significant figure in Illinois political and governmental history . The `` Lincoln Letter '' to Archibald Williams In the 1848 presidential election , Abraham Lincoln was backing General Zachary Taylor , a Mexican War hero , for the Whig Party nomination . A problem developed when Orville H. Browning , a Whig Party leader in Quincy , Illinois , supported the nomination of past Whig Party favorite Henry Clay . On April 30 , 1848 , Abraham Lincoln wrote a letter to Archibald Williams urging him to support Zachary Taylor and , if possible , also enlist the support of Browning . The letter read : Washington , April 30 , 1848 Dear Williams , I have not seen in the papers and evidence of a movement to send a delegate from your circuit to the June convention - I wish to say that I think it all important that a delegate should be sent - Mr. Clay 's chance for election is just no chance at all . He might get New York , and that would have elected in 1844 but it will not now ; because he must now at the least , have Tennessee , which he had then and , in addition , the fifteen new votes of Florida , Texas , Iowa , and Wisconsin . I know that our good friend Browning is a great admirer of Mr. Clay , and I therefore fear he is favoring his nomination . If he is , ask him to discard feeling , and try if he can possibly , as a matter of judgement , count the votes necessary to elect him . In my judgment , we can elect nobody but Gen. Taylor , and we can not elect him without a nomination - Therefore do n't fail to send a delegation - Your friend as ever , A. Lincoln This letter demonstrates the close friendship and easygoing familiarity between Abraham Lincoln and Archibald Williams . It also reveals Lincoln 's developing skills as an up and coming Illinois politician . It is not known whether Archibald Williams prevailed on Orville Browning to support Zachary Taylor for the Whig nomination for president in 1848 . What is known is that Zachary Taylor not only gained the Whig Party nomination but also won the presidency . Named U.S. District Attorney for Illinois Once in the White House in Washington , D.C. , newly elected President Zachary Taylor appointed Archibald Williams the United States District Attorney for the state of Illinois . Abraham Lincoln had sent the following letter in support of Williams 's nomination : Washington , March 8 , 1849 Hon : John M. Clayton Secretary of State Dear Sir : We Recommend that Archibald Williams , of Quincy , Illinois , be appointed U.S. District Attorney for the District of Illinois , when that office shall become vacant . Your Obt . Servts . A. Lincoln As U.S. District Attorney for Illinois , it was Archibald Williams 's job to prosecute cases in the U.S. District Court . The job became more difficult for Williams in 1850 when Congress enacted the Compromise of 1850 , which included a new Fugitive Slave Law . This law required Williams , in his role as U.S. District Attorney , to oversee the capture of runaway slaves and their return to their owners in the South . Williams was opposed to slavery personally but , in the 1850 's , acknowledged the right of slave owners in the South to keep their slaves . He fully discharged his duties under the Fugitive Slave Act . Death of Nancy Kemp Williams Archibald Williams 's wife , Nancy Kemp Williams , died on March 16 , 1854 , giving birth to a daughter , Nancy Williams . The baby survived the birth and lived to be an adult . Archibald and Nancy Williams had been married for 22 years . Candidate for the U.S. House of Representatives in 1854 In the early 1850 's , U.S. Senator Stephen Douglas of Illinois sought the adoption of the Kansas and Nebraska acts . The bills provided for Kansas and Nebraska to become territories with provision for `` popular sovereignty , '' the idea that the citizens of each new territory would be allowed to vote on whether the territory should be slave or free . This produced a sharp reaction on the part of those opposed to slavery in the territories , because the Missouri Compromise of 1820 had stated that the lands that comprised Kansas and Nebraska should be free territory , not slave territory . The result was the anti-Nebraska movement , which opposed popular sovereignty for Nebraska on the grounds that the citizens of the territory might vote for slavery and thereby spread slavery further into the territories . Archibald Williams and Abraham Lincoln both became anti-Nebraska men . For his part , Archibald Williams ran for the U.S. House of Representatives in 1854 on a strong anti-Nebraska platform . Williams was running against incumbent Democratic Representative William A. Richardson , a formidable opponent . The U.S. House district that comprised Quincy , Illinois , was strongly Democratic . On the other hand , Richardson was a close political ally of Stephen Douglas and had strongly backed popular sovereignty for Nebraska in the U.S. House . Williams and his supporters hoped the wave of anti-Nebraska sentiment sweeping the northern states might just be strong enough to defeat Richardson , despite the strong Democratic voting tendency of the House district . On October 31 , 1854 , Abraham Lincoln arrived in Quincy , Illinois , to give a speech in support of Archibald Williams 's candidacy for the U.S. House of Representatives . It took two days for him to travel by railroad and stagecoach to Quincy . In a letter to a friend and political ally , Lincoln wrote : `` I am here now going to Quincy , to try to give Mr. -LSB- Archibald -RSB- Williams a little life . '' Even with Abraham Lincoln 's help , Archibald Williams lost the election to William Richardson . The overall election was a success for the anti-Nebraska movement , however , as the anti-Nebraska forces won enough seats to gain a majority in the U.S. House of Representatives . After 1854 , Archibald Williams and Abraham Lincoln and other anti-Nebraskans took the lead in forming the Republican Party in Illinois around the issue of `` no slavery in the territories . '' An Archibald Williams Committee Influences Lincoln Abraham Lincoln wrote a letter in which he said he was ready to `` fuse '' with other anti-slavery groups according to `` principles '' adopted at a public meeting in Quincy , Illinois . The purpose of fusion was to bring many disparate anti-slavery groups together to form the Republican Party . Lincoln 's letter noted that the principles had been drawn up by a three-person committee led `` by Mr. Archibald Williams . '' The principles centered on the idea that Southern slave owners could keep their slaves but that slavery would be forbidden in the territories . Archibald Williams and his committee either influenced Lincoln directly on `` fusion , '' or else they confirmed a position on `` fusion '' that Lincoln had already adopted . At the United States Supreme Court Archibald Williams argued a case before the United States Supreme Court on December 6 and 7 , 1855 . Orville Browning , Williams 's good friend from Quincy , Illinois , was the opposing lawyer . The issue in dispute dealt with rival claims for lands and centered on whether the question of `` bad faith '' in the matter should be decided by a judge or by a jury . The Court ruled in Wright v. Mattison that `` bad faith '' should not be decided by the judge but by the jury , which had been the precedent . The Court ordered the case to be retried in a lower court . The outcome was a victory for Browning and a loss for Williams . The Beginnings of the Republican Party in Illinois In 1856 , Archibald Williams was the temporary chairman at a major anti-Nebraska convention in Bloomington , Illinois . Williams led the convention until a permanent chairman had been elected . While attending the convention , Abraham Lincoln and Archibald Williams slept in the same bed at the Bloomington home of David Davis , a close friend of both men.A historian noted : `` At Bloomington , Lincoln , Archibald Williams , his old associate in the Legislature , -LSB- and -RSB- T. Lyle Dickey , of Ottawa -LSB- Illinois -RSB- , a good lawyer , went to -LSB- David -RSB- Davis 's house and lived there during the Convention . Lincoln and Williams slept in one bed and Dickey and Whitney in another ... The course of the historic Bloomfield Convention was decisively influenced by the counsels that came from the steady men in the Davis House . '' Although the name `` Republican '' was applied at a later date , the anti-Nebraska convention in Bloomington was considered the birthplace of the Republican Party in Illinois . The Election of 1858 In 1858 , at a state party convention in Springfield , Illinois , Abraham Lincoln was nominated to be the Republican candidate for U.S. Senator from Illinois . A resolution passed at the convention stated that Lincoln `` was the first and only choice of the Republicans of Illinois for the U.S. Senate . '' In the famous Lincoln-Douglas debates in the 1858 Illinois U.S. Senate race , Democratic candidate Stephen Douglas attacked Lincoln three times for having been described as `` the first and only choice '' of Illinois Republicans for the Senate seat . All three times , Douglas pointed to Archibald Williams as an Illinois Republican who would have been an acceptable alternate choice to Lincoln in that contest . Archibald Williams traveled and spoke throughout the state of Illinois in Lincoln 's behalf during the 1858 U.S. Senate race . A newspaper in Quincy , Illinois , allied with the Republican Party , printed : `` Old Archie Williams is doing good service for the Republican cause ... He has already spoken at Macomb , Oquawka , Monmouth , Cameron , Galesburg , and other points ... to large assemblages ; and everywhere , he has created enthusiasm and confidence among our friends and animated the lukewarm ... In the winter of his life ... Mr. Williams is found battling for the cause of Republicanism . '' The Illinois state legislature chose Stephen Douglas over Abraham Lincoln in the 1858 U.S. Senate race . A close friend of Lincoln 's wrote : `` In January , 1859 , while the Democrats were celebrating the election of Stephen A. Douglas to the United States Senate , Archibald Williams ... came into Lincoln 's office and finding him writing said : ` Well , the Democrats are making a great noise over their victory . ' Looking up Lincoln replied : ` Yes , Archie , Douglas has taken this trick , but the game is not played out . ' '' The Lincoln-Douglas debates became so well-known that Lincoln gave personally signed presentation copies of the debates to his best friends and political associates . The one given to Archibald Williams was inscribed in Lincoln 's handwriting : `` To Hon : Archibald Williams , with respects of A. Lincoln . '' It was one more sign of Lincoln 's close friendship and strong political alliance with Archibald Williams . The Presidential Election of 1860 On December 25 , 1859 , a number of leading Republicans in Quincy , Illinois , including Archibald Williams , met with Horace Greeley , a prominent national journalist and editor of the New York Tribune . Greeley had famously stated `` Go west , young man . Go west ! '' Williams and the other Quincy Republicans talked to Greeley about Abraham Lincoln possibly becoming the Republican candidate for President in 1860 . Archibald Williams spoke throughout Illinois in behalf of Abraham Lincoln during Lincoln 's successful 1860 campaign for the White House in Washington , D.C. Almost on the Supreme Court , Then U.S. District Judge in Kansas Following his election to the U.S. presidency in 1860 , Abraham Lincoln offered Archibald Williams a seat on the U.S. Supreme Court . Williams refused the offer due to ill health and advanced age . Williams recommended that Lincoln appoint a younger court nominee who could live for more years and thereby serve longer on the Court . Archibald Williams was then appointed by President Lincoln to be the Judge for the U.S. District Court of Kansas . Williams was the first person to hold the office of U.S. District Court Judge in Kansas , because Kansas had just been admitted to the Union as a state . Williams moved to Topeka , Kansas , the state capital , where he served more than two years as U.S. Judge . He moved back to Quincy , Illinois , shortly before his death on September 21 , 1863 . During his tenure as the U.S. District Court Judge for Kansas , Archibald Williams worked on such issues as building a branch of the transcontinental railroad across Kansas , fair treatment of Native Americans in railroad matters , and the loyalty to the Union cause of a U.S. Army officer stationed in Kansas . Also while in Kansas , Williams married his second wife , Ellen M. Parker , on September 24 , 1861 . The marriage lasted a little less than two years until Archibald Williams death . While serving as the U.S. Judge for Kansas , Archibald Williams traveled to Washington , D.C. , and , on May 29 , 1962 , paid a last visit to his old friend Abraham Lincoln in the White House . Death and Burial of Archibald Williams Archibald Williams was praised in obituaries as a leading attorney in Illinois in the mid-19th Century . His many political and governmental activities were noted , along with his deep friendship with Abraham Lincoln . The bar association in Quincy , Illinois , donated a large marble grave marker for Williams . The base of the marker was a stack of law books ; an obelisk was placed on top of the law books . He was buried in Woodland Cemetery in Quincy , Illinois , at a grave site that overlooks the Mississippi River .",
"title": ""
},
{
"docid": "Lincoln–Douglas_debates",
"text": "The Lincoln -- Douglas Debates ( also known as The Great Debates of 1858 ) were a series of seven debates between Abraham Lincoln , the Republican candidate for the United States Senate from Illinois , and incumbent Senator Stephen Douglas , the Democratic Party candidate . At the time , U.S. senators were elected by state legislatures ; thus Lincoln and Douglas were trying for their respective parties to win control of the Illinois legislature . The debates previewed the issues that Lincoln would face in the aftermath of his victory in the 1860 presidential election . Although Illinois was a free state , the main issue discussed in all seven debates was slavery in the United States . In agreeing to the official debates , Lincoln and Douglas decided to hold one debate in each of the nine congressional districts in Illinois . Because both had already spoken in two -- Springfield and Chicago -- within a day of each other , they decided that their `` joint appearances '' would be held only in the remaining seven districts . The debates were held in seven towns in the state of Illinois : Ottawa on August 21 Freeport on August 27 Jonesboro on September 15 Charleston on September 18 Galesburg on October 7 Quincy on October 13 Alton on October 15 The debates in Freeport , Quincy and Alton drew especially large numbers of people from neighboring states , as the issue of slavery was of monumental importance to citizens across the nation . Newspaper coverage of the debates was intense . Major papers from Chicago sent stenographers to create complete texts of each debate , which newspapers across the United States reprinted in full , with some partisan edits . Newspapers that supported Douglas edited his speeches to remove any errors made by the stenographers and to correct grammatical errors , while they left Lincoln 's speeches in the rough form in which they had been transcribed . In the same way , pro-Lincoln papers edited Lincoln 's speeches , but left the Douglas texts as reported . After losing the election for Senator in Illinois , Lincoln edited the texts of all the debates and had them published in a book . The widespread coverage of the original debates and the subsequent popularity of the book led eventually to Lincoln 's nomination for President of the United States by the 1860 Republican National Convention in Chicago . The format for each debate was : one candidate spoke for 60 minutes , then the other candidate spoke for 90 minutes , and then the first candidate was allowed a 30-minute `` rejoinder . '' The candidates alternated speaking first . As the incumbent , Douglas spoke first in four of the debates .",
"title": ""
},
{
"docid": "United_States_presidential_election_in_California,_1860",
"text": "In the 1860 United States presidential election , California narrowly voted for the Republican nominee , former Illinois representative Abraham Lincoln , over the Democratic nominee , Illinois Senator Stephen A. Douglas and the Southern Democratic nominee , Vice President John C. Breckinridge .",
"title": ""
},
{
"docid": "Northern_Democratic_Party",
"text": "The Northern Democratic Party was a leg of the Democratic Party during the 1860 presidential election . It was when the party split in two due to problems with slavery . Stephen A. Douglas was the nominee and lost to Abraham Lincoln . They held two conventions before the election , in Charleston and Baltimore , where they established their platform .",
"title": ""
},
{
"docid": "William_P._Fessenden",
"text": "William Pitt Fessenden ( October 16 , 1806September 8 , 1869 ) was an American politician from the U.S. state of Maine . Fessenden was a Whig ( later a Republican ) and member of the Fessenden political family . He served in the United States House of Representatives and Senate before becoming Secretary of the Treasury under President Abraham Lincoln during the American Civil War . A lawyer , he was a leading antislavery Whig in Maine ; in Congress , he fought the Slave Power ( the plantation owners who controlled southern states ) . He built an antislavery coalition in the state legislature that elected him to the U.S. Senate ; it became Maine 's Republican organization . In the Senate , Fessenden played a central role in the debates on Kansas , denouncing the expansion of slavery . He led Radical Republicans in attacking Democrats Stephen Douglas , Franklin Pierce , and James Buchanan . Fessenden 's speeches were read widely , influencing Republicans such as Abraham Lincoln and building support for Lincoln 's 1860 Republican presidential nomination . During the war , Senator Fessenden helped shape the Union 's taxation and financial policies . He moderated his earlier radicalism , and supported Lincoln against the Radicals , becoming Lincoln 's Treasury Secretary . After the war , Fessenden was back in the Senate , as chair of the Joint Committee on Reconstruction , which established terms for resuming congressional representation for the southern states , and which drafted the Fourteenth Amendment to the United States Constitution . Later , Fessenden provided critical support that prevented Senate conviction of President Andrew Johnson , who had been impeached by the House . He was the first Republican Senator to ring out '' ... not guilty '' followed by six other Republican Senators resulting in the acquittal of President Johnson . He is the only person to have three streets in Portland named for him : William , Pitt and Fessenden streets in the city 's Oakdale neighborhood .",
"title": ""
},
{
"docid": "James_A._McDougall",
"text": "James Alexander McDougall ( November 19 , 1817 -- September 3 , 1867 ) was an American attorney and politician elected to statewide office in two U.S. states , then to the United States House of Representatives and United States Senate . A gifted orator , McDougall began his career as a civil engineer in New York , then read law , rising quickly to heights in his profession in Illinois , where he became a friend of fellow prairie attorneys Abraham Lincoln , Edward D. Baker , and Stephen Douglas . Like many Americans , McDougall was drawn to Gold Rush California in 1849 ; he resumed his law practice and was elected second attorney general for the new state of California . In the election of 1860 , Lincoln won the presidency as a Republican , Baker was elected Republican senator from Oregon , and McDougall was elected senator from California , joining Douglas in the Senate as fellow War Democrats . All three of McDougall 's Prairie State friends would die in the six years before his term as senator expired . A noted drinker , McDougall once gave an address to the Senate disparaging a proposed rule to outlaw the sale of alcohol in the United States Capitol , but died shortly after leaving the Senate , '' ... hastened by his indulgence in the bowl . ''",
"title": ""
},
{
"docid": "Lincoln's_House_Divided_Speech",
"text": "The House Divided Speech was an address given by Abraham Lincoln ( who would later become President of the United States ) on June 16 , 1858 , at what was then the Illinois State Capitol in Springfield , upon accepting the Illinois Republican Party 's nomination as that state 's United States senator . The speech became the launching point for his unsuccessful campaign for the Senate seat held by Stephen A. Douglas ; this campaign would climax with the Lincoln-Douglas debates of 1858 . Lincoln 's remarks in Springfield created an image of the danger of slavery-based disunion , and it rallied Republicans across the North . Along with the Gettysburg Address and his second inaugural address , this became one of the best-known speeches of his career . The best-known passage of the speech is : Lincoln 's goals with this speech were , firstly , to differentiate himself from Douglas , the incumbent ; and secondly , to publicly voice a prophecy for the future . Douglas had long advocated popular sovereignty , under which the settlers in each new territory decided their own status as a slave or free state ; he had repeatedly asserted that the proper application of popular sovereignty would end slavery-induced conflict , and would allow northern and southern states to resume their peaceful coexistence . Lincoln , however , responded that the Dred Scott decision had closed the door on Douglas 's preferred option and left the Union with only two remaining outcomes : the United States would inevitably become either all slave , or all free . Now that the North and the South had come to hold distinct opinions in the question of slavery , and now that this issue had come to permeate every other political question , the time would soon come when the Union would no longer be able to function .",
"title": ""
},
{
"docid": "Miller–Davis_Law_Buildings",
"text": "The Miller -- Davis Law Buildings , known commonly as the Miller Davis Building , are located on Main and Front Street in the McLean County , Illinois city of Bloomington . The law offices served future Supreme Court Justice David Davis and future Illinois State Senator Asahel Gridley . The buildings became a gathering place for local lawyers such as Abraham Lincoln and Stephen A. Douglas .",
"title": ""
},
{
"docid": "Lincoln_Oak",
"text": "The Lincoln Oak was an oak tree in Bloomington , Illinois . Stephen A. Douglas and Abraham Lincoln both gave speeches at the tree during the 1850s . The original Lincoln Oak died in 1976 .",
"title": ""
},
{
"docid": "Lincoln–Douglas_debate",
"text": "Lincoln -- Douglas debate ( commonly abbreviated as LD Debate , or simply LD ) is a type of one-on-one debate practiced mainly in the United States at the high school level . It is sometimes also called values debate because the format traditionally places a heavy emphasis on logic , ethical values , and philosophy ( also called as logos , ethos and pathos ) . The Lincoln -- Douglas Debate format is named for the 1858 Lincoln -- Douglas Debates between Abraham Lincoln and Stephen A. Douglas , because their debates focused on slavery and the morals , values , and logic behind it . LD Debates are used by the National Speech and Debate Association , or NSDA ( formerly known as the National Forensics League , or NFL ) competitions , and also widely used in related debate leagues such as the National Christian Forensics and Communication Association , the National Catholic Forensic League , the National Educational Debate Association , the Texas University Interscholastic League , Texas Forensic Association , Stoa USA and their affiliated regional organizations . The vast majority of tournaments use the current NSDA resolution .",
"title": ""
},
{
"docid": "Joseph_Arnold_(Rhode_Island)",
"text": "Joseph Arnold ( 1710 -- 1776 ) was a pre-revolutionary resident of North Kingstown and Exeter in the Colony of Rhode Island and Providence Plantations . He is most noted for having a very large progeny , having had 16 children of whom 15 grew to maturity , married , and had children of their own , giving him at least 89 grandchildren . He was the great great grandfather of presidential hopeful Stephen Arnold Douglas who debated Abraham Lincoln in 1858 , and lost to him in the 1860 presidential election . He was an ancestral link between Douglas and many prominent early Rhode Islanders such as Governor Benedict Arnold and two founders of the Rhode Island colony , Samuel Wilbore and John Porter .",
"title": ""
},
{
"docid": "Stephen_A._Douglas_Tomb",
"text": "The Stephen A. Douglas Tomb and Memorial or Stephen Douglas Monument Park is located at 636 E. 35th Street in the Bronzeville neighborhood of Chicago , Illinois ( part of the city 's Douglas community ) , near the site of the Union Army and prisoner of war Camp Douglas . A ten-foot statue of the man best remembered for debating Abraham Lincoln over slavery stands atop a 46 ft column of white marble from his native state , Vermont . Douglas died from typhoid fever on June 3 , 1861 in Chicago , where he was buried on the shore of Lake Michigan . The site was afterwards bought by the state of Illinois , and the imposing monument by Leonard Volk was built over his grave . The cornerstone was laid in 1861 and the tomb was completed in 1881 . The site was designated a Chicago Landmark on September 28 , 1977 . The tomb is maintained by the Illinois Historic Preservation Agency as a state historic site .",
"title": ""
},
{
"docid": "United_States_elections,_1860",
"text": "The 1860 United States elections elected the members of the 37th United States Congress . The election took place during the Third Party System , shortly before the start of the Civil War . The Republican Party won control of the Presidency and both houses of Congress , making it the fifth party ( following the Federalist Party , Democratic-Republican Party , Democratic Party , and Whig Party ) to accomplish that feat . The election is widely considered to be a realigning election . In the Presidential election , Republican former Representative Abraham Lincoln of Illinois defeated Democratic Vice President John C. Breckinridge ( who became the first incumbent Vice President to lose a presidential election ) and Democratic Senator Stephen A. Douglas of Illinois , as well as the Constitutional Union candidate , former Senator John Bell of Tennessee . Lincoln swept the Northern states while Breckinridge carried much of the South , foreshadowing the political alignment of the country throughout the Third Party System . At the 1860 Republican National Convention , Lincoln won on third ballot , defeating Senator William H. Seward of New York and several other candidates . The Democratic Party split its votes after three chaotic conventions . Douglas was nominated at the second Democratic convention , while the Southern Democrats nominated Breckinridge as their own candidate in a third convention . Bell ran on a platform of preserving the union regardless of the status of slavery . Lincoln 's victory made him the first Republican President . Lincoln took just under 40 percent of the popular vote , a lower share of the popular vote than any other winning presidential candidate aside from John Quincy Adams 's 1824 campaign . In the House , Republicans retained control of the chamber and won a majority for the first time after several states seceded . Democrats remained the largest minority , but several Congressmen also identified as unionists . In the Senate , Republicans made moderate gains , but won a majority after several states seceded . The Democrats remained the largest minority party , though some Congressmen identified as unionists .",
"title": ""
},
{
"docid": "Abraham_Lincoln_National_Heritage_Area",
"text": "The Abraham Lincoln National Heritage Area is a National Heritage Area in central Illinois telling the story of Abraham Lincoln . A National Heritage Area is a federal-designated area intended to encourage historic preservation and an appreciation of the history and heritage of the site . While National Heritage Areas are not federally owned or managed , the National Park Service provides an advisory role and some technical , planning and financial assistance . The Abraham Lincoln National Heritage Area was created as part of the Consolidated Natural Resources Act of 2008 ( S. 2739 ) , an omnibus bill . It was originally introduced in the Senate by Dick Durbin and in the House of Representatives by Ray LaHood , both from Illinois . The legislation also provided $ 10 million over 10 years , with no more than $ 1 million awarded in any single year , to make federal grants available for preservation , education and economic development . Grants awarded for Lincoln National Heritage Area activities must be matched dollar-for-dollar in state , local or private funds . The management authority for the Abraham Lincoln National Heritage Area is the Looking for Lincoln Heritage Coalition and follows Lincoln 's life from his birth and childhood , to his early life and career , to the Lincoln -- Douglas debates of 1858 . The legislation protects private property rights and would not require any private citizen or entity to be affiliated with the Lincoln Heritage Area . The bill names the Looking for Lincoln Heritage Coalition as the management authority for the National Heritage Area , but does not grant any zoning or land use power to the Coalition . Up to $ 10 million in federal grants would be available under this legislation The Heritage Area includes the following sites : Lincoln Home National Historic Site Lincoln Tomb State Historic Site Lincoln 's New Salem State Historic Site at New Salem , Menard County , Illinois Abraham Lincoln Presidential Library and Museum Lincoln Log Cabin State Historic Site Mount Pulaski Courthouse State Historic Site , Postville Courthouse State Historic Site and Metamora Courthouse State Historic Site Lincoln-Herndon Law Offices State Historic Site David Davis Mansion State Historic Site Vandalia State House State Historic Site Lincoln Douglas Debate Museum Macon County Log Court House Richard James Oglesby Mansion Lincoln Trail Homestead State Memorial John Wood Mansion Beardstown Courthouse Old Main at Knox College Carl Sandburg State Historic Site Bryant Cottage State Historic Site Dr. William Fithian Home Vermilion County Museum",
"title": ""
},
{
"docid": "Abe_Lincoln_in_Illinois_(play)",
"text": "Abe Lincoln in Illinois is a play written by the American playwright Robert E. Sherwood in 1938 . The play , in three acts , covers the life of President Abraham Lincoln from his childhood through his final speech in Illinois before he left for Washington . The play also covers his romance with Mary Todd and his debates with Stephen A. Douglas , and uses Lincoln 's own words in some scenes . Sherwood received the Pulitzer Prize for Drama in 1939 for his work .",
"title": ""
},
{
"docid": "Freeport_Doctrine",
"text": "The Freeport Doctrine was articulated by Stephen A. Douglas at the second of the Lincoln-Douglas debates on August 27 , 1858 , in Freeport , Illinois . Former one-term U.S. Representative Abraham Lincoln was campaigning to take Douglas ' U.S. Senate seat by strongly opposing all attempts to expand the geographic area in which slavery was practiced . Lincoln tried to force Douglas to choose between the principle of popular sovereignty proposed by the Kansas-Nebraska Act ( which left the fate of slavery in a U.S. territory up to its inhabitants ) , and the majority decision of the United States Supreme Court in the case of Dred Scott v. Sandford , which stated that slavery could not legally be excluded from U.S. territories ( since Douglas professed great respect for Supreme Court decisions , and accused the Republicans of disrespecting the court , yet this aspect of the Dred Scott decision was contrary to Douglas ' views and politically unpopular in Illinois ) . Instead of making a direct choice , Douglas ' response stated that despite the court 's ruling , slavery could be prevented from any territory by the refusal of the people living in that territory to pass laws favorable to slavery . Likewise , if the people of the territory supported slavery , legislation would provide for its continued existence . Douglas 's actual words were : The next question propounded to me by Mr. Lincoln is , Can the people of a Territory in any lawful way , against the wishes of any citizen of the United States , exclude slavery from their limits prior to the formation of a State constitution ? I answer emphatically , as Mr. Lincoln has heard me answer a hundred times from every stump in Illinois , that in my opinion the people of a Territory can , by lawful means , exclude slavery from their limits prior to the formation of a State constitution . Mr Lincoln knew that I had answered that question over and over again . He heard me argue the Nebraska bill on that principle all over the State in 1854 , in 1855 , and in 1856 , and he has no excuse for pretending to be in doubt as to my position on that question . It matters not what way the Supreme Court may hereafter decide as to the abstract question whether slavery may or may not go into a Territory under the Constitution , the people have the lawful means to introduce it or exclude it as they please , for the reason that slavery can not exist a day or an hour anywhere , unless it is supported by local police regulations . Those police regulations can only be established by the local legislature ; and if the people are opposed to slavery , they will elect representatives to that body who will by unfriendly legislation effectually prevent the introduction of it into their midst . If , on the contrary , they are for it , their legislation will favor its extension . Hence , no matter what the decision of the Supreme Court may be on that abstract question , still the right of the people to make a Slave Territory or a Free Territory is perfect and complete under the Nebraska bill . I hope Mr. Lincoln deems my answer satisfactory on that point . By taking this position , Douglas was defending his Popular Sovereignty or `` Squatter Sovereignty '' principle of 1854 , which he considered to be a compromise between pro-slavery and anti-slavery positions . It was satisfactory to the legislature of Illinois , which reelected Douglas over Lincoln to the Senate ( this was before the addition of the Seventeenth Amendment to the Constitution ) . However , the Freeport Doctrine alienated many Southern Democrats . Douglas had actually stated the essence of the doctrine previous to the debate at Freeport , but its prominent public assertion at Freeport contributed ( along with other political disputes , such as over the Lecompton Constitution ) to antagonizing those in the Southern United States who were demanding ever-increasing protections for slavery , and who subsequently insisted on the repudiation of the Freeport Doctrine ( i.e. , the passage of a congressional Slave Code for the territories ) in order to block Douglas ' presidential bid in 1860 . This led to the split of the Democratic party in 1860 , and Douglas ' loss in the 1860 presidential election .",
"title": ""
},
{
"docid": "Archibald_Dixon",
"text": "Archibald Dixon ( April 2 , 1802 -- April 23 , 1876 ) was a U.S. Senator from Kentucky . He represented the Whig Party in both houses of the Kentucky General Assembly , and was elected the 12th Lieutenant Governor of Kentucky in 1844 , serving under Governor William Owsley . In 1851 , the Whigs nominated him for governor , but he lost to Lazarus W. Powell , his former law partner . Dixon represented Henderson County at the Kentucky constitutional convention of 1849 . In this capacity , he ensured that strong protections of slave property were included in the Kentucky Constitution of 1850 . Later , the General Assembly chose Dixon to fill the unexpired Senate term of Henry Clay . He served from September 1 , 1852 , to March 3 , 1855 , and did not stand for re-election . During his short tenure , Dixon 's major accomplishment was convincing Stephen Douglas to include language in the Kansas-Nebraska Act that explicitly repealed the Missouri Compromise 's prohibition on slavery north of latitude 36 ° 30 ' . Despite his pro-slavery views , Dixon was loyal to the Union during the Civil War . He represented his county and his state in a number of failed conventions that sought to resolve the upcoming conflict before it began . In 1864 , he joined Kentucky governor Thomas E. Bramlette in an audience with President Abraham Lincoln protesting the recruitment of former slaves as Union soldiers in Kentucky . Dixon died on April 23 , 1876 .",
"title": ""
},
{
"docid": "Abraham_Jonas_(politician)",
"text": "Abraham Jonas ( born September 12 , 1801 in Exeter , England ; died June 8 , 1864 ) was the first permanent Jewish resident in Quincy , Illinois . He was a former member of the Illinois and Kentucky State Legislature , a leading lawyer , and a valued friend of Abraham Lincoln . Jonas was born in Exeter , England to Annie Ezekiel and Benjamin Jonas . Abraham 's brother , Joseph Jonas , moved to Cincinnati , Ohio becoming the first Jew to settle west of the Allegheny Mountains . Abraham and his brother Edward joined Joseph in Cincinnati in 1819 . Abraham and his two brothers were original members of Congregation B'nai Israel ( Sons of Israel ) , the first Jewish congregation west of the Allegheny Mountains . Abraham also joined the Freemasons in Cincinnati . He and Joseph married Lucy and Rachel Seixas ; daughters of the first Rabbi born in America -- Gershom Mendes Seixas . Lucy suddenly died in 1825 , and Abraham moved to Williamstown , Kentucky . There he married Louisa Block from a pioneering Jewish American family and operated a general store . He was elected to the state legislature for four years . While in Kentucky , Abraham organized a Masonic Lodge and was eventually elected Master of the lodge in 1832 . During that time he and Louisa had five children . In 1836 he moved to Columbus in Adams County , Illinois to operate another general store . Within two years he moved to Quincy , IL opening a carriage business and studying law in Orville Browning 's office . He then organized the Grand Masonic Lodge of Illinois in 1840 and was elected Grand Master . In 1842 he was elected as a Whig to the state legislature . Lucy and Abraham had three more children around this time . He decided to establish a law partnership with Henry Asbury , turning over the family business to his brothers Edward and Samuel who had joined him in Quincy in 1840 or 1841 . It is suspected that it was during his years in legislation in Springfield that Abraham Jonas met Abraham Lincoln , as Lincoln was too a member of the state legislation at the time . Jonas ran for the Illinois Senate in 1844 but was defeated by the Democratic candidate . But his loyalty to the Whig party earned him the position as postmaster of Quincy in 1849 serving until 1853 . Lincoln and Jonas remained dear friends during this time . When the Whig party died , Jonas and Lincoln both joined the new Republican Party . On November 1 , 1854 Lincoln was accused of attending a Know-Nothing Party meeting , but was vouched by Jonas who he was actually with . Jonas arranged the 1858 Lincoln-Douglas debate in Quincy , and aided Lincoln to his candidacy . It was his law partner Henry Asbury who suggested Lincoln 's candidacy in front of a group of local Republicans . Asbury 's suggestion was greeted by silence until Jonas agreed that it would be a good idea . Abraham Jonas was noted as one of the greatest orators himself in the area . He was elected Grand Orator of the Grand Lodge of Illinois in 1843 . Lincoln appointed Jonas postmaster of Quincy in 1861 until his death in 1864 . Jonas had seven children , six sons and a daughter . Four of his sons , including future U.S. Senator Benjamin F. Jonas , fought for the Confederacy during the Civil War , being residents of Louisiana ; two others fought for the Union . Lincoln personally ordered the release of his son Charles Jonas from a prisoner of war camp to be at his father 's bedside before he died .",
"title": ""
},
{
"docid": "Old_State_Capitol_State_Historic_Site",
"text": "The Old State Capitol State Historic Site , in Springfield , Illinois , is the fifth capitol building built for the U.S. state of Illinois . It was built in the Greek Revival style in 1837 -- 1840 , and served as the state house from 1840 to 1876 . It is the site of candidacy announcements by Abraham Lincoln in 1858 and Barack Obama in 2007 . It was designated a National Historic Landmark in 1961 , primarily for its association with Lincoln and his political rival Stephen Douglas .",
"title": ""
},
{
"docid": "Jesse_B._Thomas,_Jr.",
"text": "Jesse Burgess Thomas , Jr. ( July 31 , 1806 -- February 21 , 1850 ) was born in Lebanon , Ohio and was an Illinois politician who served as the Illinois Attorney General from 1835 -- 1836 and later on the state Supreme Court . After studying law at Transylvania University in Lexington , Kentucky , Thomas settled in Edwardsville , Illinois . By 1830 , Thomas was serving as the secretary to the Illinois State Senate . Four years later , he served a partial term in the Illinois House of Representatives for Madison County before being appointed Attorney General , a post he held for a single year . From 1837 through 1839 , he was a circuit court judge based in Springfield . His circuit included New Salem , where Thomas heard cases argued by Abraham Lincoln . When Stephen A. Douglas gave up his seat on the Illinois Supreme Court in 1843 after being elected to Congress , Governor Thomas Ford appointed Thomas as Douglas 's successor . After retiring from the Supreme Court in 1848 , he moved first to Galena and then to Chicago , where he died in 1850 . Thomas 's uncle was Jesse B. Thomas , one of Illinois ' first Senators . Thomas was married to one of the daughters of Illinois Supreme Court Justice Theophilus W. Smith .",
"title": ""
},
{
"docid": "Jesse_W._Fell",
"text": "Jesse W. Fell ( 1808 -- 1887 ) was a Bloomington , Illinois businessman and land owner instrumental in the establishment of communities throughout Central Illinois and for the founding of Illinois State University . A close friend of Abraham Lincoln it was Fell who urged him to challenge his opponent , Stephen A. Douglas , to their famous series of debates .",
"title": ""
},
{
"docid": "The_Lincoln_Hunters",
"text": "The Lincoln Hunters is a 1958 novel by Wilson Tucker . The novel , set in the year 2578 , details the story of a historian from the oppressive society of that year , who travels back in time to record Abraham Lincoln 's Lost Speech of May 19 , 1856 in Bloomington , Illinois . It contains a vivid description of Lincoln in the early stages of his career , seen through the eyes of a future American who feels that Lincoln and his time compare very favorably with the traveler 's own . The book is mentioned in 11/22/63 , a novel by Stephen King that also centers around time travel and an assassinated president . Furthermore , the protagonist springboards to 1958-the year `` Hunters '' first ran-to alter the timeline by 1963 . Category :1958 American novels Category :1950 s science fiction novels Category : American science fiction novels Category : Time travel novels Category : Novels by Wilson Tucker Category :1856 in fiction Category : Novels set in Illinois Category :26 th century in fiction Category : Fictional depictions of Abraham Lincoln in literature",
"title": ""
},
{
"docid": "Hampton_Roads_Conference",
"text": "The Hampton Roads Conference was a peace conference held between the United States and the Confederate States on February 3 , 1865 , aboard the steamboat River Queen in Hampton Roads , Virginia , to discuss terms to end the American Civil War . President Abraham Lincoln and Secretary of State William H. Seward , representing the Union , met with three commissioners from the Confederacy : Vice President Alexander H. Stephens , Senator Robert M. T. Hunter , and Assistant Secretary of War John A. Campbell . The representatives discussed a possible alliance against France , the possible terms of surrender , the question of whether slavery might persist after the war , and the question of whether the South would be compensated for property lost through emancipation . Lincoln and Seward reportedly offered some possibilities for compromise on the issue of slavery . The only concrete agreement reached was over prisoner-of-war exchanges . The Confederate commissioners immediately returned to Richmond at the conclusion of the conference . Confederate President Jefferson Davis announced that the North would not compromise . Lincoln drafted an amnesty agreement based on terms discussed at the Conference , but met with opposition from his Cabinet . John Campbell continued to advocate for a peace agreement and met again with Lincoln after the fall of Richmond on April 2 .",
"title": ""
}
] |
PLAIN-1973
|
quinoa
|
[
{
"docid": "MED-5042",
"text": "The Kuna Indians who reside in an archipelago on the Caribbean Coast of Panama have very low blood pressure levels, live longer than other Panamanians, and have a reduced frequency of myocardial infarction, stroke, diabetes mellitus, and cancer -- at least on their death certificates. One outstanding feature of their diet includes a very high intake of flavanol-rich cocoa. Flavonoids in cocoa activate nitric oxide synthesis in healthy humans. The possibility that the high flavanol intake protects the Kuna against high blood pressure, ischemic heart disease, stroke, diabetes mellitus, and cancer is sufficiently intriguing and sufficiently important that large, randomized controlled clinical trials should be pursued.",
"title": "Flavanols, the Kuna, Cocoa Consumption, and Nitric Oxide"
},
{
"docid": "MED-4875",
"text": "The repertoire of gastrointestinal (GI) symptoms is finite; however, the etiologies and mechanisms underlying symptom generation and perception are diverse and, in many cases, unknown. This review examines the clinical and experimental evidence exploring the putative relationship between gluten sensitivity (GS) and the generation of GI symptoms. It explores the hypothesis that, in a proportion of patients, GS causes functional bowel disorder (FBD)-like symptoms. We propose a model for investigating and understanding the induction of GI symptoms and dysfunction by gluten in FBD and organic disease. We hypothesize that, even in the absence of fully developed celiac disease, gluten can induce symptoms similar to FBD. We discuss the hypothesis that GS and post-infectious irritable bowel syndrome (IBS) provide two triggers that can explain at least part of the spectrum that constitutes IBS, further advancing an understanding of the role of mucosal responses to luminal factors in FBDs. We propose that the animal model of GS in human leukocyte antigen (HLA)-DQ8 mice allows investigation of mucosal pathophysiological changes that occur before the onset of full-blown inflammation in a GS host. A better understanding of how gluten can cause symptoms in sensitive individuals will illuminate the interaction between host genotype, diet, and intestinal microbiota in generating one of the most common GI conditions.",
"title": "Between Celiac Disease and Irritable Bowel Syndrome: The “No Man’s Land” of Gluten Sensitivity"
},
{
"docid": "MED-5154",
"text": "OBJECTIVE: To measure whole-grain intake in college students and determine the association with body mass index (BMI). DESIGN: Cross-sectional convenience sample of college students enrolled in an introductory nutrition course. SETTING: Large state university. PARTICIPANTS: 159 college students, mean age: 19.9. MAIN OUTCOME MEASURES: Intake of whole grains, refined grains, calories, and fiber from food records; BMI determined from height and weight measurements. ANALYSIS: Analysis of variance with linear contrasts; participants grouped by BMI category (P<.05). RESULTS: Average intake of cereal grains was 5.4 servings per day, of which whole-grain intake accounted for an average of 0.7 servings per day. Whole-grain intake was significantly higher in normal weight students than in overweight and obese students (based on BMI). CONCLUSIONS AND IMPLICATIONS: The low intake of whole grains in this population of college students indicates the need for interventions aiming to increase whole-grain intake to the recommended minimum of 3 servings per day. College students who are concerned about their body weight may be motivated to increase their intake of whole-grain foods; however, their intake of whole grains is likely to be influenced by the availability of these food items in campus dining halls and other locations around the college campus.",
"title": "Whole-grain intake is associated with body mass index in college students."
},
{
"docid": "MED-5041",
"text": "Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer – all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 ± 0.70 age adjusted deaths/100,000) and cancer was second (68.4 ± 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 ± 3.1) and (4.4 ± 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 ± 0.74) than in the San Blas (6.6 ± 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.",
"title": "Does Flavanol Intake Influence Mortality from Nitric Oxide-Dependent Processes? Ischemic Heart Disease, Stroke, Diabetes Mellitus, and Cancer in Panama"
}
] |
[
{
"docid": "MED-3985",
"text": "Deficiency of vitamin D is usually caused by dietary deficiency and/or lack of exposure to sunlight in dark skinned individuals living at northern latitudes. Simple vitamin D deficiency is commonly treated by prescribing a vitamin D containing calcium supplement. This report presents a patient who rejected this approach and instead, after researching alternative treatment options independently, opted to self-treat by consuming UVB-irradiated mushrooms. The beneficial effect of this on the patient's plasma biochemical markers is shown. Further research into the beneficial effect of consuming UVB-irradiated mushrooms is required.",
"title": "Vitamin D deficiency treated by consuming UVB-irradiated mushrooms"
},
{
"docid": "MED-2990",
"text": "ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. INTRODUCTION: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. MATERIALS AND METHODS: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. RESULTS AND CONCLUSIONS: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1-10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined.",
"title": "Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research."
},
{
"docid": "MED-1861",
"text": "INTRODUCTION: Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. OBJECTIVES: The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. METHODS: We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies. RESULTS: Four trials, with a total of 390 patients, met our inclusion criteria. Two studies compared Hibiscus sabdariffa to black tea; one study compared it to captopril and one to lisinopril. The studies found that Hibiscus had greater blood pressure reduction than tea but less than the ACE-inhibitors. However, all studies, except one, were short term and of poor quality with a Jadad scoring of <3 and did not meet international standards. CONCLUSION: The four randomized controlled studies identified in this review do not provide reliable evidence to support recommending Hibiscus sabdariffa for the treatment of primary hypertension in adults. Copyright 2009 Elsevier GmbH. All rights reserved.",
"title": "The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review."
},
{
"docid": "MED-1932",
"text": "There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children’s exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994–1995 birth cohort. Each child’s mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B = −0.052, s.e. = 0.021, P = 0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.",
"title": "Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study"
},
{
"docid": "MED-2673",
"text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.",
"title": "Determination of microbial transglutaminase in meat and meat products."
},
{
"docid": "MED-1071",
"text": "BACKGROUND: Elevated serum saturated fatty acid levels and hepatocyte lipoapoptosis are features of nonalcoholic fatty liver disease (NAFLD). AIM: The purpose of this study was to investigate saturated fatty acid induction of lipoapoptosis in human liver cells and the underlying mechanisms. METHODS: Human liver L02 and HepG2 cells were treated with sodium palmitate, a saturated fatty acid, for up to 48 h with or without lithium chloride, a glycogen synthase kinase-3β (GSK-3β) inhibitor, or GSK-3β shRNA transfection. Transmission electron microscopy was used to detect morphological changes, flow cytometry was used to detect apoptosis, a colorimetric assay was used to detect caspase-3 activity, and western blot analysis was used to detect protein expression. RESULTS: The data showed that sodium palmitate was able to induce lipoapoptosis in L02 and HepG2 cells. Western blot analysis showed that sodium palmitate activated GSK-3β protein, which was indicated by dephosphorylation of GSK-3β at Ser-9. However, inhibition of GSK-3β activity with lithium chloride treatment or knockdown of GSK-3β expression with shRNA suppressed sodium palmitate-induced lipoapoptosis in L02 and HepG2 cells. On a molecular level, inhibition of GSK-3β expression or activity suppressed sodium palmitate-induced c-Jun-N-terminal kinase (JNK) phosphorylation and Bax upregulation, whereas GSK-3β inhibition did not affect endoplasmic reticulum stress-induced activation of unfolded protein response. CONCLUSIONS: The present data demonstrated that saturated fatty acid sodium palmitate-induced lipoapoptosis in human liver L02 and HepG2 cells was regulated by GSK-3β activation, which led to JNK activation and Bax upregulation. This finding indicates that GSK-3β inhibition may be a potential therapeutic target to control NAFLD.",
"title": "Saturated free fatty acid sodium palmitate-induced lipoapoptosis by targeting glycogen synthase kinase-3β activation in human liver cells."
},
{
"docid": "MED-4436",
"text": "The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies.",
"title": "Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition."
},
{
"docid": "MED-3728",
"text": "On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.",
"title": "Strawberry fields forever?"
},
{
"docid": "MED-1950",
"text": "Several studies have found associations between microbial infections during pregnancy and preterm delivery (PTD). We investigated the influence of food with antimicrobial and prebiotic components on the risk of spontaneous PTD. A literature search identified microbes associated with spontaneous PTD. Subsequently, 2 main food types (alliums and dried fruits) were identified to contain antimicrobial components that affect the microbes associated with spontaneous PTD; they also contained dietary fibers recognized as prebiotics. We investigated intake in 18,888 women in the Norwegian Mother and Child Cohort (MoBa), of whom 950 (5%) underwent spontaneous PTD (<37 gestational weeks). Alliums (garlic, onion, leek, and spring onion) [OR: 0.82 (95% CI: 0.72, 0.94), P = 0.005] and dried fruits (raisins, apricots, prunes, figs, and dates) [OR: 0.82 (95% CI: 0.72, 0.94); P = 0.005] were associated with a decreased risk of spontaneous PTD. Intake of alliums was related to a more pronounced risk reduction in early spontaneous PTD (gestational weeks 28–31) [OR: 0.39 (95% CI: 0.19, 0.80)]. The strongest association in this group was with garlic [OR: 0.47 (95% CI: 0.25–0.89)], followed by cooked onions. Intake of dried fruits showed an association with preterm prelabor rupture of membranes (PPROM) [OR: 0.74 (95% CI: 0.65, 0.95)]; the strongest association in this group was with raisins [OR: 0.71 (95% CI: 0.56, 0.92)]. The strongest association with PPROM in the allium group was with garlic [OR: 0.74 (95% CI: 0.56, 0.97)]. In conclusion, intake of food with antimicrobial and prebiotic compounds may be of importance to reduce the risk of spontaneous PTD. In particular, garlic was associated with overall lower risk of spontaneous PTD. Dried fruits, especially raisins, were associated with reduced risk of PPROM.",
"title": "Intakes of Garlic and Dried Fruits Are Associated with Lower Risk of Spontaneous Preterm Delivery"
},
{
"docid": "MED-5038",
"text": "Interest in the biological activities of cocoa polyphenols is increasing steadily. In fact, the high polyphenol content of cocoa, coupled with its widespread presence in many food items, render this food of particular interest from the nutritional and \"pharmacological\" viewpoints. This paper summarizes the new findings and developments regarding the effects of cocoa and chocolate consumption on human health as presented at the International Conference \"Chocolate, Lifestyle, and Health\" (Milan, Italy, March 2, 2007) regarding the effects of cocoa and chocolate consumption on human health.",
"title": "Chocolate, lifestyle, and health."
},
{
"docid": "MED-4924",
"text": "High-dose β-carotene supplementation in high-risk persons has been linked to increased lung cancer risk in clinical trials; whether effects are similar in the general population is unclear. The authors examined associations of supplemental β-carotene, retinol, vitamin A, lutein, and lycopene with lung cancer risk among participants, aged 50–76 years, in the VITamins And Lifestyle (VITAL) cohort Study in Washington State. In 2000–2002, eligible persons (n = 77,126) completed a 24-page baseline questionnaire, including detailed questions about supplement use (duration, frequency, dose) during the previous 10 years from multivitamins and individual supplements/mixtures. Incident lung cancers (n = 521) through December 2005 were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. Longer duration of use of individual β-carotene, retinol, and lutein supplements (but not total 10-year average dose) was associated with statistically significantly elevated risk of total lung cancer and histologic cell types; for example, hazard ratio = 2.02, 95% confidence interval: 1.28, 3.17 for individual supplemental lutein with total lung cancer and hazard ratio = 3.22, 95% confidence interval: 1.29, 8.07 for individual β-carotene with small-cell lung cancer for >4 years versus no use. There was little evidence for effect modification by gender or smoking status. Long-term use of individual β-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers.",
"title": "Long-term Use of β-Carotene, Retinol, Lycopene, and Lutein Supplements and Lung Cancer Risk: Results From the VITamins And Lifestyle (VITAL) Study"
},
{
"docid": "MED-3853",
"text": "PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and -independent anticarcinogenic properties--have been associated with postmenopausal breast cancer risk, but data are limited regarding their effect on survival. Dietary lignans are metabolized to enterolignans, which are subsequently absorbed and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140 postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed between 2002 and 2005. Vital status through the end of 2009 was ascertained via local population registries, and deaths were verified by death certificates. Information on recurrences and secondary tumors was verified by clinical records and attending physicians. Associations of postdiagnostic serum enterolactone (a biomarker for dietary lignans) with overall survival and distant disease-free survival were assessed by using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L, respectively. During a median of 6.1 years of follow-up after diagnosis, 162 deaths were confirmed. Higher serum enterolactone levels were associated with significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment, 0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI, 0.35 to 1.09) for the highest quartile. The highest quartile of serum enterolactone was associated with a significantly reduced risk of death only for estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who have high serum enterolactone levels may have better survival.",
"title": "Serum enterolactone and prognosis of postmenopausal breast cancer."
},
{
"docid": "MED-1508",
"text": "The obesity epidemic is attributed in part to reduced physical activity. Evidence supports that reducing time spent sitting, regardless of activity, may improve the metabolic consequences of obesity. Analyses were conducted in a large prospective study of US adults enrolled by the American Cancer Society to examine leisure time spent sitting and physical activity in relation to mortality. Time spent sitting and physical activity were queried by questionnaire on 53,440 men and 69,776 women who were disease free at enrollment. The authors identified 11,307 deaths in men and 7,923 deaths in women during the 14-year follow-up. After adjustment for smoking, body mass index, and other factors, time spent sitting (≥6 vs. <3 hours/day) was associated with mortality in both women (relative risk = 1.34, 95% confidence interval (CI): 1.25, 1.44) and men (relative risk = 1.17, 95% CI: 1.11, 1.24). Relative risks for sitting (≥6 hours/day) and physical activity (<24.5 metabolic equivalent (MET)-hours/week) combined were 1.94 (95% CI: 1.70, 2.20) for women and 1.48 (95% CI: 1.33, 1.65) for men, compared with those with the least time sitting and most activity. Associations were strongest for cardiovascular disease mortality. The time spent sitting was independently associated with total mortality, regardless of physical activity level. Public health messages should include both being physically active and reducing time spent sitting.",
"title": "Leisure Time Spent Sitting in Relation to Total Mortality in a Prospective Cohort of US Adults"
},
{
"docid": "MED-306",
"text": "Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.",
"title": "Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure"
},
{
"docid": "MED-4227",
"text": "Epidemiologic and biological data strongly support the existence of a strict link between cancer and aging. In spite of the relevance of the problem, there were numerous pitfalls in epidemiologic investigation until a few years ago. An apparent decrease of cancer incidence in old age was revealed to be a misconception based on lack of sufficient appreciation for changing population size. But not all problems are solved by using age-specific cancer incidence, as recently stressed by some authors. At very advanced ages a slowing of the rate of increase of age-specific cancer incidence is clearly demonstrated. These findings apparently clash with the majority of biological data and suggest that some mechanism may develop at advanced ages capable of decreasing cancer susceptibility. In this paper, it will be shown that just a slowing-down kinetics is predicted for cancer incidence by using a mathematical model of mortality kinetics recently proposed in the gerontologic field. The slowing of the increasing rate or even a decreasing trend of cancer incidence of an aging population is compatible with a continuously accelerating pace of loss of physiological capacity of the single subjects, as with advancing age there is a selection of individuals with better physiological functions.",
"title": "Cancer and aging: from the kinetics of biological parameters to the kinetics of cancer incidence and mortality."
},
{
"docid": "MED-3096",
"text": "Background and objectives: Uncooked meat and poultry products are commonly enhanced by food processors using phosphate salts. The addition of potassium and phosphorus to these foods has been recognized but not quantified. Design, setting, participants, & measurements: We measured the phosphorus, potassium, and protein content of 36 uncooked meat and poultry products: Phosphorus using the Association of Analytical Communities (AOAC) official method 984.27, potassium using AOAC official method 985.01, and protein using AOAC official method 990.03. Results: Products that reported the use of additives had an average phosphate-protein ratio 28% higher than additive free products; the content ranged up to almost 100% higher. Potassium content in foods with additives varied widely; additive free products all contained <387 mg/100 g, whereas five of the 25 products with additives contained at least 692 mg/100 g (maximum 930 mg/100 g). Most but not all foods with phosphate and potassium additives reported the additives (unquantified) on the labeling; eight of 25 enhanced products did not list the additives. The results cannot be applied to other products. The composition of the food additives used by food processors may change over time. Conclusions: Uncooked meat and poultry products that are enhanced may contain additives that increase phosphorus and potassium content by as much as almost two- and three-fold, respectively; this modification may not be discernible from inspection of the food label.",
"title": "Original Articles: Phosphorus and Potassium Content of Enhanced Meat and Poultry Products: Implications for Patients Who Receive Dialysis"
},
{
"docid": "MED-1509",
"text": "AIMS/HYPOTHESIS: Sedentary (sitting) behaviours are ubiquitous in modern society. We conducted a systematic review and meta-analysis to examine the association of sedentary time with diabetes, cardiovascular disease and cardiovascular and all-cause mortality. METHODS: Medline, Embase and the Cochrane Library databases were searched for terms related to sedentary time and health outcomes. Cross-sectional and prospective studies were included. RR/HR and 95% CIs were extracted by two independent reviewers. Data were adjusted for baseline event rate and pooled using a random-effects model. Bayesian predictive effects and intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future. RESULTS: Eighteen studies (16 prospective, two cross-sectional) were included, with 794,577 participants. Fifteen of these studies were moderate to high quality. The greatest sedentary time compared with the lowest was associated with a 112% increase in the RR of diabetes (RR 2.12; 95% credible interval [CrI] 1.61, 2.78), a 147% increase in the RR of cardiovascular events (RR 2.47; 95% CI 1.44, 4.24), a 90% increase in the risk of cardiovascular mortality (HR 1.90; 95% CrI 1.36, 2.66) and a 49% increase in the risk of all-cause mortality (HR 1.49; 95% CrI 1.14, 2.03). The predictive effects and intervals were only significant for diabetes. CONCLUSIONS/INTERPRETATION: Sedentary time is associated with an increased risk of diabetes, cardiovascular disease and cardiovascular and all-cause mortality; the strength of the association is most consistent for diabetes.",
"title": "Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis."
},
{
"docid": "MED-3514",
"text": "BACKGROUND & AIMS: Lowered visceral perception thresholds have been suggested as a biological marker of irritable bowel syndrome (IBS). The current study sought to determine the prevalence of altered rectal visceral perception in patients with IBS and the correlation of altered perception thresholds with subjective symptoms. METHODS: Anorectal manometry and rectal perception thresholds to balloon distention were determined in 100 patients with IBS and 15 control subjects. Gastrointestinal and psychological symptoms were assessed by questionnaire. Perception thresholds and symptoms were reassessed after 3 months in 15 patients with IBS. RESULTS: Ninety-four percent of patients showed altered rectal perception in the form of lowered thresholds for aversive sensations (discomfort), increased intensity of sensations, or altered viscerosomatic referral. Hypersensitivity was found only for aversive sensations in response to rapid phasic distention; stool thresholds and thresholds in response to slow ramp distention were normal. Cluster analysis by physiological parameters identified three IBS subgroups with predominant patterns of symptoms. Longitudinal evaluation indicated a correlation between changes in perception thresholds and symptom severity. CONCLUSIONS: Because altered rectal perception is present in almost all patients with IBS and perception thresholds correlate with temporal changes in retrospective symptom severity, altered rectal perception represents a reliable biological marker of IBS.",
"title": "Altered rectal perception is a biological marker of patients with irritable bowel syndrome."
},
{
"docid": "MED-2336",
"text": "Accumulated evidence shows that some phytochemicals provide beneficial effects for human health. Recently, a number of mechanistic studies have revealed that direct interactions between phytochemicals and functional proteins play significant roles in exhibiting their bioactivities. However, their binding selectivities to biological molecules are considered to be lower due to their small and simple structures. In this study, we found that zerumbone, a bioactive sesquiterpene, binds to numerous proteins with little selectivity. Similar to heat-denatured proteins, zerumbone-modified proteins were recognized by heat shock protein 90, a constitutive molecular chaperone, leading to heat shock factor 1-dependent heat shock protein induction in hepa1c1c7 mouse hepatoma cells. Furthermore, oral administration of this phytochemical up-regulated heat shock protein expressions in the livers of Sprague-Dawley rats. Interestingly, pretreatment with zerumbone conferred a thermoresistant phenotype to hepa1c1c7 cells as well as to the nematode Caenorhabditis elegans. It is also important to note that several phytochemicals with higher hydrophobicity or electrophilicity, including phenethyl isothiocyanate and curcumin, markedly induced heat shock proteins, whereas most of the tested nutrients did not. These results suggest that non-specific protein modifications by xenobiotic phytochemicals cause mild proteostress, thereby inducing heat shock response and leading to potentiation of protein quality control systems. We considered these bioactivities to be xenohormesis, an adaptation mechanism against xenobiotic chemical stresses. Heat shock response by phytochemicals may be a fundamental mechanism underlying their various bioactivities.",
"title": "Non-Specific Protein Modifications by a Phytochemical Induce Heat Shock Response for Self-Defense"
},
{
"docid": "MED-2101",
"text": "The notion that a breast-gut connection might modulate the microenvironment of breast tissue was supported by the finding that breast cyst fluid contains bile acids that are characteristically found in the intestines. To establish that the gut, rather than circulating steroid precursors, is the source of bile acids in breast cyst fluid, we gave two patients deuterium-labelled chenodeoxycholic acid (three 200 mg doses by mouth), starting 9 days before aspiration of breast cysts. The chenodeoxycholic acid concentration of seven samples of aspirated cyst fluid ranged from 42 to 94 mumol/L. The corresponding serum concentrations of chenodeoxycholic acid on the same day were 0.8 and 2.9 mumol/L, of which the labelled compound comprised 13.0% (0.38 mumol/L) and 28.2% (0.23 mumol/L). The deuterated chenodeoxycholic acid concentrations in cyst fluid were 0.79 and 1.26 mumol/L in two samples from patient 1 and 3.22 mumol/L in patient 2; these values are equivalent to 11-17% of the serum concentrations [corrected]. This study shows that intestinal bile acids rapidly gain access to cyst fluid. Further studies should investigate the mechanisms that govern the exchange processes and the maintenance of the high cyst fluid to plasma concentration gradients, and the biological half-lives of individual constituents.",
"title": "Breast-gut connection: origin of chenodeoxycholic acid in breast cyst fluid."
},
{
"docid": "MED-4411",
"text": "Chronic obstructive pulmonary disease (COPD) is characterised by increased oxidative stress. Dietary factors, such as ample consumption of foods rich in antioxidants, such as fruit and vegetables, might have beneficial effects in COPD patients. The association between dietary shift to foods rich in antioxidants and lung function in COPD was investigated in a 3-yr prospective study. A total of 120 COPD patients were randomised to follow either a diet based on increased consumption of fresh fruit and vegetables (intervention group (IG)) or a free diet (control group (CG)). The mean consumption of foods containing antioxidants was higher in the IG than in the CG throughout the study period (p<0.05). The relationship between consumption of foods rich in antioxidants and percentage predicted forced expiratory volume in 1 s was assessed using a general linear model for repeated measures; the two groups overall were different in time (p = 0.03), with the IG showing a better outcome. In investigating the effect of several confounders (sex, age, smoking status, comorbid conditions and exacerbation) of group response over time, nonsignificant interactions were found between confounders, group and time. These findings suggest that a dietary shift to higher-antioxidant food intake may be associated with improvement in lung function, and, in this respect, dietary interventions might be considered in COPD management.",
"title": "Impact of dietary shift to higher-antioxidant foods in COPD: a randomised trial."
},
{
"docid": "MED-3840",
"text": "The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.",
"title": "Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo"
},
{
"docid": "MED-2815",
"text": "Curcumin, an active polyphenol of the golden spice turmeric, is a highly pleiotropic molecule with the potential to modulate the biological activity of a number of signaling molecules. Traditionally, this polyphenol has been used in Asian countries to treat such human ailments as acne, psoriasis, dermatitis, and rash. Recent studies have indicated that curcumin can target newly identified signaling pathways including those associated with microRNA, cancer stem cells, and autophagy. Extensive research from preclinical and clinical studies has delineated the molecular basis for the pharmaceutical uses of this polyphenol against cancer, pulmonary diseases, neurological diseases, liver diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, and numerous other chronic diseases. Multiple studies have indicated the safety and efficacy of curcumin in numerous animals including rodents, monkeys, horses, rabbits, and cats and have provided a solid basis for evaluating its safety and efficacy in humans. To date, more than 65 human clinical trials of curcumin, which included more than 1000 patients, have been completed, and as many as 35 clinical trials are underway. Curcumin is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan. In this review, we provide evidence for the pharmaceutical uses of curcumin for various diseases. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.",
"title": "Curcumin, a component of turmeric: from farm to pharmacy."
},
{
"docid": "MED-4952",
"text": "A vegetarian diet may have beneficial effects on human health, however when it is not well-balanced may be deficient in some nutrients, as minerals for example. The aim of the present study was to assess the nutritional status of zinc and selenium in vegetarians in the city of São Paulo. A cross-sectional study was performed, and the inclusion criteria were age > or = 18 years, both gender, no use of food or pharmaceutical supplements. Thirty vegetarian, of both genders, mean age of 27 years and 4.5 years of vegetarianism had performed the study, and their mean BMI was 21.5. Zinc plasma concentration was 71 and 62.5 microg/dL for men and women and erythrocyte concentration was 37 microg/gHb for both genders. Selenium concentration was 73.5 and 77.3 microg/L in plasma and 51.4 and 66.9 microg/L in erythrocytes for men and women, respectively. These biochemical values show that, according to the references, selenium blood levels are adequate and zinc concentration in erythrocytes is deficient in the studied population. For this reason, vegetarians should be constantly assessed and receive nutritional support to reduce the effects of inadequate zinc status.",
"title": "Zinc and selenium nutritional status in vegetarians."
},
{
"docid": "MED-4173",
"text": "OBJECTIVE: To assess the public health significance of premature weaning of infants from breast milk on later-life risk of chronic illness. DESIGN: A review and summary of recent meta-analyses of studies linking premature weaning from breast milk with later-life chronic disease risk is presented followed by an estimation of the approximate exposure in a developed Western country, based on historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion of chronic disease associated with current patterns of artificial feeding in infancy is estimated. RESULTS: After adjustment for major confounding variables, current research suggests that the risks of chronic disease are 30-200 % higher in those who were not breast-fed compared to those who were breast-fed in infancy. Exposure to premature weaning ranges from 20 % to 90 % in post-World War II age cohorts. Overall, the attributable proportion of chronic disease in the population is estimated at 6-24 % for a 30 % exposure to premature weaning. CONCLUSIONS: Breast-feeding is of public health significance in preventing chronic disease. There is a small but consistent effect of premature weaning from breast milk in increasing later-life chronic disease risk. Risk exposure in the Australian population is substantial. Approximately 90 % of current 35-45-year-olds were weaned from breast-feeding by 6 months of age. Encouraging greater duration and exclusivity of breast-feeding is a potential avenue for reducing future chronic disease burden and health system costs.",
"title": "Chronic disease and infant nutrition: is it significant to public health?"
},
{
"docid": "MED-4027",
"text": "Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.",
"title": "Dietary behavior and knowledge of dental erosion among Chinese adults"
},
{
"docid": "MED-3423",
"text": "INTRODUCTION: There are no reported studies assessing the relation between diet and sexual function in women with diabetes. AIM: In the present study, we explored the relation between consumption of a Mediterranean-type diet and sexual function in a population of type 2 diabetic women. METHODS: Patients with type 2 diabetes were enrolled if they had a diagnosis of type 2 diabetes for at least six months but less than 10 years, age 35-70 years, body mass index (BMI) of 24 or higher, HbA1c of 6.5% or higher, treatment with diet or oral drugs. All diabetic patients were invited to complete a food-frequency questionnaire and self-report measures of sexual function. A total of 595 (90.2%) of the 659 women completed both questionnaires and were analyzed in the present study. MAIN OUTCOME MEASURES: Adherence to a Mediterranean diet was assessed by a 9-point scale that incorporated the salient characteristics of this diet (range of scores, 0-9, with higher scores indicating greater adherence). The Female Sexual Function Index (FSFI) was used for assessing the key dimensions of female sexual function. RESULTS: Diabetic women with the highest scores (6-9) had lower BMI, waist circumference, and waist-to-hip ratio, a lower prevalence of depression, obesity and metabolic syndrome, a higher level of physical activity, and better glucose and lipid profiles than the diabetic women who scored <3 points on the scale. The proportion of sexually active women showed a significant increase across tertiles of adherence to Mediterranean diet (from 54.2% to 65.1%, P = 0.01). Based on the FSFI cutoff score for female sexual dysfunction (FSD) of 23, women with the highest score of adherence had a lower prevalence of sexual dysfunction as compared with women of lower tertiles (47.6%, 53.9%, and 57.8%, higher, middle, and lower tertile, respectively, P = 0.01). These associations remained significant after adjustment for many potential confounders. CONCLUSIONS: In women with type 2 diabetes, greater adherence to Mediterranean diet is associated with a lower prevalence of FSD.",
"title": "Adherence to Mediterranean diet and sexual function in women with type 2 diabetes."
},
{
"docid": "MED-4760",
"text": "The human gut is a lush microbial ecosystem containing about 100 trillion microorganisms, whose collective genome, the microbiome, contains 100-fold more genes than the entire human genome. The symbiosis of our extended genome plays a role in host homeostasis and energy extraction from diet. In this article, we summarize some of the studies that have advanced the understanding of the microbiome and its effects on metabolism, obesity, and health. Metagenomic studies demonstrated that certain mixes of gut microbiota may protect or predispose the host to obesity. Furthermore, microbiota transplantation studies in germ-free murine models showed that the efficient energy extraction traits of obese-type gut flora are transmissible. The proposed methods by which the microbiome may contribute to obesity include increasing dietary energy harvest, promoting fat deposition, and triggering systemic inflammation. Future treatments for obesity may involve modulation of gut microbiota using probiotics or prebiotics.",
"title": "The microbiome and obesity: is obesity linked to our gut flora?"
},
{
"docid": "MED-2229",
"text": "BACKGROUND/OBJECTIVES: In vitro and animal studies have reported that young broccoli sprouts improve oxidative stress status in diabetic condition. The objective of this double-blind, placebo-controlled, randomized clinical trial was to investigate the effects of broccoli sprouts powder (BSP) on some oxidative stress parameters in type 2 diabetes patients. SUBJECTS/METHODS: A total of 81 patients with type 2 diabetes were randomly assigned to one of three treatment groups for 4 weeks. The groups received either 10 g/d BSP (n=27), 5 g/d BSP (n=29) or placebo (n=25). Serum total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and oxidized low density lipoprotein (LDL) cholesterol were measured at baseline and at 4 weeks after treatment. RESULTS: In all, 63 patients in three groups were included in the analysis: 10 g/d BSP (n=21), 5 g/d (n=22) and placebo (n=20). After 4 weeks, consumption of BSP resulted in significant decrease in MDA (P=0.001 for treatment effect), oxidized low density lipoprotein cholesterol (P=0.03 for treatment effect), OSI (P=0.001 for treatment effect) and significant increase in TAC (P=0.001 for treatment effect). No effects were found on TOS. CONCLUSION: BSP had favorable effects on oxidative stress status in type 2 diabetes patients.",
"title": "Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind clinical trial."
},
{
"docid": "MED-1054",
"text": "For a long time non communicable diseases (NCDs) were discussed as burden of the developed world. Recent alarming data show a reverse trend and a dramatic increase of NCDs in the developing world, in particular in highly populated transition countries. This is true for the main mortality triggering diseases such as CVD, cancer or diabetes. Almost 4 out of 5 NCD based deaths happen in low- and middle income countries. This development is multi-factorial and is based on some main trends such as globalization, supermarket growth, rapid urbanization and increasingly sedentary lifestyles. The latter leads to overweight or obesity, which again promotes NCDs similar as high blood pressure, high cholesterol and elevated blood glucose. A high quality diet including functional food or functional ingredients, accompanied by physical activity and a non-smoking policy, is one of the most promising factors in primary and secondary prevention of NCDs. Copyright © 2011 Elsevier Inc. All rights reserved.",
"title": "A global view on the development of non communicable diseases."
}
] |
43504
|
Richmond, Virginia is home to the Federal Reserve Bank of Richmond.
|
[
{
"docid": "Richmond,_Virginia",
"text": "Richmond ( -LSB- ˈrɪtʃmənd -RSB- ) is the capital of the Commonwealth of Virginia in the Mid-Atlantic region of the United States . It is the center of the Richmond Metropolitan Statistical Area ( MSA ) and the Greater Richmond Region . It was incorporated in 1742 , and has been an independent city since 1871 . As of the 2010 census , the population was 204,214 ; in 2016 , the population was estimated to be 223,170 , the fourth-most populous city in Virginia . The Richmond Metropolitan Area has a population of 1,260,029 , the third-most populous metro in the state . Richmond is located at the fall line of the James River , 44 mi west of Williamsburg , 66 mi east of Charlottesville , and 98 mi south of Washington , D.C. Surrounded by Henrico and Chesterfield counties , the city is located at the intersections of Interstate 95 and Interstate 64 , and encircled by Interstate 295 and Virginia State Route 288 . Major suburbs include Midlothian to the southwest , Glen Allen to the north and west , Short Pump to the west and Mechanicsville to the northeast . The site of Richmond had been an important village of the Powhatan Confederacy , and was briefly settled by English colonists from Jamestown in 1609 , and in 1610 -- 1611 . The present city of Richmond was founded in 1737 . It became the capital of the Colony and Dominion of Virginia in 1780 . During the Revolutionary War period , several notable events occurred in the city , including Patrick Henry 's `` Give me liberty or give me death '' speech in 1775 at St. John 's Church , and the passage of the Virginia Statute for Religious Freedom written by Thomas Jefferson . During the American Civil War , Richmond served as the capital of the Confederate States of America . The city entered the 20th century with one of the world 's first successful electric streetcar systems . The Jackson Ward neighborhood is a national hub of African-American commerce and culture . Richmond 's economy is primarily driven by law , finance , and government , with federal , state , and local governmental agencies , as well as notable legal and banking firms , located in the downtown area . The city is home to both the United States Court of Appeals for the Fourth Circuit , one of 13 United States courts of appeals , and the Federal Reserve Bank of Richmond , one of 12 Federal Reserve Banks . Dominion Resources and MeadWestvaco , Fortune 500 companies , are headquartered in the city , with others in the metropolitan area .",
"title": ""
}
] |
[
{
"docid": "Federal_Reserve_Bank_of_Richmond_Baltimore_Branch",
"text": "The Federal Reserve Bank of Richmond Baltimore Branch Office is one of the two Federal Reserve Bank of Richmond branch offices . The Federal Reserve Bank of Richmond 's Baltimore Branch is an operational and regional center for Maryland , the metropolitan Washington D.C. area , Northern Virginia , and northeastern West Virginia . The Baltimore branch is part of the Fifth District and has the code E5 . It supports Check 21 operations , supplies coin and currency to financial institutions and works to maintain stability in the financial sector throughout the Fifth District and also works with local elected officials and non-profit organizations to support fair housing initiatives throughout the Fifth District . The Baltimore branch was founded in March 1918 and is currently headed by William R. Roberts . Each branch of the Federal Reserve Banks has a board of either seven or five directors , a majority of whom are appointed by the parent Federal Reserve Bank ; the others are appointed by the Board of Governors . Branch directors serve staggered three-year terms ( two-year terms if the Branch has five directors ) . One of the members appointed by the Federal Reserve Board is designated annually as chairman of the board of that Branch in a manner prescribed by the parent Federal Reserve Bank . The Baltimore branch currently allows private and educational tours of up to thirty people with reservations . Cell phones and cameras are not permitted inside the building . The Federal Reserve Bank of Richmond Baltimore Branch Office sponsors the annual Fed Challenge to encourage better understanding of the nation 's central bank and the forces influencing economic conditions in the United States and abroad . In 1997 , the Federal Reserve Bank of Richmond - Baltimore Branch won the silver U.S. Senate Productivity and Maryland Quality Award . In 2008 , Dorothy Voorhees received the Federal Reserve Bank of Richmond Baltimore Branch 2008 Excellence Award for outstanding achievement in the study of economics .",
"title": ""
},
{
"docid": "Federal_Reserve_Bank_of_Richmond",
"text": "The Federal Reserve Bank of Richmond is the headquarters of the Fifth District of the Federal Reserve located in Richmond , Virginia . It covers the District of Columbia , Maryland , North Carolina , South Carolina , Virginia , and most of West Virginia excluding the Northern Panhandle . Branch offices are located in Baltimore , Maryland and Charlotte , North Carolina . Currently , the position of president is vacant following the retirement of Jeffrey M. Lacker in April of 2017 . The previous president , J. Alfred Broaddus , retired in 2004 .",
"title": ""
},
{
"docid": "VCU_School_of_Business",
"text": "The Virginia Commonwealth University School of Business is located in Richmond , Virginia , home to one of the twelve Federal Reserve Banks . Because the school is located in downtown Richmond , Virginia , many students are able to receive internships and other opportunities within the city . Richmond , Virginia includes the third highest concentration of U.S. Fortune 1000 headquarters and is ranked as one of the nation 's 10 best places for business and careers .",
"title": ""
},
{
"docid": "J._Alfred_Broaddus",
"text": "J. Alfred Broaddus , Jr. ( born July 8 , 1939 in Richmond , Virginia ) was the sixth president of the Federal Reserve Bank of Richmond , headquarters of the Fifth District of the Federal Reserve System serving the District of Columbia , Maryland , North Carolina , South Carolina , Virginia , and most of West Virginia with the exception of the Northern Panhandle . Broaddus succeeded Robert P. Black and served as the Richmond Fed 's president from January 1 , 1993 until his retirement on July 31 , 2004 . He was succeeded as president by Jeffrey M. Lacker .",
"title": ""
},
{
"docid": "Federal_Reserve_Bank_of_Richmond_Charlotte_Branch",
"text": "The Federal Reserve Bank of Richmond Charlotte Branch Office is one of the two Federal Reserve Bank of Richmond branch offices . The Federal Reserve Bank of Richmond 's Charlotte Branch is an operational and regional center for the Carolinas , including the nation 's second largest financial center in Charlotte , NC.They promote the safety and soundness of large bank holding companies headquartered in Charlotte . They distribute currency and coin to financial institutions in our region and provide check adjustment services for the Federal Reserve System . Their public programs include forums and conferences , economic education outreach , tours and a speakers ' bureau.Clemson Dean Lilly has been serving as the director since 2007 .",
"title": ""
},
{
"docid": "List_of_Federal_Reserve_branches",
"text": "There are 24 Federal Reserve branches . As late as 2008 , there were 25 branches , but in October 2008 the Federal Reserve Bank of New York Buffalo Branch was closed . List of Federal Reserve branches Boston New York Federal Reserve Bank of New York Buffalo Branch ( closed ) Philadelphia Cleveland Federal Reserve Bank of Cleveland Cincinnati Branch Federal Reserve Bank of Cleveland Pittsburgh Branch Richmond Federal Reserve Bank of Richmond Baltimore Branch Federal Reserve Bank of Richmond Charlotte Branch Atlanta Federal Reserve Bank of Atlanta Birmingham Branch Federal Reserve Bank of Atlanta Jacksonville Branch Federal Reserve Bank of Atlanta Miami Branch Federal Reserve Bank of Atlanta Nashville Branch Federal Reserve Bank of Atlanta New Orleans Branch Chicago Federal Reserve Bank of Chicago Detroit Branch St Louis Federal Reserve Bank of St. Louis Little Rock Branch Federal Reserve Bank of St. Louis Louisville Branch Federal Reserve Bank of St. Louis Memphis Branch Minneapolis Federal Reserve Bank of Minneapolis Helena Branch Kansas City Federal Reserve Bank of Kansas City Denver Branch Federal Reserve Bank of Kansas City Oklahoma City Branch Federal Reserve Bank of Kansas City Omaha Branch Dallas Federal Reserve Bank of Dallas El Paso Branch Federal Reserve Bank of Dallas Houston Branch Federal Reserve Bank of Dallas San Antonio Branch San Francisco Federal Reserve Bank of San Francisco Los Angeles Branch Federal Reserve Bank of San Francisco Portland Branch Federal Reserve Bank of San Francisco Salt Lake City Branch Federal Reserve Bank of San Francisco Seattle Branch",
"title": ""
},
{
"docid": "List_of_tallest_buildings_in_Richmond,_Virginia",
"text": "This is a list of tallest buildings in Richmond , Virginia . Presently , the tallest building in Richmond is the 29-story James Monroe Building . It was the tallest building in Virginia from the time of its completion in 1981 until 2007 , when the 38-story Westin Tower in Virginia Beach opened in downtown Virginia Beach . The next three tallest skyscrapers in the city each have 26 stories within the structure , although they vary in height . The SunTrust Plaza stands at 400 ft ( 120 m ) , while the Federal Reserve Bank of Richmond , which also has 26 stories stands at 394 ft ( 119 m ) . The third tallest building is the Bank of America Center which stands at 331 ft ( 101 m ) . Typically , the first high-rise in Richmond history is often considered to be the 19-story BB&T Bank Building , which was completed in 1913 . The structure stands at 262 ft ( 80 m ) and is located in Downtown Richmond . The newest high rises in Richmond include Brandt Hall , a 17-story college dorm on the Monroe Park campus of Virginia Commonwealth University , which was completed in 2005 , along the Vistas on the James , which were completed that same year . Additionally , in downtown , the 12-story MWV Building was completed in 2010 . The 23-story Central National Bank Building , built in 1930 , is being converted into apartments after being left abandoned for over 20 years . Currently , a new 18-story office building , Gateway Plaza , is being constructed downtown for the McGuire Woods law firm . It is scheduled for completion in December , 2015 .",
"title": ""
},
{
"docid": "Central_Office_District",
"text": "The Central Office District is the central business district for Downtown Richmond , Virginia . The district contains a majority of the city core , with several high rises situated in this region of the city . The District houses the Richmond Federal Reserve Bank , Dominion Virginia Power 's corporate headquarters , Kanawha Plaza and the Virginia Tourism Corporation . U.S. Route 60 ( South 9th Street ) is the main street through the district .",
"title": ""
},
{
"docid": "Federal_banking",
"text": "Federal banking is the term for the way the Federal Reserve distributes its money . The Reserve ( often called the `` Fed '' ) operates twelve banking districts around the country which oversee money distribution within their respective districts . The twelve cities which are home to the Reserve Banks are Boston , New York City , Philadelphia , Richmond , Atlanta , Dallas , Saint Louis , Cleveland , Chicago , Minneapolis , Kansas City , and San Francisco .",
"title": ""
},
{
"docid": "Federal_Reserve_Bank_Building",
"text": "Federal Reserve Bank Building may refer to : Federal Reserve Bank of Atlanta Birmingham Branch , Birmingham , Alabama Federal Reserve Bank Building ( Little Rock , Arkansas ) Federal Reserve Bank of San Francisco , Los Angeles Branch , Los Angeles , California Federal Reserve Bank of San Francisco ( San Francisco , California ) Federal Reserve Bank Building ( Seattle ) Federal Reserve Bank of Richmond , Baltimore Branch , Baltimore , Maryland Federal Reserve Bank Building ( Boston , Massachusetts ) Federal Reserve Bank of Chicago Detroit Branch Building , Detroit , Michigan 925 Grand , the former Federal Reserve Building in Kansas City , Missouri Federal Reserve Bank of Kansas City , Kansas City , Missouri Federal Reserve Bank of New York , New York , New York Federal Reserve Bank of Cleveland , Cleveland , Ohio Old Federal Reserve Bank Building ( Philadelphia ) , Philadelphia , Pennsylvania Federal Reserve Bank of Atlanta , Nashville , Tennessee Eccles Building , Washington , D.C. , home to the board of governors of the Federal Reserve System",
"title": ""
},
{
"docid": "Crestar_Bank",
"text": "Crestar Bank was a regional bank headquartered in Richmond , Virginia with branches throughout Virginia and in Maryland . The bank was originally chartered as State Planters Bank Of Commerce And Trusts on December 8 , 1865 in Richmond . It was renamed United Virginia Bank/State Planters on February 15 , 1969 , and became United Virginia Bankshares , Inc. on December 15 , 1971 . With plans for expansion outside of the Commonwealth of Virginia , the Bank changed its name to Crestar Financial Corporation on September 1 , 1987 . In 1995 , Crestar acquired the assets of Loyola Federal Savings and Loan of Maryland , according to The New York Times . On March 14 , 1997 , Crestar acquired Citizens Bank of Maryland . On January 1 , 2000 , Crestar was acquired by Suntrust Bank . Now known as the SunTrust Plaza , Crestar 's former headquarters , a 26 story office tower , located a block from the Virginia State Capitol in the heart of downtown Richmond is one of Richmond 's premiere class `` A '' office buildings .",
"title": ""
},
{
"docid": "John_Brockenbrough",
"text": "John Brockenbrough ( 1775 -- 1852 ) was a business man and civic leader in Richmond , Virginia . He was president of the Bank of Virginia . His home in Richmond 's Court End District later served as the `` White House '' for the Confederate States of America .",
"title": ""
},
{
"docid": "Columbia_(Richmond,_Virginia)",
"text": "Columbia , also known as the Philip Haxall House , is a historic home located in Richmond , Virginia . It was built in 1817-1818 , and is a two-story , three bay Federal style brick dwelling on a high basement . The entrance features an elliptical fanlight opening sheltered by a one-story Doric porch . It was added when the entrance was moved from the Lombardy Street side to the Grace Street side in 1924 , when the building was expanded to house the T.C. Williams School of Law of the University of Richmond . It housed the School of Law from 1917 to 1954 . After 1834 , the house was the main academic building of Richmond College , which grew to become the present University of Richmond . It was listed on the National Register of Historic Places in 1982 .",
"title": ""
},
{
"docid": "Central_National_Bank_(Richmond,_Virginia)",
"text": "The Central National Bank building is a 23-story Art Deco skyscraper located in Richmond , Virginia . Completed in 1929 , it was one of the first skyscrapers in the city of Richmond not in the heart of the financial district . According to architectural historian Richard Guy Wilson , it and the West Hospital building , are the only two skyscrapers in Richmond to have used the fashionable Art Deco ziggurat-inspired setback , and only a few others exist elsewhere in Virginia . When the bank later changed hands , it was known as the Central Fidelity Bank . It was used as a branch bank for Wachovia Corp. until that closed in 2000 . After nearly fifteen years of vacancy , it was converted into apartments , and the first resident moved into the building in mid-2016 . The redevelopment is called to `` Deco at CNB , '' a 200-apartment development by Douglas Development Corp. . It was added to the National Register of Historic Places in 1979 . It is located in the Grace Street Commercial Historic District .",
"title": ""
},
{
"docid": "Mayor_of_Richmond,_Virginia",
"text": "The Mayor of the City of Richmond , Virginia is head of the executive branch of Richmond , Virginia 's city government . The mayor 's office administers all city services , public property , police and fire protection , most public agencies , and enforces all city , state and federal laws within Richmond , Virginia . The mayor looks over a city budget at roughly $ 765 million a year .",
"title": ""
},
{
"docid": "Call_Federal_Credit_Union",
"text": "Call Federal Credit Union is a federally insured , not-for-profit financial cooperative headquartered in Richmond , Virginia . It is regulated under the authority of the National Credit Union Administration ( NCUA ) of the U.S. federal government . Call Federal Credit Union is the second-largest Richmond-based credit union . As of December 31 , 2011 , Call Federal Credit Union had $ 350 million USD in assets and 31,000 members . In accordance with the Federal Credit Union Act of 1934 , Call Federal Credit Union is a tax-exempt , federally chartered , federally insured , not-for-profit financial cooperative . Call Federal Credit Union accounts are insured up to $ 250,000 through the NCUA , which is comparable to the insurance provided to accounts at traditional banks via the Federal Deposit Insurance Corporation .",
"title": ""
},
{
"docid": "Sports_in_Richmond,_Virginia",
"text": "Richmond , Virginia , United States , is home to three professional sports teams , though none of which compete in any major professional league . Virginia is the most populated state without a major sports team . In 2008 , the Richmond Braves minor league baseball team left for Gwinnett County , Georgia , and was replaced by the Richmond Flying Squirrels in 2010 . But now , the Flying Squirrels ' owner has threatened to leave Richmond if they do not replace their current stadium , The Diamond . The Richmond Kickers are a non-profit soccer team that plays at City Stadium . Richmond has also come into the national spotlight in recent years due to the success of the region 's two Division I college basketball teams , the VCU Rams and Richmond Spiders . The VCU Rams men 's basketball team reached the Final Four of the 2011 NCAA Men 's Division I Basketball Tournament , while the Richmond Spiders men 's basketball team reached the Sweet 16 of the same tournament . As of 2016 , Richmond is also home to its first women 's sports team , the Richmond Black Widows . They are in the Women 's Football Alliance and play at Hovey Field . The expansion team plays in Tier III of the Women 's Football Alliance and is the National Conference Champion .",
"title": ""
},
{
"docid": "Richmond_Metropolitan_Authority",
"text": "The Richmond Metropolitan Authority is an independent authority and political subdivision which serves the Richmond , Virginia metropolitan area . Created by an act of the Virginia General Assembly in 1966 , the RMA was originally tasked with building and maintaining a toll expressway system for the Richmond area . Since then , the role of the RMA has been expanded , and it currently owns and operates other facilities , including a number of parking decks and The Diamond , home stadium of the Richmond Braves minor league baseball team until 2008 , and the current home of the Richmond Flying Squirrels . The Authority also operates historic Main Street Station on behalf of the City of Richmond . Facilities operated by the RMA include : Downtown Expressway Powhite Parkway Boulevard Bridge The Diamond Main Street Station",
"title": ""
},
{
"docid": "First_National_Bank_Building_(Richmond,_Virginia)",
"text": "First National Bank Building , also known as the Old First and Merchants National Bank Building and BB&T Bank Building , is a historic bank and office building located in Richmond , Virginia . It was designed by noted architect Alfred Bossom and built in 1912-1913 . It is a 19-story , four bay by five bay , Classical Revival style steel frame building clad in brick , limestone , and granite . The building features rich architectural ornament that follows the Corinthian order both within and without . It was the first high-rise office tower to be built in Richmond . The First & Merchants Bank would eventually become Sovran Bank . It was listed on the National Register of Historic Places in 1982 . It is located in the Main Street Banking Historic District .",
"title": ""
},
{
"docid": "Richmond_WCT",
"text": "The Richmond WCT ( also known as United Virginia Bank Tennis Classic ) was a men 's tennis tournament played in Richmond , Virginia from 1971-1984 . The event was part of the WCT Tour and was held on indoor carpet courts .",
"title": ""
},
{
"docid": "East_Rutherford_Operations_Center",
"text": "The East Rutherford Operations Center ( EROC ) at 100 Orchard Street , East Rutherford , New Jersey , is the regional office for cash handling and processing of the Federal Reserve Bank of New York . The facility , which was constructed by Torcon , features a 400000 sqft three-story structure which sits on 13 acres . The structure is designed to house fail-safe operations in a secure environment . The facility also has a state-of-the art automated vault measuring one million cubic feet , used for storing United States currency . The vault can hold at least USD 60 billion . It was from this facility that the United States shipped some $ 12 billion to Iraq much of which money subsequently is unaccounted for . The center is one of three Federal Reserve Automation Services ( FRAS ) facilities in the Federal Reserve Banks system . They provide support for mission-critical payment systems . They are the survivors of the FedNet 5-year initiative started in 1990 to reengineer the Federal Reserve 's fund transfer system , and consolidate twelve data centers into 3 . If operations at East Rutherford fail , then the Federal Reserve Bank of Richmond serve as backup , with the Federal Reserve Bank of Dallas as secondary backup . In 2000 , the facility processed 1.39 billion checks , and USD$ 320 billion . The center 's bank check processing unit was shut down in 2006 as part of the Federal Reserve 's check restructuring process due to more checks being processed digitally . Check processing operations were moved to the Federal Reserve Bank of Philadelphia .",
"title": ""
},
{
"docid": "CSS_Richmond",
"text": "CSS Richmond , an ironclad ram , was built at Gosport ( Norfolk ) Navy Yard to the design of John L. Porter with money and scrap iron collected by the citizens of Virginia , whose imagination had been captured by the ironclad CSS Virginia . Consequently , she was sometimes referred to as Virginia II , Virginia No. 2 or Young Virginia in the South and as Merrimack No. 2 , New Merrimack or Young Merrimack by Union writers , months before the actual CSS Virginia II was ever laid down . Begun in March 1862 , Richmond was launched May 6 and towed up to the Confederate capital that very night to escape Federal forces again in possession of Norfolk Navy Yard and the lower James River . Richmond was thus finished at Richmond , Virginia in July 1862 and placed in commission by Commander Robert B. Pegram , CSN as part of the James River Squadron . Twenty-two inches of yellow pine and oak plus 4 inches of iron on her casemate protected her roof , and `` she is ironed 3 1/2 feet below her load lines , '' wrote Shipyard Superintendent John H. Burroughs . During 1863 and early 1864 the James front was quiet , but from May 1864 momentous events followed in quick succession . The Confederate Navy had three new ironclads in Captain French Forrest 's squadron there , and minor actions were frequent . During 1864 Richmond , under Lieutenant William Harwar Parker , CSN , took part in engagements at Dutch Gap on August 13 , Fort Harrison on September 29 -- October 1 , and Chaffin 's Bluff on October 22 . On January 23 -- 24 , 1865 , she was under heavy fire while aground with Virginia II above the obstructions at Trent 's Reach -- at an angle that caused Federal projectiles to ricochet harmlessly off their casemates . But Richmond '' 's unarmored tender , CSS Scorpion , being lashed alongside Richmond , was severely damaged by the explosion of CSS Drewry 's magazine . The ironclads were forced to withdrew under the Confederate batteries at Chaffin 's Bluff . A few weeks later , however , Richmond '' had to be destroyed to avoid capture by order of Rear Admiral Raphael Semmes , CSN squadron commander , prior to the evacuation of the Confederate capital on April 3 .",
"title": ""
},
{
"docid": "City_Stadium_(Richmond)",
"text": "City Stadium is a sports stadium in Richmond , Virginia . It is owned by the City of Richmond and is located south of the Carytown district off the Downtown Expressway . The stadium was built in 1929 and seats approximately 22,000 people . It is used by the Richmond Kickers of the United Soccer League since 1993 . The stadium was used by the University of Richmond for American football from 1929 to 2009 . The University of Richmond 's final home football game at the stadium was played on December 5 , 2009 against Appalachian State University in the quarterfinals of the Football Championship Subdivision playoffs . From 1964 through 1967 , the stadium was home to the Richmond Rebels of the Atlantic Coast Football League and the Continental Football League . The Rebels left the Continental Football League in 1967 to become the Richmond Mustangs of the United American Football League . University of Richmond Stadium served as the site of the NCAA Division I Men 's Soccer Championship from 1995-1998 . For a time in the mid-2000s , the stadium also hosted Virginia 's high school football state championship games .",
"title": ""
},
{
"docid": "Richmond,_Kentucky",
"text": "Richmond is a home rule-class city in and the county seat of Madison County , Kentucky , United States . It is named after Richmond , Virginia , and is the home of Eastern Kentucky University . The population was 33,533 in 2015 . Richmond is the third-largest city in the Bluegrass region ( after Louisville and Lexington ) and the state 's sixth-largest city . Richmond serves as the center for work and shopping for south-central Kentucky . Richmond is the principal city of the Richmond -- Berea Micropolitan Statistical Area , which includes all of Madison and Rockcastle counties .",
"title": ""
},
{
"docid": "Chickahominy_people",
"text": "The Chickahominy are a tribe of Virginian Indians who primarily live in Charles City County , located along the James River midway between Richmond and Williamsburg in the Commonwealth of Virginia . This area of the Tidewater is not far from where they lived in 1600 , prior to English colonization . They were officially recognized by the state in 1983 . The Eastern Chickahominy split from the main tribe in 1983 and were recognized separately by the state . They are based in New Kent County , about 25 mi east of Richmond . Neither tribe has an Indian reservation , having lost their land to English colonists in the 18th century , but they have purchased lands that they devote to communal purposes . Both tribes are among the 11 who have organized and been officially recognized by Virginia since 1983 . Neither has received recognition from the federal government . In 2009 , a bill was proposed in Congress to federally recognize six `` landless '' Virginia tribes already recognized by the state , including these two . Although passed by the House , it did not gain Senate approval .",
"title": ""
},
{
"docid": "Robert_P._Black",
"text": "Robert P. Black ( 1927 - ) , a native of Hickman , Kentucky , was the fifth president ( 1973 -- 1992 ) of the Federal Reserve Bank of Richmond , the headquarters of the Fifth District of the Federal Reserve System . He was preceded in that position by Aubrey N. Heflin and succeeded by J. Alfred Broaddus ( 1993 -- 2004 ) and Jeffrey Lacker ( August 1 , 2004 -- April 4 , 2017 ) .",
"title": ""
},
{
"docid": "2011_Richmond_Revolution_season",
"text": "The Richmond Revolution season was the team 's second season as a professional indoor football franchise and second in the Indoor Football League ( IFL ) . One of twenty-two teams competing in the IFL for the 2011 season , the Richmond , Virginia-based Richmond Revolution were members of the Atlantic Division of the United Conference . Under the leadership of head coach Tony Hawkins , the team played their home games at the Arthur Ashe Athletic Center in Richmond , Virginia .",
"title": ""
},
{
"docid": "Reveille_(Richmond,_Virginia)",
"text": "Reveille , also known as the Brick House , is a historic home located in Richmond , Virginia . The house consists of three sections . The main 2 1/2 - story house dates to about 1806 ; the 1 1/2 - story west wing dates to 1839 ; and a rear kitchen wing was added to the west wing in 1920 . The house is an example of an early 19th-century Federal style country residence . In 1950 the property and house were acquired by the Reveille United Methodist Church . It was listed on the National Register of Historic Places in 1979 .",
"title": ""
},
{
"docid": "Richmond_County_Bank_Ballpark",
"text": "The Richmond County Bank Ballpark at St. George ( RCB Ballpark ) is a baseball stadium located on the north-eastern tip of Staten Island . The ballpark is the home of the Staten Island Yankees , the NY-Penn League affiliate of the New York Yankees , and of Wagner College Seahawks Baseball . The ballpark was also home of the city 's Pro Cricket team the New York Storm in 2004 . In addition , local high schools have the chance to play at least one game at the Richmond County Bank Ballpark . The Ballpark at St. George is more commonly referred to as Staten Island Yankees Stadium instead of its much longer name , whose naming rights were given to Richmond County Savings Bank .",
"title": ""
},
{
"docid": "Richmond_Revolution",
"text": "The Richmond Revolution was a professional indoor football team based in Richmond , Virginia that played in the Indoor Football League from 2010 to 2011 . For the 2010 season , they played their home games at the Arthur Ashe Athletic Center . Because of space issues at that facility the owner decided to move onto the SportsQuest campus in nearby Chesterfield for the 2011 season and play all home games outdoors , since the proposed arena had not yet been built . However , in late August , Richmond BizSense 's writer Aaron Kremer ( 8/25/11 ) reported that Charlie Hildbold , the general manager , was laid off . He had moved to Virginia to help launch the indoor arena football team . According to Steve Burton , the owner of the team , Richmond Revolution will sit out the 2012 season and be reinstated in 2013 . Scott Bass a writer for Style Weekly reported ( 3/9/2011 ) nearly half of the 40 players on the Raiders ' training camp roster for 2011 defected from Richmond Revolution , as well as the Revolution 's head coach , Steve Criswell . On February 9 , 2012 the Virginia attorney general 's office filed a civil suit against SportsQuest , the company that owns the Revolution . This was Richmond 's third attempt at trying to build a long lasting indoor professional football team . The demise of Richmond Revolution left the Richmond Raiders the only team in the area . Previous teams were the Richmond Speed of the Af2 and the Richmond Bandits of the AIFL . When the team was first organized a name-the-team contest was held on the SportsQuest webpage . Nominations continued until August 11 , 2009 , with the five finalist names Blitz , Rush , Rivermen , Revolution , and Reign chosen the next day . Voting continued until August 21 with the Revolution name unveiled on August 24 . The Indoor Football League announced on June 23 , 2010 , that the Revolution had won the 2010 IFL Franchise of the Year award . In addition the team also took home the League 's Media Relations of the Year . Revolution QB Bryan Randall was named the 2010 IFL Most Valuable Player , and head coach Steve Criswell was named the IFL Coach of the Year . Later in the Steve Criswell left the team and on October 7 , 2010 , Richmond Revolution announced their new head coach would be former local standout Tony Hawkins . Hawkins is the all-time leading passer in Virginia State University history .",
"title": ""
}
] |
738
|
How prudent would it be to invest (stocks/equity) in businesses that are based on Cash transactions?
|
[
{
"docid": "341119",
"text": "If they're hiding their profits from the government, what makes you think they wouldn't hide their profits from their shareholders?",
"title": ""
},
{
"docid": "424439",
"text": "Every listed company needs to maintain book of accounts, when you are investing in companies you would have to look at what is stated in the books and along with other info decide to invest in it.",
"title": ""
}
] |
[
{
"docid": "177946",
"text": "\"I think the \"\"right\"\" way to approach this is for your personal books and your business's books to be completely separate. You would need to really think of them as separate things, such that rather than being disappointed that there's no \"\"cross transactions\"\" between files, you think of it as \"\"In my personal account I invested in a new business like any other investment\"\" with a transfer from your personal account to a Stock or other investment account in your company, and \"\"This business received some additional capital\"\" which one handles with a transfer (probably from Equity) to its checking account or the like. Yes, you don't get the built-in checks that you entered the same dollar amount in each, but (1) you need to reconcile your books against reality anyway occasionally, so errors should get caught, and (2) the transactions really are separate things from each entity's perspective. The main way to \"\"hack it\"\" would be to have separate top-level placeholder accounts for the business's Equity, Income, Expenses, and Assets/Liabilities. That is, your top-level accounts would be \"\"Personal Equity\"\", \"\"Business Equity\"\", \"\"Personal Income\"\", \"\"Business Income\"\", and so on. You can combine Assets and Liabilities within a single top-level account if you want, which may help you with that \"\"outlook of my business value\"\" you're looking for. (In fact, in my personal books, I have in the \"\"Current Assets\"\" account both normal things like my Checking account, but also my credit cards, because once I spend the money on my credit card I want to think of the money as being gone, since it is. Obviously this isn't \"\"standard accounting\"\" in any way, but it works well for what I use it for.) You could also just have within each \"\"normal\"\" top-level placeholder account, a placeholder account for both \"\"Personal\"\" and \"\"My Business\"\", to at least have a consistent structure. Depending on how your business is getting taxed in your jurisdiction, this may even be closer to how your taxing authorities treat things (if, for instance, the business income all goes on your personal tax return, but on a separate form). Regardless of how you set up the accounts, you can then create reports and filter them to include just that set of business accounts. I can see how just looking at the account list and transaction registers can be useful for many things, but the reporting does let you look at everything you need and handles much better when you want to look through a filter to just part of your financial picture. Once you set up the reporting (and you can report on lists of account balances, as well as transaction lists, and lots of other things), you can save them as Custom Reports, and then open them up whenever you want. You can even just leave a report tab (or several) open, and switch to it (refreshing it if needed) just like you might switch to the main Account List tab. I suspect once you got it set up and tried it for a while you'd find it quite satisfactory.\"",
"title": ""
},
{
"docid": "250530",
"text": "Canadian Couch Potato has an article which is somewhat related. Ask the Spud: Can You Time the Markets? The argument roughly boils down to the following: That said, I didn't follow the advice. I inherited a sum of money, more than I had dealt with before, and I did not feel I was emotionally capable of immediately dumping it into my portfolio (Canadian stocks, US stocks, world stocks, Canadian bonds, all passive indexed mutual funds), and so I decided to add the money into my portfolio over the course of a year, twice a month. The money that I had not yet invested, I put into a money market account. That worked for me because I was purchasing mutual funds with no transaction costs. If you are buying ETFs, this strategy makes less sense. In hindsight, this was not financially prudent; I'd have been financially better off to buy all the mutual funds right at the beginning. But I was satisfied with the tradeoff, knowing that I did not have hindsight and I would have been emotionally hurt had the stock market crashed. There must be research that would prove, based on past performance, the statistically optimal time frame for dollar-cost averaging. However, I strongly suppose that the time frame is rather small, and so I would advise that you either invest the money immediately, or dollar-cost average your investment over the course of the year. This answer is not an ideal answer to your question because it is lacking such a citation.",
"title": ""
},
{
"docid": "333755",
"text": "\"There are many different methods for a corporation to get money, but they mostly fall into three categories: earnings, debt and equity. Earnings would be just the corporation's accumulation of cash due to the operation of its business. Perhaps if cash was needed for a particular reason immediately, a business may consider selling a division or group of assets to another party, and using the proceeds for a different part of the business. Debt is money that (to put it simply) the corporation legally must repay to the lender, likely with periodic interest payments. Apart from the interest payments (if any) and the principal (original amount leant), the lender has no additional rights to the value of the company. There are, basically, 2 types of corporate debt: bank debt, and bonds. Bank debt is just the corporation taking on a loan from a bank. Bonds are offered to the public - ie: you could potentially buy a \"\"Tesla Bond\"\", where you give Tesla $1k, and they give you a stated interest rate over time, and principal repayments according to a schedule. Which type of debt a corporation uses will depend mostly on the high cost of offering a public bond, the relationships with current banks, and the interest rates the corporation thinks it can get from either method. Equity [or, shares] is money that the corporation (to put it simply) likely does not have a legal obligation to repay, until the corporation is liquidated (sold at the end of its life) and all debt has already been repaid. But when the corporation is liquidated, the shareholders have a legal right to the entire value of the company, after those debts have been paid. So equity holders have higher risk than debt holders, but they also can share in higher reward. That is why stock prices are so volatile - the value of each share fluctuates based on the perceived value of the entire company. Some equity may be offered with specific rules about dividend payments - maybe they are required [a 'preferred' share likely has a stated dividend rate almost like a bond, but also likely has a limited value it can ever receive back from the corporation], maybe they are at the discretion of the board of directors, maybe they will never happen. There are 2 broad ways for a corporation to get money from equity: a private offering, or a public offering. A private offering could be a small mom and pop store asking their neighbors to invest 5k so they can repair their business's roof, or it could be an 'Angel Investor' [think Shark Tank] contributing significant value and maybe even taking control of the company. Perhaps shares would be offered to all current shareholders first. A public offering would be one where shares would be offered up to the public on the stock exchange, so that anyone could subscribe to them. Why a corporation would use any of these different methods depends on the price it feels it could get from them, and also perhaps whether there are benefits to having different shareholders involved in the business [ie: an Angel investor would likely be involved in the business to protect his/her investment, and that leadership may be what the corporation actually needs, as much or more than money]. Whether a corporation chooses to gain cash from earnings, debt, or equity depends on many factors, including but not limited to: (1) what assets / earnings potential it currently has; (2) the cost of acquiring the cash [ie: the high cost of undergoing a public offering vs the lower cost of increasing a bank loan]; and (3) the ongoing costs of that cash to both the corporation and ultimately the other shareholders - ie: a 3% interest rate on debt vs a 6% dividend rate on preferred shares vs a 5% dividend rate on common shares [which would also share in the net value of the company with the other current shareholders]. In summary: Earnings would be generally preferred, but if the company needs cash immediately, that may not be suitable. Debt is generally cheap to acquire and interest rates are generally lower than required dividend rates. Equity is often expensive to acquire and maintain [either through dividend payments or by reduction of net value attributable to other current shareholders], but may be required if a new venture is risky. ie: a bank/bondholder may not want to lend money for a new tech idea because it is too risky to just get interest from - they want access to the potential earnings as well, through equity.\"",
"title": ""
},
{
"docid": "273947",
"text": "\"Exactly what accounts are affected by any given transaction is not a fixed thing. Just for example, in a simple accounting system you might have one account for \"\"stock on hand\"\". In a more complex system you might have this broken out into many accounts for different types of stock, stock in different locations, etc. So I can only suggest example specific accounts. But account type -- asset, liability, capital (or \"\"equity\"\"), income, expense -- should be universal. Debit and credit rules should be universal. 1: Sold product on account: You say it cost you $500 to produce. You don't say the selling price, but let's say it's, oh, $700. Credit (decrease) Asset \"\"Stock on hand\"\" by $500. Debit (increase) Asset \"\"Accounts receivable\"\" by $700. Credit (increase) Income \"\"Sales\"\" by $700. Debit (increase) Expense \"\"Cost of goods sold\"\" by $500. 2: $1000 spent on wedding party by friend I'm not sure how your friend's expenses affect your accounts. Are you asking how he would record this expense? Did you pay it for him? Are you expecting him to pay you back? Did he pay with cash, check, a credit card, bought on credit? I just don't know what's happening here. But just for example, if you're asking how your friend would record this in his own records, and if he paid by check: Credit (decrease) Asset \"\"checking account\"\" by $1000. Debit (increase) Expense \"\"wedding expenses\"\" by $1000. If he paid with a credit card: Credit (increase) Liability \"\"credit card\"\" by $1000. Debit (increase) Expense \"\"wedding expenses\"\" by $1000. When he pays off the credit card: Debit (decrease) Liability \"\"credit card\"\" by $1000. Credit (decrease) Asset \"\"cash\"\" by $1000. (Or more realistically, there are other expenses on the credit card and the amount would be higher.) 3: Issue $3000 in stock to partner company I'm a little shakier on this, I haven't worked with the stock side of accounting. But here's my best stab: Well, did you get anything in return? Like did they pay you for the stock? I wouldn't think you would just give someone stock as a present. If they paid you cash for the stock: Debit (increase) Asset \"\"cash\"\". Credit (decrease) Capital \"\"shareholder equity\"\". Anyone else want to chime in on that one, I'm a little shaky there. Here, let me give you the general rules. My boss years ago described it to me this way: You only need to know three things to understand double-entry accounting: 1: There are five types of accounts: Assets: anything you have that has value, like cash, buildings, equipment, and merchandise. Includes things you may not actually have in your hands but that are rightly yours, like money people owe you but haven't yet paid. Liabilities: Anything you owe to someone else. Debts, merchandise paid for but not yet delivered, and taxes due. Capital (some call it \"\"capital\"\", others call it \"\"equity\"\"): The difference between Assets and Liabilities. The owners investment in the company, retained earnings, etc. Income: Money coming in, the biggest being sales. Expenses: Money going out, like salaries to employees, cost of purchasing merchandise for resale, rent, electric bill, taxes, etc. Okay, that's a big \"\"one thing\"\". 2: Every transaction must update two or more accounts. Each update is either a \"\"debit\"\" or a \"\"credit\"\". The total of the debits must equal the total of the credits. 3: A dollar bill in your pocket is a debit. With a little thought (okay, sometimes a lot of thought) you can figure out everything else from there.\"",
"title": ""
},
{
"docid": "178303",
"text": "\"Some thoughts: 1) Do you have a significant emergency fund (3-6 months of after-tax living expenses)? If not, you stand to take a significant loss if you have an unexpected need for cash that is tied up in investments. What if you lose/hate your job or your car breaks down? What if a you want to spend some time with a relative or significant other who learns they only have a few months to live? Having a dedicated emergency fund is an important way to avoid downside risk. 2) Lagerbaer has a good suggestion. Given that if you'd reinvested your dividends, the S&P 500 has returned about 3.5% over the last 5 years, you may be able to get a very nice risk-free return. 3) Do you have access to employer matching funds, such as in a 401(k) at work? If you get a dollar-for-dollar match, that is a risk-free pre-tax 100% return and should be a high priority. 4) What do you mean by \"\"medium\"\" volatility? Given that you are considering a 2/3 equity allocation, it would not be at all out of the realm of possibility that your balance could fall by 15% or more in any given year and take several years to recover. If that would spook you, you may want to consider lowering your equity weights. A high quality bond fund may be a good fit. 5) Personally, I would avoid putting money into stocks that I didn't need back for 10 years. If you only want to tie your money up for 2-5 years, you are taking a significant risk that if prices fall, you won't have time to recover before you need your money back. The portfolio you described would be appropriate for someone with a long-term investment horizon and significant risk tolerance, which is usually the case for young people saving for retirement. However, if your goals are to invest for 2-5 years only, your situation would be significantly different. 6) You can often borrow from an investment account to purchase a primary residence, but you must pay that amount back in order to avoid significant taxes and fees, unless you plan to liquidate assets. If you plan to buy a house, saving enough to avoid PMI is a good risk-free return on your money. 7) In general, and ETF or index fund is a good idea, the key being to minimize the compound effect of expenses over the long term. There are many good choices a la Vanguard here to choose from. 8) Don't worry about \"\"Buy low, sell high\"\". Don't be a speculator, be an investor (that's my version of Anthony Bourdain's, \"\"don't be a tourist, be a traveler\"\"). A speculator wants to sell shares at a higher price than they were purchased at. An investor wants to share in the profits of a company as a part-owner. If you can consistently beat the market by trying to time your transactions, good for you - you can move to Wall Street and make millions. However, almost no one can do this consistently, and it doesn't seem worth it to me to try. I don't mean to discourage you from investing, just make sure you have your bases covered so that you don't have to cash out at a bad time. Best of luck! Edit Response to additional questions below. 1) Emergency fund. I would recommend not investing in anything other than cash equivalents (money market, short-term CDs, etc.) until you've built up an emergency fund. It makes sense to want to make the \"\"best\"\" use of your money, but you also have to account for risk. My concern is that if you were to experience one or more adverse life events, that you could lose a lot of money, or need to pay a lot in interest on credit card debt, and it would be prudent to self-insure against some of those risks. I would also recommend against using an investment account as an emergency fund account. Taking money out of investment accounts is inefficient because the commissions/taxes/fees can easily eat up a significant portion of your returns. Ideally, you would want to put money in and not touch it for a long time in order to take advantage of compounding returns. There are also high penalties for early disbursements from retirement funds. Just like you need enough money in your checking account to buy food and pay the rent every month, you need enough money in an emergency fund to pay for things that are a real possibility, even if they are less common. Using a credit card or an investment account is a relatively expensive way to do this. 2) Invest at all? I would recommend starting an emergency fund, and then beginning to invest for retirement. Once your retirement savings are on track, you can begin saving for whatever other goals you may have\"",
"title": ""
},
{
"docid": "526422",
"text": "\"The question is asking for a European equivalent of the so-called \"\"Couch Potato\"\" portfolio. \"\"Couch Potato\"\" portfolio is defined by the two URLs provided in question as, Criteria for fund composition Fixed-income: Regardless of country or supra-national market, the fixed-income fund should have holdings throughout the entire length of the yield curve (most available maturities), as well as being a mix of government, municipal (general obligation), corporate and high-yield bonds. Equity: The common equity position should be in one equity market index fund. It shouldn't be a DAX-30 or CAC-40 or DJIA type fund. Instead, you want a combination of growth and value companies. The fund should have as many holdings as possible, while avoiding too much expense due to transaction costs. You can determine how much is too much by comparing candidate funds with those that are only investing in highly liquid, large company stocks. Why it is easier for U.S. and Canadian couch potatoes It will be easier to find two good funds, at lower cost, if one is investing in a country with sizable markets and its own currency. That's why the Couch Potato strategy lends itself most naturally to the U.S.A, Canada, Japan and probably Australia, Brazil, South Korea and possibly Mexico too. In Europe, pre-EU, any of Germany, France, Spain, Italy or the Scandinavian countries would probably have worked well. The only concern would be (possibly) higher equity transactions costs and certainly larger fixed-income buy-sell spreads, due to smaller and less liquid markets other than Germany. These costs would be experienced by the portfolio manager, and passed on to you, as the investor. For the EU couch potato Remember the criteria, especially part 2, and the intent as described by the Couch Potato name, implying extremely passive investing. You want to choose two funds offered by very stable, reputable fund management companies. You will be re-balancing every six months or a year, only. That is four transactions per year, maximum. You don't need a lot of interaction with anyone, but you DO need to have the means to quickly exit both sides of the trade, should you decide, for any reason, that you need the money or that the strategy isn't right for you. I would not choose an ETF from iShares just because it is easy to do online transactions. For many investors, that is important! Here, you don't need that convenience. Instead, you need stability and an index fund with a good reputation. You should try to choose an EU based fund manager, or one in your home country, as you'll be more likely to know who is good and who isn't. Don't use Vanguard's FTSE ETF or the equivalent, as there will probably be currency and foreign tax concerns, and possibly forex risk. The couch potato strategy requires an emphasis on low fees with high quality funds and brokers (if not buying directly from the fund). As for type of fund, it would be best to choose a fund that is invested in mostly or only EU or EEU (European Economic Union) stocks, and the same for bonds. That will help minimize your transaction costs and tax liability, while allowing for the sort of broad diversity that helps buy and hold index fund investors.\"",
"title": ""
},
{
"docid": "378137",
"text": "Diversification is just one aspect in an investment portfolio. The other aspects in Investment are Risk Taking Ability, Liquidity, Local Regulations, Tax benefits, Ease & Convenience, Cost of carrying out transactions etc. Investing in other regions is prone FX risk and other risks depending on the region of investment. For example investing in Emerging markets there is a risk of Local Regulations being changed, additional tax being levied, or Political instability and host of such risks. Investing in local markets give you better understanding of such changes and the risk associated is less plus the Ease of carrying out transactions is great, less expensive compared to cost of transactions in other markets. Diversification in Investment should also be looked upon how much you invest in; Equities Debt Bullion Real Estate Once you have a sizeable amount of investment in Equities or Debt, it would then make more sense to diversify this portion more to include funds from other regions. Unless you are an Running your own business, it makes sense to invest in your line of business if that is performing well. The reason being that the benefit / returns from the equities is much greater than the salary rise / bonus. For example I am in Information Technology and yet invest in all leading IT companies because the returns from companies in these segments have been good.",
"title": ""
},
{
"docid": "123263",
"text": "\"If you are looking for numerical metrics I think the following are popular: Price/Earnings (P/E) - You mentioned this very popular one in your question. There are different P/E ratios - forward (essentially an estimate of future earnings by management), trailing, etc.. I think of the P/E as a quick way to grade a company's income statement (i.e: How much does the stock cost verusus the amount of earnings being generated on a per share basis?). Some caution must be taken when looking at the P/E ratio. Earnings can be \"\"massaged\"\" by the company. Revenue can be moved between quarters, assets can be depreciated at different rates, residual value of assets can be adjusted, etc.. Knowing this, the P/E ratio alone doesn't help me determine whether or not a stock is cheap. In general, I think an affordable stock is one whose P/E is under 15. Price/Book - I look at the Price/Book as a quick way to grade a company's balance sheet. The book value of a company is the amount of cash that would be left if everything the company owned was sold and all debts paid (i.e. the company's net worth). The cash is then divided amoung the outstanding shares and the Price/Book can be computed. If a company had a price/book under 1.0 then theoretically you could purchase the stock, the company could be liquidated, and you would end up with more money then what you paid for the stock. This ratio attempts to answer: \"\"How much does the stock cost based on the net worth of the company?\"\" Again, this ratio can be \"\"massaged\"\" by the company. Asset values have to be estimated based on current market values (think about trying to determine how much a company's building is worth) unless, of course, mark-to-market is suspended. This involves some estimating. Again, I don't use this value alone in determing whether or not a stock is cheap. I consider a price/book value under 10 a good number. Cash - I look at growth in the cash balance of a company as a way to grade a company's cash flow statement. Is the cash account growing or not? As they say, \"\"Cash is King\"\". This is one measurement that can not be \"\"massaged\"\" which is why I like it. The P/E and Price/Book can be \"\"tuned\"\" but in the end the company cannot hide a shrinking cash balance. Return Ratios - Return on Equity is a measure of the amount of earnings being generated for a given amount of equity (ROE = earnings/(assets - liabilities)). This attempts to measure how effective the company is at generating earnings with a given amount of equity. There is also Return on Assets which measures earnings returns based on the company's assets. I tend to think an ROE over 15% is a good number. These measurements rely on a company accurately reporting its financial condition. Remember, in the US companies are allowed to falsify accounting reports if approved by the government so be careful. There are others who simply don't follow the rules and report whatever numbers they like without penalty. There are many others. These are just a few of the more popular ones. There are many other considerations to take into account as other posters have pointed out.\"",
"title": ""
},
{
"docid": "329637",
"text": "You need to be clear about who gets your money: If you pay the existing owner $25K and (s)he gives you half the business, then you now own half of a $50K business an the original owner has an extra $25K in spending cash. The value of the business has not changed. If you contribute $25 to the company, new equity shares are created. Shares should be priced correctly, meaning you now own $25K worth of shares in a company worth $75k, so you should have 1/3 of the outstanding shares (counting both old and new shares). If you get more or less than this, then the transaction has happened in an unfair way. If this is a public company, that would most likely be illegal and the SEC may throw you in jail. If it was a private company and your friend created enough shares that you own half the company, then (s)he has given you a gift. If you are contributing to the company at a fair price, you would need to contribute $50K in order to end up with half the equity of the new and now more valuable firm. In that case the firm would be worth $100K after your contribution. Bottom line, this is a common and not complex transaction and should end up with a completely fair outcome. Any unfair situation you can imagine is probably based on false assumptions or a situation where a non-arms-length transaction is transferring wealth contrary to normal rules and procedures.",
"title": ""
},
{
"docid": "40966",
"text": "It took me a while to understand the concept, so I'll break it down as best as I can. There are three parts to the accounting equation: Assets = Liabilities + Owner's Equity We'll look at this in two ways 1. As a business owner you invest (say) 10,000 USD into your bank. The entry would be: Debit: Assets: Cash for 10,000 Credit: Owner's Equity: Contributions for 10,000 In this case, you have assets of 10,000 from your deposit, but it is due to owner contributions and not business transactions. Another example (say a sale): Debit: Assets: Cash for 10,000 Credit: Owner's Equity: Sales for 10,000 Debit: Assets: Cash for 10,000 Credit: Liabilities: Deposits for 10,000 Deposits are a banking term to reflect a bank's obligation to return the amount on demand (though the bank has free reign with it, see fractional banking) You will NEVER debit or credit your bank as it is assumed you will be storing your money there, note bank reconciliation. Hope this helps, comment with any more questions.",
"title": ""
},
{
"docid": "425888",
"text": "How you should record the mortgage payments depends on if you are trying to achieve correct accounting, according to the standards, or if you are just tracking everything for you and your friends. If you're just keeping track for personal reasons, I'd suggest that you set up your check (or journal entry, your preference) how you'd like it to be recorded. Then, memorize that transaction. This allows you to use it as many times as you need to, without having to set it up each time. (Also note: there is no way to record a transaction that decreases cash and increases equity.) If you're trying to keep track of everything according to accounting standards, which it should be if you've set up an official business, then you have a lot more tracking to do with each payment. Mortgage payments technically do not affect the equity accounts of the owners. Each mortgage payment should decrease the bank balance, increase interest expense and decrease the mortgage balance, not to mention tracking any escrow account you may have. The equity accounts would be affected if the owners are contributing funds to the bank account, but equity would increase at the time the funds are deposited, not when the mortgage payments are made. Hope this helps!",
"title": ""
},
{
"docid": "546313",
"text": "\"Training8m Corporate Technologies Pty Ltd, Australia Australia ABN 48133544297 UK Company Number: 7538482 Maiden Pre-IPO offer from Training8m Corporate Technologies Pty Ltd, Australia!! Unique opportunity for investors!!! Move to a most profitable and defensive investment!!! We offer Preferential Allotment / Private Placement of Debt / Equity. Most Profitable offer from The Global Leader!! www.training8m.com Subscription Offer Open: First ever pre-IPO offer from Training8m Australia Group!! Unique opportunity for investors!!! Move to a most profitable and defensive investment!!! Preferential Allotment / Private Placement of Debt / Equity to multiple business investors pre IPO from $ 50k to $ 25 Mn for start up venture set up and Capital market Listing on Frankfurt Stock Exchange. We offer Preferential Allotment / Private Placement of Equity to multiple business investors Pre- IPO from $ 50K to $ 25 Mn. Higher investment welcome for this International public issue. Equivalent Debt / Equity / Options / Preference Shares can be discussed. Minority Equity participation can be discussed. We at Training8m Australia are Going Public Soon on Frankfurt Stock Exchange. Status: Approved funding by major Global Private Equity Fund. We are pleased to write that our major funding, raising funds from the equity market listing on Frankfurt Stock Exchange, is approved by major and most reputed Private Equity Group. This is one of the largest upcoming IPO, highly profitable with high ROI. Subscription: Open to Institutional and Retail Investors Pre IPO offer in Debt / Equity / Preference Shares / Options Serious investors only please. We would like to conclude this current deal immediately. We at Training8m, Australia are willing to discuss on the Debt / Equity / Options / preference shares and will be liberal for this transaction, which will be issued to you directly from our fund managers. This is definitely a really profitable and high return investment. Payback period: 1 - 2 years (expected turnover at least $ 2 Bn in 3 years) Start up Stage of business. This investment has very attractive returns. Unique opportunity to associate prior to the IPO on Global Stock Exchanges Location: Head Quartered in Gold Coast, Australia with Global Operating Offices. Set up including Property Investment, Recruitment and Appointment of permanent personnel, Fees for Listing on major Global Stock Exchange, other expenses as needed for the business. Business Models: Training8m Corporate Technologies Pty Ltd, Australia Corporate Training, Marketing, Premium Recruitment Portal, Premium and Moderated Recruitment Social Networking, Training and Development for all industry Verticals, Global Business Solutions. Advanced Lighting Designers Pty Ltd, Australia We offer International Lighting Technologies, Design, Specifications, Software Solutions and High End Information Technology Services to Global Industry sectors. Please do note that we are officially registered in Australia and UK for our Global Business ventures. With appropriate funding for takeovers, mergers and Acquisitions, we will be listing the companies Training8m Corporate Technologies Pty Ltd, and Advanced Lighting Designers Pty Ltd, on major global stock exchanges. The punch line of Advanced Lighting Designers Pty Ltd is “Go Green with Force Green\"\" in which we will be focussing on Green Energy Worldwide. Please feel free to ask details privately. Offer for limited time and closes on receipt of funds. E- Mails: [email protected], [email protected] Shrikant G. Shete Chairman and Managing Director Training8m, Australia LinkedIn: http://au.linkedin.com/in/shrikantshete +61-400769125 ................................Australia Mobiles +61-434415521 ................................Australia Mobiles\"",
"title": ""
},
{
"docid": "414505",
"text": "\"The key difference I've found between a stock split and a stock dividend – of the exact same stock and class, as opposed to a spin-off – seems to be from the company's own accounting perspective. There doesn't appear to be any actual transfer of value to the shareholder with either kind of transaction; i.e. in theory, each transaction would be immaterial to the value of your holdings. With respect to the company's accounting, a stock split affects the par value of the shares, whereas a stock dividend reduces the retained earnings account in order to increase paid-in or contributed capital. I found a good online source which explains the history behind this accounting difference: McGraw-Hill - Intermediate Accounting eBook, 6/e - Chapter 18 - Stock Dividends and Splits. Small quote: [...] Besides being based on fallacious reasoning, accounting for stock dividends by artificially reclassifying “earned” capital as “invested” capital conflicts with the reporting objective of reporting shareholders' equity by source. Despite these limitations, this outdated accounting standard still applies. Since neither the corporation nor its shareholders apparently benefits from stock dividends, why do companies declare them?23 Occasionally, a company tries to give shareholders the illusion that they are receiving a real dividend. Another reason is merely to enable the corporation to take advantage of the accepted accounting practice of capitalizing retained earnings. Specifically, a company might wish to reduce an existing balance in retained earnings—otherwise available for cash dividends—so it can reinvest the earned assets represented by that balance without carrying a large balance in retained earnings. [...] There's a lot more on that page, before and after, worth reading. From another book: Google Books - Comparative Income Taxation, a Structural Analysis - page 314 - Stock Dividends. Small quote: The distribution of dividends in the form of stock or \"\"bonus\"\" shares to existing shareholders typically involves a transfer for corporate law purposes of retained earnings into stated capital. It can been [sic] viewed as a deemed distribution of a cash dividend to the shareholders followed by a corresponding contribution to capital or as solely as an event at the corporate level which has no effect on the shareholders whose economic interest in the corporation is unchanged by the receipt of additional shares. The systems have taken varied approaches to the stock dividend problem. The treatment is in part a function of the rules dealing with distributions of stated capital. [emphases above are mine] [... continues w/descriptions of different countries' tax treatments of the kinds of stock dividends. Includes U.S., Sweden, Japan, Netherlands, Canada, Australia, U.K., France, Germany. ...] As far as why a corporation might want to capitalize earnings and reduce the equity otherwise available for dividends, I can only imagine that, ignoring taxes for a moment, that it may have something to do with capital ratios that need to be maintained for financing or regulatory purposes? Yet, I remain curious. If I discover more on this then I'll update my answer. Additional resources:\"",
"title": ""
},
{
"docid": "5710",
"text": "\"As Michael Pryor answered, a bond fund is a mutual fund that invests in bonds. I'd also consider an ETF based on bonds to be a bond fund, but I'm not sure that all investors would consider these as \"\"bond funds\"\". Not all bond funds are the same -- just like stock funds. You can classify bond funds based on the issuer of the bonds: You can also classify funds based on the time to maturity: In general, bond funds have lower risk and lower expected return than stock funds. Sometimes bond funds have price movements that are not tightly correlated to the price movements in the equity markets. This can make them a decent hedge against declines in your equity investments. See Michal Pryor's answer for some info on how you can get tax free treatment for your bond fund investments.\"",
"title": ""
},
{
"docid": "190891",
"text": "\"The price of real estate reacts to both demand for property and the rate of inflation and rate of income growth. Mortgage rates generally move as treasury rates move. See this paragraph: As we mentioned, intermediate term bonds and long-term mortgages (more properly, Mortgage-Backed Securities, or MBS) compete for the same fixed-income investor dollar. Treasury issues are 100% guaranteed to be repaid, but mortgages are not; therefore mortgages carry more risk of default or early repayment, which could potentially disturb the return on the investment. Therefore, mortgage rates must be priced higher to compensate for that risk. But how much higher are mortgages priced? In a normal market, the average \"\"spread\"\" or markup above the 100% secured Treasury is about 170 basis points, or 1.7%. That markup -- the spread relationship -- widens and contracts with a range of market conditions, investor appetites and supply of available product -- as well as the presence of competing investment opportunities, like corporate bonds or domestic (or foreign) equity markets Source: What Moves Mortgage Rates? And when the stock market crashes, investors tend to run to bonds and treasuries, which causes prices to go up and treasury yields to drop. Theoretically, this would also cause mortgage rates to drop, although most mortgage rates have a base price below which they cannot fall. How easy is it to profit from recent stock market drops and at what frequency? Incredibly difficult. The issue with your strategy is that you cannot predict the bottom of the market (at least us mortals can't). Just take the month of August for example. Stocks fell something like 15%? After the first 5-10% drop, people felt that the bottom was there, so they rushed in, only to have the market fall even more. How will you know when to invest? Even if the market falls by 50%, and there's a huge buying opportunity, and you increase the mortgage on your house, odds are your rates will increase because of the equity you take out. What if the market stays low for a very long time? Will you be able to maintain mortgage payments? Japan's stock bubble popped in the early 90's, and they've had two lost decade's now. Furthermore, there are issues of liquidity. What if you need more capital? Can you just sell a property or can you buy now property to draw equity against? What if the market is moving too fast for you to take advantage of. Don't ignore transaction costs and taxes either. Overall, there are a lot of ways that your idea can go wrong, and not many ways it can go right.\"",
"title": ""
},
{
"docid": "474467",
"text": "You only got 75 shares, so your basis is the fair market value of the stock as of the grant date times the number of shares you got: $20*75. Functionally, it's the same thing as if your employer did this: As such, the basis in that stock is $1,500 ($20*75). The other 25 shares aren't yours and weren't ever yours, so they aren't part of your basis (for net issuance; if they were sell to cover, then the end result would be pretty similar, but there'd be another transaction involved, but we won't go there). To put it another way, suppose your employer paid you a $2000 bonus, leaving you with a $1500 check after tax withholding. Being a prudent person and not wishing to blow your bonus on luxury goods, you invest that $1500 in a well-researched investment. You wouldn't doubt that your cost basis in that investment at $1500.",
"title": ""
},
{
"docid": "161230",
"text": "This is a bit of an open-ended answer as certain assumptions must be covered. Hope it helps though. My concern is that you have 1 year of university left - is there a chance that this money will be needed to fund this year of uni? And might it be needed for the period between uni and starting your first job? If the answer is 'yes' to either of these, keep any money you have as liquid as possible - ie. cash in an instant access Cash ISA. If the answer is 'no', let's move on... Are you likely to touch this money in the next 5 years? I'm thinking house & flat deposits - whether you rent or buy, cars, etc, etc. If yes, again keep it liquid in a Cash ISA but this time, perhaps look to get a slightly better interest rate by fixing for a 1 year or 2 year at a time. Something like MoneySavingExpert will show you best buy Cash ISAs. If this money is not going to be touched for more than 5 years, then things like bonds and equities come into play. Ultimately your appetite for risk determines your options. If you are uncomfortable with swings in value, then fixed-income products with fixed-term (ie. buy a bond, hold the bond, when the bond finishes, you get your money back plus the yield [interest]) may suit you better than equity-based investments. Equity-based means alot of things - stocks in just one company, an index tracker of a well-known stock market (eg. FTSE100 tracker), actively managed growth funds, passive ETFs of high-dividend stocks... And each of these has different volatility (price swings) and long-term performance - as well as different charges and risks. The only way to understand this is to learn. So that's my ultimate advice. Learn about bonds. Learn about equities. Learn about gilts, corporate bonds, bond funds, index trackers, ETFs, dividends, active v passive management. In the meantime, keep the money in a Cash ISA - where £1 stays £1 plus interest. Once you want to lock the money away into a long-term investment, then you can look at Stocks ISAs to protect the investment against taxation. You may also put just enough into a pension get the company 'match' for contributions. It's not uncommon to split your long-term saving between the two routes. Then come back and ask where to go next... but chances are you'll know yourself by then - because you self-educated. If you want an alternative to the US-based generic advice, check out my Simple Steps concept here (sspf.co.uk/seven-simple-steps) and my free posts on this framework at sspf.co.uk/blog. I also host a free weekly podcast at sspf.co.uk/podcast (also on iTunes, Miro, Mixcloud, and others...) They were designed to offer exactly that kind of guidance to the UK for free.",
"title": ""
},
{
"docid": "250354",
"text": "\"Well, this sub is generally pretty darn good. Among us are investment bankers, private equity analysts, valuation analysts, portfolio managers, traders, brokers, bachelors, masters, and doctorate students, etc. We're helpful, though sometimes snarky, and have an exceedingly low tolerance for bullshit. I love it here. And while your logic is sound, we can actually explore private equity directly, as while private and public equity are related, they are different enough to study separately, in my opinion. Private equity deals with private companies. By definition, these investments are illiquid (they cannot be easily sold like public stocks), and unmarketable (there is no ready market to trade these investments, like stock). They are generally held for longer time periods. At its earliest stage, private equity is synonymous with \"\"initial investment\"\" or \"\"seed funding.\"\" This includes (if we are maybe slightly liberal with our definition), the initial investment an entrepreneur makes into his business. At this stage, friends and family, angel investors and venture capital are present. At different points of a company lifecycle, different financiers become interested/applicable (mezzanine investors, etc.). The investment made into a company allocates a certain percentage of the ownership of the company to the investor in exchange for cash (usually). This cash is used to cover expenses and take on capital projects. The goal of these investments is to directly make the company (and its value, and thus the investor's value) grow. At some points in time, a new investor will show up and either invest directly in the company (same as before) or buy another investor's holding in the company (in which case, cash goes to *that specific investor* and *not* the company). At every stage of investment leading up to IPO, the deals are negotiated between the parties. The results of a given negotiation determines the value of that company's equity. For example, if I pay you $100 for 50% of your company, the company's implied worth is $200. If two days later, Joe comes and offers to buy 33% of the company for $100, the Company is worth $300. (Special note: these percentages are assumed to be the allocation of equity **after** the deal. In this last case, the ownership of your company would be 33% you, 33% me, and 33% Joe. This illustrates something called *dilution,* which is very important to investors as it effects their eventual potential payoff later down the road, along with some other things). At this point, do you have any questions?\"",
"title": ""
},
{
"docid": "130631",
"text": "\"In the US you are not required to have a corporation to use business expenses to offset your income. The technical term you need is \"\"deducting business expenses\"\", and in matters of taxes it's usually best to go straight to the horse's mouth: the IRS's explanations Deducting Business Expenses Business expenses are the cost of carrying on a trade or business. These expenses are usually deductible if the business operates to make a profit. What Can I Deduct? Cost of Goods Sold, Capital Expenses, Personal versus Business Expenses, Business Use of Your Home, Business Use of Your Car, Other Types of Business Expenses None of this requires any special incorporation or tax arrangements, and are a normal part of operating a business. However, there is a bit of a problem with your scenario. You said you \"\"invested\"\" into a business, but you mentioned buying specific things for the business which is not generally how one accounts for investment. If you are not an owner/operator of the business, then the scenario is not so straight-forward, as you can't simply claim someone else's business expenses as your own because you invested in it. Investments are taxed differently than expenses, and based upon your word choices I'm concerned that you could be getting yourself into a bit of a pickle. I would strongly advise you to speak with a professional, such as a Certified Public Accountant (CPA), to go over your current arrangement and advise you on how you should be structuring your ongoing investment into this shared business. If you are investing you should be receiving equity to reflect your ownership (or stock in the company, etc), and investments of this sort generally cannot be deducted as an expense on your taxes - it's just an investment, the same as buying stock or CDs. If you are just buying things for someone else's benefit, it's possible that this could be looked upon as a personal gift, and you may be in a precarious legal position as well (where the money is, indeed, just a gift). And gifts of this sort aren't deductible, either. Depending on how this is all structured, it's possible that you should both consider a different form of legal organization, such as a formal corporation or at least an official business partnership. A CPA and an appropriate business attorney should be able to advise you for a nominal (few hundred dollars, at most) fee. If a new legal structure is advisable, you can potentially do the work yourself for a few hundred dollars, or pay to have it done (especially if the situation is more complex) for a few hundred to a few thousand. That's a lot less than you'd be on the hook for if this business is being accounted for improperly, or if either of your tax returns are being reported improperly!\"",
"title": ""
},
{
"docid": "517323",
"text": "The stock market is just like any other market, but stocks are bought and sold here. Just like you buy and sell your electronics at the electronics market, this is a place where buyers and sellers come together to buy and sell shares or stocks or equity, no matter what you call it. What are these shares? A share is nothing but a portion of ownership of a company. Suppose a company has 100 shares issued to it, and you were sold 10 out of those, it literally means you are a 10% owner of the company. Why do companies sell shares? Companies sell shares to grow or expand. Suppose a business is manufacturing or producing and selling goods or services that are high in demand, the owners would want to take advantage of it and increase the production of his goods or services. And in order to increase production he would need money to buy land or equipment or labor, etc. Now either he could go get a loan by pledging something, or he could partner with someone who could give him money in exchange for some portion of the ownership of the company. This way, the owner gets the money to expand his business and make more profit, and the lender gets a portion of profit every time the company makes some. Now if the owner decides to sell shares rather than getting a loan, that's when the stock market comes into the picture. Why would a person want to trade stocks? First of all, please remember that stocks were never meant to be traded. You always invest in stocks. What's the difference? Trading is short term and investing is long term, in very simple language. It's the greed of humans which led to this concept of trading stocks. A person should only buy stocks if he believes in the business the company is doing and sees the potential of growth. Back to the question: a person would want to buy stocks of the company because: How does a stock market help society? Look around you for the answer to this question. Let me give you a start and I wish everyone reading this post to add at least one point to the answer. Corporations in general allow many people come together and invest in a business without fear that their investment will cause them undue liability - because shareholders are ultimately not liable for the actions of a corporation. The cornerstone North American case of how corporations add value is by allowing many investors to have put money towards the railroads that were built across America and Canada. For The stock market in particular, by making it easier to trade shares of a company once the company sells them, the number of people able to conveniently invest grows exponentially. This means that someone can buy shares in a company without needing to knock door to door in 5 years trying to find someone to sell to. Participating in the stock market creates 'liquidity', which is essentially the ease with which stocks are converted into cash. High liquidity reduces risk overall, and it means that those who want risk [because high risk often creates high reward] can buy shares, and those who want low risk [because say they are retiring and don't have a risk appetite anymore] can sell shares.",
"title": ""
},
{
"docid": "574327",
"text": "\"First, what structure does your index fund have? If it is an open-end mutual fund, there are no bid/ask spread as the structure of this security is that it is priced once a day and transactions are done with that price. If it is an exchange-traded fund, then the question becomes how well are authorized participants taking advantage of the spread to make the fund track the index well? This is where you have to get into the Creation and Redemption unit construct of the exchange-traded fund where there are \"\"in-kind\"\" transactions done to either create new shares of the fund or redeem out shares of the fund. In either case, you are making some serious assumptions about the structure of the fund that don't make sense given how these are built. Index funds have lower expense ratios and are thus cheaper than other mutual funds that may take on more costs. If you want suggested reading on this, look at the investing books of John C. Bogle who studied some of this rather extensively, in addition to being one of the first to create an index fund that became known as \"\"Bogle's Folly,\"\" where a couple of key ones would be \"\"Common Sense on Mutual Funds: New Imperatives for the Intelligent Investor\"\" and \"\"Bogle on Mutual Funds: New Perspectives for the Intelligent Investor.\"\" In the case of an open-end fund, there has to be a portion of the fund in cash to handle transaction costs of running the fund as there are management fees to come from running the fund in addition to dividends from the stocks that have to be carefully re-invested and other matters that make this quite easy to note. Vanguard 500 Index Investor portfolio(VFINX) has .38% in cash as an example here where you could look at any open-end mutual fund's portfolio and notice that there may well be some in cash as part of how the fund is managed. It’s the Execution, Stupid would be one of a few articles that looks at the idea of \"\"tracking error\"\" or how well does an index fund actually track the index where it can be noted that in some cases, there can be a little bit of active management in the fund. Just as a minor side note, when I lived in the US I did invest in index funds and found them to be a good investment. I'd still recommend them though I'd argue that while some want to see these as really simple investments, there can be details that make them quite interesting to my mind. How is its price set then? The price is computed by taking the sum value of all the assets of the fund minus the liabilities and divided by the number of outstanding shares. The price of the assets would include the closing price on the stock rather than a bid or ask, similar pricing for bonds held by the fund, derivatives and cash equivalents. Similarly, the liabilities would be costs a fund has to pay that may not have been paid yet such as management fees, brokerage costs, etc. Is it a weighted average of all the underlying stock spreads, or does it stand on its own and stems from the usual supply & demand laws ? There isn't any spread used in determining the \"\"Net Asset Value\"\" for the fund. The fund prices are determined after the market is closed and so a closing price can be used for stocks. The liabilities could include the costs to run the fund as part of the accounting in the fund, that most items have to come down to either being an asset, something with a positive value, or a liability, something with a negative value. Something to consider also is the size of the fund. With over $7,000,000,000 in assets, a .01% amount is still $700,000 which is quite a large amount in some ways.\"",
"title": ""
},
{
"docid": "202355",
"text": "\"Is the mortgage debt too high? The rental property is in a hot RE market, so could be easily sold with significant equity. However, they would prefer to keep it. Given the current income, there is no stress. However in absence of any other liquid [cash/near cash] assets, having everything locked into Mortgage is quite high. Even if real estate builds assets, these are highly illiquid investments. Have debt on such investments is risky; if there are no other investments. Essentially everything looks fine now, but if there is an crisis, unwinding mortgage debt is time consuming and if it forces distress sale, it would wipe out any gains. Can they afford another mortgage, and in what amount? (e.g. they are considering $50K for a small cabin, which could be rented out). I guess they can. But should they? Or diversify into other assets like stocks etc. Other than setting cash aside, what would be some good uses of funds to make sure the money would appreciate and outpace inflation and add a nice bonus to retirement? Mutual Funds / Stocks / bullions / 401K or other such retirement plans. They are currently in mid-30's. If there is ONE key strategy or decision they could make today that would help them retire \"\"early\"\" (say, mid-50's), what should it be? This opinion based ... it depends on \"\"what their lifestyle is\"\" and what would they want their \"\"lifestyle\"\" to be when they retire. They should look at saving enough corpus that would give an year on year yield equivalent to the retirement expenses.\"",
"title": ""
},
{
"docid": "561997",
"text": "I think your premise is slightly flawed. Every investment can add or reduce risk, depending on how it's used. If your ordering above is intended to represent the probability you will lose your principal, then it's roughly right, with caveats. If you buy a long-term government bond and interest rates increase while you're holding it, its value will decrease on the secondary markets. If you need/want to sell it before maturity, you may not recover your principal, and if you hold it, you will probably be subject to erosion of value due to inflation (inflation and interest rates are correlated). Over the short-term, the stock market can be very volatile, and you can suffer large paper losses. But over the long-term (decades), the stock market has beaten inflation. But this is true in aggregate, so, if you want to decrease equity risk, you need to invest in a very diversified portfolio (index mutual funds) and hold the portfolio for a long time. With a strategy like this, the stock market is not that risky over time. Derivatives, if used for their original purpose, can actually reduce volatility (and therefore risk) by reducing both the upside and downside of your other investments. For example, if you sell covered calls on your equity investments, you get an income stream as long as the underlying equities have a value that stays below the strike price. The cost to you is that you are forced to sell the equity at the strike price if its value increases above that. The person on the other side of that transaction loses the price of the call if the equity price doesn't go up, but gets a benefit if it does. In the commodity markets, Southwest Airlines used derivatives (options to buy at a fixed price in the future) on fuel to hedge against increases in fuel prices for years. This way, they added predictability to their cost structure and were able to beat the competition when fuel prices rose. Even had fuel prices dropped to zero, their exposure was limited to the pre-negotiated price of the fuel, which they'd already planned for. On the other hand, if you start doing things like selling uncovered calls, you expose yourself to potentially infinite losses, since there are no caps on how high the price of a stock can go. So it's not possible to say that derivatives as a class of investment are risky per se, because they can be used to reduce risk. I would take hedge funds, as a class, out of your list. You can't generally invest in those unless you have quite a lot of money, and they use strategies that vary widely, many of which are quite risky.",
"title": ""
},
{
"docid": "156747",
"text": "\"Equity could mean stock options. If that's the case if the company makes it big, you'll have the option to buy stocks cheap (which can then be sold at a huge profit) How are you going to buy those without income? 5% equity is laughable. I'd be looking for 30-40% if not better without salary. Or even better, a salary. To elaborate, 5% is fine, and even normal for an early employee taking a mild pay cut in exchange for a chance at return. That chance of any return on the equity is only about 1/20 (94% of startups fail) There is no reason for an employee to work for no pay. An argument could be made for a cofounder, with direct control and influence in the company to work for equity only, but it would be a /lot/ more (that 30-40%), or an advisory role (5% is reasonable) I also just noticed you mentioned \"\"investing\"\" in the startup with cash. As an angel investor, I'd still expect far more than 5%, and preferred shares at that. More like 16-20%. Read this for more info on how equity is usually split.\"",
"title": ""
},
{
"docid": "371012",
"text": "I was merely trying to be helpful - Conceptually, you have dump this idea that something is skewed. It isn't. Firm A sold for $500 (equity value aka purchase price to shareholders) + debt (zero) - cash (50) for 450. Enterprise value is the cash free, debt free sale price. The implied ev multiple is 4.5x on A - that is the answer. The other business sold for a higher multiple of 5x. If you would pile on more cash onto A, the purchase price would increase, but the EV wouldn't. The idea is to think hard about the difference between equity value and enterprise value when examining a transaction.",
"title": ""
},
{
"docid": "282483",
"text": "In general, investors with a long period of time until they would need to withdraw the cash are best off holding mostly equities. While the dividends that equities would return are less than the interest you would get in peer-to-peer lending, over long periods of time not only do you get the dividends from equity investment but the value of the stock will grow faster than interest on loans. The higher returns from stocks, however, comes with more risk of big downturns. Many people pull their investments out of stocks right after crashes which really hurts their long term returns. So, in order to get the benefit of investing in stocks you need to be strong enough to continue to hold the stocks through the crash and into the recovery. As for which stocks to invest in, generally it is best to invest in low-fee index funds/etfs where you own a broad collection of stocks so that if (when) any one stock goes bust that your portfolio does not take much damage. Try to own both international and domestic stocks to get good diversification. The consensus recommends adding just a little bit of REITs and bonds to your investments, but for someone at 25 it might not be worth it yet. Warren Buffett had some good thoughts on index investing.",
"title": ""
},
{
"docid": "328745",
"text": "It lowers the cost of capital. Debt is generally a 'cheaper' form of financing, and in addition you have the benefit of interest being tax deductible. Assume you have no capital to expand an existing business. How do you fund it? You could sell/issue some stock to outside investors for cash (or inject your personal cash into the business if you have it), or you can borrow the money. General the borrowing is 'cheaper' as debt investors need a lower return than equity investors, because debt is less risky (has claims on the business assets before equity holders) than equity.",
"title": ""
},
{
"docid": "383682",
"text": "One other consideration is that by paying off your mortgage early versus, for example, investing that capital in a mutual fund is that you are reducing your net liquidity to some degree. That is, if you find yourself needing an emergency infusion of cash it is easier to sell a stock/fund than to sell your house or get a equity loan. I suppose if you were planning to need a lot of cash to start a business or invest in real estate, then maybe it would make sense to keep your cash more liquid. However, in your situation I agree with Joe. Pay it off. It feels REALLY good to write that last check!",
"title": ""
},
{
"docid": "275249",
"text": "\"There are three (or four) ways that a company can grow: (Crowdfunding is a relatively new (in mainstream businesses) alternative financing method where people will finance a company with the expectation that they will benefit from the product or service that they provide.) Obviously a startup has no prior income to use, so it must either raise money through equity or debt. People say that one must borrow contingent on their salary. Banks lend money based on the ability to pay the loan back plus interest. For individuals, their income is their primary source of cash flow, so, yes, it is usually the determining factor in getting a loan. For a business the key factor is future cash flows. So a business will borrow money, say, to buy a new asset (like a factory) that will be used to generate cash flows in the future so that they can pay down the debt. If the bank believes that the use of the money is going to be profitable enough that they will get their money back with interest, they'll loan the money. Equity investors are essentially the same, but since they don't get a guaranteed payback (they only get paid through non-guaranteed dividends or liquidation), their risk is higher and they are looking for higher expected returns. So the question I'd have as a bank or equity investor is \"\"what are you going to do with the money?\"\" What is your business strategy? What are you going to do that will make profits in the future? Do you have a special idea or skill that you can turn into a profitable business? (Crowdfunding would be similar - people are willing to give you money based on either the social or personal benefit of some product or service.) So any business either starts small and grows over time (which is how the vast majority of businesses grow), or has some special idea, asset, skill, or something that would make a bank willing to take a risk on a huge loan. I know, again, that people here tend to turn blind eyes on unfortunate realities, but people do make giant businesses without having giant incomes. The \"\"unfortunate reality\"\" is that most startups fail. Which may sound bad, but also keep in mind that most startups are created by people that are OK with failing. They are people that are willing to fail 9 times with the thought that the 10th one will take off and make up for the losses of the first 9. So I would say - if you have some great idea or skill and a viable strategy and plan to take it to market, then GO FOR IT. You don't need a huge salary to start off. You need something that you can take to market and make money. Most people (myself included) either do not have that idea or skill to go out on their own, or don't have the courage to take that kind of risk. But don't go in assuming all you need is a loan and you'll be an instant millionaire. You might, but the odds are very long.\"",
"title": ""
},
{
"docid": "89714",
"text": "With a long enough time horizon, no matter when you buy, equities almost always outperform cash and bonds. There's an article here with some info: http://www.fool.co.uk/investing-basics/how-when-and-where-to-invest/ Holding period where shares have beaten cash There was a similar study done which showed if you picked any day in the last 100 years, no matter if the market was at a high or low, after 1 year your probability of being in profit was only 0.5, but after 10-20 years it was almost certainly 1.0. Equities compound dividends too, and the best place to invest is in diversified stock indices such as the S&P500, FTSE100, DOW30 or indices/funds which pay dividends. The best way to capture returns is to dollar cost average (e.g. place a lump sum, then add $x every month), to re-invest dividends, and oh, to forget about it in an IRA or SIPP (Self invested pension) or other vehicle which discourages tampering with your investment. Yes, values rise and fall but we humans are so short sighted, if we had bought the S&P in 2007 and sold in 2009 in fear, we would have missed out on the 25% gain (excluding dividends) from 2007-2014. That's about 3% a year gain even if you bought the 2007 high -beating cash or bonds even after the financial crisis. Now imagine had you dollar cost averaged the entire period from 2007-2014 where your gain would be. Your equity curve would have the same shape as the S&P (with its drastic dip in 2009) but an accelerated growth after. There are studies if you dig that demonstrate the above. From experience I can tell you timing the market is nigh impossible and most fund managers are unable to beat the indices. Far better to DCA and re-invest dividends and not care about market gyrations! ..",
"title": ""
}
] |
482
|
Guanine nucleotide exchange factors (GEFs) mediate RhoA activation in response to tensional forces on fibronectin-binding integrins.
|
[
{
"docid": "10991183",
"text": "How individual cells respond to mechanical forces is of considerable interest to biologists as force affects many aspects of cell behaviour. The application of force on integrins triggers cytoskeletal rearrangements and growth of the associated adhesion complex, resulting in increased cellular stiffness, also known as reinforcement. Although RhoA has been shown to play a role during reinforcement, the molecular mechanisms that regulate its activity are unknown. By combining biochemical and biophysical approaches, we identified two guanine nucleotide exchange factors (GEFs), LARG and GEF-H1, as key molecules that regulate the cellular adaptation to force. We show that stimulation of integrins with tensional force triggers activation of these two GEFs and their recruitment to adhesion complexes. Surprisingly, activation of LARG and GEF-H1 involves distinct signalling pathways. Our results reveal that LARG is activated by the Src family tyrosine kinase Fyn, whereas GEF-H1 catalytic activity is enhanced by ERK downstream of a signalling cascade that includes FAK and Ras.",
"title": "The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins"
}
] |
[
{
"docid": "33076846",
"text": "Polyploidization can precede the development of aneuploidy in cancer. Polyploidization in megakaryocytes (Mks), in contrast, is a highly controlled developmental process critical for efficient platelet production via unknown mechanisms. Using primary cells, we demonstrate that the guanine exchange factors GEF-H1 and ECT2, which are often overexpressed in cancer and are essential for RhoA activation during cytokinesis, must be downregulated for Mk polyploidization. The first (2N-4N) endomitotic cycle requires GEF-H1 downregulation, whereas subsequent cycles (>4N) require ECT2 downregulation. Exogenous expression of both GEF-H1 and ECT2 prevents endomitosis, resulting in proliferation of 2N Mks. Furthermore, we have shown that the mechanism by which polyploidization is prevented in Mks lacking Mkl1, which is mutated in megakaryocytic leukemia, is via elevated GEF-H1 expression; shRNA-mediated GEF-H1 knockdown alone rescues this ploidy defect. These mechanistic insights enhance our understanding of normal versus malignant megakaryocytopoiesis, as well as aberrant mitosis in aneuploid cancers.",
"title": "Role of RhoA-specific guanine exchange factors in regulation of endomitosis in megakaryocytes."
},
{
"docid": "24881307",
"text": "Synapses are specialized cell-cell contacts that mediate communication between neurons. Most excitatory synapses in the brain are housed on dendritic spines, small actin-rich protrusions extending from dendrites. During development and in response to environmental stimuli, spines undergo marked changes in shape and number thought to underlie processes like learning and memory. Improper spine development, in contrast, likely impedes information processing in the brain, since spine abnormalities are associated with numerous brain disorders. Elucidating the mechanisms that regulate the formation and plasticity of spines and their resident synapses is therefore crucial to our understanding of cognition and disease. Rho-family GTPases, key regulators of the actin cytoskeleton, play essential roles in orchestrating the development and remodeling of spines and synapses. Precise spatio-temporal regulation of Rho GTPase activity is critical for their function, since aberrant Rho GTPase signaling can cause spine and synapse defects as well as cognitive impairments. Rho GTPases are activated by guanine nucleotide exchange factors (GEFs) and inhibited by GTPase-activating proteins (GAPs). We propose that Rho-family GEFs and GAPs provide the spatiotemporal regulation and signaling specificity necessary for proper Rho GTPase function based on the following features they possess: (i) existence of multiple GEFs and GAPs per Rho GTPase, (ii) developmentally regulated expression, (iii) discrete localization, (iv) ability to bind to and organize specific signaling networks, and (v) tightly regulated activity, perhaps involving GEF/GAP interactions. Recent studies describe several Rho-family GEFs and GAPs that uniquely contribute to spinogenesis and synaptogenesis. Here, we highlight several of these proteins and discuss how they occupy distinct biochemical niches critical for synaptic development.",
"title": "Control of synapse development and plasticity by Rho GTPase regulatory proteins"
},
{
"docid": "8093935",
"text": "Sec7-related guanine nucleotide exchange factors (GEFs) initiate vesicle budding from the Golgi membrane surface by converting the GTPase ARF to a GTP-bound, membrane-associated form. Here we report the crystal structure of the catalytic Sec7 homology domain of Arno, a human GEF for ARF1, determined at 2.2 angstroms resolution. The Sec7 domain is an elongated, all-helical protein with a distinctive hydrophobic groove that is phylogenetically conserved. Structure-based mutagenesis identifies the groove and an adjacent conserved loop as the ARF-interacting surface. The sites of Sec7 domain interaction on ARF1 have subsequently been mapped, by protein footprinting experiments, to the switch 1 and switch 2 GTPase regions, leading to a model for the interaction between ARF GTPases and Sec7 domain exchange factors.",
"title": "Structure of the Guanine Nucleotide Exchange Factor Sec7 Domain of Human Arno and Analysis of the Interaction with ARF GTPase"
},
{
"docid": "14461101",
"text": "Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp)-producing Neisseria gonorrhoeae (P(+)GC) induces an immediate recruitment of caveolin-1 (Cav1) in the host cell, which subsequently prevents bacterial internalization by triggering cytoskeletal rearrangements via downstream phosphotyrosine signaling. A broad and unbiased analysis of potential interaction partners for tyrosine-phosphorylated Cav1 revealed a direct interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role in the Cav1-mediated prevention of bacterial uptake. Our findings, which have been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing bacteria avoid host cell uptake. Further, our data establish a mechanistic link between Cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and advance our understanding of caveolin function.",
"title": "Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements"
},
{
"docid": "10530014",
"text": "Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteopetrosis at an early age. These symptoms are consistent with but more severe than those reported for people with leukocyte adhesion deficiency III (LAD-III). Mechanistically, these symptoms arose from an inability to activate the integrins expressed on hematopoietic cells, including platelets and leukocytes. Immortalized lymphocyte cell lines isolated from the two individuals showed integrin activation defects. Several proteins previously implicated in integrin activation, including Ras-associated protein-1 (RAP1) and calcium and diacylglycerol-regulated guanine nucleotide exchange factor-1 (CALDAG-GEF1), were present and functional in these cell lines. The genetic basis for this disease was traced to a point mutation in the coding region of the KINDLIN3 (official gene symbol FERMT3) gene. When wild-type KINDLIN-3 was expressed in the immortalized lymphocytes, their integrins became responsive to activation signals. These results identify a genetic disease that severely compromises the health of the affected individuals and establish an essential role of KINDLIN-3 in integrin activation in humans. Furthermore, allogeneic bone marrow transplantation was shown to alleviate the symptoms of the disease.",
"title": "A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans"
},
{
"docid": "10669582",
"text": "The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.",
"title": "Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin"
},
{
"docid": "14119470",
"text": "Ran is an abundant nuclear GTPase with a clear role in nuclear transport during interphase but with roles in mitotic regulation that are less well understood. The nucleotide-binding state of Ran is regulated by a GTPase activating protein, RanGAP1, and by a guanine nucleotide exchange factor, RCC1. Ran also interacts with a guanine nucleotide dissociation inhibitor, RanBP1. RanBP1 has a high affinity for GTP-bound Ran, and it acts as a cofactor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on Ran approximately tenfold. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian cells and in Xenopus egg extracts (our unpublished observations). We investigated how increased concentrations of RanBP1 disturb mitosis. We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is added to M phase Xenopus egg extracts. We present evidence that the role of Ran in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.",
"title": "The Ran GTPase regulates mitotic spindle assembly"
},
{
"docid": "32532238",
"text": "To understand how cells sense and adapt to mechanical stress, we applied tensional forces to magnetic microbeads bound to cell-surface integrin receptors and measured changes in bead displacement with sub-micrometer resolution using optical microscopy. Cells exhibited four types of mechanical responses: (1) an immediate viscoelastic response; (2) early adaptive behavior characterized by pulse-to-pulse attenuation in response to oscillatory forces; (3) later adaptive cell stiffening with sustained (>15 second) static stresses; and (4) a large-scale repositioning response with prolonged (>1 minute) stress. Importantly, these adaptation responses differed biochemically. The immediate and early responses were affected by chemically dissipating cytoskeletal prestress (isometric tension), whereas the later adaptive response was not. The repositioning response was prevented by inhibiting tension through interference with Rho signaling, similar to the case of the immediate and early responses, but it was also prevented by blocking mechanosensitive ion channels or by inhibiting Src tyrosine kinases. All adaptive responses were suppressed by cooling cells to 4 degrees C to slow biochemical remodeling. Thus, cells use multiple mechanisms to sense and respond to static and dynamic changes in the level of mechanical stress applied to integrins.",
"title": "Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels."
},
{
"docid": "20943272",
"text": "ADAM13 is a member of the disintegrin and metalloprotease protein family that is expressed on cranial neural crest cells surface and is essential for their migration. ADAM13 is an active protease that can cleave fibronectin in vitro and remodel a fibronectin substrate in vivo. Using a recombinant secreted protein containing both disintegrin and cysteine-rich domains of ADAM13, we show that this \"adhesive\" region of the protein binds directly to fibronectin. Fibronectin fusion proteins corresponding to the various functional domains were used to define the second heparin-binding domain as the ADAM13 binding site. Mutation of the syndecan-binding site (PPRR --> PPTM) within this domain abolishes binding of the recombinant disintegrin and cysteine-rich domains of ADAM13. We further show that the adhesive disintegrin and cysteine-rich domain of ADAM13 can promote cell adhesion via beta(1) integrins. This adhesion requires integrin activation and can be prevented by antibodies to the cysteine-rich domain of ADAM13 and beta(1) integrin. Finally, wild type, but not the E/A mutant of ADAM13 metalloprotease domain, can be shed from the cell surface, releasing the metalloprotease domain associated with the disintegrin and cysteine-rich domains. This suggests that ADAM13 shedding may involve its own metalloprotease activity and that the released protease may interact with both integrins and extracellular matrix proteins.",
"title": "ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin."
},
{
"docid": "9507605",
"text": "The transition of cell–matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II–driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein–tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136–143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force.",
"title": "Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCKindependent mechanism"
},
{
"docid": "9185195",
"text": "AIMS The vascular endothelial growth factor (VEGF) stimulates angiogenesis by induction of vessel permeability, proliferation, and migration of endothelial cells, an important process in ischaemic diseases. ADP-ribosylation factor (ARF) nucleotide-binding site opener (ARNO) (cytohesin-2) is a guanine exchange factor important for cellular signalling through ARF GTPases. However, a role for ARNO in VEGF-dependent endothelial processes has so far not been documented. Therefore, we investigated whether ARNO has a role in VEGF-dependent activation of endothelial cells and thus vessel permeability. METHODS AND RESULTS ARNO expression was observed in endothelial cells in vitro by RT-PCR, western blotting, and immunofluorescence as well as ex vivo by immunohistochemical staining of mouse aorta. Treatment with the cytohesin inhibitor SecinH3 or with an ARNO siRNA prevented VEGF-dependent Akt activation, assessed by detection of phosphorylated Akt, and proliferation of endothelial cells in vitro, measured by methylthiazoletetrazolium (MTT) reduction. In addition, ARNO suppression reduced VEGF-induced permeability in vessels of the mouse (C57BL/6) cremaster muscle in vivo, as measured by extravasation of fluorescein isothiocyanate (FITC)-dextran. Moreover, ARNO knock-down accelerated ligand-induced reduction in vascular endothelial growth factor receptor-2 (VEGFR-2) surface expression, internalization, and degradation, as assessed by flow cytometry and western blotting, respectively. CONCLUSION Our findings indicate an important and novel role for endothelial ARNO in VEGF-dependent initiation of angiogenesis by regulation of VEGFR-2 internalization in endothelial cells, resulting in the activation of the Akt pathway, vessel permeability, and ultimately endothelial proliferation. Thus, ARNO may be a new essential player in endothelial signalling and angiogenesis.",
"title": "ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression."
},
{
"docid": "23141360",
"text": "The morphogenesis of developing embryos and organs relies on the ability of cells to remodel their contacts with neighbouring cells. Using quantitative modelling and laser nano-dissection, we probed the mechanics of a morphogenetic process, the elongation of Drosophila melanogaster embryos, which results from polarized cell neighbour exchanges. We show that anisotropy of cortical tension at apical cell junctions is sufficient to drive tissue elongation. We estimated its value through comparisons between in silico and in vivo data using various tissue descriptors. Nano-dissection of the actomyosin network indicates that tension is anisotropically distributed and depends on myosin II accumulation. Junction relaxation after nano-dissection also suggests that cortical elastic forces are dominant in this process. Interestingly, fluctuations in vertex position (points where three or more cells meet) facilitate neighbour exchanges. We delineate the contribution of subcellular tensile activity polarizing junction remodelling, and the permissive role of vertex fluctuations during tissue elongation.",
"title": "Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis"
},
{
"docid": "21164071",
"text": "Integrins are membrane receptors which mediate cell-cell or cell-matrix adhesion. Integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) acts as a fibrinogen receptor of platelets and mediates platelet aggregation. Platelet activation is required for alpha IIb beta 3 to shift from noncompetent to competent for binding soluble fibrinogen. The steps involved in this transition are poorly understood. We have studied a variant of Glanzmann thrombasthenia, a congenital bleeding disorder characterized by absence of platelet aggregation and fibrinogen binding. The patient's platelets did not bind fibrinogen after platelet activation by ADP or thrombin, though his platelets contained alpha IIb beta 3. However, isolated alpha IIb beta 3 was able to bind to an Arg-Gly-Asp-Ser affinity column, and binding of soluble fibrinogen to the patient's platelets could be triggered by modulators of alpha IIb beta 3 conformation such as the Arg-Gly-Asp-Ser peptide and alpha-chymotrypsin. These data suggested that a functional Arg-Gly-Asp binding site was present within alpha IIb beta 3 and that the patient's defect was not secondary to a blockade of alpha IIb beta 3 in a noncompetent conformational state. This was evocative of a defect in the coupling between platelet activation and alpha IIb beta 3 up-regulation. We therefore sequenced the cytoplasmic domain of beta 3, following polymerase chain reaction (PCR) on platelet RNA, and found a T-->C mutation at nucleotide 2259, corresponding to a Ser-752-->Pro substitution. This mutation is likely to be responsible for the uncoupling of alpha IIb beta 3 from cellular activation because (i) it is not a polymorphism, (ii) it is the only mutation in the entire alpha IIb beta 3 sequence, and (iii) genetic analysis of the family showed that absence of the Pro-752 beta 3 allele was associated with the normal phenotype. Our data thus identify the C-terminal portion of the cytoplasmic domain of beta 3 as an intrinsic element in the coupling between alpha IIb beta 3 and platelet activation.",
"title": "Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia."
},
{
"docid": "20313748",
"text": "Adherens junctions (AJs), which are organized by adhesion proteins and the underlying actin cytoskeleton, probably sense pulling forces from adjacent cells and modulate opposing forces to maintain tissue integrity, but the regulatory mechanism remains unknown at the molecular level. Although the possibility that α-catenin acts as a direct linker between the membrane and the actin cytoskeleton for AJ formation and function has been minimized, here we show that α-catenin recruits vinculin, another main actin-binding protein of AJs, through force-dependent changes in α-catenin conformation. We identified regions in the α-catenin molecule that are required for its force-dependent binding of vinculin by introducing mutant α-catenin into cells and using in vitro binding assays. Fluorescence recovery after photobleaching analysis for α-catenin mobility and the existence of an antibody recognizing α-catenin in a force-dependent manner further supported the notion that α-catenin is a tension transducer that translates mechanical stimuli into a chemical response, resulting in AJ development.",
"title": "α-Catenin as a tension transducer that induces adherens junction development"
},
{
"docid": "16511863",
"text": "BACKGROUND Although numerous signaling pathways are known to be activated in experimental cardiac hypertrophy, the molecular basis of the hypertrophic response inherent in human heart diseases remains largely unknown. Integrin-linked kinase (ILK) is a multifunctional protein kinase that physically links beta-integrins with the actin cytoskeleton, suggesting a potential mechanoreceptor role. METHODS AND RESULTS Here, we show a marked increase in ILK protein levels in hypertrophic ventricles of patients with congenital and acquired outflow tract obstruction. This increase in ILK was associated with activation of the Rho family guanine triphosphatases, Rac1 and Cdc42, and known hypertrophic signaling kinases, including extracellular signal-related kinases (ERK1/2) and p70 S6 kinase. Transgenic mice with cardiac-specific expression of a constitutively active ILK (ILK(S343D)) or wild-type ILK (ILK(WT)) exhibited a compensated ventricular hypertrophic phenotype and displayed an activation profile of guanine triphosphatases and downstream protein kinases concordant with that seen in human hypertrophy. In contrast, transgenic mice with cardiomyocyte-restricted expression of a kinase-inactive ILK (ILK(R211A)) were unable to mount a compensatory hypertrophic response to angiotensin II in vivo. CONCLUSIONS Taken together, these results identify ILK-regulated signaling as a broadly adaptive hypertrophic response mechanism relevant to a wide range of clinical heart disease.",
"title": "Integrin-linked kinase expression is elevated in human cardiac hypertrophy and induces hypertrophy in transgenic mice."
},
{
"docid": "44640124",
"text": "SIGNIFICANCE The extracellular matrix (ECM) fulfills essential functions in multicellular organisms. It provides the mechanical scaffold and environmental cues to cells. Upon cell attachment, the ECM signals into the cells. In this process, reactive oxygen species (ROS) are physiologically used as signalizing molecules. RECENT ADVANCES ECM attachment influences the ROS-production of cells. In turn, ROS affect the production, assembly and turnover of the ECM during wound healing and matrix remodeling. Pathological changes of ROS levels lead to excess ECM production and increased tissue contraction in fibrotic disorders and desmoplastic tumors. Integrins are cell adhesion molecules which mediate cell adhesion and force transmission between cells and the ECM. They have been identified as a target of redox-regulation by ROS. Cysteine-based redox-modifications, together with structural data, highlighted particular regions within integrin heterodimers that may be subject to redox-dependent conformational changes along with an alteration of integrin binding activity. CRITICAL ISSUES In a molecular model, a long-range disulfide-bridge within the integrin β-subunit and disulfide bridges within the genu and calf-2 domains of the integrin α-subunit may control the transition between the bent/inactive and upright/active conformation of the integrin ectodomain. These thiol-based intramolecular cross-linkages occur in the stalk domain of both integrin subunits, whereas the ligand-binding integrin headpiece is apparently unaffected by redox-regulation. FUTURE DIRECTIONS Redox-regulation of the integrin activation state may explain the effect of ROS in physiological processes. A deeper understanding of the underlying mechanism may open new prospects for the treatment of fibrotic disorders.",
"title": "Redox-relevant aspects of the extracellular matrix and its cellular contacts via integrins."
},
{
"docid": "4662264",
"text": "The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1). This Ser118 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro and in cells treated with epidermal growth factor (EGF) and insulin-like growth factor (IGF) in vivo. Overexpression of MAPK kinase (MAPKK) or of the guanine nucleotide binding protein Ras, both of which activate MAPK, enhanced estrogen-induced and antiestrogen (tamoxifen)-induced transcriptional activity of wild-type ER, but not that of a mutant ER with an alanine in place of Ser118. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.",
"title": "Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase."
},
{
"docid": "23863576",
"text": "UNLABELLED Morphological characteristics of dendritic spines form the basis of cognitive ability. However, molecular mechanisms involved in fine-tuning of spine morphology during development are not fully understood. Moreover, it is unclear whether, and to what extent, these developmental mechanisms determine the normal adult spine morphological features. Here, we provide evidence that α2-isoform of Rac-specific GTPase-activating protein α-chimaerin (α2-chimaerin) is involved in spine morphological refinement during late postnatal period, and furthermore show that this developmental α2-chimaerin function affects adult spine morphologies. We used a series of mice with global and conditional knock-out of α-chimaerin isoforms (α1-chimaerin and α2-chimaerin). α2-Chimaerin disruption, but not α1-chimaerin disruption, in the mouse results in an increased size (and density) of spines in the hippocampus. In contrast, overexpression of α2-chimaerin in developing hippocampal neurons induces a decrease of spine size. Disruption of α2-chimaerin suppressed EphA-mediated spine morphogenesis in cultured developing hippocampal neurons. α2-Chimaerin disruption that begins during the juvenile stage results in an increased size of spines in the hippocampus. Meanwhile, spine morphologies are unaltered when α2-chimaerin is deleted only in adulthood. Consistent with these spine morphological results, disruption of α2-chimaerin beginning in the juvenile stage led to an increase in contextual fear learning in adulthood; whereas contextual learning was recently shown to be unaffected when α2-chimaerin was deleted only in adulthood. Together, these results suggest that α2-chimaerin signaling in developmental stages contributes to determination of the morphological features of adult spines and establishment of normal cognitive ability. SIGNIFICANCE STATEMENT Recent studies of neurodevelopmental disorders in humans and their animal models have led to an attractive hypothesis that spine morphogenesis during development forms the basis of adult cognition. In particular, the roles of Rac and its regulators, such as Rac-specific GTPase-activating proteins (RacGAPs) and Rac guanine nucleotide exchange factors, are a topic of focus in spine morphogenesis and cognitive ability. Using a series of mice with global and conditional knock-out (KO) of RacGAP α-chimaerin isoforms (α1-chimaerin and α2-chimaerin), we provide compelling evidence demonstrating that α2-chimaerin is involved in spine morphological refinement during late postnatal development and that this developmental α2-chimaerin function affects adult spine morphologies. Furthermore, our results clearly showed that α2-chimaerin signaling during late postnatal development contributes to normal cognitive ability in adult mice.",
"title": "Developmental RacGAP α2-Chimaerin Signaling Is a Determinant of the Morphological Features of Dendritic Spines in Adulthood."
},
{
"docid": "2060137",
"text": "Cell-to-cell adhesions are crucial in maintaining the structural and functional integrity of cardiac cells. Little is known about the mechanosensitivity and mechanotransduction of cell-to-cell interactions. Most studies of cardiac mechanotransduction and myofibrillogenesis have focused on cell-extracellular matrix (ECM)-specific interactions. This study assesses the direct role of intercellular adhesion, specifically that of N-cadherin-mediated mechanotransduction, on the morphology and internal organization of neonatal ventricular cardiac myocytes. The results show that cadherin-mediated cell attachments are capable of eliciting a cytoskeletal network response similar to that of integrin-mediated force response and transmission, affecting myofibrillar organization, myocyte shape, and cortical stiffness. Traction forces mediated by N-cadherin were shown to be comparable to those sustained by ECM. The directional changes in predicted traction forces as a function of imposed loads (gel stiffness) provide the added evidence that N-cadherin is a mechanoresponsive adhesion receptor. Strikingly, the mechanical sensitivity response (gain) in terms of the measured cell-spread area as a function of imposed load (adhesive substrate rigidity) was consistently higher for N-cadherin-coated surfaces compared with ECM protein-coated surfaces. In addition, the cytoskeletal architecture of myocytes on an N-cadherin adhesive microenvironment was characteristically different from that on an ECM environment, suggesting that the two mechanotransductive cell adhesion systems may play both independent and complementary roles in myocyte cytoskeletal spatial organization. These results indicate that cell-to-cell-mediated force perception and transmission are involved in the organization and development of cardiac structure and function.",
"title": "Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing."
},
{
"docid": "17997584",
"text": "Regulatory T (Treg) cells play a pivotal role in suppressing self-harmful T cell responses, but how Treg cells mediate suppression to maintain immune homeostasis and limit responses during inflammation is unclear. Here we show that effector Treg cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. Thus, our results identify a mechanism by which Treg cells suppress exuberant immune responses, highlighting a key role for effector Treg-cell-mediated activation of latent TGF-β in suppression of self-harmful T cell responses during active inflammation.",
"title": "Integrin αvβ8-Mediated TGF-β Activation by Effector Regulatory T Cells Is Essential for Suppression of T-Cell-Mediated Inflammation"
},
{
"docid": "19912367",
"text": "Age-related changes in the niche have long been postulated to impair the function of somatic stem cells. Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs). Deletion of the gene encoding FN from young regenerating muscles replicates the aging phenotype and leads to a loss of MuSC numbers. By using an extracellular matrix (ECM) library screen and pathway profiling, we characterize FN as a preferred adhesion substrate for MuSCs and demonstrate that integrin-mediated signaling through focal adhesion kinase and the p38 mitogen-activated protein kinase pathway is strongly de-regulated in MuSCs from aged mice because of insufficient attachment to the niche. Reconstitution of FN levels in the aged niche remobilizes stem cells and restores youth-like muscle regeneration. Taken together, we identify the loss of stem cell adhesion to FN in the niche ECM as a previously unknown aging mechanism.",
"title": "Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice"
},
{
"docid": "8698857",
"text": "TNF expression of macrophages is under stringent translational control that depends on the p38 MAPK/MK2 pathway and the AU-rich element (ARE) in the TNF mRNA. Here, we elucidate the molecular mechanism of phosphorylation-regulated translation of TNF. We demonstrate that translation of the TNF-precursor at the ER requires expression of the ARE-binding and -stabilizing factor human antigen R (HuR) together with either activity of the p38 MAPK/MK2 pathway or the absence of the ARE-binding and -destabilizing factor tristetraprolin (TTP). We show that phosphorylation of TTP by MK2 decreases its affinity to the ARE, inhibits its ability to replace HuR, and permits HuR-mediated initiation of translation of TNF mRNA. Since translation of TTP's own mRNA is also regulated by this mechanism, an intrinsic feedback control of the inflammatory response is ensured. The phosphorylation-regulated TTP/HuR exchange at target mRNAs provides a reversible switch between unstable/non-translatable and stable/efficiently translated mRNAs.",
"title": "The p38/MK2-Driven Exchange between Tristetraprolin and HuR Regulates AU–Rich Element–Dependent Translation"
},
{
"docid": "12650610",
"text": "We have previously shown that the integrin beta6 is neo-expressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin beta6 promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin beta6 signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin beta6 signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it. The activation of Fyn recruited and activated focal adhesion kinase to this complex. This complex was necessary to activate Shc and to couple beta6 signaling to the Raf-ERK/MAPK pathway. This pathway transcriptionally activated the matrix metalloproteinase-3 gene and promoted oral SCC cell proliferation and experimental metastasis in vivo. These findings indicate that integrin beta6 signaling activates Fyn and thus promotes oral cancer progression.",
"title": "Alphavbeta6-Fyn signaling promotes oral cancer progression."
},
{
"docid": "25191216",
"text": "Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gs alpha, leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin alpha v beta 3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during intramembranous but not endochondral ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos, which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for intramembranous ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gs alpha-cyclic adenosine monophosphate-c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease.",
"title": "Periostin, a novel marker of intramembranous ossification, is expressed in fibrous dysplasia and in c-Fos-overexpressing bone lesions."
},
{
"docid": "19482914",
"text": "Integrin-mediated platelet adhesion and aggregation are essential for sealing injured blood vessels and preventing blood loss, and excessive platelet aggregation can initiate arterial thrombosis, causing heart attacks and stroke. To ensure that platelets aggregate only at injury sites, integrins on circulating platelets exist in a low-affinity state and shift to a high-affinity state (in a process known as integrin activation or priming) after contacting a wounded vessel. The shift is mediated through binding of the cytoskeletal protein Talin to the β subunit cytoplasmic tail. Here we show that platelets lacking the adhesion plaque protein Kindlin-3 cannot activate integrins despite normal Talin expression. As a direct consequence, Kindlin-3 deficiency results in severe bleeding and resistance to arterial thrombosis. Mechanistically, Kindlin-3 can directly bind to regions of β-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis.",
"title": "Kindlin-3 is essential for integrin activation and platelet aggregation"
},
{
"docid": "13953762",
"text": "The Plk1-interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase bridges (UFBs) in mitosis alongside a complex of DNA repair proteins, including the Bloom's syndrome protein (BLM). However, very little is known about the function of PICH or how it is recruited to UFBs. Using a combination of microfluidics, fluorescence microscopy, and optical tweezers, we have defined the properties of PICH in an in vitro model of an anaphase bridge. We show that PICH binds with a remarkably high affinity to duplex DNA, resulting in ATP-dependent protein translocation and extension of the DNA. Most strikingly, the affinity of PICH for binding DNA increases with tension-induced DNA stretching, which mimics the effect of the mitotic spindle on a UFB. PICH binding also appears to diminish force-induced DNA melting. We propose a model in which PICH recognizes and stabilizes DNA under tension during anaphase, thereby facilitating the resolution of entangled sister chromatids.",
"title": "PICH: a DNA translocase specially adapted for processing anaphase bridge DNA."
},
{
"docid": "24554740",
"text": "Cell cycle progression in mammalian cells is strictly regulated by both integrin-mediated adhesion to the extracellular matrix and by binding of growth factors to their receptors. This regulation is mediated by G1 phase cyclin-dependent kinases (CDKs), which are downstream of signaling pathways under the integrated control of both integrins and growth factor receptors. Recent advances demonstrate a surprisingly diverse array of integrin-dependent signals that are channeled into the regulation of the G1 phase CDKs. Regulation of cyclin D1 by the ERK pathway may provide a paradigm for understanding how cell adhesion can determine cell cycle progression.",
"title": "Integrins and cell proliferation: regulation of cyclin-dependent kinases via cytoplasmic signaling pathways."
},
{
"docid": "18231257",
"text": "The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here, we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases.",
"title": "Dynamic control of excitatory synapse development by a Rac1 GEF/GAP regulatory complex."
},
{
"docid": "17805221",
"text": "Sport fishermen keep tension on their lines to prevent hooked fish from releasing. A molecular version of this angler's trick, operating at kinetochores, ensures accuracy during mitosis: the mitotic spindle attaches randomly to chromosomes and then correctly bioriented attachments are stabilized due to the tension exerted on them by opposing microtubules. Incorrect attachments, which lack tension, are unstable and release quickly, allowing another chance for biorientation. Stabilization of molecular interactions by tension also occurs in other physiological contexts, such as cell adhesion, motility, hemostasis, and tissue morphogenesis. Here, we review models for the stabilization of kinetochore attachments with an eye toward emerging models for other force-activated systems. Although attention in the mitosis field has focused mainly on one kinase-based mechanism, multiple mechanisms may act together to stabilize properly bioriented kinetochores and some principles governing other tension-sensitive systems may also apply to kinetochores.",
"title": "Catch and release: how do kinetochores hook the right microtubules during mitosis?"
},
{
"docid": "2988714",
"text": "Local translation mediates axonal responses to Semaphorin3A (Sema3A) and other guidance cues. However, only a subset of the axonal proteome is locally synthesized, whereas most proteins are trafficked from the soma. The reason why only specific proteins are locally synthesized is unknown. Here we show that local protein synthesis and degradation are linked events in growth cones. We find that growth cones exhibit high levels of ubiquitination and that local signalling pathways trigger the ubiquitination and degradation of RhoA, a mediator of Sema3A-induced growth cone collapse. Inhibition of RhoA degradation is sufficient to remove the protein-synthesis requirement for Sema3A-induced growth cone collapse. In addition to RhoA, we find that locally translated proteins are the main targets of the ubiquitin-proteasome system in growth cones. Thus, local protein degradation is a major feature of growth cones and creates a requirement for local translation to replenish proteins needed to maintain growth cone responses.",
"title": "Coupled local translation and degradation regulate growth cone collapse"
}
] |
263
|
Citrullinated proteins externalized in neutrophil extracellular traps act indirectly to disrupt the inflammatory cycle.
|
[
{
"docid": "11328820",
"text": "The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease.",
"title": "NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis."
},
{
"docid": "30041340",
"text": "BACKGROUND Histone deimination regulates gene function and contributes to antimicrobial response, allowing the formation of neutrophil extracellular traps (NETs). Deiminated proteins are target of anti-citrullinated peptides antibodies (ACPA) in rheumatoid arthritis (RA). OBJECTIVE The objective of this paper is to test the hypothesis that RA sera react with deiminated histones contained in NETs. METHODS Neutrophils from peripheral blood were stimulated with A23187 and acid treated; NETosis was induced by phorbol myristate acetate, and NET proteins were isolated. Sera were tested by immunoblot on acid extracted proteins from neutrophils and from NETs, and by ELISA on deiminated histone H4 or H4-derived peptides. Bands reactive with RA sera were excised from gels, digested with trypsin and subjected to matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) analysis, before and after derivatisation to detect citrullinated peptides. RESULTS RA sera reacted with a deiminated antigen of 11 KDa from activated neutrophils, recognised also by anti-H4 and antideiminated H4 antibodies. A similar reactivity was observed with NET proteins. The antigen from neutrophils or NETs was identified as citrullinated H4 by MALDI-TOF analysis. By ELISA, RA sera bound in vitro citrullinated H4. Citrullinated H4 14-34 and 31-50 peptides detected antibodies in 67% and 63% of RA sera and in less than 5% of controls; antibody titre was correlated with anti-CCP2. CONCLUSIONS Citrullinated H4 from activated neutrophils and NETs is a target of antibodies in RA, and synthetic citrullinated H4-derived peptides are a new substrate for ACPA detection. As NETosis can generate antigens for ACPA, these data suggest a novel connection between innate and adaptive immunity in RA.",
"title": "Antibodies from patients with rheumatoid arthritis target citrullinated histone 4 contained in neutrophils extracellular traps."
},
{
"docid": "14853989",
"text": "Autoantibodies to DNA and histones (chromatin) are the defining antigen specificity in systemic lupus erythematosus (SLE) and related musculoskeletal disorders but the mechanisms responsible for their induction remain mysterious. That situation rapidly changed once neutrophil extracellular chromatin traps (NETs) were discovered and observed to play a conserved role in innate immune responses to a broad variety of microbial pathogens. At the center of an infectious process, neutrophils exert various antimicrobial defenses, including the release of nuclear chromatin into the extracellular space. The externalized NETs, a complex meshwork of nuclear chromatin and antimicrobial proteins, serve to immobilize and degrade microbial pathogens. Here, we critically evaluate the evidence supporting NETs versus apoptotic bodies as a source for nuclear antigens in autoimmunity. We also discuss the possibility that NET chromatin forms an essential component of immune deposits in the pathogenesis of glomerulonephritis in SLE and other autoimmune immune complex diseases.",
"title": "Neutrophil extracellular chromatin traps connect innate immune response to autoimmunity"
}
] |
[
{
"docid": "17967608",
"text": "Neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs). We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation. However, the role of PAD4 in NET-mediated bacterial trapping and killing has not been tested. Here, we use PAD4 knockout mice to show that PAD4 is essential for NET-mediated antibacterial function. Unlike PAD4(+/+) neutrophils, PAD4(-/-) neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. In a mouse infectious disease model of necrotizing fasciitis, PAD4(-/-) mice are more susceptible to bacterial infection than PAD4(+/+) mice due to a lack of NET formation. Moreover, we found that citrullination decreased the bacterial killing activity of histones and nucleosomes, which suggests that PAD4 mainly plays a role in chromatin decondensation to form NETs instead of increasing histone-mediated bacterial killing. Our results define a role for histone hypercitrullination in innate immunity during bacterial infection.",
"title": "PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps"
},
{
"docid": "28149602",
"text": "PURPOSE OF REVIEW Recent discoveries implicate neutrophils as important regulators of innate and adaptive immunity and in the development of organ damage in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). RECENT FINDINGS Various putative SLE biomarkers are neutrophil-related, including neutrophil granular proteins and histones undergoing post-translational modifications during neutrophil extracellular trap (NET) formation. In the bone marrow, lupus neutrophils can drive B and T cell abnormalities, at least in part, by their enhanced production of type-I interferons, tumor necrosis factor-alpha (TNFα) and the B-cell stimulating factors B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Lupus neutrophils and, in particular, lupus low-density granulocytes (a distinct pathogenic subset) display epigenetic modifications and genomic alterations that may be relevant to their deleterious roles in SLE. Proteins and enzymes externalized by lupus NETs can affect vascular health by inducing endothelial apoptosis and oxidizing lipoproteins. Hampering NET formation through peptidylarginine deiminase inhibitors abrogates lupus phenotype and atherosclerosis in murine studies. SUMMARY Recent discoveries support the notion that neutrophils, low-density granulocytes and aberrant NET formation and clearance play important roles in lupus pathogenesis. Future studies should focus on how to selectively target these immunostimulatory pathways in this disease.",
"title": "The role of neutrophils in the pathogenesis of systemic lupus erythematosus."
},
{
"docid": "36089763",
"text": "Neutrophils phagocytose and kill microbes upon phagolysosomal fusion. Recently we found that activated neutrophils form extracellular fibres that consist of granule proteins and chromatin. These neutrophil extracellular traps (NETs) degrade virulence factors and kill Gram positive and negative bacteria. Here we show for the first time that Candida albicans, a eukaryotic pathogen, induces NET-formation and is susceptible to NET-mediated killing. C. albicans is the predominant aetiologic agent of fungal infections in humans, particularly in immunocompromised hosts. One major virulence trait of C. albicans is its ability to reversibly switch from singular budding cells to filamentous hyphae. We demonstrate that NETs kill both yeast-form and hyphal cells, and that granule components mediate fungal killing. Taken together our data indicate that neutrophils trap and kill ascomycetous yeasts by forming NETs.",
"title": "Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms."
},
{
"docid": "1049501",
"text": "Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mitochondrial reactive oxygen species (ROS) for maximal NET stimulation. After RNP IC stimulation of neutrophils, mitochondria become hypopolarized and translocate to the cell surface. Extracellular release of oxidized mitochondrial DNA is proinflammatory in vitro, and when this DNA is injected into mice, it stimulates type I interferon (IFN) signaling through a pathway dependent on the DNA sensor STING. Mitochondrial ROS are also necessary for spontaneous NETosis of low-density granulocytes from individuals with systemic lupus erythematosus. This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures. Mitochondrial ROS inhibition in vivo reduces disease severity and type I IFN responses in a mouse model of lupus. Together, these findings highlight a role for mitochondria in the generation not only of NETs but also of pro-inflammatory oxidized mitochondrial DNA in autoimmune diseases.",
"title": "Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease"
},
{
"docid": "3330111",
"text": "Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, more recent evidence has extended the functions of these cells. The newly discovered repertoire of effector molecules in the neutrophil armamentarium includes a broad array of cytokines, extracellular traps and effector molecules of the humoral arm of the innate immune system. In addition, neutrophils are involved in the activation, regulation and effector functions of innate and adaptive immune cells. Accordingly, neutrophils have a crucial role in the pathogenesis of a broad range of diseases, including infections caused by intracellular pathogens, autoimmunity, chronic inflammation and cancer.",
"title": "Neutrophils in the activation and regulation of innate and adaptive immunity"
},
{
"docid": "29399239",
"text": "Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed \"NETosis. \" Here we review our understanding of how NETs are made, their function in infections and as danger signals, and their emerging importance in autoimmunity and coagulation.",
"title": "Neutrophil extracellular traps: Is immunity the second function of chromatin?"
},
{
"docid": "1800734",
"text": "Upon activation, neutrophils release DNA fibers decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). Although NETs are bactericidal and contribute to innate host defense, excessive NET formation has been linked to the pathogenesis of autoinflammatory diseases. However, the mechanisms regulating NET formation, particularly during chronic inflammation, are poorly understood. Here we show that the G protein–coupled receptor (GPCR) CXCR2 mediates NET formation. Downstream analyses showed that CXCR2-mediated NET formation was independent of NADPH oxidase and involved Src family kinases. We show the pathophysiological relevance of this mechanism in cystic fibrosis lung disease, characterized by chronic neutrophilic inflammation. We found abundant NETs in airway fluids of individuals with cystic fibrosis and mouse cystic fibrosis lung disease, and NET amounts correlated with impaired obstructive lung function. Pulmonary blockade of CXCR2 by intra-airway delivery of small-molecule antagonists inhibited NET formation and improved lung function in vivo without affecting neutrophil recruitment, proteolytic activity or antibacterial host defense. These studies establish CXCR2 as a receptor mediating NADPH oxidase–independent NET formation and provide evidence that this GPCR pathway is operative and druggable in cystic fibrosis lung disease.",
"title": "CXCR2 mediates NADPH oxidase–independent neutrophil extracellular trap formation in cystic fibrosis airway inflammation"
},
{
"docid": "9878167",
"text": "Neutrophil extracellular traps (NETs) represent extracellular structures able to bind and kill microorganisms. It is believed that they are generated by neutrophils undergoing cell death, allowing these dying or dead cells to kill microbes. We show that, following priming with granulocyte/macrophage colony-stimulating factor (GM-CSF) and subsequent short-term toll-like receptor 4 (TLR4) or complement factor 5a (C5a) receptor stimulation, viable neutrophils are able to generate NETs. Strikingly, NETs formed by living cells contain mitochondrial, but no nuclear, DNA. Pharmacological or genetic approaches to block reactive oxygen species (ROS) production suggested that NET formation is ROS dependent. Moreover, neutrophil populations stimulated with GM-CSF and C5a showed increased survival compared with resting neutrophils, which did not generate NETs. In conclusion, mitochondrial DNA release by neutrophils and NET formation do not require neutrophil death and do also not limit the lifespan of these cells.",
"title": "Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps"
},
{
"docid": "43054703",
"text": "Neutrophil extracellular traps (NETs) are webs of DNA covered with antimicrobial molecules that constitute a newly described killing mechanism in innate immune defense. Previous publications reported that NETs take up to 3-4 h to form via an oxidant-dependent event that requires lytic death of neutrophils. In this study, we describe neutrophils responding uniquely to Staphylococcus aureus via a novel process of NET formation that did not require neutrophil lysis or even breach of the plasma membrane. The multilobular nucleus rapidly became rounded and condensed. During this process, we observed the separation of the inner and outer nuclear membranes and budding of vesicles, and the separated membranes and vesicles were filled with nuclear DNA. The vesicles were extruded intact into the extracellular space where they ruptured, and the chromatin was released. This entire process occurred via a unique, very rapid (5-60 min), oxidant-independent mechanism. Mitochondrial DNA constituted very little if any of these NETs. They did have a limited amount of proteolytic activity and were able to kill S. aureus. With time, the nuclear envelope ruptured, and DNA filled the cytoplasm presumably for later lytic NET production, but this was distinct from the vesicular release mechanism. Panton-Valentine leukocidin, autolysin, and a lipase were identified in supernatants with NET-inducing activity, but Panton-Valentine leukocidin was the dominant NET inducer. We describe a new mechanism of NET release that is very rapid and contributes to trapping and killing of S. aureus.",
"title": "A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus."
},
{
"docid": "24928817",
"text": "The initiation and progression of adult-onset periodontitis has been associated with infection of the gingival sulcus by Porphyromonas gingivalis. This organism utilizes a multitude of virulence factors to evade host defenses as it establishes itself as one of the predominant pathogens in periodontal pockets. A feature common to many other oral pathogens is the production of ammonia due to its protective effect during acidic cleansing cycles in the mouth. Additionally, ammonia production by P. gingivalis has been proposed as a virulence factor due to its negative effects on neutrophil function. In this study, we describe the first purification of a peptidylarginine deiminase (PAD) from a prokaryote. PAD exhibits biochemical characteristics and properties that suggest that it may be a virulence agent. PAD deiminates the guanidino group of carboxyl-terminal arginine residues on a variety of peptides, including the vasoregulatory peptide-hormone bradykinin, to yield ammonia and a citrulline residue. The soluble protein has an apparent mass of 46 kDa, while the DNA sequence predicts a full-length protein of 61.7 kDa. PAD is optimally active at 55 degrees C, stable at low pH, and shows the greatest activity above pH 9.0. Interestingly, in the presence of stabilizing factors, PAD is resistant to limited proteolysis and retains significant activity after short-term boiling. We propose that PAD, acting in concert with arginine-specific proteinases from P. gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses.",
"title": "Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase."
},
{
"docid": "28015516",
"text": "Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a breakdown of tolerance to nuclear antigens and the development of immune complexes. Genomic approaches have shown that human SLE leukocytes homogeneously express type I interferon (IFN)-induced and neutrophil-related transcripts. Increased production and/or bioavailability of IFN-α and associated alterations in dendritic cell (DC) homeostasis have been linked to lupus pathogenesis. Although neutrophils have long been shown to be associated with lupus, their potential role in disease pathogenesis remains elusive. Here, we show that mature SLE neutrophils are primed in vivo by type I IFN and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). SLE NETs contain DNA as well as large amounts of LL37 and HMGB1, neutrophil proteins that facilitate the uptake and recognition of mammalian DNA by plasmacytoid DCs (pDCs). Indeed, SLE NETs activate pDCs to produce high levels of IFN-α in a DNA- and TLR9 (Toll-like receptor 9)-dependent manner. Our results reveal an unsuspected role for neutrophils in SLE pathogenesis and identify a novel link between nucleic acid-recognizing antibodies and type I IFN production in this disease.",
"title": "Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus."
},
{
"docid": "20459964",
"text": "Neutrophil is a key cell in pathophysiology of granulomatosis with polyangiitis. Recently, neutrophil extracellular traps were described in this disease. Mitochondrial DNA is also released during traps formation. We measured circulating cell-free mitochondrial and genomic DNA in serum of patients with granulomatosis with polyangiitis. Subjects with the disease (14 active and 11 in remission stage) and 10 healthy controls were enrolled. Quantitative real-time polymerase chain reaction (PCR) was used to measure 79 base pairs (bp) and 230 bp mtDNA fragments. Alu repeats were quantified to evaluate abundance of nuclear DNA in serum at the presence of plasmid control. Both fragments of mtDNA (79 bp and 230 bp) and genomic DNA were elevated significantly in granulomatosis with polyangiitis compared to controls. Only the shorter 79 bp mtDNA correlated with active stage of granulomatosis with polyangiitis and clinical symptoms. A mechanism of extracellular release of mitochondrial DNA accompanies the active stage of the disease. Circulating mtDNA is extremely high in untreated patients. This suggests that biomarker properties of mtDNA are useful for monitoring of treatment.",
"title": "Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis."
},
{
"docid": "52925737",
"text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.",
"title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration"
},
{
"docid": "17741440",
"text": "Small-vessel vasculitis (SVV) is a chronic autoinflammatory condition linked to antineutrophil cytoplasm autoantibodies (ANCAs). Here we show that chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 (PR3) and myeloperoxidase (MPO). Deposition of NETs in inflamed kidneys and circulating MPO-DNA complexes suggest that NET formation triggers vasculitis and promotes the autoimmune response against neutrophil components in individuals with SVV.",
"title": "Netting neutrophils in autoimmune small-vessel vasculitis"
},
{
"docid": "2236768",
"text": "Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask.",
"title": "Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo"
},
{
"docid": "46517055",
"text": "Uncontrolled proteolysis by neutrophil serine proteases (NSPs) in lung secretions is a hallmark of cystic fibrosis (CF). We have shown that the active neutrophil elastase, protease 3, and cathepsin G in CF sputum resist inhibition in part by exogenous protease inhibitors. This resistance may be due to their binding to neutrophil extracellular traps (NETs) secreted by the activated neutrophils in CF sputum and to genomic DNA released from senescent and dead neutrophils. Treating CF sputum with DNase dramatically increases its elastase activity, which can then be stoichiometrically inhibited by exogenous elastase inhibitors. However, DNase treatment does not increase the activities of protease 3 and cathepsin G, indicating their different distribution and/or binding in CF sputum. Purified blood neutrophils secrete NETs when stimulated by the opportunistic CF bacteria Pseudomonas aeruginosa and Staphylococcus aureus. The activities of the three proteases were unchanged in these conditions, but subsequent DNase treatment produced a dramatic increase in all three proteolytic activities. Neutrophils activated with a calcium ionophore did not secrete NETs but released huge amounts of active proteases whose activities were not modified by DNase. We conclude that NETs are reservoirs of active proteases that protect them from inhibition and maintain them in a rapidly mobilizable status. Combining the effects of protease inhibitors with that of DNA-degrading agents could counter the deleterious proteolytic effects of NSPs in CF lung secretions.",
"title": "Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum."
},
{
"docid": "28712203",
"text": "Elastases of both the neutrophil and macrophage have been implicated in lung disease initiation and progression. Although it is unlikely that these proteases evolved for the purpose of injuring lung tissue, the elastin-rich connective tissue framework of the lungs appears to be particularly susceptible to the action of elastolytic proteases. Assuming that neutrophil elastase most likely plays a role in the migration of neutrophils toward a site of inflammation and degradation of proteins from invading organisms or other products of the inflammatory response, it is the role of inhibitors of this protease to protect normal tissues from its effects. In alpha-1 antitrypsin deficiency we find an experiment of nature that disrupts this protease-anti-protease balance, resulting in an increased risk of destructive lung disease.",
"title": "Neutrophil elastase-mediated lung disease."
},
{
"docid": "13106686",
"text": "Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxidative damage in DNA, potentiated cytosolic immune recognition by decreasing its susceptibility to 3' repair exonuclease 1 (TREX1)-mediated degradation. Oxidizative modifications arose physiologically in pathogen DNA during lysosomal reactive oxygen species (ROS) exposure, as well as in neutrophil extracellular trap (NET) DNA during the oxidative burst. 8-OHG was also abundant in UV-exposed skin lesions of LE patients and colocalized with type I interferon (IFN). Injection of oxidized DNA in the skin of lupus-prone mice induced lesions that closely matched respective lesions in patients. Thus, oxidized DNA represents a prototypic damage-associated molecular pattern (DAMP) with important implications for infection, sterile inflammation, and autoimmunity.",
"title": "Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing."
},
{
"docid": "21487212",
"text": "Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.",
"title": "Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting."
},
{
"docid": "13578199",
"text": "Human transglutaminase 2 (TG2), a member of a large family of enzymes that catalyze protein crosslinking, plays an important role in the extracellular matrix biology of many tissues and is implicated in the gluten-induced pathogenesis of celiac sprue. Although vertebrate transglutaminases have been studied extensively, thus far all structurally characterized members of this family have been crystallized in conformations with inaccessible active sites. We have trapped human TG2 in complex with an inhibitor that mimics inflammatory gluten peptide substrates and have solved, at 2-A resolution, its x-ray crystal structure. The inhibitor stabilizes TG2 in an extended conformation that is dramatically different from earlier transglutaminase structures. The active site is exposed, revealing that catalysis takes place in a tunnel, bridged by two tryptophan residues that separate acyl-donor from acyl-acceptor and stabilize the tetrahedral reaction intermediates. Site-directed mutagenesis was used to investigate the acyl-acceptor side of the tunnel, yielding mutants with a marked increase in preference for hydrolysis over transamidation. By providing the ability to visualize this activated conformer, our results create a foundation for understanding the catalytic as well as the non-catalytic roles of TG2 in biology, and for dissecting the process by which the autoantibody response to TG2 is induced in celiac sprue patients.",
"title": "Transglutaminase 2 Undergoes a Large Conformational Change upon Activation "
},
{
"docid": "5172048",
"text": "Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood. One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK). Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading. Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation. We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders. Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis. Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment. These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK–ERK–MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.",
"title": "Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling"
},
{
"docid": "5273056",
"text": "Eukaryotes have numerous checkpoint pathways to protect genome fidelity during normal cell division and in response to DNA damage. Through a screen for G2/M checkpoint regulators in zebrafish, we identified ticrr (for TopBP1-interacting, checkpoint, and replication regulator), a previously uncharacterized gene that is required to prevent mitotic entry after treatment with ionizing radiation. Ticrr deficiency is embryonic-lethal in the absence of exogenous DNA damage because it is essential for normal cell cycle progression. Specifically, the loss of ticrr impairs DNA replication and disrupts the S/M checkpoint, leading to premature mitotic entry and mitotic catastrophe. We show that the human TICRR ortholog associates with TopBP1, a known checkpoint protein and a core component of the DNA replication preinitiation complex (pre-IC), and that the TICRR-TopBP1 interaction is stable without chromatin and requires BRCT motifs essential for TopBP1's replication and checkpoint functions. Most importantly, we find that ticrr deficiency disrupts chromatin binding of pre-IC, but not prereplication complex, components. Taken together, our data show that TICRR acts in association with TopBP1 and plays an essential role in pre-IC formation. It remains to be determined whether Ticrr represents the vertebrate ortholog of the yeast pre-IC component Sld3, or a hitherto unknown metazoan replication and checkpoint regulator.",
"title": "A vertebrate gene, ticrr, is an essential checkpoint and replication regulator."
},
{
"docid": "195683603",
"text": "Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses.",
"title": "Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A."
},
{
"docid": "15248287",
"text": "Neutrophil apoptosis is a highly regulated process essential for inflammation resolution, the molecular mechanisms of which are only partially elucidated. In this study, we describe a survival pathway controlled by proliferating cell nuclear antigen (PCNA), a nuclear factor involved in DNA replication and repairing of proliferating cells. We show that mature neutrophils, despite their inability to proliferate, express high levels of PCNA exclusively in their cytosol and constitutively associated with procaspases, presumably to prevent their activation. Notably, cytosolic PCNA abundance decreased during apoptosis, and increased during in vitro and in vivo exposure to the survival factor granulocyte colony-stimulating factor (G-CSF). Peptides derived from the cyclin-dependent kinase inhibitor p21, which compete with procaspases to bind PCNA, triggered neutrophil apoptosis thus demonstrating that specific modification of PCNA protein interactions affects neutrophil survival. Furthermore, PCNA overexpression rendered neutrophil-differentiated PLB985 myeloid cells significantly more resistant to TNF-related apoptosis-inducing ligand- or gliotoxin-induced apoptosis. Conversely, a decrease in PCNA expression after PCNA small interfering RNA transfection sensitized these cells to apoptosis. Finally, a mutation in the PCNA interdomain-connecting loop, the binding site for many partners, significantly decreased the PCNA-mediated antiapoptotic effect. These results identify PCNA as a regulator of neutrophil lifespan, thereby highlighting a novel target to potentially modulate pathological inflammation.",
"title": "Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival"
},
{
"docid": "20608982",
"text": "PURPOSE OF REVIEW As the migration of neutrophils from blood to inflamed tissues is an essential component of innate immunity and a key contributing factor to the pathogenesis of inflammatory disorders, this aspect of leukocyte biology continues to be a highly dynamic field of research. This review summarizes recent findings in this area, focusing on the mechanisms that mediate neutrophil transmigration, an area where significant progress has been made. RECENT FINDINGS The topics to be covered will include responses that are prerequisite to neutrophil migration through venular walls, such as leukocyte luminal crawling and cellular and molecular changes in leukocytes and endothelial cells (e.g. formation of protrusions) that collectively support leukocyte transendothelial cell migration. Advances in both paracellular and transcellular neutrophil migration through endothelial cells will be discussed, addressing the associated roles and regulation of expression of endothelial cell luminal and junctional adhesion molecules. Beyond the endothelium, migration through the vascular pericyte coverage and basement membrane will be reviewed. SUMMARY The unquestionable role of neutrophils in the development and progression of inflammatory conditions suggests that a better understanding of the tissue-specific and stimulus-specific mechanisms that mediate this response may identify novel pathways that could be exploited for the development of more specific anti-inflammatory interventions.",
"title": "Recent developments and complexities in neutrophil transmigration."
},
{
"docid": "6417632",
"text": "BACKGROUND COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. METHODS To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. RESULTS Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). CONCLUSIONS Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation.",
"title": "Neutrophilic infiltration within the airway smooth muscle in patients with COPD."
},
{
"docid": "10443642",
"text": "RNAIII is the intracellular effector of the quorum-sensing system in Staphylococcus aureus. It is one of the largest regulatory RNAs (514 nucleotides long) that are known to control the expression of a large number of virulence genes. Here, we show that the 3' domain of RNAIII coordinately represses at the post-transcriptional level, the expression of mRNAs that encode a class of virulence factors that act early in the infection process. We demonstrate that the 3' domain acts primarily as an antisense RNA and rapidly anneals to these mRNAs, forming long RNA duplexes. The interaction between RNAIII and the mRNAs results in repression of translation initiation and triggers endoribonuclease III hydrolysis. These processes are followed by rapid depletion of the mRNA pool. In addition, we show that RNAIII and its 3' domain mediate translational repression of rot mRNA through a limited number of base pairings involving two loop-loop interactions. Since Rot is a transcriptional regulatory protein, we proposed that RNAIII indirectly acts on many downstream genes, resulting in the activation of the synthesis of several exoproteins. These data emphasize the multitude of regulatory steps affected by RNAIII and its 3' domain in establishing a network of S. aureus virulence factors.",
"title": "Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism."
},
{
"docid": "12058271",
"text": "The bone marrow is the primary site for neutrophil production and release into the circulation. Because the CXC chemokine receptor-4/stromal derived factor-1 (CXCR4/SDF-1) axis plays a central role in the interactions of hematopoietic stem cells, lymphocytes, and developing neutrophils in the marrow, we investigated whether reciprocal CXCR4-dependent mechanisms might be involved in neutrophil release and subsequent return to the marrow following circulation. Neutralizing antibody to CXCR4 reduced marrow retention of infused neutrophils (45.7% +/- 0.5% to 6.9% +/- 0.5%) and was found to mobilize neutrophils from marrow (34.4% +/- 4.4%). Neutrophil CXCR4 expression and SDF-1-induced calcium flux decreased with maturation and activation of the cells, corresponding to the decreased marrow homing associated with these characteristics in vivo. Infusion of the inflammatory mediator and CXCR2 ligand KC led to mobilization of neutrophils from marrow by itself and was augmented 3-fold by low doses of CXCR4-blocking antibody that otherwise had no mobilizing effect. Examination of KC and SDF-1 calcium signaling demonstrated that the effect of KC may, in part, be due to heterologous desensitization to SDF-1. These results suggest that the CXCR4/SDF-1 axis is critical in circulating neutrophil homeostasis and that it may participate in the rapid release of neutrophils from the marrow during inflammation through a novel interaction with inflammatory CXC chemokines.",
"title": "Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis."
},
{
"docid": "14119470",
"text": "Ran is an abundant nuclear GTPase with a clear role in nuclear transport during interphase but with roles in mitotic regulation that are less well understood. The nucleotide-binding state of Ran is regulated by a GTPase activating protein, RanGAP1, and by a guanine nucleotide exchange factor, RCC1. Ran also interacts with a guanine nucleotide dissociation inhibitor, RanBP1. RanBP1 has a high affinity for GTP-bound Ran, and it acts as a cofactor for RanGAP1, increasing the rate of GAP-mediated GTP hydrolysis on Ran approximately tenfold. RanBP1 levels oscillate during the cell cycle [4], and increased concentrations of RanBP1 prolong mitosis in mammalian cells and in Xenopus egg extracts (our unpublished observations). We investigated how increased concentrations of RanBP1 disturb mitosis. We found that spindle assembly is dramatically disrupted when exogenous RanBP1 is added to M phase Xenopus egg extracts. We present evidence that the role of Ran in spindle assembly is independent of nuclear transport and is probably mediated through changes in microtubule dynamics.",
"title": "The Ran GTPase regulates mitotic spindle assembly"
},
{
"docid": "21395936",
"text": "Chronic obstructive pulmonary disease (COPD) is a chronic airway disorder characterized by obstructive airflow limitation which is not completely reversible with treatment. Inflammatory changes in the peripheral airways, especially those with the diameter less than 2mm (so-called small airway disease) have been speculated to be initial steps of COPD. And so it must be quite clear that neutrophils and macrophages play an essential role in the pathogenesis of these lesions. Studies with bronchoalveolar lavage demonstrated an increase in neutrophil numbers and the neutrophil chemoattractant interleukin-8. Recent studies demonstrated that neutrophils and macrophages are increased and contain a variety of proteases, which are involved in cell infiltration and activation. Studies with gene-engineered animals and anti-cytokine treatment will facilitate better understanding the role of neutrophils and macrophages, and eventual novel therapy.",
"title": "[Neutrophils and macrophages related to the pathogenesis and disease development of chronic obstructive pulmonary disease by the inflammatory reaction]."
}
] |
1118
|
Sweet taste receptors on the tongue are deactivated by between 1 and 10 mM glucose.
|
[
{
"docid": "23351136",
"text": "The tastes of sugars (sweet) and glutamate (umami) are thought to be detected by T1r receptors expressed in taste cells. Molecular genetics and heterologous expression implicate T1r2 plus T1r3 as a sweet-responsive receptor,and T1r1 plus T1r3,as well as a truncated form of the type 4 metabotropic glutamate receptor (taste-mGluR4),as umami-responsive receptors. Here,we show that mice lacking T1r3 showed no preference for artificial sweeteners and had diminished but not abolished behavioral and nerve responses to sugars and umami compounds. These results indicate that T1r3-independent sweet- and umami-responsive receptors and/or pathways exist in taste cells.",
"title": "Detection of sweet and umami taste in the absence of taste receptor T1r3."
}
] |
[
{
"docid": "20829129",
"text": "Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut \"taste\" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut \"taste cells\" may provide an important treatment for obesity, diabetes and abnormal gut motility.",
"title": "Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1."
},
{
"docid": "718601",
"text": "Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities.",
"title": "Coding of Sweet, Bitter, and Umami Tastes Different Receptor Cells Sharing Similar Signaling Pathways"
},
{
"docid": "5293024",
"text": "Our attitude towards candy—“if it tastes that good, it can't be healthy”—betrays society's puritanical stance towards pleasure. Candy has been blamed for various ills, including hyperactivity in children; however, clinical trials have not supported this.1 Candy—sugar confectionery and chocolate—is not a recent invention: the ancient Arabs, Chinese, and Egyptians candied fruits and nuts in honey, and the Aztecs made a chocolate drink from the bean of the cacao tree. Today, Americans gratify themselves with, on average, 5.4 kg of sugar candy and 6.5 kg of chocolate per person annually.2 Since candy has existed for centuries, we surmised that it cannot be totally unhealthy. We decided to investigate whether candy consumption was associated with longevity. Subjects were from the Harvard alumni health study, an ongoing study of men entering Harvard University as undergraduates between 1916 and 1950. We included 7841 men, free of cardiovascular disease and cancer, who responded to a health survey …",
"title": "Life is sweet: candy consumption and longevity."
},
{
"docid": "12943966",
"text": "Ghrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (i) ghrelin release via α-gustducin and (ii) food intake and gastric emptying via the release of ghrelin. The mouse stomach contains two ghrelin cell populations: cells containing octanoyl and desoctanoyl ghrelin, which were colocalized with α-gustducin and α-transducin, and cells staining for desoctanoyl ghrelin. Gavage of T2R-agonists increased plasma octanoyl ghrelin levels in WT mice but the effect was partially blunted in gust(-/-) mice. Intragastric administration of T2R-agonists increased food intake during the first 30 min in WT but not in gust(-/-) and ghrelin receptor knockout mice. This increase was accompanied by an increase in the mRNA expression of agouti-related peptide in the hypothalamus of WT but not of gust(-/-) mice. The temporary increase in food intake was followed by a prolonged decrease (next 4 h), which correlated with an inhibition of gastric emptying. The delay in emptying, which was partially counteracted by ghrelin, was not mediated by cholecystokinin and GLP-1 but involved a direct inhibitory effect of T2R-agonists on gastric contractility. This study is unique in providing functional evidence that activation of bitter taste receptors stimulates ghrelin secretion. Modulation of endogenous ghrelin levels by tastants may provide novel therapeutic applications for the treatment of weight -and gastrointestinal motility disorders.",
"title": "Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying."
},
{
"docid": "10247282",
"text": "In the rat isolated perfused kidney, arachidonic acid elicits cyclooxygenase-dependent vasoconstriction through activation of PGH2/TxA2 receptors; responses are enhanced in kidneys from diabetic rats. This study examined the roles of cyclooxygenase-1/cyclooxygenase-2 in the enhanced renal vasoconstrictor effect of arachidonic acid in streptozotocin-diabetic rats. Release of 20-HETE was also determined, as this eicosanoid has been reported to elicit cyclooxygenase-dependent vasoconstriction. We confirmed that vasoconstrictor responses to arachidonic acid were enhanced in the diabetic rat kidney associated with a 2-fold-greater increase in the release of 6-ketoPGF1alpha, which was used as an index of cyclooxygenase activity. One and three micrograms of arachidonic acid increased perfusion pressure by 85+/-37 and 186+/-6 mm Hg, respectively, in diabetic rat kidneys compared with 3+/-1 and 17+/-8 mm Hg, respectively, in control rat kidneys. Inhibition of both cyclooxygenase isoforms with indomethacin (10 micromol/L) abolished the vasoconstrictor response to arachidonic acid in both diabetic and control rat kidneys, whereas inhibition of cyclooxygenase-2 with nimesulide (5 micromol/L) reduced perfusion pressure responses to 1 and 3 microg arachidonic acid only in the diabetic rat kidney to 15+/-8 and 108+/-26 mm Hg, respectively, consistent with a 3-fold increase in the renal cortical expression of cyclooxygenase-2. 20-HETE release from the diabetic rat kidney was reduced almost 6-fold and was not increased in response to arachidonic acid. These results demonstrate that the renal vasoconstrictor effect of arachidonic acid is solely dependent on cyclooxygenase activity, with no evidence for a contribution from 20-HETE; in the diabetic rat, cyclooxygenase-2 activity contributes to the renal vasoconstrictor effect of arachidonic acid.",
"title": "Arachidonic Acid in the Diabetic Rat Kidney"
},
{
"docid": "4857093",
"text": "Objective:To assess the relative validity and acceptability of the computerised 24-h recall ‘Young Adolescent's Nutrition Assessment on Computer (YANA-C)’.Design:Food and nutrient intakes assessed with YANA-C were compared with food records (study 1) and 24-h dietary recall interviews (study 2).Main outcome measures:Intakes of food groups (fruit, fruit juice, vegetables, potatoes, bread, cereals, milk, cheese, other milk products, soft drinks, diet soft drinks, sugar/sweets, pastry/cookies, savoury snacks, butter/sauces, eggs, fish, meat) and nutrients (energy, carbohydrates, protein, fat, fiber, calcium, vitamin C and iron).Subjects and setting:A total of 237 pupils (11–14 y) from two primary and four secondary schools (study 1: n=136; study 2: n=101) in Belgium-Flanders. Results:YANA-C proved to agree well with both standard methods in categorizing subjects in consumers and nonconsumers (κstudy 1=0.48–0.92; κstudy 2=0.38–0.90). Spearman's correlations for energy and nutrient intakes ranged between 0.44 and 0.79 for study 1 and between 0.44 and 0.86 for study 2. Nutrient and energy intakes were in general (excluding calcium) significantly higher in YANA-C in comparison with the food record, but not in comparison with the interview (only fiber). Statistics used to investigate whether YANA-C agreed with the other methods in ranking portions/amounts in consumers only were fair to moderate for most of the food groups (weighted κ study 1=0.11–0.55; study 2=0.04–0.73); amounts in consumers only, were significantly lower in YANA-C against both standards for cereals; amounts were significantly higher in YANA-C against the food record for milk, soft drinks, sugar/sweets and savoury snacks and against the interview for potatoes. Only a few pupils evaluated the program negatively. Conclusion:YANA-C is a promising method to collect detailed dietary information from young adolescents with relatively low staff resources, useful in many nutrition research applications.",
"title": "Young adolescents' nutrition assessment on computer (YANA-C)"
},
{
"docid": "26058927",
"text": "Thiazolidinediones (TZDs) improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). There is growing evidence from in vivo and in vitro studies that TZDs improve pancreatic beta-cell function. The aim of this study was to determine whether TZD-induced improvement in glycemic control is associated with improved beta-cell function. We studied 11 normal glucose-tolerant and 53 T2DM subjects [age 53+/-2 yr; BMI 29.4+/-0.8 kg/m2; fasting plasma glucose (FPG) 10.3+/-0.4 mM; Hb A1c 8.2+/-0.3%]. Diabetic patients were randomized to receive placebo or TZD for 4 mo. Subjects received 1) 2-h OGTT with determination of plasma glucose, insulin, and C-peptide concentrations and 2) two-step euglycemic insulin (40 and 160 mU.m-2.min-1) clamp with [3-(3)H]glucose. T2DM patients were then randomized to receive 4 mo of treatment with pioglitazone (45 mg/day), rosiglitazone (8 mg/day), or placebo. Pioglitazone and rosiglitazone similarly improved FPG, mean plasma glucose during OGTT, Hb A1c, and insulin-mediated total body glucose disposal (Rd) and decreased mean plasma FFA during OGTT (all P<0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [DeltaISR(AUC)/Deltaglucose(AUC)/IR] was significantly improved in all TZD-treated groups: +1.8+/-0.7 (PIO+drug-naïve diabetics), +0.7+/-0.3 (PIO+sulfonylurea-treated diabetics), and 0.7+/-0.2 (ROSI+sulfonylurea-withdrawn diabetics) vs. -0.2+/-0.3 in the two placebo groups (P<0.01, all TZDs vs. placebo, ANOVA). Improved insulin secretion correlated positively with increased body weight, fat mass, and Rd and inversely with decreased plasma glucose and FFA during the OGTT. In T2DM patients, TZD treatment leads to improved beta-cell function, which correlates strongly with improved glycemic control.",
"title": "Thiazolidinediones improve beta-cell function in type 2 diabetic patients."
},
{
"docid": "18346333",
"text": "Glutamate receptors mediate the majority of excitatory synaptic transmission in the CNS. The AMPA-subtype has rapid kinetics, with activation, deactivation and desensitization proceeding on the millisecond timescale or faster. Crystallographic, biochemical, and functional studies suggest that GluR2 Cys mutants which form intermolecular disulfide cross-links between the lower D2 lobes of the ligand binding cores can be trapped in a conformation that represents the desensitized state. We used multi-channel rapid perfusion techniques to examine the state dependence of cross-linking in these mutants. Under reducing conditions, both wild-type GluR2 and the G725C and S729C mutants have normal activation and desensitization kinetics, but the Cys mutants can be efficiently trapped in nonconducting states when oxidized. In contrast the I664C mutant is only partially inactivated under oxidizing conditions. For S729C, disulfide cross-links form rapidly when receptors are desensitized in the presence of glutamate, but receptors also become trapped at rest, in the absence of agonist. We assessed such spontaneous trapping in various conditions, including CNQX, a competitive antagonist; kainate, a weak partial agonist; or when desensitization was blocked by the L483Y mutation that stabilizes the D1 dimer interface. These experiments suggest that trapping in the absence of glutamate is due to two motions: Spontaneous breaking of the D1 dimer interface and hyperextension of the lower lobes of the ligand binding core. These data show that the glutamate binding domains are surprisingly mobile in the absence of ligand, which could influence receptor activity in the brain.",
"title": "AMPA receptor ligand binding domain mobility revealed by functional cross linking."
},
{
"docid": "28633594",
"text": "BACKGROUND In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. METHODS The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. FINDINGS We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. INTERPRETATION We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. FUNDING Bill & Melinda Gates Foundation.",
"title": "International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project."
},
{
"docid": "11090688",
"text": "The weight lowering potential of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP-1R on body weight response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has not yet been evaluated. Fifty-seven obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m2) were assigned to liraglutide 1.2 mg QD s.c. for 12 weeks and classified as strong responders regarding weight loss if they lost 5 % or more of their initial body weight. They were genotyped for common GLP-1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of measures of obesity were measured before and at the end of the treatment. Twenty out of 57 subjects were strong responders and lost 7.38 ± 1.74 compared to 2.11 ± 2.17 kg lost in poor responders. Carriers of at least one polymorphic rs10305420 allele had poor treatment response compared to carriers of two wild type alleles (OR = 0.27, 95 % CI = 0.09–0.85, P = 0.025). Carriers of at least one polymorphic rs6923761 allele tended to have stronger treatment response compared to carriers of two wild type alleles (OR = 3.06, 95 % CI = 0.96–9.74, P = 0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT) comparably decreased in both groups when compared to baseline, whereas no within treatment differences were found in androgen profile. Gastrointestinal adverse events were transit and balanced between strong and poor responders. GLP-1R rs10305420 polymorphism explained some of the inter-individual differences in response to liraglutide regarding weight loss in obese PCOS women.",
"title": "Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study"
},
{
"docid": "16361581",
"text": "Notch receptors expressed on hematopoietic stem cells interact with their ligands on bone marrow stromal cells and thereby control cell fate decisions and survival. We recently demonstrated that Notch signaling is involved in proliferation and survival of B cell-derived tumor cells of classic Hodgkin disease and described a novel mechanism for the oncogenic capacity of Notch. In this study we investigated whether Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment, which are essential for tumor cell growth in multiple myeloma (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are highly expressed in cultured and primary MM cells, whereas nonneoplastic counterparts show low to undetectable levels of Notch. Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo.",
"title": "Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells."
},
{
"docid": "15563864",
"text": "Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts. Treatment with EGCG also led to significant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-kappaB activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18). Expression of related genes at the protein level were also confirmed by Western blot analysis. These data demonstrate potent and specific antimyeloma activity of EGCG and provide the rationale for its clinical evaluation.",
"title": "Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications."
},
{
"docid": "4506414",
"text": "BACKGROUND The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. METHODS We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. FINDINGS During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. INTERPRETATION The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. FUNDING Medical Research Council, National Institute for Health Research, and Wellcome Trust.",
"title": "Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people"
},
{
"docid": "3981033",
"text": "The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical trials for their ability to induce tumor necrosis factor (TNF)-mediated apoptosis of cancer cells. However, cIAP1 and cIAP2 are recurrently homozygously deleted in multiple myeloma (MM), resulting in constitutive activation of the noncanonical nuclear factor (NF)-κB pathway. To our surprise, we observed robust in vivo anti-myeloma activity of LCL161 in a transgenic myeloma mouse model and in patients with relapsed-refractory MM, where the addition of cyclophosphamide resulted in a median progression-free-survival of 10 months. This effect was not a result of direct induction of tumor cell death, but rather of upregulation of tumor-cell-autonomous type I interferon (IFN) signaling and a strong inflammatory response that resulted in the activation of macrophages and dendritic cells, leading to phagocytosis of tumor cells. Treatment of a MM mouse model with LCL161 established long-term anti-tumor protection and induced regression in a fraction of the mice. Notably, combination of LCL161 with the immune-checkpoint inhibitor anti-PD1 was curative in all of the treated mice.",
"title": "IAP antagonists induce anti-tumor immunity in multiple myeloma"
},
{
"docid": "10648422",
"text": "Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.",
"title": "Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection"
},
{
"docid": "29387024",
"text": "BACKGROUND Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.",
"title": "Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial"
},
{
"docid": "20767776",
"text": "Objective:A number of case reports describe multiple family members with gastroesophageal reflux disease and Barrett's esophagus. The wider importance of familial factors in gastroesophageal reflux disease has not been established. Therefore, we have studied the prevalence of reflux symptoms and medication use among relatives of patients with documented gastroesophageal reflux disease. Methods:A postal questionnaire study of the first degree relatives of six groups of matched patients. The groups comprised patients with 1) no dyspeptic symptoms; 2) reflux symptoms and a normal pH study; 3) reflux symptoms, an abnormal pH study, and a lower esophageal sphincter (LOS) pressure more than 10 mm Hg; 4) reflux symptoms, an abnormal pH study, and a LOS pressure less than 10 mm Hg; 5) Barrett's esophagus; and 6) peptic stricture. Results:Four hundred eighteen subjects replied (78% response). Infrequent reflux symptoms were equally common in all groups of relatives. Frequent reflux symptoms, however, were more common among relatives of patients with an abnormal pH study and normal (26%, p= 0.007) or low LOS pressure (27%, p= 0.01) or Barrett's esophagus (30%, p= 0.003), compared with relatives of nondyspeptic patients (9%). Frequent reflux symptoms were no more common among relatives of patients with a normal pH study (16%) or peptic stricture (18%). Reflux medication use showed a similar pattern. Conclusions:Familial clustering of reflux symptoms is seen in relatives of patients with reflux symptoms and increased esophageal acid exposure and in relatives of patients with Barrett's esophagus.",
"title": "Familial clustering of reflux symptoms"
},
{
"docid": "14300799",
"text": "A key feature of speech is its stereotypical 5 Hz rhythm. One theory posits that this rhythm evolved through the modification of rhythmic facial movements in ancestral primates. If the hypothesis has any validity, then a comparative approach may shed some light. We tested this idea by using cineradiography (X-ray movies) to characterize and quantify the internal dynamics of the macaque monkey vocal tract during lip-smacking (a rhythmic facial expression) versus chewing. Previous human studies showed that speech movements are faster than chewing movements, and the functional coordination between vocal tract structures is different between the two behaviors. If rhythmic speech evolved through a rhythmic ancestral facial movement, then one hypothesis is that monkey lip-smacking versus chewing should also exhibit these differences. We found that the lips, tongue, and hyoid move with a speech-like 5 Hz rhythm during lip-smacking, but not during chewing. Most importantly, the functional coordination between these structures was distinct for each behavior. These data provide empirical support for the idea that the human speech rhythm evolved from the rhythmic facial expressions of ancestral primates.",
"title": "Cineradiography of Monkey Lip-Smacking Reveals Putative Precursors of Speech Dynamics"
},
{
"docid": "145416918",
"text": "The effects of product information on responses to frankfurter sausages and chocolate bars were studied by comparing sensory and hedonic ratings in two conditions: blind tasting and tasting with information present. Furthermore, the effect of information alone was investigated by having the subjects rate the expected sensory and hedonic intensities of the products on the basis of packages with different claims. Three groups of subjects were tested by giving them different information: The basic group (no added claims, n = 31), the reduced-fat group (products claimed to have reduced-fat, n=29) and the flavorful group (products claimed to have full meat/chocolate flavor, n = 31). Product information increased the rated pleasantness of the frankfurter in all three information groups compared to the blind ratings. The information did not affect the pleasantness of the chocolate bars. The expected attribute intensities of the frankfurters and chocolates were rated lower by the reduced-fat group than by the other groups. Overall, the effect of product information was more clearly seen in ratings of sensory attributes than in pleasantness ratings.",
"title": "The effect of information related to fat content and taste on consumer responses to a reduced-fat frankfurter and a reduced-fat chocolate bar"
},
{
"docid": "33554389",
"text": "Abstract The effect of increased levels of cAMP upon the differentiation of primary cultures of chick myo blasts has been investigated. 0.1 mM But 2 cAMP or 1 mM 3-isobutyl-1-methylxanthine was added to the cultures 24 h after plating and maintained throughout the 70 h period of culture examined. Both reagents were found to markedly delay the time of fusion of the myoblasts but had no observable effect upon the increase in activity of creatine phosphokinase. Morphological examination of the cells revealed no difference in the relative numbers of myoblasts and fibroblasts between the control, But 2 cAMP and 3-isobutyl-1-methylxanthine cultures, but the latter reagent appeared to cause some inhibition of cell proliferation.",
"title": "The relationship of the level of cyclic amp to differentiation in primary cultures of chick muscle cells."
},
{
"docid": "12280462",
"text": "Bile acids are recognized as metabolic modulators. The present study was aimed at evaluating the effects of a potent Asbt inhibitor (264W94), which blocks intestinal absorption of bile acids, on glucose homeostasis in Zucker Diabetic Fatty (ZDF) rats. Oral administration of 264W94 for two wk increased fecal bile acid concentrations and elevated non-fasting plasma total Glp-1. Treatment of 264W94 significantly decreased HbA1c and glucose, and prevented the drop of insulin levels typical of ZDF rats in a dose-dependent manner. An oral glucose tolerance test revealed up to two-fold increase in plasma total Glp-1 and three-fold increase in insulin in 264W94 treated ZDF rats at doses sufficient to achieve glycemic control. Tissue mRNA analysis indicated a decrease in farnesoid X receptor (Fxr) activation in small intestines and the liver but co-administration of a Fxr agonist (GW4064) did not attenuate 264W94 induced glucose lowering effects. In summary, our results demonstrate that inhibition of Asbt increases bile acids in the distal intestine, promotes Glp-1 release and may offer a new therapeutic strategy for type 2 diabetes mellitus.",
"title": "Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes."
},
{
"docid": "19205437",
"text": "Uncoupling protein 1 (UCP1) plays a central role in nonshivering thermogenesis in brown fat; however, its role in beige fat remains unclear. Here we report a robust UCP1-independent thermogenic mechanism in beige fat that involves enhanced ATP-dependent Ca2+ cycling by sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2). Inhibition of SERCA2b impairs UCP1-independent beige fat thermogenesis in humans and mice as well as in pigs, a species that lacks a functional UCP1 protein. Conversely, enhanced Ca2+ cycling by activation of α1- and/or β3-adrenergic receptors or the SERCA2b-RyR2 pathway stimulates UCP1-independent thermogenesis in beige adipocytes. In the absence of UCP1, beige fat dynamically expends glucose through enhanced glycolysis, tricarboxylic acid metabolism and pyruvate dehydrogenase activity for ATP-dependent thermogenesis through the SERCA2b pathway; beige fat thereby functions as a 'glucose sink' and improves glucose tolerance independently of body weight loss. Our study uncovers a noncanonical thermogenic mechanism through which beige fat controls whole-body energy homeostasis via Ca2+ cycling.",
"title": "UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis"
},
{
"docid": "11201004",
"text": "Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P < 0.01). No associations were observed with consumption of added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.",
"title": "Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity."
},
{
"docid": "13445579",
"text": "BACKGROUND AND PURPOSE IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.",
"title": "Results of screening for intracranial aneurysms in patients with coarctation of the aorta."
},
{
"docid": "42800527",
"text": "BACKGROUND Adverse effects of metformin are primarily related to gastrointestinal (GI) intolerance that could limit titration to an efficacious dose or cause discontinuation of the medication. Because some metformin side effects may be attributable to shifts in the GI microbiome, we tested whether a GI microbiome modulator (GIMM) used in combination with metformin would ameliorate the GI symptoms. METHODS A 2-period crossover study design was used with 2 treatment sequences, either placebo in period 1 followed by GIMM in period 2 or vice versa. Study periods lasted for 2 weeks, with a 2-week washout period between. During the first week, type 2 diabetes patients (T2D) who experienced metformin GI intolerance took 500 mg metformin along with their assigned NM504 (GIMM) or placebo treatment with breakfast and with dinner. In the second week, the 10 subjects took 500 mg metformin (t.i.d.), with GIMM or placebo consumed with the first and third daily metformin doses. Subjects were permitted to discontinue metformin dosing if it became intolerable. RESULTS The combination of metformin and GIMM treatment produced a significantly better tolerance score to metformin than the placebo combination (6.78 ± 0.65 [mean ± SEM] versus 4.45 ± 0.69, P = .0006). Mean fasting glucose levels were significantly (P < .02) lower with the metformin-GIMM combination (121.3 ± 7.8 mg/dl) than with metformin-placebo (151.9 ± 7.8 mg/dl). CONCLUSION Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.",
"title": "Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels."
},
{
"docid": "1171121",
"text": "A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5 %) with lower MVD (≤ 214.8 microvesells/mm(2)) and 49 (28.5 %) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P = 0.000) and in estrogen (P = 0.046) or progesterone receptors (P = 0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1 %) and was significantly associated with higher grade (P = 0.000), steroid receptors negativity (P = 0.000), cytokeratin5/6 positivity (P = 0.026), topoisomerase IIα overexpression (P = 0.005) and higher proliferation rate (P = 0.001). In univariate analysis, higher MVD (P = 0.016) and p53 negativity (P = 0.023) were significantly related with longer DFS (median follow-up 36 months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.",
"title": "Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group"
},
{
"docid": "21547032",
"text": "Objective:In mice and in humans, treatment with the second-generation antipsychotic drug olanzapine (OLZ) produces excessive weight gain, adiposity and secondary metabolic complications, including loss of glucose and insulin homeostasis. In mice consuming a high-fat (HF) diet, a similar phenotype develops, which is inhibited by the analgesic acetaminophen (APAP) and by the antioxidant tetrahydroindenoindole (THII). Therefore, we examined the ability of APAP and THII to prevent metabolic changes in mice receiving OLZ.Design and Measurement:C57BL/6J mice received either a normal diet or a HF diet, and were administered daily dosages of OLZ (3 mg kg−1 body weight), alone or with APAP (30 mg kg−1 body weight) or THII (4.5 mg kg−1 body weight), for 10 weeks. Parameters of body composition and metabolism, including glucose and insulin homeostasis and oxidative stress, were examined. Results:OLZ treatment doubled the HF diet-induced increases in body weight and percent body fat. These increases were partially prevented by both APAP and THII, although food consumption was constant in all groups. The THII protection was associated with an increase in whole body and mitochondrial respiration. OLZ also exacerbated, and both APAP and THII prevented, HF diet-induced loss of glucose tolerance and insulin resistance. As increased body fat promotes insulin resistance by a pathway involving oxidative stress, we evaluated production of reactive oxygen and lipid peroxidation in white adipose tissue (WAT). HF diet caused an increase in lipid peroxidation, NADPH-dependent O2 uptake and H2O2 production, which were further exacerbated by OLZ. APAP, THII and the NADPH oxidase inhibitor, diphenyleneiodonium chloride, each abolished oxidative stress in WAT.Conclusions:We conclude that both APAP and THII intervene in the development of obesity and metabolic complications associated with OLZ treatment.",
"title": "Protection from olanzapine-induced metabolic toxicity in mice by acetaminophen and tetrahydroindenoindole"
},
{
"docid": "13492264",
"text": "Glomerular basement membrane (GBM) and podocalyxin are essential for podocyte morphology. We provide evidence of functional interconnections between basement membrane components (collagen IV and laminin), the expression of podocalyxin and the morphology of human glomerular epithelial cells (podocytes). We demonstrated that GBM and laminin, but not collagen IV, up-regulated the expression of podocalyxin. Scanning electron microscopy revealed that laminin induced a modified morphology of podocytes with process formation, which was more extensive in the presence of GBM. Under high magnification, podocytes appeared ruffled. Using transmission electron microscopy we observed that raised areas occurred in the basal cell surface. Furthermore, the presence of anti-podocalyxin antibody increased the extent of adhesion and spreading of podocytes to both collagen IV and laminin, thus podocalyxin apparently inhibits cell-matrix interactions. We also performed adhesion and spreading assays on podocytes grown under increased glucose concentration (25 mM). Under these conditions, the expression of podocalyxin was almost totally suppressed. The cells adhered and spread to basement membrane components but there was no increase in the extent of adhesion and spreading in the presence of anti-podocalyxin antibody, or ruffling of the cell edges. Additionally, in podocytes expressing podocalyxin, the presence of anti-podocalyxin antibody partially reversed the inhibition of adhesion to collagen IV provoked by anti-beta1 integrin antibody, thus podocalyxin should compete with beta1-related cell adhesion. We suggest that the observed podocalyxin-mediated inhibition of binding to the matrix could be in part responsible for the specialized conformation of the basal surface of podocytes.",
"title": "Summary"
},
{
"docid": "21931005",
"text": "Permeabilized rat kidney cells rapidly released glucose 6-phosphate dehydrogenase (G6PD) following stimulation with peptide growth factors (Stanton, R.C., Seifter, J.L., Boxer, D.C., Zimmerman, E., and Cantley, L. C. (1991) J. Biol. Chem. 266, 12442-12448). To evaluate the signal transduction pathways mediating release of G6PD, two cell lines transfected with wild type or mutant platelet-derived growth factor (PDGF) receptors (PDGFR) were studied using two permeabilization protocols. G6PD release was evaluated by enzyme activity and Western blot analysis. PDGF caused a significant increase in G6PD release in 1 min in cells transfected with wild type PDGFR. PDGF did not stimulate G6PD release in cells transfected with tyrosine kinase-deficient PDGFR. PDGF did not stimulate G6PD release in cells transfected with partially autophosphorylation-deficient PDGFR in which four known signaling proteins do not associate with the PDGFR. The PDGF-stimulated release of G6PD was partially restored in PDGFR mutants in which either phosphatidylinositol-3-kinase or phospholipase C gamma 1 could associate with the PDGFR. Lastly, there was no basal or PDGF-stimulated phosphorylation of G6PD. We conclude that release of G6PD: 1) requires intrinsic PDGFR tyrosine kinase activity; 2) requires PDGFR autophosphorylation; 3) is mediated by signaling proteins that associate with the PDGFR; 4) is not mediated by direct phosphorylation of G6PD.",
"title": "Signal transduction proteins that associate with the platelet-derived growth factor (PDGF) receptor mediate the PDGF-induced release of glucose-6-phosphate dehydrogenase from permeabilized cells."
},
{
"docid": "12438901",
"text": "BACKGROUND For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.",
"title": "Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial"
}
] |
4699
|
Can one use Google Finance to backtest (i.e. simulate trades in the past)?
|
[
{
"docid": "239683",
"text": "Yes, add the stocks/mutual funds that you want and then you would just need to add all the transactions that you theoretically would have made. Performing the look up on the price at each date that you would have sold or bought is quite tedious as well as adding each transaction.",
"title": ""
},
{
"docid": "239137",
"text": "If you use Google Finance, you will get incorrect results because Google Finance does not show the dividend history. Since your requirement is that dividends are re-invested, you should use Yahoo Finance instead, downloading the historical 'adjusted' price.",
"title": ""
},
{
"docid": "154559",
"text": "I've used yahoo to perform the exercise you're asking about. It allows you to download price data, month end if you wish, and by manipulating via a spreadsheet to add a column for purchases, you can easily see how your £100/mo would end after so long a time period.",
"title": ""
}
] |
[
{
"docid": "78342",
"text": "\"What do I mean by infrastructure? Well, if you're doing algorithmic trading, you have to have something monitoring data and making decisions on its own, presumably. How do you set that up? There are many ways, and some are better than others. First is a problem of scale. If you're a newbie starting out with some small set of equity tick data, perhaps just trades for instance, you can whip together something that can handle that pretty easily. Check out http://www.marketdatapeaks.com/ though. That's your messaging rates you have to deal with once you go full data feeds direct from all the exchanges. 6.65 million messages/events per second. That's a lot. And if you fall behind, you lose your lunch. Building a robust system that allows you to easily backtest and deploy strategies is crucial as well. The speed at which you're able to conduct the backtest matters a lot. Doing that rapidly, and accurately is not easy. For a broad market-data handling algo design (and now, clearly, for very specific things you can design one that'll handle stuff better for that one corner case, but this is for general algo trading), optimally you have some sort of setup where you have a: [feed handlers] -> [tickerplant] -> [mkt data subscribers/CEP] -> [order management system] -> [broker] in this setup you have feed handlers that are taking the raw exchange feeds and pushing them to a consolidated tickerplant, where CEP subscribers can come through and sub to the data they want (perhaps I just want ES futures on one, and only want to arb CMCSA and CMCSK on another -- you dont want each CEP subscriber getting your full feed for all tickers all the time, its a waste). so more or less, each independent strategy is its own subscriber to the tickerplant, taking whatever data it wants and only that data (could be \"\"give me all the trades and quotes for all nasdaq stocks, but not book depth\"\" for instance). your CEP does whatever maths it has to do to figure out trading decisions, and when it does, it sends it to your order management system which does your risk checks, etc (\"\"do you have enough money to place this trade?\"\" \"\"do you already have a position in this?\"\" \"\"are you trading against yourself?\"\" ... million other things). your OMS knows how to talk to your broker/directly to the exchange depending on your setup. Assuming all your risk checks pass, off the order goes to the exchange, and it deals with the fill msgs, etc. Now, as far as speed is concerned - try to do all of this at 6.5 million events/second. It's hard. Some strats/cep subscribers will run faster than others, some are slower, some need to keep a full book to work while some work on just trades. Your OMS depending on if youre using only market data sources may need to keep its own book to place orders on behalf of your subscribers if they lack information about various markets (think all the twitter trading bots these days for instance), etc. If you look back at the above setup as well, you'll notice some interesting things. [tickerplant] -> [cep subscriber] portion can stay the same for live trading or backtesting. This is huge. The only thing that changes here for backtesting is that if you're trying to backtest, you can take historical data (query it out of your hopefully column-store database) and push it into your tickerplant rather than having it come from a live feed through the feed handler. Your tickerplant and cep subscriber will never know the difference, so you can use the same exact code for backtesting as you can for live. On the other end, you obviously cant send historical orders to your live broker, so you need to code a simulated OMS that does the backtest simulation (another huge piece of software to code that is hard to do well). But, for backtesting, your setup is staying largely the same except those two end pieces. This means that testing/deving/deploying strats can be pretty rapid, and uses the same code base for live and historical, which helps you eliminate bugs and have to code everything twice. Backtesting design: [historical mkt data db] -> [tickerplant] -> [mkt data subscribers/CEP] -> [order management system simulator/backtester] These are just a few of the many problems that you hit when trying to dev good infra. There are like a million more. Point was simply, it's complicated. And C++ is a good lang. I use a wide variety of languages depending on exactly whats going on and how fast the code needs to be. With a proper tickerplant design, youre using some ipc protocol so a subscriber can be coded in any language. Check out http://www.zeromq.org/ -- thats an excellent piece of software to use to make a tickerplant out of, think they even have a design for one in the docs if I recall. With that, your CEP subscribers can be in any language - perhaps pure C if you need the speed, perhaps .NET or Java if you dont (check out http://esper.codehaus.org/ for a Java implement of a CEP subscriber, nEsper for the C# port of that I believe). But I use C, C++, C#, python, R, x86 asm for a few very minor things, and a lang or two I can't mention here.\"",
"title": ""
},
{
"docid": "154525",
"text": "You would have to compare your backtesting to what you will be doing in real trading, and try to have the backtesting as close to your real trading as possible. Note: you may never get the backtesting to match your real trading exactly but you need to get as close as possible. The whole purpose of backtesting is to check if your trading strategies - your signals, entries and exits, and your stops - are profitable over various market conditions. As you would be using actual closes to do your real trading you should be using this to also do your backtesting. Rather than using adjusted data to get an idea of your total return from your backtesting, you can always add the value of the dividends and other corporate actions to the results from using the actual data. You may even find a way to add any dividends and other corporate action to your results automatically, i.e. any dividend amount added to your total return if the stock is held during the ex-dividend date. If you are using adjusted data in your backtesting this may affect any stops you have placed, i.e. it may cause your stop to be triggered earlier or later than in real trading. So you will need to determine how you will treat your stops in real trading. Will you adjust them when there is corporate action such as dividends? Or will you leave them constant until actual prices have gone up? If you will be leaving your stops constant then you should definitely be using actual data in your backtesting to better match your real trading.",
"title": ""
},
{
"docid": "49893",
"text": "About 10 years ago, I used to use MetaStock Trader which was a very sound tool, with a large number of indicators, but it has been a number of years since I have used it, so my comments on it will be out of date. At the time it relied upon me purchasing trading data myself, which is why I switched to Incredible Charts. I currently use Incredible Charts which I have done for a number of years, initially on the free adware service, now on the $10/year for EOD data access. There are quicker levels of data access, which might suit you, but I can't comment on these. It is web-based which is key for me. The data quality is very good and the number of inbuilt indicators is excellent. You can build search routines on the basis of specific indicators which is very effective. I'm looking at VectorVest, as a replacement for (or in addition to) Incredible Charts, as it has very powerful backtesting routines and the ability to run test portfolios with specific buy/sell criteria that can simulate and backtest a number of trading scenarios at the same time. The advantage of all of these is they are not tied to a particular broker.",
"title": ""
},
{
"docid": "396657",
"text": "The study of technical analysis is generally used (sometimes successfully) to time the markets. There are many aspects to technical analysis, but the simplest form is to look for uptrends and downtrends in the charts. Generally higher highs and higher lows is considered an uptrend. And lower lows and lower highs is considered a downtrend. A trend follower would go with the trend, for example see a dip to the trend-line and buy on the rebound. A simple strategy for this is shown in the chart below: I would be buying this stock when the price hits or gets very close to the trendline and then it bounces back above it. I would then have sold this stock once it has broken through below the trendline. This may also be an appropriate time if you were looking to short this stock. Other indicators could also be used in combination for additional confirmation of what is happening to the price. Another type of trader is called a bottom fisher. A bottom fisher would wait until a break above the downtrend line (second chart) and buy after confirmation of a higher high and possibly a higher low (as this could be the start of a new uptrend). There are many more strategies dealing with the study of technical analysis, and if you are interested you would need to find and learn about ones that suit your investment styles, whether you prefer short term trading or longer term investing, and your appetite for risk. You can develop strategies using various indicators and then paper trade or backtest these strategies. You can also manually backtest a strategy in most charting packages. You can go back in time on the chart so that the right side of the chart shows a date in the past (say one year ago or 10 years ago), then you can click forward one day at a time (or one week at a time if using weekly charts). With your indicators on the chart you can do virtual trades to buy or sell whenever a signal is given as you move forward in time. This way you may be able to check years of data in a day to see if your strategy works. Whatever you do, you need to document your strategies in writing in a written trading or investment plan together with a risk management strategy. You should always follow the rules in your written plan to avoid you making decisions based on emotions. By backtesting or paper trading your strategies it will give you confidence that they will work over the long term. There is a lot of work involved at the start, but once you have developed a documented strategy that has been thoroughly backtested, it will take you minimal time to successfully manage your investments. In my shorter term trading (positions held from a couple of days to a few weeks) I spend about half an hour per night to manage my trades and am up about 50% over the last 7 months. For my longer term investing (positions held from months to years) I spend about an hour per week and have been averaging over 25% over the last 4 years. Technical Analysis does work for those who have a documented plan, have approached it in a systematic way and use risk management to protect their existing and future capital. Most people who say that is doesn't work either have not used it themselves or have used it ad-hock without putting in the initial time and work to develop a documented and systematic approach to their trading or investing.",
"title": ""
},
{
"docid": "588481",
"text": "\"I think you're on the wrong track. Getting more and more samples from the real world does not make your backtest more accurate, it just confirms that your strategy can withstand one particular sample path of a stochastic process. The reason why you find it simple to incorporate fees, commissions, taxes, etc. is because they're a static and constant process -- well they might change over time but most definitely uncorrelated to the markets. Modelling overnight returns or the top levels of the order book the next day is serious work. First you have to select a suitable model (that's mostly theoretical work but experience can help a lot). Then, in order to do it data-driven, you'd have to plough through thousands of days of sample data on a set of thousands of instruments to get a \"\"feeling\"\" (aka significant model parameters). Apropos data mining, I think Excel might be the wrong tool for the job. Level-2 data (even just the first 10 levels) is a massive blob. For example, the NYSE OpenBook historical data weighs in at a massive 15 TB compressed (uncompressed 74 TB) for the last 10 years, and costs USD 200k. Anyway, as for other factors to take into account: So how to account for all this in a backtest? Personally, I would put in some penalty terms (as % on a return basis) for every factor you want to consider, don't hardcode them. You can then run a stress test by exploring these parameters (i.e. assign some values in the range of 0 to whatever fits). Explore them individually (only set one penalty term at a time) to get a feeling how the strategy might react to stress from that factor. Then you can run the backtest with typical (or observed) combinations of penalty factors and slowly stress them altogether. Edit Just to avoid confusion about terminology. A backtest in the strict sense (had I implemented this strategy X years ago, what would have happened?) won't benefit from any modelling simply because the real-world \"\"does the sampling\"\" for us. However, to evaluate a strategy's robustness you should account for the additional factors and run some stress tests. If the strategy performs well in the real-world or no-stress scenario but produces losses once a tiny slippage occurs every now and again, you could conclude that the strategy is very fragile. The key is to explore the maximum stress the strategy can handle (by whatever measure); if a lot you can call the strategy robust. The latter is what I personally call a backtest; the first procedure would go by the name \"\"extension towards the past\"\" or so. Some lightweight literature:\"",
"title": ""
},
{
"docid": "573708",
"text": "\"A couple options that I know of: Interactive Brokers offers a \"\"paper trading\"\" mode to its account holders that allows you to start with a pretend stack of money and place simulated trades to test trading ideas. They also provide an API that allows you to interface with their platform programmatically for retrieving quotes, placing orders, and the such. As you noted, however, it's not free; you must hold a funded brokerage account in order to qualify for access to their platform. In order to maintain an account, there are minimums for required equity and monthly activity (measured in dollars that you spend on commissions), so you won't get access to their platform without having a decent amount of skin in the game. IB's native API is Java-based; IbPy is an unofficial wrapper that makes the interface available in Python. I've not used IB at all myself, but I've heard good things about their API and its accessibility via IbPy. Edit: IB now supports Python natively via their published API, so using IbPy is no longer needed, unless you wish to use Python 2.x. The officially supported API is based on Python 3. TD Ameritrade also offers an API that is usable by its brokerage clients. They do not offer any such \"\"paper trading\"\" mode, so you would need to \"\"execute\"\" transactions based on quotes at the corresponding trade times and then keep track of your simulated account history yourself. The API supports quote retrieval, price history, and trade execution, among other functions. TDA might be more attractive than IB if you're looking for a low-cost link into market data, as I believe their minimum-equity levels are lower. To get access, you'll need to sign up for an API developer account, which I believe requires an NDA. I don't believe there is an official Python implementation of the API, but if you're a capable Python writer, you shouldn't have trouble hooking up to the published interfaces. Some caveats: as when doing any strategy backtesting, you'll want to be sure to be pessimistic when doing so, so your optimism doesn't make your trades look more successful than they would be in the real world. At a minimum, you'll want to ensure that your simulations transact at the posted bid/ask prices, not necessarily the last trade's price, as well as any commissions and fees associated with the trade. A more robust scheme would also take into account the depth of the order book (also known as level 2 quotes), which can cause additional slippage in the prices at which you buy/sell your security. An even more robust scheme would take into account the potential latency of trade execution, looking at all prices over some time period that covers the maximum expected latency and simulating the trade at the worst-possible price.\"",
"title": ""
},
{
"docid": "484730",
"text": "Sounds like you are a candidate for stock trading simulators. Or just pick stocks and use Yahoo! or Google finance tools to track and see how you do. I wouldn't suggest you put real money into it. You need to learn about research and timing and a bunch of other topics you can learn about here. I personally just stick to life cycle funds that are managed products that offer me a cruise control setting for investing.",
"title": ""
},
{
"docid": "146632",
"text": "\"Yes. There are several downsides to this strategy: You aren't taking into account commissions. If you pay $5 each time you buy or sell a stock, you may greatly reduce or even eliminate any possible gains you would make from trading such small amounts. This next point sounds obvious, but remember that you pay a commission on every trade regardless of profit, so every trade you make that you make at a loss also costs you commissions. Even if you make trades that are profitable more often than not, if you make quite a few trades with small amounts like this, your commissions may eat away all of your profits. Commissions represent a fixed cost, so their effect on your gains decreases proportionally with the amount of money you place at risk in each trade. Since you're in the US, you're required to follow the SEC rules on pattern day trading. From that link, \"\"FINRA rules define a “pattern day trader” as any customer who executes four or more “day trades” within five business days, provided that the number of day trades represents more than six percent of the customer’s total trades in the margin account for that same five business day period.\"\" If you trip this rule, you'll be required to maintain $25,000 in a margin brokerage account. If you can't maintain the balance, your account will be locked. Don't forget about capital gains taxes. Since you're holding these securities for less than a year, your gains will be taxed at your ordinary income tax rates. You can deduct your capital losses too (assuming you don't repurchase the same security within 30 days, because in that case, the wash sale rule prevents you from deducting the loss), but it's important to think about gains and losses in real terms, not nominal terms. The story is different if you make these trades in a tax-sheltered account like an IRA, but the other problems still apply. You're implicitly assuming that the stock's prices are skewed in the positive direction. Remember that you have limit orders placed at the upper and lower bounds of the range, so if the stock price decreases before it increases, your limit order at the lower bound will be triggered and you'll trade at a loss. If you're hoping to make a profit through buying low and selling high, you want a stock that hits its upper bound before hitting the lower bound the majority of the time. Unless you have data analysis (not just your intuition or a pattern you've talked yourself into from looking at a chart) to back this up, you're essentially gambling that more often than not, the stock price will increase before it decreases. It's dangerous to use any strategy that you haven't backtested extensively. Find several months or years of historical data, either intra-day or daily data, depending on the time frame you're using to trade, and simulate your strategy exactly. This helps you determine the potential profitability of your strategy, and it also forces you to decide on a plan for precisely when you want to invest. Do you invest as soon as the stock trades in a range (which algorithms can determine far better than intuition)? It also helps you figure out how to manage your risk and how much loss you're willing to accept. For risk management, using limit orders is a start, but see my point above about positively skewed prices. Limit orders aren't enough. In general, if an active investment strategy seems like a \"\"no-brainer\"\" or too good to be true, it's probably not viable. In general, as a retail investor, it's foolish to assume that no one else has thought of your simple active strategy to make easy money. I can promise you that someone has thought of it. Trading firms have quantitative researchers that are paid to think of and implement trading strategies all the time. If it's viable at any scale, they'll probably already have utilized it and arbitraged away the potential for small traders to make significant gains. Trust me, you're not the first person who thought of using limit orders to make \"\"easy money\"\" off volatile stocks. The fact that you're asking here and doing research before implementing this strategy, however, means that you're on the right track. It's always wise to research a strategy extensively before deploying it in the wild. To answer the question in your title, since it could be interpreted a little differently than the body of the question: No, there's nothing wrong with investing in volatile stocks, indexes, etc. I certainly do, and I'm sure many others on this site do as well. It's not the investing that gets you into trouble and costs you a lot of money; it's the rapid buying and selling and attempting to time the market that proves costly, which is what you're doing when you implicitly bet that the distribution of the stock's prices is positively skewed. To address the commission fee problem, assuming a fee of $8 per trade ... and a minimum of $100 profit per sale Commissions aren't your only problem, and counting on $100 profit per sale is a significant assumption. Look at point #4 above. Through your use of limit orders, you're making the implicit assumption that, more often than not, the price will trigger your upper limit order before your lower limit order. Here's a simple example; let's assume you have limit orders placed at +2 and -2 of your purchase price, and that triggering the limit order at +2 earns you $100 profit, while triggering the limit order at -2 incurs a loss of $100. Assume your commission is $5 on each trade. If your upper limit order is triggered, you earn a profit of 100 - 10 = 90, then set up the same set of limit orders again. If your lower limit order is triggered this time, you incur a loss of 100 + 10 = 110, so your net gain is 90 - 110 = -20. This is a perfect example of why, when taking into account transaction costs, even strategies that at first glance seem profitable mathematically can actually fail. If you set up the same situation again and incur a loss again (100 + 10 = 110), you're now down -20 - 110 = -130. To make a profit, you need to make two profitable trades, without incurring further losses. This is why point #4 is so important. Whenever you trade, it's critical to completely understand the risk you're taking and the bet you're actually making, not just the bet you think you're making. Also, according to my \"\"algorithm\"\" a sale only takes place once the stock rises by 1 or 2 points; otherwise the stock is held until it does. Does this mean you've removed the lower limit order? If yes, then you expose yourself to downside risk. What if the stock has traded within a range, then suddenly starts declining because of bad earnings reports or systemic risks (to name a few)? If you haven't removed the lower limit order, then point #4 still stands. However, I never specified that the trades have to be done within the same day. Let the investor open up 5 brokerage accounts at 5 different firms (for safeguarding against being labeled a \"\"Pattern Day Trader\"\"). Each account may only hold 1 security at any time, for the span of 1 business week. How do you control how long the security is held? You're using limit orders, which will be triggered when the stock price hits a certain level, regardless of when that happens. Maybe that will happen within a week, or maybe it will happen within the same day. Once again, the bet you're actually making is different from the bet you think you're making. Can you provide some algorithms or methods that do work for generating some extra cash on the side, aside from purchasing S&P 500 type index funds and waiting? When I purchase index funds, it's not to generate extra liquid cash on the side. I don't invest nearly enough to be able to purchase an index fund and earn substantial dividends. I don't want to get into any specific strategies because I'm not in the business of making investment recommendations, and I don't want to start. Furthermore, I don't think explicit investment recommendations are welcome here (unless it's describing why something is a bad idea), and I agree with that policy. I will make a couple of points, however. Understand your goals. Are you investing for retirement or a shorter horizon, e.g. some side income? You seem to know this already, but I include it for future readers. If a strategy seems too good to be true, it probably is. Educate yourself before designing a strategy. Research fundamental analysis, different types of orders (e.g., so you fully understand that you don't have control over when limit orders are executed), different sectors of the market if that's where your interests lie, etc. Personally, I find some sectors fascinating, so researching them thoroughly allows me to make informed investment decisions as well as learn about something that interests me. Understand your limits. How much money are you willing to risk and possibly lose? Do you have a risk management strategy in place to prevent unexpected losses? What are the costs of the risk management itself? Backtest, backtest, backtest. Ideally your backtesting and simulating should be identical to actual market conditions and incorporate all transaction costs and a wide range of historical data. Get other opinions. Evaluate those opinions with the same critical eye as I and others have evaluated your proposed strategy.\"",
"title": ""
},
{
"docid": "492503",
"text": "I will assume that you are not asking in the context of high frequency trading, as this is Personal Finance Stack Exchange. It is completely acceptable to trade odd lots for retail brokerage customers. The odd lot description that you provided in your link, from Interactive Brokers is correct. But even in that context, it says, regarding the acceptability of odd lots to stock exchanges: The exception is that odd lots can be routed to NYSE/ARCA/AMEX, but only as part of a basket order or as a market-on-close (MOC) order. Google GOOG is traded on the NASDAQ. Everything on the NASDAQ is electronic, and always has been. You will have no problem selling or buying less than 100 shares of Google. There is also an issue of higher commissions with odd lots: While trading commissions for odd lots may still be higher than for standard lots on a percentage basis, the popularity of online trading platforms and the consequent plunge in brokerage commissions means that it is no longer as difficult or expensive for investors to dispose of odd lots as it used to be in the past. Notice what it says about online trading making it easier, not more difficult, to trade odd lots.",
"title": ""
},
{
"docid": "471131",
"text": "Usually backtests for (long-term) strategies are evaluated on a end-of-day basis where you only consider close prices. If your strategy performs well in these backtests, hopes are that if you use a market-on-close (MOC) order your performance will not diverge too much from the backtest. The fact that it won't diverge much is important if you keep backtesting the strategy along with the real trading to see regime changes or similar. If you used end-of-day prices for the backtests but some arbitrary intraday market order, you'd have some difficulties to explain deviations between the two. What it is: MOC orders can be submitted during the day, but they won't be executed until shortly before the market (or more precise the current session) closes.",
"title": ""
},
{
"docid": "251893",
"text": "If you have a great technical trading system that gets you winning trading 80-85% of the time in backtesting, the question should be why are you not trading it? To get a better idea of how good your trading system is you should work out your expectancy per trade. This will tell you how much you should make on average for every trade you take. Expectancy not only considers your win rate but also you win size to loss size ratio. For example if you are getting winning trades 80% of the time but your average win size is $100, and your 20% of losses average $500, then you will still be losing money. You should be aiming for an average win size of at least 2.5 to 3 times you average loss size. This will provide you a profitable trading system even if your win rate is 50%. If your trading system is really that good and provides a win size of at least 2.5 times your loss size then you should be actively trading it. Also, if you put your trading system out there in the public domain together with your trading results you will actually find that, quite opposite to what the consensus above is, your results from your trading plan should actually improve further. The more people acting on the outcome of a signal in the same direction the higher the probability that the movement in the desired direction will actually occur. If you are looking to make money from your trading ideas, no one will pay anything unless you have real results to back it up. So if you are so confident about your system you should start trading it with real money. Of course you should start off small and build it up over time as your results eventuate as per your simulations.",
"title": ""
},
{
"docid": "381195",
"text": "i have been trading with dollarbird Trading firm for past 1 year there is absolutly no problem everything is fine you can google them to find anything about them.they have provided me with LASER trading platform which requires a bit of training as in to know the software but i can say one thing trading in US Equity market exp. is very diffrent from indian market they are very mature market and highly liqd and have good volatality to trade best equity market to trade with great trading platform you should have a exp. to trade on US equity it is diffrent",
"title": ""
},
{
"docid": "98532",
"text": "Our Finance organization does much of their reporting out of Excel being fed out of SSAS cubes, and beyond that, there's significant need for PowerPivot charts, forecasting, and Monte Carlo simulation, as well as significant use of various plugins and VBA code. We kept Office 365 ProPlus around for Finance and HR. For the rest of the organization, they don't need particularly advanced capabilities for slides, drawing, or word processing, or light spreadsheet capability and we're quite content to output to PDF, Google Sheets, and other things as needed, as well as using cost free alternatives to MS Exchange/Outlook, Visio, and Project. The collaboration is a particular plus, and Google Hangouts is really convenient working from multiple sites/screen sharing. We've done our best to keep our data centralized and universally accessible, in lieu of living in Excel spreadsheets and MS Access databases as tribal knowledge.",
"title": ""
},
{
"docid": "467373",
"text": "After looking at both S&P GSCI Crude Oil Index Excess Return (INDEXSP:SPGSCLP) and CS VS 3x LC ETN NYSEARCA: UWTI they seem to track well (using Google Finance). I'm not seeing where your statement this ETN loses whether oil is gaining or not holds true. Both have posted a year-over-year loss. In the past year the Crude Oil index has fallen from a high of 494 on October 6, 2014 to a low of 213 as of today October 5th, 2015. So of course the UWTI will lose as well. Please also notice that that, as stated in the prospectus for UWTI: The ETNs are intended to be daily trading tools for sophisticated investors to manage daily trading risks. They are designed t o achieve their stated investment objectives on a daily basis, but their performance over different periods of time can differ significantly fr om their stated daily objectives. The ETNs are riskier than securities that have intermediate or long-term investment objectives, and may not be sui table for investors who plan to hold them for a period other than one day. You might want to look into investing in an ETF for long term investment goals and objectives. Oil ETF List",
"title": ""
},
{
"docid": "97180",
"text": "Using any simulator will never be exactly the same as real trading. One reason is that a simulator will always execute your trades at the exact price you want, but that may not always happen in real life. For example, if you place a limit order to buy 1000 shares of a stock at 10.50, and the price drops down to exactly 10.50, then the simulator will execute your trade and you will have 1000 shares at 10.50. But in real life, the price of the stock may drop to 10.50, but other people may have buy orders ahead of you. If the price of the stock drops to 10.50 but then starts going up again, you may not get all the shares that you wanted (or you may not even get any shares at all) due to the fact that people were ahead of you. In real trading there is also slippage, which you don't see in a simulator. For example, if you have a stop order to sell 1000 shares of a stock if it drops to 7.50, then the simulator will sell all 1000 shares at 7.50 if the price drops to 7.50. But in real trading, if the price drops to 7.50, then you may not be able to sell all 1000 shares at 7.50 if there's not enough liquidity or the market is moving very fast. You may end up selling 100 shares at 7.50, 100 shares at 7.49, 100 shares at 7.48, 50 shares at 7.47, 50 shares at 7.46, 200 shares at 7.45, and 400 shares at 7.44. Another thing is that you don't experience the emotional aspect of trading with a simulator. If you buy a stock in a simulator and it goes down, it's not real money, so you may be more willing to hold it and wait for it to come back up. But if you are trading real money and the stock goes down, you may not be so willing to hold if it goes down. You may be more apt to sell the stock for a small loss before the loss gets too big.",
"title": ""
},
{
"docid": "181425",
"text": "\"Because an equity option can be constructed at essentially any price by two willing counterparties on an exchange, there are not enough ISINs to represent the entire (i.e. infinite) option chain for even a single stock on a single expiration date. As a result, ISINs are not generated for each individual possible options contract. Instead the ISIN is used only to refer to the \"\"underlying\"\" symbol, and a separate formula is used to refer to the specific option contract for that symbol: So that code you pasted is not an ISIN but rather the standard US equity option naming scheme that you need to provide in addition to the ISIN when talking to your broker. Note that ISINs and formulas for referring to option contracts in other countries can behave quite differently. Also, there are many countries and markets that don't need ISINs because the products in question only exist on a single exchange. In those cases the exchange is pretty much free to make up whatever ID scheme it wants. P.S. Now I'm curious how option chains are identified for strike prices above $99,999. I looked up the only stock I can think of that trades above that price (BRK.A), but it doesn't seem to have an option chain (or at least Google doesn't show it) ...\"",
"title": ""
},
{
"docid": "128281",
"text": "\"The professional financial advisors do have tools which will take a general description of a portfolio and run monte-carlo simulations based on the stock market's historical behavior. After about 100 simulation passes they can give a statistical statement about the probable returns, the risk involved in that strategy, and their confidence in these numbers. Note that they do not just use the historical data or individual stocks. There's no way to guarantee that the same historical accidents would have occurred that made one company more successful than another, or that they will again. \"\"Past performance is no guarantee of future results\"\"... but general trends and patterns can be roughly modelled. Which makes that a good fit for those of us buying index funds, less good for those who want to play at a greater level of detail in the hope of doing better. But that's sorta the point; to beat market rate of return with the same kind of statistical confidence takes a lot more work.\"",
"title": ""
},
{
"docid": "81865",
"text": "This is going to be a bit of a shameless plug, but I've build a portfolio tracking website to track your portfolio and be able to share it (in read-only mode) as well. It is at http://frano.carelessmusings.com and currently in beta. Most portfolio trackers are behind a login wall and thus will lack the sharing function you are looking for. Examples of these are: Yahoo Finance, Google Finance, Reuters Portfolios, MorningStart Portfolios, and many others. Another very quick and easy solution (if you are not trading too often) is a shared google docs spreadsheet. Gdocs has integration with google finance and can retrieve prices for stocks by symbol. A spreadsheet can contain the following: Symbol, Quantity, Avg. Buy Price, Price, P/L, P/L% and so on. The current price and P/L data can be functions that use the google finance API. Hope this helps, and if you check out my site please let me know what you think and what I could change.",
"title": ""
},
{
"docid": "241423",
"text": "\"See Solid reading/literature for investment/retirement/income taxes? – not exactly the same question, but a great reading list for you. You are putting the cart before the horse here, first, you learn, then you invest. There's a large danger in confusing intelligent investing with \"\"fooling around\"\". The idea that you think you'd like to use derivatives without knowing how or why is a tough one. I suggest you go to Yahoo! Finance and set yourself up with a portfolio (click on the \"\"My Portfolios\"\" tab), in effect, creating your own simulated account. Assume you are starting with some reasonable amount of money, say $10,000, but not $1M, as part of real investing is to learn how to asset allocate the funds you have. Learning that way for a time is the smarter way to start. That said, individual stocks are not for everyone. Most investors can lead a successful investing life by using ETFs or mutual funds of one type or another. Learning to pick individual stocks can be a life's work, and if you put too little time into it, are likely to be disappointed. But learning by 'paper trading' can be a good learning experience nonetheless.\"",
"title": ""
},
{
"docid": "371720",
"text": "Most of stock trading occurs on what is called a secondary market. For example, Microsoft is traded on NASDAQ, which is a stock exchange. An analogy that can be made is that of selling a used car. When you sell a used car to a third person, the maker of your car is unaffected by this transaction and the same goes for stock trading. Still within the same analogy, when the car is first sold, money goes directly to the maker (actually more complicated than that but good enough for our purposes). In the case of stock trading, this is called an Initial Public Offering (IPO) / Seasoned Public Offering (SPO), for most purposes. What this means is that a drop of value on a secondary market does not directly affect earning potential. Let me add some nuance to this. Say this drop from 20$ to 10$ is permanent and this company needs to finance itself through equity (stock) in the future. It is likely that it would not be able to obtain as much financing in this matter and would either 1) have to rely more on debt and raise its cost of capital or 2) obtain less financing overall. This could potentially affect earnings through less cash available from financing. One last note: in any case, financing does not affect earnings except through cost of capital (i.e. interest paid) because it is neither revenue nor expense. Financing obtained from debt increases assets (cash) and liabilities (debt) and financing obtained from stock issuance increases assets (cash) and shareholder equity.",
"title": ""
},
{
"docid": "445971",
"text": "\"Back-testing itself is flawed. \"\"Past performance is no guarantee of future results\"\" is an important lesson to understand. Market strategies of one kind or another work until they don't. Edited in -- AssetPlay.net provides a tool that's halfway to what you are looking for. It only goes back to 1972, however. Just to try it, I compared 100% S&P to a 60/40 blend of S&P with 5 yr t-bills (a misnamed asset, 5 yr treasuries are 'notes' not 'bills') I found the mix actually had a better return with lower volatility. Now, can I count on that to work moving forward? Rates fell during most of this entire period so bonds/notes both looked pretty good. This is my point regarding the backtest concept. GeniusTrader appears more sophisticated, but command line work on PCs is beyond me. It may be worth a look for you, JP. ETF Replay appears to be another backtest tool. It has its drawbacks, however, (ETFs only)\"",
"title": ""
},
{
"docid": "206756",
"text": "How would this trade behave IRL? I don't know how the simulation handles limit orders and bid/ask spreads to know it's feasible, but buying at 4.04 when the current ask is 8.00 seems unlikely. That would mean that all other sell orders between 8.00 and 4.04 were fulfilled, which means that there were very few sellers or that sell pressure spiked, both of which seem unlikely. In reality, it seems more likely that your order would have sat there until the ask dropped to $4.04 (if it ever did), and then you'd have to wait until the bid rose to $7.89 in order to sell them at that price. However, that kind of swing in option prices in not unrealistic. Options near at-the-money tend to move in price at about 50% of the change in the underlying, so if amazon suddenly dropped by $5, the option price could drop by $2.60 (from 6.66 to $4.04), and then rise back to $7.89 if the price rose $8 (which would be 1% swing and not unheard of intra-day). But it sounds like you got very lucky (or the simulation doesn't handle option trading realistically) - I've traded options in the past and have had some breaks similar to yours. I've also had bad breaks where I lost my entire investment (the options expire out-of-the money). So it should be a very limited part of your portfolio, and probably only used for risk management (e.g. buying put options to lock in some gains but keeping some upside potential).",
"title": ""
},
{
"docid": "88105",
"text": "Based on my experience with OpenQuant, which is a development platform for automated trading strategies (and therefore can be easily be used for backtesting your personal strategy), I can give a little insight into what you might look for in such a platform. OpenQuant is a coding environment, which reads data feeds from a variety of sources (more on that in the second point), and runs the code for your strategy on that data and gives you the results. The data could be imported from a live data feed or from historical data, either through numerous API's, CSV/Excel, etc. You can write your own strategies using the custom C# libraries included with the software, which spares you from implementing your own code for technical indicators, basic statistical functions, etc. Getting the data is another issue. You could use joe's strategy and calculate option prices yourself, although you need to exercise caution when doing this to test a strategy. However, there is no substitute for backtesting a strategy on real data. Markets change over time, and depending on how far back you're interested in testing your strategy, you may run into problems. The reason there is no substitute for using real data is that attempting to replicate the data may fail in some circumstances, and you need a method of verifying that the data you're generating is correct and realistic. Calculating a few values, comparing them to the real values, and calibrating accordingly is a good idea, but you have to decide for yourself how many checks you want to do. More is better, but it may not be enough to realistically test your strategy. Disclaimer: Lest you interpret my post as a shameless plug for the OpenQuant platform, I'll state that I found the interface awful (it looked vaguely like Office 2000 but ten years too late) and the documentation woefully incomplete. I last used the software in 2010, so it may have improved in the intervening years, but your mileage may vary. I only use it as an example to give some insight into what you might look for in a backtesting platform. When you actually begin trading, a different platform is likely in order. That being said, it responded fairly quickly and the learning curve wasn't too steep. The platform wasn't too expensive at the time (about $700 for a license with no data feeds, I think) but I was happy that the cost wasn't coming out of my pocket. It's only gotten more expensive and I'm not sure it's worth it.",
"title": ""
},
{
"docid": "577585",
"text": "Pivots Points are significant levels technical analysts can use to determine directional movement, support and resistance. Pivot Points use the prior period's high, low and close to formulate future support and resistance. In this regard, Pivot Points are predictive or leading indicators. There are at least five different versions of Pivot Points. I will focus on Standard Pivot Points here as they are the simplest. If you are looking to trade off daily charts you would work out your Pivot Points from the prior month's data. For example, Pivot Points for first trading day of February would be based on the high, low and close for January. They remain the same for the entire month of February. New Pivot Points would then be calculated on the first trading day of March using the high, low and close for February. To work out the Standard Pivot Points you use the High, Low and Close from the previous period (i.e. for daily charts it would be from the previous month) in the following formulas: You will now have 5 horizontal lines: P, R1, R2, S1 and S2 which will set the general tone for price action over the next month. A move above the Pivot Point P suggests strength with a target to the first resistance R1. A break above first resistance shows even more strength with a target to the second resistance level R2. The converse is true on the downside. A move below the Pivot Point P suggests weakness with a target to the first support level S1. A break below the first support level shows even more weakness with a target to the second support level S2. The second resistance and support levels (R2 & S2) can also be used to identify potentially overbought and oversold situations. A move above the second resistance level R2 would show strength, but it would also indicate an overbought situation that could give way to a pullback. Similarly, a move below the second support level S2 would show weakness, but would also suggest a short-term oversold condition that could give way to a bounce. This could be used together with a momentum indicator such as RSI or Stochastic to confirm overbought or oversold conditions. Pivot Points offer a methodology to determine price direction and then set support and resistance levels, however, it is important to confirm Pivot Point signals with other technical analysis indicators, such as candle stick reversal patterns, stochastic and general Support and Resistance Levels in the price action. These pivot points can be handy but I actually haven’t used them for trade setups and entries myself. I prefer to use candle sticks together with stochastic to determine potential turning points and then take out trades based on these. You can then use the Pivot Points Resistance and Support levels to help you estimate profit targets or areas to start becoming cautious and start tightening your stops. Say, for example, you have gone long from a signal you got a few days ago, you are now in profit and the price is now approaching R2 whilst the Stochastic is approaching overbought, you might want to start tightening your stop loss as you might expect some weakness in the price in the near future. If prices continue up you keep increasing your profits, if prices do reverse then you keep the majority of your existing profits. This would become part of your trade management. If you are after finding potential market turning points and take out trades based on these, then I would suggest using candlestick charting reversal patterns for your trade setups. The patterns I like to use most in my trading can be described as either the Hammer or One White Soldier for Bullish reversals and Shooting Star or One Black Crow for Bearish reversals. Below are diagrams of where to place your entries and exits on both Bullish and Bearish reversal patterns. Bullish Reversal Pattern So after some period of weakness in the price you would look for a bullish day where the price closes above the previous day’s high, you place your buy order here just before market close and place your initial stop just below the low of the day. You would apply this either for an uptrending stock where the price has retracted from or near the trendline or Moving Average, or a ranging stock where price is bouncing off the support line. The trade is reinforced if the Stochastic is in or near the oversold and crossing back upwards, volume on the up day is higher than volume on the down days, and the market as a whole is moving up as well. The benefit with this entry is that you are in early so you capture any bullish move up at the open of the next day, such as gaps. The drawbacks are that you need to be in front of your screen before market close to get your price close to the market close and you may get whipsawed if prices reverse at the open of the next day, thus being stopped out with a small loss. As the price moves up you would move your stop loss to just below the low of each day. Alternative Bullish Reversal Entry An alternative, entry would be to wait for after market close and then start your analysis (easier to do after market close than whilst the market is open and less emotions involved). Place a stop buy order to buy at the open of next trading day just above the high of the bullish green candle. Your stop is placed exactly the same, just below the low of the green bullish candle. The benefits of this alternative entry include you avoid the trade if the price reverses at the open of next day, thus avoiding a potential small loss (in other words you wait for further confirmation on the next trading day), and you avoid trading during market open hours where your emotions can get the better of you. I prefer to do my trading after market close so prefer this alternative. The drawback with this alternative is that you may miss out on bullish news prior to and at the next open, so miss out on some potential profits if prices do gap up at the open. This may also increase your loss on the trade if the prices gaps up then reverses and hits your stop on the same day. However, if you choose this method, then you will just need to incorporate this into your trading plan as potential slippage. Bearish Reversal Pattern So after some short period of strength in the price you would look for a bearish day where the price closes below the previous day’s low, you place your sell short order here just before market close and place your initial stop just above the high of the day. You would apply this either for an downtrending stock where the price has retracted from or near the trendline or Moving Average, or a ranging stock where price is bouncing off the resistance line. The trade is reinforced if the Stochastic is in or near the overbought and crossing back downwards, volume on the up day is higher than volume on the up days, and the market as a whole is moving down as well. The benefit with this entry is that you are in early so you capture any bearish move down at the open of the next day, such as gaps. The drawbacks are that you need to be in front of your screen before market close to get your price close to the market close and you may get whipsawed if prices reverse at the open of the next day, thus being stopped out with a small loss. As the price moves down you would move your stop loss to just above the high of each day. Alternative Bearish Reversal Entry An alternative, entry would be to wait for after market close and then start your analysis (easier to do after market close than whilst the market is open and less emotions involved). Place a stop sell short order to sell at the open of next trading day just below the low of the bearish red candle. Your stop is placed exactly the same, just above the high of the red bearish candle. The benefits of this alternative entry include you avoid the trade if the price reverses at the open of next day, thus avoiding a potential small loss (in other words you wait for further confirmation on the next trading day), and you avoid trading during market open hours where your emotions can get the better of you. I prefer to do my trading after market close so prefer this alternative. The drawback with this alternative is that you may miss out on bearish news prior to and at the next open, so miss out on some potential profits if prices do gap down at the open. This may also increase your loss on the trade if the prices gaps down then reverses and hits your stop on the same day. However, if you choose this method, then you will just need to incorporate this into your trading plan as potential slippage. You could also trade other candle stick patterns is similar ways. And with the long entries you can also use them to get into the market with longer term trend following strategies, you would usually just use a larger stop for longer term trading. To determine the size of your order you would use the price difference between your entry and your stop. You should not be risking more than 1% of your trading capital on any one trade. So if your trading capital is $20,000 your risk per trade should be $200. If you were looking to place your buy at 5.00 and had your initial stop at $4.60, you would divide $200 by $0.40 to get 500 stocks to buy. Using this form of money management you keep your losses down to a maximum of $200 (some trades may be a bit higher due to some slippage which you should allow for in your trading plan), which becomes your R-multiple. Your aim is to have your average win at 3R or higher (3 x your average loss), which will give you a positive expectancy even with a win ratio under 50%. Once you have written down your trading rules you can search stock charts for potential setups. When you find one you can backtest the chart for similar setup over the past few years. For each setup in the past jot down the prices you would have entered at, where you would have set your stop, work out your R, and go day by day, moving your stop as you go, and see where you would have been stopped out. Work out your profit or loss in terms of R for each setup and then add them up. If you get a positive R multiple, then this may be a good stock to trade on this setup. If you get a negative R multiple, then maybe give this stock a miss and look for the next setup. You can setup watch-lists of stocks that perform well for both long setups and short setups, and then trade these stocks when you get a new signal. It can take some time starting off, but once you have got your watch-lists for a particular setup, you just need to keep monitoring those stocks. You can create other watch-lists for other type of setups you have backtested as well.",
"title": ""
},
{
"docid": "234892",
"text": "Yes, exactly. VaR is just a single tailed confidence interval. To go from model to strategy, you need to design some kind of indicator (i.e. when to buy and when to short or stay out). In practice, this will look like a large matrix with values ranging from -1 to 1 (corresponding to shorting and holding respectively) for each security and each day (or hour, or minute, or tick, etc.), which you then just multiply with the matrix of the stock returns. The resulting matrix will be your daily returns for each stock, you can then just row sum for daily returns of a portfolio, or calculate a cumulative product for cumulative returns. A simple example of an indicator would be something like a value of 1 when the price of the stock is below the 30 day moving average, and 0 otherwise. You can use a battery of econometric models to design these indicators, but the rest of the strategy design is essentially the same, and it's *relatively* easy to build a one-size-fits-all back-testing code. I'll try to edit this post later and link a blog that goes through some of the code. Edit: [Here](http://www.signalplot.com/simple-machine-learning-model-trade-spy/) is a post that discusses implementing a simple ML strategy. You can ignore most of the content but if you go through the github, you'll see how the ML model is implemented as a strategy. An even easier example can be found from [the github connected to this post](http://www.signalplot.com/how-to-measure-the-performance-of-a-trading-strategy/), where the author is just using a totally arbitrary signal. As you can see, deriving a signal can be a ton of work, but once you have, actually simulating the strategy can be done in just a few lines of code. Hopefully the author won't mind me linking his page here, but I find his coding style to be very clean and good for educational purposes.",
"title": ""
},
{
"docid": "383399",
"text": "Algo traders/quants/market backtesters/coders/et al. I am looking to backtest basic things like the correlation of P/E, EV/EBITDA, etc. to market performance. I know a little R and Python. What is the easiest way to learn to backtest this sort of stuff? I want to eventually get into algo trading sort of stuff. I'd **greatly** appreciate it!",
"title": ""
},
{
"docid": "568043",
"text": "\"Though you're looking to repeat this review with multiple securities and events at different times, I've taken liberty in assuming you are not looking to conduct backtests with hundreds of events. I've answered below assuming it's an ad hoc review for a single event pertaining to one security. Had the event occurred more recently, your full-service broker could often get it for you for free. Even some discount brokers will offer it so. If the stock and its options were actively traded, you can request \"\"time and sales,\"\" or \"\"TNS,\"\" data for the dates you have in mind. If not active, then request \"\"time and quotes,\"\" or \"\"TNQ\"\" data. If the event happened long ago, as seems to be the case, then your choices become much more limited and possibly costly. Below are some suggestions: Wall Street Journal and Investors' Business Daily print copies have daily stock options trading data. They are best for trading data on actively traded options. Since the event sounds like it was a major one for the company, it may have been actively traded that day and hence reported in the papers' listings. Some of the print pages have been digitized; otherwise you'll need to review the archived printed copies. Bloomberg has these data and access to them will depend on whether the account you use has that particular subscription. I've used it to get detailed equity trading data on defunct and delisted companies on specific dates and times and for and futures trading data. If you don't have personal access to Bloomberg, as many do not, you can try to request access from a public, commercial or business school library. The stock options exchanges sell their data; some strictly to resellers and others to anyone willing to pay. If you know which exchange(s) the options traded on, you can contact the exchange's market data services department and request TNS and / or TNQ data and a list of resellers, as the resellers may be cheaper for single queries.\"",
"title": ""
},
{
"docid": "485757",
"text": "I stumbled on the same discrepancy, and was puzzled by a significant difference between the two prices on ETR and FRA. For example, today is Sunday, and google shows the following closing prices for DAI. FRA:DAI: ETR:DAI: So it looks like there are indeed two different exchanges trading at different prices. Now, the important value here, is the last column (Volume). According to Wikipedia, the trading on Frankfort Stock Exchange is done today exclusively via Xetra platform, thus the volume on ETR:DAI is much more important than on FRA:DAI. Obviously, they Wikipedia is not 100% accurate, i.e. not all trading is done electronically via Xetra. According to their web-page, Frankfort exchange has a Specialist Trading on Frankfurt Floor service which has slightly different trading hours. I suspect what Google and Yahoo show as Frankfort exchange is this manual trading via a Specialist (opposed to Xetra electronic trading). To answer your question, the stock you're having is exactly the same, meaning if you bought an ETR:BMW you can still sell it on FRA (by calling a FRA Trading Floor Specialist which will probably cost you a fee). On the other hand, for the portfolio valuation and performance assessments you should only use ETR:BMW prices, because it is way more liquid, and thus better reflect the current market valuation.",
"title": ""
},
{
"docid": "535470",
"text": "\"With my current, limited knowledge (see end), I understand it the following way: Are share prices really described as \"\"memoryless\"\"? Yes. Is there a technical meaning of the term? What does it really mean? The meaning comes from Markov Models: Think of the behavior of the stock market over time as a Markov Chain, i.e. a probabilistic model with states and probabilistic transitions. A state is the current price of all stocks of the market, a transition is a step in time. Memoryless means that transitions that the stock market might make can be modelled by a relation from one state to another, i.e. it only depends on the current state. The model is a Markov Chain, as opposed to a more general Stochastic Process where the next state depends on more than the current state. So in a Markov Chain, all the history of one stock is \"\"encoded\"\" already in its current price (more precisely in all stock's prices). The memorylessness of stocks is the main statement of the Efficient Market Theory (EMT). If a company's circumstances don't change, then a drop in its share price is going to be followed by a rise later. So if the EMT holds, your statement above is not necessarily true. I personally belief the EMT is a good approximation - only large corporations (e.g. Renaissance Technologies) have enough ressources (hundreds of mathematicians, billions of $) to be able to leverage tiny non-random movements that stem from a not completely random, mostly chaotic market. The prices can of course change when the company's circumstances change, but they aren't \"\"memoryless\"\" either. A company's future state is influenced by its past. In the EMT, a stock's future state is only influenced by its past as much as is encoded in its current price (more precisely, the complete market's current state). Whether that price was reached by a drop or a rise makes no difference. The above is my believe, but I'm by far no finance expert. I am working professionally with probabilistic models, but have only read one book on finance: Kommer's \"\"Souverän investieren mit Indexfonds und ETFs\"\". It's supposed to contain many statements of Malkiel's \"\"A Random Walk Down Wall Street\"\".\"",
"title": ""
},
{
"docid": "127263",
"text": "The article links to William Bernstein’s plan that he outlined for Business Insider, which says: Modelling this investment strategy Picking three funds from Google and running some numbers. The international stock index only goes back to April 29th 1996, so a run of 21 years was modelled. Based on 15% of a salary of $550 per month with various annual raises: Broadly speaking, this investment doubles the value of the contributions over two decades. Note: Rebalancing fees are not included in the simulation. Below is the code used to run the simulation. If you have Mathematica you can try with different funds. Notice above how the bond index (VBMFX) preserves value during the 2008 crash. This illustrates the rationale for diversifying across different fund types.",
"title": ""
}
] |
10406
|
Can you use external money to pay trading commissions in tax-free and tax-deferred accounts?
|
[
{
"docid": "569953",
"text": "According to Publication 590, broker's commissions for stock transactions within an IRA cannot be paid in addition to the IRA contribution(s), but they are deductible as part of the contribution, or add to the basis if you are making a nondeductible contribution to a Traditional IRA. (Top of Page 10, and Page 12, column 1, in the 2012 edition of Pub 590). On the other hand, trustees' administrative fees can be paid from outside the IRA if they are billed separately, and are even deductible as a Miscellaneous Deduction on Schedule A of your income tax return (subject to the 2% of AGI threshold). A long time ago, when my IRA account balances were much smaller, I used to get a bill from my IRA custodian for a $20 annual administrative fee which I paid separately (but never got to deduct due to the 2% threshold). My custodian also allowed the option of doing nothing in which case the $20 would be collected from (and thus reduce) the amount of money in my IRA. Note that this does not apply to the expenses charged by the mutual funds that you might have in your IRA; these expenses are treated the same as brokerage commissions and must be paid from within the IRA.",
"title": ""
},
{
"docid": "361639",
"text": "Nice idea. When I started my IRAs, I considered this as well, and the answer from the broker was that this was not permitted. And, aside from transfers from other IRAs or retirement accounts, you can't 'deposit' shares to the IRA, only cash.",
"title": ""
}
] |
[
{
"docid": "308150",
"text": "\"If I understand correctly, the Traditional IRA, if you have 401k with an employer already, has the following features: Actually, #1 and #2 are characteristics of Roth IRAs, not Traditional IRAs. Only #3 is a characteristic of a Traditional IRA. Whether you have a 401(k) with your employer or not makes absolutely no difference in how your IRAs are taxed for the vast majority of people. (The rules for IRAs are different if you have a very high income, though). You're allowed to have and contribute to both kinds of accounts. (In fact, I personally have both). Traditional IRAs are tax deferred (not tax-free as people sometimes mistakenly call them - they're very different), meaning that you don't have to pay taxes on the contributions or profits you make inside the account (e.g. from dividends, interest, profits from stock you sell, etc.). Rather, you pay taxes on any money you withdraw. For Roth IRAs, the contributions are taxed, but you never have to pay taxes on the money inside the account again. That means that any money you get over and above the contributions (e.g. through interest, trading profits, dividends, etc.) are genuinely tax-free. Also, if you leave any of the money to people, they don't have to pay any taxes, either. Important point: There are no tax-free retirement accounts in the U.S. The distinction between different kinds of IRAs basically boils down to \"\"pay now or pay later.\"\" Many people make expensive mistakes in their retirement strategy by not understanding that point. Please note that this applies equally to Traditional and Roth 401(k)s as well. You can have Roth 401(k)s and Traditional 401(k)s just like you can have Roth IRAs and Traditional IRAs. The same terminology and logic applies to both kinds of accounts. As far as I know, there aren't major differences tax-wise between them, with two exceptions - you're allowed to contribute more money to a 401(k) per year, and you're allowed to have a 401(k) even if you have a high income. (By way of contrast, people with very high incomes generally aren't allowed to open IRAs). A primary advantage of a Traditional IRA is that you can (in theory, at least) afford to contribute more money to it due to the tax break you're getting. Also, you can defer taxes on any profits you make (e.g. through dividends or selling stock at a profit), so you can grow your money faster.\"",
"title": ""
},
{
"docid": "350082",
"text": "I know of no way to answer your question without 'spamming' a particular investment. First off, if you are a USA citizen, max out your 401-K. Whatever your employer matches will be an immediate boost to your investment. Secondly, you want your our gains to be tax deferred. A 401-K is tax deferred as well as a traditional IRA. Thirdly, you probably want the safety of diversification. You achieve this by buying an ETF (or mutual fund) that then buys individual stocks. Now for the recommendation that may be called spamming by others : As REITs pass the tax liability on to you, and as an IRA is tax deferred, you can get stellar returns by buying a mREIT ETF. To get you started here are five: mREITs Lastly, avoid commissions by having your dividends automatically reinvested by using that feature at Scottrade. You will have to pay commissions on new purchases but your purchases from your dividend Reinvestment will be commission free. Edit: Taking my own advice I just entered orders to liquidate some positions so I would have the $ on hand to buy into MORL and get some of that sweet 29% dividend return.",
"title": ""
},
{
"docid": "51086",
"text": "\"The primary tax-sheltered investing vehicles in Canada include: The RRSP. You can contribute up to 18% of your prior year's earned income, up to a limit ($24,930 in 2015, plus past unused contribution allowance) and receive an income tax deduction for your contributions. In an RRSP, investments grow on a tax-deferred basis. No tax is due until you begin withdrawals. When you withdraw funds, the withdrawn amount will be taxed at marginal income tax rates in effect at that time. The RRSP is similar to the U.S. \"\"traditional\"\" IRA, being an individual account with pre-tax contributions, tax-deferred growth, and ordinary tax rates applied to withdrawals. Yet, RRSPs have contribution limits higher than IRAs; higher, even, than U.S. 401(k) employee contribution limits. But, the RRSP is dissimilar to the IRA and 401(k) since an individual's annual contribution allowance isn't use-it-or-lose-it—unused allowance accumulates. The TFSA. Once you turn 18, you can put in up to $5,500 each year, irrespective of earned income. Like the RRSP, contribution room accumulates. If you were 18 in 2009 (when TFSAs were introduced) you'd be able to contribute $36,500 if you'd never contributed to one before. Unlike the RRSP, contributions to a TFSA are made on an after-tax basis and you pay no tax when you withdraw money. The post-tax nature of the TFSA and completely tax-free withdrawals makes them comparable to Roth-type accounts in the U.S.; i.e. while you won't get a tax deduction for contributing, you won't pay tax on earnings when withdrawn. Yet, unlike U.S. Roth-type accounts, you are not required to use the TFSA strictly for retirement savings—there is no penalty for pre-retirement withdrawal of TFSA funds. There are also employer-sponsored defined benefit (DB) and defined contribution (DC) retirement pension plans. Generally, employees who participate in these kinds of plans have their annual RRSP contribution limits reduced. I won't comment on these kinds of plans other than to say they exist and if your employer has one, check it out—many employees lose out on free money by not participating. The under-appreciated RESP. Typically used for education savings. A lifetime $50,000 contribution limit per beneficiary, and you can put that all in at once if you're not concerned about maximizing grants (see below). No tax deduction for contributions, but investments grow on a tax-deferred basis. Original contributions can be withdrawn tax-free. Qualified educational withdrawals of earnings are taxed as regular income in the hands of the beneficiary. An RESP beneficiary is typically a child, and in a child's case the Canadian federal government provides matching grant money (called CESG) of 20% on the first $2500 contributed each year, up to age 18, to a lifetime maximum of $7200 per beneficiary. Grant money is subject to additional conditions for withdrawal. While RESPs are typically used to save for a child's future education, there's nothing stopping an adult from opening an RESP for himself. If you've never had one, you can deposit $50,000 of after-tax money to grow on a tax-deferred basis for up to 36 years ... as far as I understand. An adult RESP will not qualify for CESG. Moreover, if you use the RESP strictly as a tax shelter and don't make qualified educational withdrawals when the time comes, your original contributions still come out free of tax but you'll pay ordinary income tax plus 20% additional tax on the earnings portion. That's the \"\"catch\"\"*. *However, if at that time you have accumulated sufficient RRSP contribution room, you may move up to $50,000 of your RESP earnings into your RRSP without any tax consequences (i.e. also avoiding the 20% additional tax) at time of transfer. Perhaps there's something above you haven't considered. Still, be sure to do your own due diligence and to consult a qualified, experienced, and conflict-free financial advisor for advice particular to your own situation.\"",
"title": ""
},
{
"docid": "109540",
"text": "Guaranteed 8.2% annual return sounds too good to be true. Am I right? Are there likely high fees, etc.? You're right. Guaranteed annual return is impossible, especially when you're talking about investments for such a long period of time. Ponzi (and Madoff) schemed their investors using promises of guaranteed return (see this note in Wikipedia: In some cases returns were allegedly determined before the account was even opened.[72]). Her financial advisor doesn't charge by the hour--he takes a commission. So there's obviously some incentive to sell her things, even if she may not need them. Definitely not a good sign, if the advisor gets a commission from the sale then he's obviously not an advisor but a sales person. The problem with this kind of investment is that it is very complex, and it is very hard to track. The commission to the broker makes it hard to evaluate returns (you pay 10% upfront, and it takes awhile to just get that money back, before even getting any profits), and since you're only able to withdraw in 20 years or so - there's no real way to know if something wrong, until you get there and discover that oops- no money! Also, many annuity funds (if not all) limit withdrawals to a long period, i.e.: you cannot touch money for like 10 years from investment (regardless of the tax issues, the tax deferred investment can be rolled over to another tax deferred account, but in this case - you can't). I suggest you getting your own financial advisor (that will work for you) to look over the details, and talk to your mother if it is really a scam.",
"title": ""
},
{
"docid": "11998",
"text": "\"I have a couple other important considerations regarding external HSA accounts vs employer sponsored HSA accounts. Depending on your personal financial situation and goals; some people like to use HSA accounts as an extra retirement account (since the money can be withdrawn penalty free in retirement for non-medical expenses, and completely tax & penalty free at any time for medical expenses). If your intended use for the HSA account is an investment vehicle for retirement, then you may find more use/benefit out of an external provider that may provide more or better investment options than your employers HSA investment options. There can be a lot of additional value in those extra investment options over greater periods of time. Another VERY important consideration for FICA taxes (FICA includes Social Security & Medicare) that I don't believe was mentioned before - for those earners who are under the maximum social security wage limit, you are paying 6.2% of each paycheck into social security taxes. As others have mentioned you can \"\"save\"\" this tax through your employer’s plan if you set up the account to be funded pre-tax from your paychecks. However, in doing so, you are lowering your overall contributions into social security, which may lower your social security benefits in your retirement years! If this is ultimately going to lower your SSA benefits in retirement then that is a big future cost that may steer you against the pre-tax employer contributions. Think of social security as part of your retirement plan, not as a tax but instead as an additional check you put away for yourself for retirement every month. Of course, this is only an important consideration if SSA is still going to be around when you retire, but let's assume that it will be. This is not an issue for higher earners, earning well above the max SSA taxable wages. There is no wage limit on the 1.45% Medicare tax withholding's, and there is certainly no harm in saving Medicare taxes because it will not affect future Medicare benefits. So for taxpayers earning well over the max SSA wages, they will just save the 1.45% Medicare taxes without affecting their SSA contributions and resulting retirement benefits. So again, it all comes down to personal situations. Depending on your earnings and goals, employer plan may or may not be the way to go. Personally, for my lower earning clients, friends and family, I tend to recommend that they do whatever they can to maximize their social security benefits in retirement. So I would advise them to either use the external provider account, or the employer plan but with post-tax contributions so you don't lower the SSA withholding's but can still claim the income tax deduction on your tax return. YMMV -Dan\"",
"title": ""
},
{
"docid": "359515",
"text": "A 401-K is something you get through an employer. I recommend getting a self-directed IRA. You can open an IRA with Scottrade with $500 The money you put into an IRA is tax deferred, meaning that you do not have to pay taxes on profits. It may also lower your tax liability. Scottrade has a feature to automatically reinvest any dividends from the securities you own. This feature allows you to avoid commissions on those automatic purchases. Don't try to time the market. Pick a good ETF (exchange traded fund) that pays dividends. It will give you diversification. Avoid the urge to buy and sell constantly. This only gives commissions to the broker.",
"title": ""
},
{
"docid": "587768",
"text": "4.7 is a pretty low rate, especially if you are deducting that from your taxes. If you reduce the number by your marginal tax rate to get the real cost of the money you end up with a number that isn't far off from inflation, and also represents a pretty low 'yield' in terms of paying off the loan early. (e.g. if your marginal tax rate is 28%, then the net you are paying in interest after the tax deduction is 4.7 * .72 = 3.384) While I'm all for paying off loans with higher rates (since it's in effect the same as making that much risk free on the money) it doesn't make a lot of sense when you are down at 3.4 unless there is a strong 'security factor' (which really makes a difference to some folks) to be had that really helps you sleep at night. (to be realistic, for some folks close to retirement, there can be a lot to be said for the security of not having to worry about house payments, although you don't seem to be in that situation yet) As others have said, first make sure you have enough liquid 'emergency money' in something like a money market account, or a ladder of short term CD's If you are sure that the sprouts will be going to college, then there's a lot to be said for kicking a decent amount into a 529, Coverdell ESA (Educational Savings Account), uniform gift to minors account, or some combination of those. I'm not sure if any of those plans can be used for a kid that has not been born yet however. I'd recommend http://www.savingforcollege.com as a good starting point to get more information on your various options. As with retirement savings, money put in earlier has a lot more 'power' over the final balance due to compounding interest, so there's a lot to be said for starting early, although depending on what it takes to qualify for the plans there could be such a thing as too early ;-) ). There's nothing wrong with Managed mutual funds as long as the fund objective and investing style is in alignment with your objectives and risk tolerance; The fund is giving you a good return relative to the market as a whole; You are not paying high fees or load charges; You are not losing a lot to taxes. I would always look at the return after expenses when comparing to other options, and if the money is not in a tax deferred account, also look at what sort of tax burden you will be faced with. A fund that trades a lot will generate more short term gains which means more taxes than compared to a more passive fund. Anything lost to taxes is money lost to you so needs to come out of the total return when you calculate that. Sometimes such funds are better off as a choice inside an IRA or 401K, and you can instead use more tax efficient vehicles for money where you have to pay the taxes every year on the gains. The reason a lot of folks like index funds better is that: Given your described age, it's not appropriate now, but in the long run as you get closer to retirement, you may want to start looking at building up some investments that are geared more towards generating income, such as bonds, or depending on taxes where you live, Municipal bonds. In any case, the more money you can set aside for retirement now, both inside and outside of tax deferred accounts, the sooner you will get to the point of the 'critical mass' you need to retire, at that point you can work because you want to, not because you have to.",
"title": ""
},
{
"docid": "318338",
"text": "\"Assuming that the will that bequeathed the money to your son did not stipulate any restrictions or set up a trust to hold the money until your son turns 25, or something like that, I don't think you have much choice except to put the money in a UTMA account (which of course can be invested in whatever the trustee (which could be you, or you and your wife jointly) decides. Note: not a UGMA account since the money is not a gift. You also don't have any option except to turn the account over to your son when he turns eighteen. The point is, the investment can be in anything as long as the account is registered as a UTMA account. But do remember also that your son is entitled to sue you for breach of fiduciary duty if you don't take good care of the money, so that blowing it all in risky investments is also not a good idea. If you are worried about taxes and your son's income being taxed at your rate, one way of deferring the issue is to buy US Savings Bonds. The interest can be deferred from taxation until the bonds are redeemed. Edit added in response to JoeTaxpayer's comments: But a better strategy is to declare the accrued interest each year as unearned income of the child on the kiddie tax form that is part of your tax return, and pay the tax, if any, that results To ease your mind or conscience, think of the tax that you pay on your child's behalf as a gift to your child! In any case, there will likely not be much tax due since the first $950 of unearned income of a child is tax-free and the next $950 taxed at 10%. Then, when the bonds are cashed in, the interest that accrued (and was \"\"taxed\"\") in earlier years can be deducted from the interest (cash in price minus purchase price) that you (or your son) will be told is the interest that the bonds earned. Of course, if kiddie tax is not a concern (and it shouldn't be, given the amount available for investment), an even better strategy is to set up the UTMA account(s) in long-term investments in low-cost index funds or ETFs (as JoeTaxpayer suggests) and pay the tax, if any, as it comes due.\"",
"title": ""
},
{
"docid": "264023",
"text": "\"when you contribute to a 401k, you get to invest pre-tax money. that means part of it (e.g. 25%) is money you would otherwise have to pay in taxes (deferred money) and the rest (e.g. 75%) is money you could otherwise invest (base money). growth in the 401k is essentially tax free because the taxes on the growth of the base money are paid for by the growth in the deferred portion. that is of course assuming the same marginal tax rate both now and when you withdraw the money. if your marginal tax rate is lower in retirement than it is now, you would save even more money using a traditional 401k or ira. an alternative is to invest in a roth account (401k or ira). in which case the money goes in after tax and the growth is untaxed. this would be advantageous if you expect to have a higher marginal tax rate during retirement. moreover, it reduces tax risk, which could give you peace of mind considering u.s. marginal tax rates were over 90% in the 1940's. a roth could also be advantageous if you hit the contribution limits since the contributions are after-tax and therefore more valuable. lastly, contributions to a roth account can be withdrawn at any time tax and penalty free. however, the growth in a roth account is basically stuck there until you turn 60. unlike a traditional ira/401k where you can take early retirement with a SEPP plan. another alternative is to invest the money in a normal taxed account. the advantage of this approach is that the money is available to you whenever you need it rather than waiting until you retire. also, investment losses can be deducted from earned income (e.g. 15-25%), while gains can be taxed at the long term capital gains rate (e.g. 0-15%). the upshot being that even if you make money over the course of several years, you can actually realize negative taxes by taking gains and losses in different tax years. finally, when you decide to retire you might end up paying 0% taxes on your long term capital gains if your income is low enough (currently ~50k$/yr for a single person). the biggest limitation of this strategy is that losses are limited to 3k$ per year. also, this strategy works best when you invest in individual stocks rather than mutual funds, increasing volatility (aka risk). lastly, this makes filing your taxes more complicated since you need to report every purchase and sale and watch out for the \"\"wash sale\"\" rules. side note: you should contribute enough to get all the 401k matching your employer offers. even if you cash out the whole account when you want the money, the matching (typically 50%-200%) should exceed the 10% early withdrawal penalty.\"",
"title": ""
},
{
"docid": "388145",
"text": "Yes, absolutely. The HSA, when used for medical expenses, allows you to essentially pay for your medical expenses tax free. Even if you don't have extra room in your budget, you can fund the HSA as you incur medical expenses, then withdraw money to pay the expenses, and you'll see an immediate tax benefit at tax time. However, let's say that you have plenty of room in your budget and you don't have a lot of medical expenses. You already contribute the maximum to your 401(k) or IRA, and you want to do more. The HSA acts like a retirement account in this case, allowing you to contribute before-tax money and let it grow untaxed. The HSA does have a huge benefit that no other retirement account has. If you choose not to reimburse yourself for medical expenses, but you keep track of the unreimbursed expenses you incur, then you can reimburse yourself for these expenses at any point in the future completely tax free. Essentially, your contributions are treated like a traditional IRA, but your withdrawals are treated like a Roth IRA, and can be done at any age. If you don't acquire enough medical expenses, you can still withdraw whatever is left at age 65 and those withdrawals will be taxed like a traditional IRA. The HSA provides for tax-free contributions and growth if used for medical expenses, and tax-deferred growth if withdrawn after age 65 without medical expenses.",
"title": ""
},
{
"docid": "329596",
"text": "\"tl;dr Roth earnings are not necessarily \"\"tax deferred\"\", but they might be. This is a great question because IMHO, the use of the wording \"\"tax deferred\"\" is slightly misleading when talking about a Roth IRA (and Roth 401k too). The phrase \"\"tax deferred\"\" actually means you save tax now and you pay tax later, i.e. you \"\"defer\"\" the tax. As you pointed out, this is the normal terminology used for describing a Traditional IRA/401k. Earnings on a Roth IRA are tax free (not deferred), but only if your distributions are qualified. For the most part distributions are considered qualified if you wait until you are 59.5 years old before taking the money out, but there are some exceptions. If you choose to distribute more than your contributions, meaning you are now taking out earnings, the earnings are tax free only if your distribution is qualified. For example, if you take out the earnings before you are 59.5 (and no other exceptions apply), then you would pay tax on the earnings and also a 10% penalty. So, perhaps a better way to say it is that earnings in a Roth IRA are \"\"conditionally tax deferred\"\".\"",
"title": ""
},
{
"docid": "206442",
"text": "\"It is important to remember that the stock price in principle reflects the value of the company, so the market cap should drop upon issuance of the the dividend. However, the above reasoning neglects to consider taxes, which make the question a bit more interesting. The key fact is that different investors are going to get taxed on the dividend to varying degrees, ranging from 20% for qualified dividends in the USA for a high-income individual in a taxable account (and even worse for non-qualified dividends) to 0% for tax-exempt nonprofits, retirement accounts, and low-income individuals. The high-tax investors are going to be a bit averse to paying tax on that dividend, whereas the tax-free investors are not. Hence in a tax-rational market the tax-free investors are going to be the ones buying right before a dividend and the tax-paying investors will be buying right afterwards. Tax-exempt investors could in principle make some amount of money buying dividends to keep them off the tax-paying investors' books. (Of course, the strategy could backfire if too many people did it all at once.) That said, the tax-payers have the tax disincentive to prevent them from fully exploiting the opposite strategy of selling just before a dividend. In particular, they are subject to capital gains tax when they sell at a profit (unless they have enough compensating capital losses), and it is to their after-tax profit to defer taxation by not trading. That said, the stock market has well-known irrationality when it comes to considering tax consequences, so logic based on assumed rationality of the market does not always apply to the extent one would expect. The foremost example of tax-irrationality is the so-called \"\"dividend paradox\"\", which basically states that corporations should favor stock buybacks (or perhaps loan repayment) to the complete exclusion of dividends because capital gains are taxed less harshly than dividends in a variety of ways, some of which are subtle: 1) Historically (although not currently in the USA for qualified dividends) the tax rate was higher for dividends. (In Canada, for example, dividends are taxed at twice the rate of capital gains.) 2) If you die holding appreciated stock then you (meaning your heirs) completely escape US the capital gains tax on the accrual during your lifetime. 3) Capital gains tax can be deferred by simply not selling. In comparison to dividends, this is roughly equivalent to getting a tax-free loan from the government which is invested for profit and paid at a later date after inflation has eaten away at the real value of the loan. For example, if all your stock investments increase by 10%/year but you sell every year, in a high-tax bracket situation you're total after-tax return will be only 8% per year. In contrast, if you hold the same investments for many many years and then sell, your total return will be nearly 10% per year, because you only pay 20% once (at the end). 4) A capital gain can often be neutralized by a capital loss in another stock, so that no tax results. If you loose money on a stock that is paying dividends, you're still going to have to pay tax on that dividend. There are companies that borrow money to pay out that taxable-dividend each quarter, which seems like gross tax malpractice on the part of the CFO. (If the dividend paradox doesn't make sense, first consider the case that you owned ALL the shares of a company. It wouldn't matter to you at all on a pre-tax basis whether you got a $1000 company buyback or a $1000 dividend, because after the buyback/dividend you'd still own the entire company and $1000. The number of shares would be reduced, but objecting that you owned fewer shares after the buyback would be like saying you have become shorter if your height is measured in inches rather than centimeters.) [Of course, in the case of many shareholders you can get burned by failing to sell into the buyback when the share price is too high, but that is another matter.]\"",
"title": ""
},
{
"docid": "438038",
"text": "\"You don't want to do that. DON'T LIE TO THE IRS!!! We live overseas as well and have researched this extensively. You cannot make $50k overseas and then say you only made $45k to put $5k into retirement. I have heard from some accountants and tax attorneys who interpret the law as saying that the IRS considers Foreign Earned Income as NOT being compensation when computing IRA contribution limits, regardless of whether or not you exclude it. Publication 590-A What is Compensation (scroll down a little to the \"\"What Is Not Compensation\"\" section). Those professionals say that any amounts you CAN exclude, not just ones you actually do exclude. Then there are others that say the 'can' is not implied. So be careful trying to use any foreign-earned income to qualify for retirement contributions. I haven't ran across anyone yet who has gotten caught doing it and paid the price, but that doesn't mean they aren't out there. AN ALTERNATIVE IN CERTAIN CASES: There are two things you can do that we have found to have some sort of taxable income that is preferably not foreign so that you can contribute to a retirement account. We do this by using capital gains from investments as income. Since our AGI is always zero, we pay no short or long term capital gains taxes (as long as we keep short term capital gains lower than $45k) Another way to contribute to a Roth IRA when you have no income is to do an IRA Rollover. Of course, you need money in a tax-deferred account to do this, but this is how it works: I always recommend those who have tax-deferred IRA's and no AGI due to the FEIE to roll over as much as they can every year to a Roth IRA. That really is tax free money. The only tax you'll pay on that money is sales tax when you SPEND IT!! =)\"",
"title": ""
},
{
"docid": "535340",
"text": "\"As user quid states in his answer, all you need to do is open an account with a stock broker in order to gain access to the world's stock markets. If you are currently banking with one of the six big bank, then they will offer stockbroking services. You can shop around for the best commission rates. If you wish to manage your own investments, then you will open a \"\"self-directed\"\" account. You can shelter your investments from all taxation by opening a TFSA account with your stock broker. Currently, you can add $5,500 per year to your TFSA. Unused allowances from previous years can still be used. Thus, if you have not yet made any TFSA contributions, you can add upto $46,500 to your TFSA and enjoy the benefits of tax free investing. Investing in what you are calling \"\"unmanaged index funds\"\" means investing in ETFs (Exchange Traded Funds). Once you have opened your account you can invest in any ETFs traded on the stock markets accessible through your stock broker. Buying shares on foreign markets may carry higher commission rates, but for the US markets commissions are generally the same as they are for Canadian markets. However, in the case of buying foreign shares you will carry the extra cost and risk of selling Canadian dollars and buying foreign currency. There are also issues to do with foreign withholding taxes when you trade foreign shares directly. In the case of the US, you will also need to register with the US tax authorities. Foreign withholding taxes payable are generally treated as a tax credit with respect to Canadian taxation, so you will not be double taxed. In today's market, for most investors there is generally no need to invest directly in foreign market indices since you can do so indirectly on the Toronto stock market. The large Canadian ETF providers offer a wide range of US, European, Asian, and Global ETFs as well as Canadian ETFs. For example, you can track all of the major US indices by trading in Toronto in Canadian dollars. The S&P500, the Dow Jones, and the NASDAQ100 are offered in both \"\"currency hedged\"\" and \"\"unhedged\"\" forms. In addition, there are ETFs on the total US Market, US Small Caps, US sectors such as banks, and more exotic ETFs such as those offering \"\"covered call\"\" strategies and \"\"put write\"\" strategies. Here is a link to the BMO ETF website. Here is a link to the iShares (Canada) ETF website.\"",
"title": ""
},
{
"docid": "8861",
"text": "\"Sure. For starters, you can put it in a savings account. Don't laugh, they used to pay noticeable interest. You know, back in the olden days. You could buy an I-bond from Treasury Direct. They're a government savings bond that pays a specified amount of interest (currently 0%, I believe), plus the amount of the inflation rate (something like 3.5% currently, I believe). You don't get paid the money -- the I-bond grows in value till you sell it. You can open a discount brokerage account, and buy 1 or more shares of stock in a company you like. Discount brokerages generally have a minimum of $500 or so, but will waive that if you set the account up as an IRA. Scot Trade, for instance. (An IRA, in case you didn't know, is a type of account that's tax free but you can't touch it till you turn 59 1/2. It's meant to help you save for retirement.) Incidentally, watch out of \"\"small account\"\" fees that some brokerages might charge you. Generally they're annual or monthly charges they'd charge you to cover their costs on your account -- since they're certainly not going to make it in commissions. That IRA at Scot Trade is no-fee. Speaking of commissions, those will be a big chunk of that $100. It'll be like $7-$10 to buy that stock -- a pretty big bite. However, many of these discount brokerages also offer some mutual funds for no commission. Those mutual funds, in turn, have minimums too, but once again if your account's an IRA many will waive the minimum or set it low -- like $100.\"",
"title": ""
},
{
"docid": "473658",
"text": "ETFs offer the flexibility of stocks while retaining many of the benefits of mutual funds. Since an ETF is an actual fund, it has the diversification of its potentially many underlying securities. You can find ETFs with stocks at various market caps and style categories. You can have bond or mixed ETFs. You can even get ETFs with equal or fundamental weighting. In short, all the variety benefits of mutual funds. ETFs are typically much less expensive than mutual funds both in terms of management fees (expense ratio) and taxable gains. Most of them are not actively managed; instead they follow an index and therefore have a low turnover. A mutual fund may actively trade and, if not balanced with a loss, will generate capital gains that you pay taxes on. An ETF will produce gains only when shifting to keep inline with the index or you yourself sell. As a reminder: while expense ratio always matters, capital gains and dividends don't matter if the ETF or mutual fund is in a tax-advantaged account. ETFs have no load fees. Instead, because you trade it like a stock, you will pay a commission. Commissions are straight, up-front and perfectly clear. Much easier to understand than the various ways funds might charge you. There are no account minimums to entry with ETFs, but you will need to buy complete shares. Only a few places allow partial shares. It is generally harder to dollar-cost average into an ETF with regular automated investments. Also, like trading stocks, you can do those fancy things like selling short, buying on margin, options, etc. And you can pay attention to the price fluctuations throughout the day if you really want to. Things to make you pause: if you buy (no-load) mutual funds through the parent company, you'll get them at no commission. Many brokerages have No Transaction Fee (NTF) agreements with companies so that you can buy many funds for free. Still look out for that expense ratio though (which is probably paying for that NTF advantage). As sort of a middle ground: index funds can have very low expense ratios, track the same index as an ETF, can be tax-efficient or tax-managed, free to purchase, easy to dollar-cost average and easier to automate/understand. Further reading:",
"title": ""
},
{
"docid": "10089",
"text": "Congratulations on deciding to save for retirement. Since you cite Dave Ramsey as the source of your 15% number, what does he have to say about where to invest the money? If you want to have instantaneous penalty-free access to your retirement money, all you need to do is set up one or more ordinary accounts that you think of as your retirement money. Just be careful not to put the money into CDs since Federal law requires a penalty of three months interest if you cash in the CD before its maturity date (penalty!) or put the money into those pesky mutual funds that charge a redemption fee (penalty!) if you take the money out within x months of investing it where x can be anywhere from 3 to 24 or more. In Federal tax law (and in most state tax laws as well) a retirement account has special privileges accorded to it in that the interest, dividends, capital gains, etc earned on the money in your retirement account are not taxed in the year earned (as they would be in a non-retirement account), but the tax is either deferred till you withdraw money from the account (Traditional IRAs, 401ks etc) or is waived completely (Roth IRAs, Roth 401ks etc). In return for this special treatment, penalties are imposed (in addition to tax) if you withdraw money from your retirement account before age 59.5 which presumably is on the distant horizon for you. (There are some exceptions (including first-time home buying and extraordinary medical expenses) to this rule that I won't bother going into). But You are not required to invest your retirement money into such a specially privileged retirement account. It is perfectly legal to keep your retirement money in an ordinary savings account if you wish, and pay taxes on the interest each year. You can invest your retirement money into municipal bonds whose interest is free of Federal tax (and usually free of state tax as well if the municipality is located in your state of residence) if you like. You can keep your retirement money in a sock under your mattress if you like, or buy a collectible item (e.g. a painting) with it (this is not permitted in an IRA), etc. In short, if you are concerned about the penalties imposed by retirement accounts on early withdrawals, forgo the benefits of these accounts and put your retirement money elsewhere where there is no penalty for instant access. If you use a money management program such as Mint or Quicken, all you need to do is name one or more accounts or a portfolio as MyRetirementMoney and voila, it is done. But those accounts/portfolios don't have to be retirement accounts in the sense of tax law; they can be anything at all.",
"title": ""
},
{
"docid": "475397",
"text": "There is no advantage to using one type of account or the other if you are in the same tax bracket at retirement that you are in during your working years. However, for tax planning reasons, it is good to have some money in both a Roth and a traditional IRA plan. JoeTaxpayer has often advocated a good rule of thumb to use a Roth when your tax bracket is 15% or lower, and use a traditional account when in the 25% bracket or above. The reason for this rule of thumb is that you are less likely to be in the higher tax bracket when you are living off retirement savings unless you put away an awful lot of money between now and then. If you are making enough money to be paying a 25% marginal rate on some of the money you would be putting away for retirement, then by all means, put all of that money in a traditional 401k. If after contributing that portion of your savings taxed at the higher rate, you still have money to put away for retirement, put the rest in a Roth and pay the 15% taxes on it. When you are younger, it is likely that you are making less than you will a few years hence, and it is also likely that a larger portion of your income will be paying tax deductible interest on a mortgage. If those are true for you, then by all means, use the Roth. That was true of me when I was single and just getting started. When you do finally retire, it is possible that the tax brackets will be increased to match inflation, and if so, then there is no benefit to having tax free money at retirement vs. paying taxes on deferred accounts, but there is also usually more flexibility in when to spend money. You may find that you have a year where you have to spend a lot, so it is good to be able to pull money out without it increasing your marginal rate for that year, and other years where you spend relatively smaller amounts, and you can withdraw taxable money and pay a lower rate on that money. No one knows what the tax code will look like in 40 years, but having some money in each type of account will give you flexibility to minimize your tax bill at retirement.",
"title": ""
},
{
"docid": "173088",
"text": "\"What is a stock? A share of stock represents ownership of a portion of a corporation. In olden times, you would get a physical stock certificate (looking something like this) with your name and the number of shares on it. That certificate was the document demonstrating your ownership. Today, physical stock certificates are quite uncommon (to the point that a number of companies don't issue them anymore). While a one-share certificate can be a neat memento, certificates are a pain for investors, as they have to be stored safely and you'd have to go through a whole annoying process to redeem them when you wanted to sell your investment. Now, you'll usually hold stock through a brokerage account, and your holdings will just be records in a database somewhere. You'll pick a broker (more on that in the next question), instruct them to buy something, and they'll keep track of it in your account. Where do I get a stock? You'll generally choose a broker and open an account. You can read reviews to compare different brokerages in your country, as they'll have different fees and pricing. You can also make sure the brokerage firm you choose is in good standing with the financial regulators in your country, though one from a major national bank won't be unsafe. You will be required to provide personal information, as you are opening a financial account. The information should be similar to that required to open a bank account. You'll also need to get your money in and out of the account, so you'll likely set up a bank transfer. It may be possible to request a paper stock certificate, but don't be surprised if you're told this is unavailable. If you do get a paper certificate, you'll have to deal with considerably more hassle and delay if you want to sell later. Brokers charge a commission, which is a fee per trade. Let's say the commission is $10/trade. If you buy 5 shares of Google at $739/share, you'd pay $739 * 5 + $10 = $3705 and wind up with $3695 worth of stock in your account. You'd pay the same commission when you sell the stock. Can anyone buy/own/use a stock? Pretty much. A brokerage is going to require that you be a legal adult to maintain an account with them. There are generally ways in which a parent can open an account on behalf of an underage child though. There can be different types of restrictions when it comes to investing in companies that are not publicly held, but that's not something you need to worry about. Stocks available on the public stock market are available to, well, the public. How are stocks taxed? Taxes differ from country to country, but as a general rule, you do have to provide the tax authorities with sufficient information to determine what you owe. This means figuring out how much you purchased the stock for and comparing that with how much you sold it for to determine your gain or loss. In the US (and I suspect in many other countries), your brokerage will produce an annual report with at least some of this information and send it to the tax authorities and you. You or someone you hire to do your taxes will use that report to compute the amount of tax owed. Your brokerage will generally keep track of your \"\"cost basis\"\" (how much you bought it for) for you, though it's a good idea to keep records. If you refuse to tell the government your cost basis, they can always assume it's $0, and then you'll pay more tax than you owe. Finding the cost basis for old investments can be difficult many years later if the records are lost. If you can determine when the stock was purchased, even approximately, it's possible to look back at historical price data to determine the cost. If your stock pays a dividend (a certain amount of money per-share that a company may pay out of its profits to its investors), you'll generally need to pay tax on that income. In the US, the tax rate on dividends may be the same or less than the tax rate on normal wage income depending on how long you've held the investment and other rules.\"",
"title": ""
},
{
"docid": "69841",
"text": "A UTMA may or may not fit your situation. The main drawbacks to a UTMA account is that it will count against your child for financial aid (it counts as the child's asset). The second thing to consider is that taxes aren't deferred like in a 529 plan. The last problem of course is that when he turns 18 he gets control of the account and can spend the money on random junk (which may or may not be important to you). A 529 plan has a few advantages over a UTMA account. The grandparents can open the account with your son as the beneficiary and the money doesn't show up on financial aid for college (under current law which could change of course). Earnings grow tax free which will net you more total growth. You can also contribute substantially more without triggering the gift tax ~$60k. Also many states provide a state tax break for contributing to the state sponsored 529 plan. The account owner would be the grandparents so junior can't spend the money on teenage junk. The big downside to the 529 is the 10% penalty if the money isn't used for higher education. The flip side is that if the money is left for 20 years you will also have additional growth from the 20 years of tax free growth which may be a wash depending on your tax bracket and the tax rates in effect over those 20 years.",
"title": ""
},
{
"docid": "432902",
"text": "\"Your question is based on incorrect assumptions. Generally, there's no \"\"penalty\"\", per se, to make a withdrawal from your RRSP, even if you make a withdrawal earlier than retirement, however you define it. A precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant.* Our U.S. neighbours have a 10% penalty on non-hardship early withdrawals (before age 59 ½) from retirement accounts like the 401k and IRA. It's an additional measure designed to discourage early withdrawals, and raise more tax. Yet, in Canada, there is no similar penalty. Individual investments inside your RRSP may have associated penalties, such as the dreaded \"\"deferred sales charge\"\" (DSC) of some back-end loaded mutual funds, or such as LSVCC funds that generated additional special tax credits that could get clawed back. Yet, these early withdrawal penalties are distinct from the RRSP nature of your account. Choose your investments carefully to avoid these kinds of surprises. Rather, an RRSP is a tax-deferred account, and it works like this: The government allows you to claim a nice juicy tax deduction, which can reduce your income tax at your marginal rate in the year you make a contribution, or later if you should choose to defer the deduction. The resulting pre-tax money accumulated in your RRSP benefits from further tax deferral: assets can grow without attracting annual income tax on earned interest, dividends, or capital gains. You don't need to declare on your income tax return any of the income earned inside your RRSP, unlike a regular investment account. Here's the rub: Once you decide to withdraw money from your RRSP, the entire amount withdrawn is considered regular income in the year in which you make the withdrawal. Thus, your withdrawals are subject to income tax, and yes, at your marginal rate. This is always the case, whether before or after retirement. You mentioned two special programs: The Home Buyers' Plan (HBP), and the Lifelong Learning Plan (LLP). Neither the HBP nor the LLP permit tax-free withdrawals. Rather, each of these programs are special kinds of loans that you can borrow from your own RRSP. HBP and LLP loan money isn't taxed when you get it because you are required to pay it back, and you pay it back into your own RRSP: You always pay income tax at your marginal rate on your RRSP withdrawals.** * Above, I said a precise meaning for \"\"retirement\"\" with respect to RRSPs is largely irrelevant. Yet, there are ages that matter: By the end of the year in which you turn 71, you are required to convert your RRSP to a RRIF. It's similar, but you can no longer contribute, and you must withdraw a minimum amount each year. Other circumstances related to age may qualify for minor tax relief intended for retirees, such as the Age Amount or the Pension Income Credit. Generally, such measures don't significantly change the fact that you pay income tax on RRSP withdrawals at your marginal rate – these measures raise the minimum you can take out without attracting tax, but most do nothing at the margin.** ** Exception: One might split eligible pension income with a spouse or common-law partner, which may reduce tax at the margin.\"",
"title": ""
},
{
"docid": "417388",
"text": "The 401(k) contribution is Federal tax free, when you make the contribution, and most likely State too. I believe that is true for California, specifically. There was a court case some years ago about people making 401(k) or IRA contributions in New York, avoiding the New York state income tax. Then they moved to Florida (no income tax), and took the money out. New York sued, saying they had to pay the New York income tax that had been deferred, but the court said no. So you should be able to avoid California state income tax, and then later if you were to move to, for example, Texas (no income tax), have no state income tax liability. At the Federal level, you will have different problems. You won't have the money; it will be held by the 401(k) trustee. When you try to access the money (cash the account out), you will have to pay the deferred taxes. Effectively, when you remove the money it becomes income in the year it is removed. You can take the money out at any time, but if you are less than 59 1/2 at the time that you take it, there is a 10% penalty. The agreement is that the Feds let you defer paying the tax because it is going to finance your retirement, and they will tax it later. If you take it out before 59 1/2, they figure you are not retired yet, and are breaking your part of the agreement. Of course you can generally leave the money in the 401(k) plan with your old employer and let it grow until you are 59.5, or roll it over into another 401(k) with a new employer (if they let you), or into an IRA. But if you have returned to your own country, having an account in the U.S. would introduce both investment risk and currency risk. If you are in another country when you want the money, the question would be where your U.S. residence would be. If you live in California, then go to, say France, your U.S. residence would still be California, and you would still owe California income tax. If you move from California to Texas and then to France, your U.S. residence would be Texas. This is pretty vague, as you might have heard in the Rahm Emanual case -- was he a resident of Chicago or Washington, D.C.? Same problem with Howard Hughes who was born in Texas, but then spent most his life in California, then to Nevada, then to Nicaragua, and the Bahamas. When he died Texas, California and Nevada all claimed him as a resident, for estate taxes. The important thing is to be able to make a reasonable case that you are a resident of where ever you want to be -- driver's license, mailing address, living quarters, and so on.",
"title": ""
},
{
"docid": "170717",
"text": "In the US, the key to understanding the benefits of retirement accounts is to understand capital gains taxes and how they work. Retirement accounts are designed for making investments throughout your career, then after several decades of contributions, withdrawing that money to pay for your needs when your full-time employment has concluded. Normally when you invest money in a brokerage account, if the value of your investment increases, and you sell in less than a year, those investments are considered short-term gains and taxed as ordinary income. If you hold that same investment for over a year, the same investment is taxed at a lower capital gains rate (depending on which tax bracket you are in during that year, the amount due could be up to 20%, but much lower than your regular income tax rate). When you place your money in a retirement account, you are choosing to either pay the tax due on the income when you put it in the account, or put the money in tax free and pay the tax when you withdraw (these are called tax-deferred accounts). When you have money invested several decades, the raw dollar amount increases greatly, but inflation is also reducing the value of those dollars. Imagine you bought some bonds that payed 4% over 40 years, but inflation was 2% during those same years. When you sell those bonds 40 years later, you will owe capital gains on the entire gain even though half of the gain came from inflation. Retirement accounts allow you to buy and sell according to your investment needs and goals without any consideration about whether the gains are short-term or long-term, and they also allow you to pay taxes just once, either when you put it in, or when you take it out, with no worries about whether you're paying taxes on inflated gains.",
"title": ""
},
{
"docid": "299690",
"text": "\"As other people have indicated, traditional IRAs are tax deductable for a particular year. Please note, though, that traditional IRAs are tax deferred (not tax-free) accounts, meaning that you'll have to pay taxes on any money you take out later regardless of why you're making the withdrawal. (A lot of people mistakenly call them tax free, which they're not). There is no such thing as a \"\"tax-free\"\" retirement account. Really, in terms of Roth vs. Traditional IRAs, it's \"\"pay now or pay later.\"\" With the exception of special circumstances like this, I recommend investing exclusively in Roth IRAs for money that you expect to grow much (or that you expect to produce substantial income over time). Just to add a few thoughts on what to actually invest in once you open your IRA, I strongly agree with the advice that you invest mostly in low-cost mutual funds or index funds. The advantage of an open-ended mutual fund is that it's easier to purchase them in odd increments and you may be able to avoid at least some purchase fees, whereas with an ETF you have to buy in multiples of that day's asking price. For example, if you were investing $500 and the ETF costs $200 per share, you could only purchase 2 shares, leaving $100 uninvested (minus whatever fee your broker charged for the purchase). The advantage of an ETF is that it's easy to buy or sell quickly. Usually, when you add money to a mutual fund, it'll take a few days for it to hit your account, and when you want to sell it'll similarly take a few days for you to get your money; when I buy an ETF the transaction can occur almost instantly. The fees can also be lower (if the ETF is just a passive index fund). Also, there's a risk with open-ended mutual funds that if too many people pull money out at once the managers could be forced to sell stocks at an unfavorable price.\"",
"title": ""
},
{
"docid": "38585",
"text": "This is something better asking a licensed professional (EA/CPA licensed in the US) who's also familiar with your home country tax law and the tax treaty your home country has with the US. Assuming no tax treaty and adverse tax consequences at home, you can have this scenario: The last step is critical - unless there's a tax treaty, not every country allows foreign tax credit (tax treaties usually have a provision to avoid double taxation), and you may end up paying both the US tax and local tax on the same money. If there's a tax treaty - step #4 is most likely guaranteed. Step #4 may not work in some places that would not consider the penalty as tax. Again - check it with an accountant proficient with the local law. Step #3 depends on your country. Some countries ignore foreign deferred compensation rules and consider the 401k amounts income to you when it was deposited (the US treats foreign tax deferred accounts this way, I believe that is also the case in India). So you should check locally. In this case you have probably paid taxes (or were exempt) on this amount when you earned it and will not pay taxes again. But then you might also not be able to claim the 10% back as credit. Leaving it is an option, although with such an amount is hardly worth it. You'll have to check how your country deals with foreign accounts of its citizens (the US, for example, puts an enormous reporting and tax burden on these, some countries forbid them altogether). This also applies to step #1.",
"title": ""
},
{
"docid": "335857",
"text": "\"You probably want to think about pools of money separately if they have separate time horizons or are otherwise not interchangeable. A classic example is your emergency fund (which has a potentially-immediate time horizon) vs. your retirement savings. The emergency fund would be all in cash or very short-term bonds, and would not count in your retirement asset allocation. Since the emergency fund usually has a capped value (a certain amount of money you want to have for emergencies) rather than a percentage of net worth value, this especially makes sense; you have to treat the emergency fund separately or you'd have to keep changing your asset allocation percentages as your net worth rises (hopefully) with respect to the capped emergency amount. Similarly, say you are saving for a car in 3 years; you'd probably invest that money very conservatively. Also, it could not go in tax-deferred retirement accounts, and when you buy the car the account will go to zero. So probably worth treating this separately. On the other hand, say you have some savings in tax-deferred retirement accounts and some in taxable accounts, but in both cases you're expecting to use the money for retirement. In that case, you have the same time horizon and goals, and it can pay to think about the taxable and nontaxable accounts as a whole. In particular you can use \"\"asset location\"\" (put less-tax-efficient assets in tax-deferred accounts). In this case maybe you would end up with mostly bonds in the tax-deferred accounts and mostly equities in the taxable accounts, for tax reasons; the asset allocation would only make sense considering all the accounts, since the taxable account would be too equity-heavy and the tax-deferred one too bond-heavy. There can be practical reasons to treat each account separately, too, though. For example if your broker has a convenient automatic rebalancing tool on their website, it probably only works within an account. Treating each account by itself would let you use the automatic rebalancing feature on the website, while a more complicated asset location strategy where you rebalance across multiple accounts might be too hard and in practice you wouldn't get around to it. Getting around to rebalancing could be more important than tax-motivated asset location. You could also take a keep-it-simple attitude: as long as your asset allocation is pretty balanced (say 40% bonds) and includes a cash allocation that would cover emergencies, you could just put all your money in one big portfolio, and think of it as a whole. If you have an emergency, withdraw from the cash allocation and then rebuild it over time; if you have a major purchase, you could redeem some bonds and then rebuild the bond portion over time. (When I say \"\"over time\"\" I'm thinking you might start putting new contributions into the now-underallocated assets, or you might dollar-cost-average back into them by selling bits of the now-overallocated assets.) Anyway there's no absolute rule, it depends on what's simple enough to be manageable for you in practice, and what separate shorter-horizon investing goals you have in addition to retirement. You can always make things complex but remember that a simple plan that happens in real life is better than a complex plan you don't keep up with in practice (or a complex plan that takes away from activities you'd enjoy more).\"",
"title": ""
},
{
"docid": "106501",
"text": "The $50k is subject to the appropriate income taxes, which may include FICA taxes including the employer share if you are self employed. The after tax money can then be invested with the amount invested being the cost basis (I.e., if you invest $40k you will have a cost basis of $40k). In future years you will have taxes due if any of those investments pay dividends (or capital gain distributions). Once you sell you will have a capital gain or loss that you will pay taxes on (or take a deduction if a loss). Now you can improve this picture if you are able to put some of your money into a retirement account (either a tax deductible or a ROTH). With retirement accounts you do not pay tax on the capital gains or dividends. If you use a tax deferred account your tax is higher but that is because you were also investing Uncle Sam's portion of your pay check.",
"title": ""
},
{
"docid": "396792",
"text": "\"Paypal linked with my bank account. 1.Can I use my Saving bank account to receive payments from my clients? Or is it necessary to open a current account? Yes you can get funds into your savings account. However it is advisable to keep a seperate account as it would help with your IT Returns. 2.I will be paying a certain % as commission on every sales to a couple of sales guys (who are not my employees but only working on commission). Can I show this as an expense in my IT returns? As you are earning as freelancer, you are eligible for certain deductions like Phone calls, Laptop, other hardware, payments to partners. It is important that you maintain a book of records. An accountant for a small fee of Rs 5 K should be able to help you. In the Returns you have to show Net income after all these deductions, there is no place to enter expenses. 3.Since I will be receiving all the payments in Euros so am I falling under a category of \"\"Exporter of services\"\"? The work you are doing can be Free Lancing. 4.Do I need an Import Export Code (IEC) for smoothly running this small business? You can run this without one as Free lancing. IEC would be when you grow big and are looking for various benefits under tax and pay different taxes and are incorporated as a company.\"",
"title": ""
},
{
"docid": "236732",
"text": "\"The 529 plan does outline your scenarios. There are stipulations for providing the funds should the child get the scholarship. If the child decides not to go into further education (vocational and community schools count), the money can be withdrawn with a 10% penalty and taxes paid on interest earnings. Taxes wouldn't have to be paid for contributions as taxes were already paid on that money by the gift giver. The 529 could also be transferred to another child in the family (including grandchildren). Here's an excerpt from www.savingforcollege.com: You'll never lose all of your savings. A 529 plan offers tax-free earnings and tax-free withdrawals as long as the money is used to pay for college. If you end up taking a non-qualified withdrawal, you'll incur income tax as well as a 10% penalty - but only on the earnings portion of the withdrawal. Since your contributions were made with after-tax money, they will never be taxed or penalized. You can avoid the penalty if you get a scholarship. There are a few special exceptions to the 10% penalty rule, including when the beneficiary becomes incapacitated, attends a U.S. Military Academy or gets a scholarship. In the case of a scholarship, non-qualified withdrawals up to the amount of the tax-free scholarship can be taken out penalty-free, but you'll have to pay income tax on the earnings. As Savingforcollege.com founder Joe Hurley likes to say, \"\"the scholarships have turned your tax-free 529 investment into a tax-deferred 529 investment\"\". Note, a 529 is ideal for the sum of money you are looking at. A proper trust, set up by a lawyer, will cost as much as $2000 to set up, and would require an annual tax return, both unnecessary burdens. To make matters worse, the trust counts as the child's asset where financial aid is concerned. The 529 counts, but to a much lesser extent.\"",
"title": ""
},
{
"docid": "114912",
"text": "The simplest explanation is that a traditional IRA is a method of deferring taxes. That is, normally you pay taxes on money you earn at the ordinary rate then invest the rest and only pay the capital gains rate. However, with a traditional IRA you don't pay taxes on the money when you earn it, you defer the payment of those taxes until you retire. So in the end it ends up being treated the same. That said, if you are strategic about it you can wind up paying less taxes with this type of account.",
"title": ""
}
] |
PLAIN-1574
|
marketing
|
[
{
"docid": "MED-5151",
"text": "Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.",
"title": "The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease."
},
{
"docid": "MED-5086",
"text": "BACKGROUND: Acrylamide, a probable human carcinogen, was detected in various heat-treated carbohydrate-rich foods in 2002. The few epidemiologic studies done thus far have not shown a relationship with cancer. Our aim was to investigate the association between acrylamide intake and endometrial, ovarian, and breast cancer risk. METHODS: The Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline (1986), a random subcohort of 2,589 women was selected using a case cohort analysis approach for analysis. The acrylamide intake of subcohort members and cases was assessed with a food frequency questionnaire and was based on chemical analysis of all relevant Dutch foods. Subgroup analyses were done for never-smokers to eliminate the influence of smoking; an important source of acrylamide. RESULTS: After 11.3 years of follow-up, 327, 300, and 1,835 cases of endometrial, ovarian, and breast cancer, respectively, were documented. Compared with the lowest quintile of acrylamide intake (mean intake, 8.9 mug/day), multivariable-adjusted hazard rate ratios (HR) for endometrial, ovarian, and breast cancer in the highest quintile (mean intake, 40.2 mug/day) were 1.29 [95% confidence interval (95% CI), 0.81-2.07; P(trend)=0.18], 1.78 (95% CI, 1.10-2.88; P(trend)=0.02), and 0.93 (95% CI, 0.73-1.19; P(trend)=0.79), respectively. For never-smokers, the corresponding HRs were 1.99 (95% CI, 1.12-3.52; P(trend)=0.03), 2.22 (95% CI, 1.20-4.08; P(trend)=0.01), and 1.10 (95% CI, 0.80-1.52; P(trend)=0.55). CONCLUSIONS: We observed increased risks of postmenopausal endometrial and ovarian cancer with increasing dietary acrylamide intake, particularly among never-smokers. Risk of breast cancer was not associated with acrylamide intake.",
"title": "A prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer."
},
{
"docid": "MED-4912",
"text": "Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.",
"title": "Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain."
},
{
"docid": "MED-5146",
"text": "Cocoa powder is rich in polyphenols, such as catechins and procyanidins, and has been shown in a variety of subject models to inhibit oxidized LDL and atherogenesis. Our study evaluated plasma LDL cholesterol and oxidized LDL concentrations following the intake of different levels of cocoa powder (13, 19.5, and 26 g/d) in normocholesterolemic and mildly hypercholesterolemic humans. In this comparative, double-blind study, we examined 160 subjects who ingested either cocoa powder containing low-polyphenolic compounds (placebo-cocoa group) or 3 levels of cocoa powder containing high-polyphenolic compounds (13, 19.5, and 26 g/d for low-, middle-, and high-cocoa groups, respectively) for 4 wk. The test powders were consumed as a beverage after the addition of hot water, twice each day. Blood samples were collected at baseline and 4 wk after intake of the test beverages for the measurement of plasma lipids. Plasma oxidized LDL concentrations decreased in the low-, middle-, and high-cocoa groups compared with baseline. A stratified analysis was performed on 131 subjects who had a LDL cholesterol concentrations of > or =3.23 mmol/L at baseline. In these subjects, plasma LDL cholesterol, oxidized LDL, and apo B concentrations decreased, and the plasma HDL cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups. The results suggest that polyphenolic substances derived from cocoa powder may contribute to a reduction in LDL cholesterol, an elevation in HDL cholesterol, and the suppression of oxidized LDL.",
"title": "Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different leve..."
},
{
"docid": "MED-5149",
"text": "BACKGROUND: Cocoa powder is rich in polyphenols such as catechins and procyanidins and has been shown in various models to inhibit LDL oxidation and atherogenesis. OBJECTIVE: We examined whether long-term intake of cocoa powder alters plasma lipid profiles in normocholesterolemic and mildly hypercholesterolemic human subjects. DESIGN: Twenty-five subjects were randomly assigned to ingest either 12 g sugar/d (control group) or 26 g cocoa powder and 12 g sugar/d (cocoa group) for 12 wk. Blood samples were collected before the study and 12 wk after intake of the test drinks. Plasma lipids, LDL oxidative susceptibility, and urinary oxidative stress markers were measured. RESULTS: At 12 wk, we measured a 9% prolongation from baseline levels in the lag time of LDL oxidation in the cocoa group. This prolongation in the cocoa group was significantly greater than the reduction measured in the control group (-13%). A significantly greater increase in plasma HDL cholesterol (24%) was observed in the cocoa group than in the control group (5%). A negative correlation was observed between plasma concentrations of HDL cholesterol and oxidized LDL. At 12 wk, there was a 24% reduction in dityrosine from baseline concentrations in the cocoa group. This reduction in the cocoa group was significantly greater than the reduction in the control group (-1%). CONCLUSION: It is possible that increases in HDL-cholesterol concentrations may contribute to the suppression of LDL oxidation and that polyphenolic substances derived from cocoa powder may contribute to an elevation in HDL cholesterol.",
"title": "Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-c..."
},
{
"docid": "MED-4892",
"text": "OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.",
"title": "Egg Consumption and Risk of Type 2 Diabetes in Men and Women"
},
{
"docid": "MED-2823",
"text": "Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells.",
"title": "Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies"
},
{
"docid": "MED-5003",
"text": "Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor beta. In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) alpha and beta expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 microM and higher, with 50 microM genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 microM) increased cell viability and higher concentrations (25 and 50 microM) decreased it by 16.48+/-1.35% (P<.0001) and 50.68+/-1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERalpha and ERbeta expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens.",
"title": "Genistein inhibits differentiation of primary human adipocytes."
},
{
"docid": "MED-5085",
"text": "In this study, the adhesion factors examined were time between frying and coating, surface oil content, chip temperature, oil composition, NaCl size, NaCl shape, and electrostatic coating. Three different surface oil content potato chips, high, low, and no, were produced. Oils used were soybean, olive, corn, peanut, and coconut. After frying, chips were coated immediately, after 1 d, and after 1 mo. NaCl crystals of 5 different particle sizes (24.7, 123, 259, 291, and 388 microm) were coated both electrostatically and nonelectrostatically. Adhesion of cubic, dendritic, and flake crystals was examined. Chips were coated at different temperatures. Chips with high surface oil had the highest adhesion of salt, making surface oil content the most important factor. Decreasing chip temperature decreased surface oil and adhesion. Increasing time between frying and coating reduced adhesion for low surface oil chips, but did not affect high and no surface oil chips. Changing oil composition did not affect adhesion. Increasing salt size decreased adhesion. Salt size had a greater effect on chips with lower surface oil content. When there were significant differences, cubic crystals gave the best adhesion followed by flake crystals then dendritic crystals. For high and low surface oil chips, electrostatic coating did not change adhesion of small size crystals but decreased adhesion of large salts. For no surface oil content chips, electrostatic coating improved adhesion for small salt sizes but did not affect adhesion of large crystals.",
"title": "Factors dominating adhesion of NaCl onto potato chips."
},
{
"docid": "MED-4731",
"text": "BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.",
"title": "No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-..."
},
{
"docid": "MED-5148",
"text": "CONTEXT: Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear. OBJECTIVE: To determine effects of low doses of polyphenol-rich dark chocolate on BP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled, investigator-blinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006. INTERVENTION: Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate. MAIN OUTCOME MEASURES: Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols. RESULTS: From baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by -2.9 (1.6) mm Hg (P < .001) and diastolic BP by -1.9 (1.0) mm Hg (P < .001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (P < .001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers. CONCLUSIONS: Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00421499.",
"title": "Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial."
},
{
"docid": "MED-5153",
"text": "OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.",
"title": "Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function."
},
{
"docid": "MED-4911",
"text": "Arsenic exposures contribute significantly to the burden of preventable disease worldwide, specifically related to increased risks of cancer, diabetes, and cardiovascular disease. Most exposures are associated with natural contamination of groundwater, which is difficult to mitigate when these sources are used for drinking water. An anthropogenic source of arsenic exposure stems from the widespread use of arsenical drugs in food-animal production in the United States and China, among many countries. This use results in residual contamination of food products from animals raised with the drugs, as well as environmental contamination associated with disposal of wastes from these animals. Land disposal of these wastes can contaminate surface and ground water, and the conversion of animal wastes into fertilizer pellets for home use as well as the introduction of animal waste incinerators may increase opportunities for exposure. As an intentional additive to animal feed, use of arsenical drugs is a preventable source of human exposure. The domestic practice of using these drugs in poultry production has been the subject of media attention and limited research, though the use of these drugs in domestic swine production and in the rapidly growing foreign animal production industry remains largely uncharacterized. This continued expansion of arsenical drug use may likely increase the burden of global human arsenic exposure and risk.",
"title": "The environmental and public health risks associated with arsenical use in animal feeds."
},
{
"docid": "MED-5110",
"text": "Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.",
"title": "Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?"
},
{
"docid": "MED-2810",
"text": "Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be \"Curecumin\".",
"title": "Curcumin as \"Curecumin\": from kitchen to clinic."
},
{
"docid": "MED-5089",
"text": "BACKGROUND: Acrylamide, a probable human carcinogen, was recently detected in various heat-treated carbohydrate-rich foods. Epidemiologic studies on the relation with cancer have been few and largely negative. OBJECTIVE: We aimed to prospectively examine the association between dietary acrylamide intake and renal cell, bladder, and prostate cancers. DESIGN: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women aged 55-69 y. At baseline (1986), a random subcohort of 5000 participants was selected for a case-cohort analysis approach using Cox proportional hazards analysis. Acrylamide intake was assessed with a food-frequency questionnaire at baseline and was based on chemical analysis of all relevant Dutch foods. RESULTS: After 13.3 y of follow-up, 339, 1210, and 2246 cases of renal cell, bladder, and prostate cancer, respectively, were available for analysis. Compared with the lowest quintile of acrylamide intake (mean intake: 9.5 microg/d), multivariable-adjusted hazard rates for renal cell, bladder, and prostate cancer in the highest quintile (mean intake: 40.8 microg/d) were 1.59 (95% CI: 1.09, 2.30; P for trend = 0.04), 0.91 (95% CI: 0.73, 1.15; P for trend = 0.60), and 1.06 (95% CI: 0.87, 1.30; P for trend = 0.69), respectively. There was an inverse nonsignificant trend for advanced prostate cancer in never smokers. CONCLUSIONS: We found some indications for a positive association between dietary acrylamide and renal cell cancer risk. There were no positive associations with bladder and prostate cancer risk.",
"title": "Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer."
},
{
"docid": "MED-2322",
"text": "The global demand for more affordable therapeutics and concerns about side effects of commonly used drugs are refocusing interest on Eastern traditional medicines, particularly those of India and China.",
"title": "From exotic spice to modern drug?"
},
{
"docid": "MED-5087",
"text": "Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted. (c) 2008 Wiley-Liss, Inc.",
"title": "Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study."
},
{
"docid": "MED-2489",
"text": "A historical view on how our agricultural systems evolved and how they are contributing to obesity and disease.",
"title": "Agricultural policies, food and public health"
},
{
"docid": "MED-5150",
"text": "A single-dose ingestion of flavanol-rich cocoa acutely reverses endothelial dysfunction. To investigate the time course of endothelial function during daily consumption of high-flavanol cocoa, we determined flow-mediated dilation (FMD) acutely (for up to 6 hours after single-dose ingestion) and chronically (administration for 7 days). The study population represented individuals with smoking-related endothelial dysfunction; in addition to FMD, plasma nitrite and nitrate were measured. The daily consumption of a flavanol-rich cocoa drink (3 x 306 mg flavanols/d) over 7 days (n=6) resulted in continual FMD increases at baseline (after overnight fast and before flavanol ingestion) and in sustained FMD augmentation at 2 hours after ingestion. Fasted FMD responses increased from 3.7 +/- 0.4% on day 1 to 5.2 +/- 0.6%, 6.1 +/- 0.6%, and 6.6 +/- 0.5% (each P < 0.05) on days 3, 5, and 8, respectively. FMD returned to 3.3 +/- 0.3% after a washout week of cocoa-free diet (day 15). Increases observed in circulating nitrite, but not in circulating nitrate, paralleled the observed FMD augmentations. The acute, single-dose consumption of cocoa drinks with 28 to 918 mg of flavanols led to dose-dependent increases in FMD and nitrite, with a maximal FMD at 2 hours after consumption. The dose to achieve a half-maximal FMD response was 616 mg (n=6). Generally applied biomarkers for oxidative stress (plasma, MDA, TEAC) and antioxidant status (plasma ascorbate, urate) remained unaffected by cocoa flavanol ingestion. The daily consumption of flavanol-rich cocoa has the potential to reverse endothelial dysfunction in a sustained and dose-dependent manner.",
"title": "Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week."
},
{
"docid": "MED-4730",
"text": "We successfully optimized an analytical method using gel permeation chromatography followed by direct sample introduction comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry to quantify multiple groups of targeted persistent organic pollutants and halogenated natural products (HNPs) simultaneously in fish oil samples. This new method has a wider analytical scope than the traditional approach to use multiple methods to cover each class of compounds. Our analysis revealed that the relatively more volatile and lighter organic compounds, such as polychlorinated biphenyls (PCBs), organochlorine pesticides, and other smaller organohalogen compounds, were still present in two brands of \"PCB-free\" cod liver oils, albeit at much lower levels than in an untreated commercial sample. Moreover, the less volatile organic compounds, such as polybrominated diphenyl ethers and brominated HNPs, were detected at similar levels in all three cod liver oils. This suggests that the commercial molecular distillation treatment used for removal of organic/inorganic toxic contaminants is only effective for the lighter organic contaminants.",
"title": "Simultaneous quantitation of multiple classes of organohalogen compounds in fish oils with direct sample introduction comprehensive two-dimensional..."
},
{
"docid": "MED-4943",
"text": "Fish and seal oil dietary supplements, marketed to be rich in omega-3 fatty acids, are frequently consumed by Canadians. Samples of these supplements (n = 30) were collected in Vancouver, Canada, between 2005 and 2007. All oil supplements were analyzed for polychlorinated biphenyls (PCBs) and organochlorine insecticides (OCs) and each sample was found to contain detectable residues. The highest SigmaPCB and SigmaDDT (1,1,1-trichloro-di-(4-chlorophenyl)ethane) concentrations (10400 ng/g and 3310 ng/g, respectively) were found in a shark oil sample while lowest levels were found in supplements prepared using mixed fish oils (anchovy, mackerel, and sardine) (0.711 ng SigmaPCB/g and 0.189 ng SigmaDDT/g). Mean SigmaPCB concentrations in oil supplements were 34.5, 24.2, 25.1, 95.3, 12.0, 5260, 321, and 519 ng/g in unidentified fish, mixed fish containing no salmon, mixed fish with salmon, salmon, vegetable with mixed fish, shark, menhaden (n = 1), and seal (n = 1), respectively. Maximum concentrations of the other OCs were generally observed in the seal oil. The hexachlorinated PCB congeners were the dominant contributors to SigmaPCB levels, while SigmaDDT was the greatest contributor to organochlorine levels. Intake estimates were made using maximum dosages on manufacturers' labels and results varied widely due to the large difference in residue concentrations obtained. Average SigmaPCB and SigmaDDT intakes were calculated to be 736 +/- 2840 ng/d and 304 +/- 948 ng/d, respectively.",
"title": "Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides."
},
{
"docid": "MED-4893",
"text": "Background Prospective studies evaluating associations between food intake and risk of heart failure (HF) in diverse populations are needed. Objectives Relationships between incident HF (death or hospitalization) and intake of seven food categories (whole grains, fruits/vegetables, fish, nuts, high-fat dairy, eggs, red meat) were investigated in an observational cohort of 14,153 African-American and white adults, age 45 to 64 years, sampled from four US communities. Methods Between baseline (1987–1989) and Exam 3 (1993–1995), dietary intake was based on responses to a 66-item food frequency questionnaire administered at baseline; thereafter, intake was based on averaged baseline and Exam 3 responses. Hazard ratios (HR [95% CI]) for HF were calculated per 1–daily serving difference in food group intake. Results During a mean of 13 years, 1,140 HF hospitalizations were identified. After multivariable adjustment (energy intake, demographics, lifestyle factors, prevalent cardiovascular disease, diabetes, hypertension), HF risk was lower with greater whole-grain intake (0.93 [0.87, 0.99]), but HF risk was higher with greater intake of eggs (1.23 [1.08, 1.41]) and high-fat dairy (1.08 [1.01, 1.16]). These associations remained significant independent of intakes of the five other food categories, which were not associated with HF. Conclusions In this large, population-based sample of African-American and white adults, whole-grain intake was associated with lower HF risk, whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders.",
"title": "Incident Heart Failure Is Associated with Lower Whole-Grain Intake and Greater High-Fat Dairy and Egg Intake in the Atherosclerosis Risk in Communities (ARIC) Study"
},
{
"docid": "MED-5062",
"text": "BACKGROUND: We undertook a randomised, double-blinded, placebo-controlled, crossover trial to test whether intake of artificial food colour and additives (AFCA) affected childhood behaviour. METHODS: 153 3-year-old and 144 8/9-year-old children were included in the study. The challenge drink contained sodium benzoate and one of two AFCA mixes (A or B) or a placebo mix. The main outcome measure was a global hyperactivity aggregate (GHA), based on aggregated z-scores of observed behaviours and ratings by teachers and parents, plus, for 8/9-year-old children, a computerised test of attention. This clinical trial is registered with Current Controlled Trials (registration number ISRCTN74481308). Analysis was per protocol. FINDINGS: 16 3-year-old children and 14 8/9-year-old children did not complete the study, for reasons unrelated to childhood behaviour. Mix A had a significantly adverse effect compared with placebo in GHA for all 3-year-old children (effect size 0.20 [95% CI 0.01-0.39], p=0.044) but not mix B versus placebo. This result persisted when analysis was restricted to 3-year-old children who consumed more than 85% of juice and had no missing data (0.32 [0.05-0.60], p=0.02). 8/9-year-old children showed a significantly adverse effect when given mix A (0.12 [0.02-0.23], p=0.023) or mix B (0.17 [0.07-0.28], p=0.001) when analysis was restricted to those children consuming at least 85% of drinks with no missing data. INTERPRETATION: Artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.",
"title": "Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled..."
},
{
"docid": "MED-2783",
"text": "Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
"title": "Multitargeting by turmeric, the golden spice: From kitchen to clinic."
},
{
"docid": "MED-2323",
"text": "Low molecular weight phenols of plant origin are undoubtedly semiochemicals although not all of them can be easily classified as typical allelochemicals, which straightforwardly benefit the releaser. We have selected and surveyed this particular class of secondary metabolites, which shares high chemical reactivity with intrinsic biocompatibility and affinity for variety of molecular targets gained through evolution, because their suitability as prospective lead compounds for medicinal chemistry seems high but relatively unexplored. In particular, plant phenolics could be perceived as a natural product library, which contains privileged scaffolds, as evidenced by examples of endogenous phenols, phytochemicals containing aryl hydroxyl groups and phenolic synthetic drugs. It is postulated that application of bio-chemo-informatic tools to such library can be helpful in pulling out new drug candidates as well as in validating ADMET compatibility and suitability of the old ones. After short survey of structural diversity represented by plant phenolics, we focus on the compounds which either have obvious dietary significance or rich record of pharmacological studies, or both. It can be seen that apart from growing use of phytochemicals in dietary supplements, slow progress through clinical trials towards new drug registration is observed in that category of natural products. Such waste of resources on the way of transformation from renewable materials to high tech/high value products aimed for improved human healthcare is deplorable and should be reformed in name of sustainability. We attempt to answer the question why popular plant phenolics with well established health benefits and reasonably well recognized molecular pharmacology (such as: catechins, curcumin, resveratrol, quercetin and its glycosides, genistein, silymarin) have difficulties in attaining registered drug or even IND level.",
"title": "Plant phenolics as drug leads -- what is missing?"
},
{
"docid": "MED-5088",
"text": "Potato products contain high amounts of acrylamide, which sometimes exceeds the concentration of 1 mg/L. However, many strategies for acrylamide reduction in potato products are possible. In this work, the different approaches for reducing acrylamide formation have been reviewed, keeping in mind that in the application of strategies for acrylamide formation, the main criteria to be maintained are the overall organoleptic and nutritional qualities of the final product.",
"title": "Mitigation strategies to reduce acrylamide formation in fried potato products."
},
{
"docid": "MED-2809",
"text": "Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.",
"title": "Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials"
},
{
"docid": "MED-5063",
"text": "Evidence supports a trial period of eliminating colourings and preservatives from the diet",
"title": "Food additives and hyperactivity"
},
{
"docid": "MED-5147",
"text": "There has been considerable work on the relationships between nutrition and the immune response, particularly on studies that have focused on adaptive responses. There is increasing recognition of the importance of innate immunity in host protection and initiation of cytokine networks. In this study, we examined the effect of select cocoa flavanols and procyanidins on innate responses in vitro. Peripheral blood mono-nuclear cells (PBMCs), as well as purified monocytes and CD4 and CD8 T cells, were isolated from healthy volunteers and cultured in the presence of cocoa flavanol fractions that differ from another by the degree of flavanol polymerization: short-chain flavanol fraction (SCFF), monomers to pentamers; and long-chain flavanol fraction (LCFF), hexamers to decamers. Parallel investigations were also done with highly purified flavanol monomers and procyanidin dimers. The isolated cells were then challenged with lipopolysaccharide (LPS) with quantitation of activation using CD69 and CD83 expression and analysis of secreted tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, and granulocyte macrophage colony-stimulating factor (GM-CSF). The chain length of flavanol fractions had a significant effect on cytokine release from both unstimulated and LPS-stimulated PBMCs. For example, there was a striking increase of LPS-induced synthesis of IL-1beta, IL-6, IL-10, and TNF-alpha in the presence of LCFF. LCFF and SCFF, in the absence of LPS, stimulated the production of GM-CSF. In addition, LCFF and SCFF increased expression of the B cell markers CD69 and CD83. There were also unique differential responses in the mononuclear cell populations studied. We conclude that the oligomers are potent stimulators of both the innate immune system and early events in adaptive immunity.",
"title": "Immune effects of cocoa procyanidin oligomers on peripheral blood mononuclear cells."
},
{
"docid": "MED-5152",
"text": "OBJECTIVES: Strong evidence has secured aging as a powerful predictor of both cardiovascular risk and endothelial dysfunction, yet specific treatment is not available. We tested the hypothesis that vascular responsiveness to flavanol-rich cocoa increases with advancing age. We have previously shown that flavanol-rich cocoa induced peripheral vasodilation, improving endothelial function via a nitric oxide (NO)-dependent mechanism. METHODS: We studied blood pressure and peripheral arterial responses to several days of cocoa in 15 young (< 50 years) and 19 older (> 50) healthy subjects. RESULTS: The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME) induced significant pressor responses following cocoa administration only among the older subjects: systolic blood pressure (SBP) rose 13 +/- 4 mmHg, diastolic blood pressure (DBP) 6 +/- 2 mmHg (P = 0.008 and 0.047, respectively); SBP was significantly higher in the older subjects (P < 0.05). Flow-mediated vasodilation, measured by tonometry in the finger, was enhanced with flavanol-rich cocoa in both groups, but significantly more so among the old (P = 0.01). Finally, basal pulse wave amplitude (PWA) followed a similar pattern. Four to six days of flavanol-rich cocoa caused a rise in PWA in both groups. At peak vasodilation following acute cocoa intake on the final day, both groups showed a further, significant rise in PWA. The response in the older subjects was more robust; P < 0.05. L-NAME significantly reversed dilation in both groups. CONCLUSIONS: Flavanol-rich cocoa enhanced several measures of endothelial function to a greater degree among older than younger healthy subjects. Our data suggest that the NO-dependent vascular effects of flavanol-rich cocoa may be greater among older people, in whom endothelial function is more disturbed.",
"title": "Aging and vascular responses to flavanol-rich cocoa."
},
{
"docid": "MED-2488",
"text": "Cardiovascular diseases (CVD) cost Americans billions of dollars per year. High cholesterol levels, which are closely related to dietary habits, are a major contributor to CVD. In this article, we study whether changes in food prices are related to cholesterol levels and whether taxes or subsidies on particular foods would be effective in lowering cholesterol levels and, consequently, CVD costs. We find that prices of vegetables, processed foods, whole milk and whole grains are significantly associated with blood cholesterol levels. Having analyzed the costs and benefits of government interventions, we find that a subsidy of vegetables and whole grains would be an efficient way to reduce CVD expenditures. Published by Elsevier B.V.",
"title": "Food prices and blood cholesterol."
},
{
"docid": "MED-4729",
"text": "In East Greenland polar bears (Ursus maritimus), anthropogenic organohalogen compounds (OHCs) (e.g., polychlorinated biphenyls, dichlorodiphenyltrichloroethane, and polybrominated diphenyl ethers) contributed to renal lesions and are believed to reduce bone mineral density. Because OHCs are also hepatotoxic, we investigated liver histology of 32 subadult, 24 adult female, and 23 adult male East Greenland polar bears sampled during 1999–2002. Light microscopic changes consisted of nuclear displacement from the normal central cytoplasmic location in parenchymal cells, mononuclear cell infiltrations (mainly portally and as lipid granulomas), mild bile duct proliferation accompanied by fibrosis, and fat accumulation in hepatocytes and pluripotent Ito cells. Lipid accumulation in Ito cells and bile duct hyperplasia accompanied by portal fibrosis were correlated to age, whereas no changes were associated with either sex or season (summer vs. winter). For adult females, hepatocytic intracellular fat increased significantly with concentrations of the sum of hexachlorocyclohexanes, as was the case for lipid granulomas and hexachlorobenzene in adult males. Based on these relationships and the nature of the chronic inflammation, we suggest that these findings were caused by aging and long-term exposure to OHCs. Therefore, these changes may be used as biomarkers for OHC exposure in wildlife and humans. To our knowledge, this is the first time liver histology has been evaluated in relation to OHC concentrations in a mammalian wildlife species, and the information is important to future polar bear conservation strategies and health assessments of humans relying on OHC-contaminated food resources.",
"title": "Do Organohalogen Contaminants Contribute to Histopathology in Liver from East Greenland Polar Bears (Ursus maritimus)?"
},
{
"docid": "MED-4732",
"text": "Background Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives In this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis. Methods PCB-77 or 2,2′,4,4,5,5′-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR)−/− mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE−/− mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis. Results Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol–3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor γ, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR−/− mice. ApoE−/− mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. Conclusions Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.",
"title": "Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis"
},
{
"docid": "MED-5004",
"text": "BACKGROUND: Cross-sectional studies have shown that vegetarians and vegans are leaner than omnivores. Longitudinal data on weight gain in these groups are sparse. OBJECTIVE: We investigated changes in weight and body mass index (BMI) over a 5-year period in meat-eating, fish-eating, vegetarian, and vegan men and women in the UK. DESIGN: Self-reported anthropometric, dietary and lifestyle data were collected at baseline in 1994-1999 and at follow-up in 2000-2003; the median duration of follow-up was 5.3 years. SUBJECTS: A total of 21,966 men and women participating in Oxford arm of the European Prospective Investigation into Cancer and Nutrition aged 20-69 years at baseline. RESULTS: The mean annual weight gain was 389 (SD 884) g in men and 398 (SD 892) g in women. The differences between meat-eaters, fish-eaters, vegetarians and vegans in age-adjusted mean BMI at follow-up were similar to those seen at baseline. Multivariable-adjusted mean weight gain was somewhat smaller in vegans (284 g in men and 303 g in women, P<0.05 for both sexes) and fish-eaters (338 g, women only, P<0.001) compared with meat-eaters. Men and women who changed their diet in one or several steps in the direction meat-eater --> fish-eater --> vegetarian --> vegan showed the smallest mean annual weight gain of 242 (95% CI 133-351) and 301 (95% CI 238-365) g, respectively. CONCLUSION: During 5 years follow-up, the mean annual weight gain in a health-conscious cohort in the UK was approximately 400 g. Small differences in weight gain were observed between meat-eaters, fish-eaters, vegetarians and vegans. Lowest weight gain was seen among those who, during follow-up, had changed to a diet containing fewer animal food.",
"title": "Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-Oxford."
}
] |
[
{
"docid": "MED-1451",
"text": "OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. METHODS: Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. RESULTS: A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. CONCLUSIONS: Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.",
"title": "The link between workforce health and safety and the health of the bottom line: tracking market performance of companies that nurture a \"culture of..."
},
{
"docid": "MED-3087",
"text": "Sixty random samples of bulk farm milk, market milk, locally manufactured processed cheese, and milk powder were collected to be analyzed for aluminum (Al) concentration using graphite furnace atomic absorption spectrometry (GFAAS). The results were compared with provisional acceptable permissible limits (PAPLs). The maximum estimated dietary intake (MEDI) of Al for the examined samples was calculated. In addition, an experimental study was conducted to determine the possible leaching of Al from cookware in milk during boiling. The obtained results showed that Al concentration in examined bulk farm milk samples was found to be negligible. In contrast, market milk revealed higher concentration, 65.0% of the examined samples were above the PAPLs. The results revealed significant difference of Al concentration among them. The Al levels in processed cheese wrapped in Al foil were significantly higher than those found in samples packed in glass containers with a significant difference of Al concentration between them. Also, 20% of the examined milk powder samples exceeded the PAPLs (0.01 to 0.4 mg/kg). The MEDI for Al in bulk farm milk, control market milk, market milk boiled in Al cookware, market milk boiled in stainless-steel cookware, processed cheese wrapped in Al foil, processed cheese packed in glass containers, and milk powder were calculated as 3.0%, 61.0%, 63.0%, 61.0%, 428.0%, 220.0%, and 166.0% from \"PTDI,\" respectively. The results of the experimental study showed no marked significant differences of Al concentration between market milk (control group) and those boiled in Al cookware, as well as to those boiled in stainless-steel cookware. PRACTICAL APPLICATION: The results of the present study indicate that Al level in milk kept in Al containers and dairy products packed in Al foil is beyond the permissible limits, suggesting health hazard. Therefore, all milk cans should be constructed of stainless steel, prevent the entrance of tap water into milk, and the processed cheese should be packed in glass containers and not wrapped in Al foil. Leaching of Al increased to a significant percent more during storage than during boiling, so milk should be kept in stainless steel or glass containers in the refrigerator.",
"title": "Prevalence and public health significance of aluminum residues in milk and some dairy products."
},
{
"docid": "MED-4727",
"text": "The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.",
"title": "Dietary intake of organotin compounds in Finland: a market-basket study."
},
{
"docid": "MED-3490",
"text": "Liquid dietary supplements represent a fast growing market segment, including botanically-based beverages containing mangosteen, acai, and noni. These products often resemble fruit juice in packaging and appearance, but may contain pharmacologically active ingredients. While little is known about the human health effects or safety of consuming such products, manufacturers make extensive use of low-quality published research to promote their products. This report analyzes the science-based marketing claims of two of the most widely consumed mangosteen liquid dietary supplements, and compares them to the findings of the research being cited. The reviewer found that analyzed marketing claims overstate the significance of findings, and fail to disclose severe methodological weaknesses of the research they cite. If this trend extends to other related products that are similarly widely consumed, it may pose a public health threat by misleading consumers into assuming that product safety and effectiveness are backed by rigorous scientific data.",
"title": "Science in Liquid Dietary Supplement Promotion: The Misleading Case of Mangosteen Juice"
},
{
"docid": "MED-4366",
"text": "BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail (\"junk mail\"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.",
"title": "The marketing of dietary supplements in North America: the emperor is (almost) naked."
},
{
"docid": "MED-1760",
"text": "OBJECTIVE: To examine the effects of cumulative, real-world marketing and brand exposures on young children by testing the influence of branding from a heavily marketed source on taste preferences. DESIGN: Experimental study. Children tasted 5 pairs of identical foods and beverages in packaging from McDonald's and matched but unbranded packaging and were asked to indicate if they tasted the same or if one tasted better. SETTING: Preschools for low-income children. PARTICIPANTS: Sixty-three children (mean +/- SD age, 4.6 +/- 0.5 years; range, 3.5-5.4 years). MAIN EXPOSURE: Branding of fast foods. OUTCOME MEASURES: A summary total taste preference score (ranging from -1 for the unbranded samples to 0 for no preference and +1 for McDonald's branded samples) was used to test the null hypothesis that children would express no preference. RESULTS: The mean +/- SD total taste preference score across all food comparisons was 0.37 +/- 0.45 (median, 0.20; interquartile range, 0.00-0.80) and significantly greater than zero (P<.001), indicating that children preferred the tastes of foods and drinks if they thought they were from McDonald's. Moderator analysis found significantly greater effects of branding among children with more television sets in their homes and children who ate food from McDonald's more often. CONCLUSION: Branding of foods and beverages influences young children's taste perceptions. The findings are consistent with recommendations to regulate marketing to young children and also suggest that branding may be a useful strategy for improving young children's eating behaviors.",
"title": "Effects of fast food branding on young children's taste preferences."
},
{
"docid": "MED-4964",
"text": "The microbial quality of raw fillets of aquacultured catfish, salmon, tilapia, and trout was evaluated. A total of 272 fillets from nine local and nine Internet retail markets were tested. Mean values were 5.7 log CFU/g for total aerobic mesophiles, 6.3 log CFU/g for psychrotrophs, and 1.9 log most probable number (MPN) per gram for coliforms. Differences in these microbial levels between the two kinds of markets and among the four types of fish were not significant (P > 0.05), except that Internet trout fillets had about 0.8-log higher aerobic mesophiles than did trout fillets purchased locally. Although Escherichia coli was detected in 1.4, 1.5, and 5.9% of trout, salmon, and tilapia, respectively, no sample had > or = 1.0 log MPN/g. However, E. coli was found in 13.2% of catfish, with an average of 1.7 log MPN/g. About 27% of all fillets had Listeria spp., and a positive correlation between the prevalence of Listeria spp. and Listeria monocytogenes was observed. Internet fillets had a higher prevalence of both Listeria spp. and L. monocytogenes than did those fillets purchased locally. L. monocytogenes was present in 23.5% of catfish but in only 5.7, 10.3, and 10.6% of trout, tilapia, and salmon, respectively. Salmonella and E. coli O157 were not found in any sample. A follow-up investigation using catfish operation as a model revealed that gut waste exposed during evisceration is a potential source of coliforms and Listeria spp.",
"title": "Microbial quality of raw aquacultured fish fillets procured from Internet and local retail markets."
},
{
"docid": "MED-1959",
"text": "Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.",
"title": "Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source."
},
{
"docid": "MED-2751",
"text": "Recent data on fishmeal and fish-oil supply are presented identifying key producer countries and raw material sources and distinguishing between whole fish and by-products. The conversion of these raw materials into marine ingredients is discussed and global volumes presented. This is followed by a summary of the main countries using these marine ingredients over recent years. Uses of fishmeal and fish-oil by market segment are then presented. From this, a global mass balance of inputs and outputs is derived which allows the calculation of the input-to-output ratios (fish in:fish out; FIFO) for the main aquaculture production types to be made. Current areas of focus by the industry include the need to demonstrate sustainable practice, more strategic use of marine ingredients, greater use of fishery and land-animal by-products as well as vegetable substitutes, and novel sources of essential omega-3 fats, notably the long-chain polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Implications are drawn for future supply prospects of fishmeal and fish-oil and their future role in aquaculture, agriculture and human health. © 2013 The Fisheries Society of the British Isles.",
"title": "Global fishmeal and fish-oil supply: inputs, outputs and markets."
},
{
"docid": "MED-2016",
"text": "BACKGROUND: Coeliac disease is a common, autoimmune disorder, for which the only treatment is lifelong adherence to a gluten-free diet. This study evaluates the economic burden of adhering to a gluten-free diet. METHODS: A market basket of products identified by name brand, weight or package size for both regular wheat-based products and gluten-free counterparts was developed. The differences in price between purchase venues, both type of store (general grocery store, an upscale grocery store and a health food store and four internet-based grocery sites) and region was also analysed. RESULTS: Availability of gluten-free products varied between the different venues, regular grocery stores carried 36%, while upscale markets carried 41%, and health food stores 94%, compared with 100% availability on the internet. Overall, every gluten-free product was more expensive than their wheat-based counterpart (P <or= 0.05). Bread and pasta was twice as expensive as their wheat-based counterparts. Cost was affected more by shopping venue than geographic location. CONCLUSIONS: This study demonstrated that gluten-free foods have poor availability and are more expensive than their gluten-containing counterparts. The impact of these findings on dietary compliance and the quality of life needs to be addressed.",
"title": "Economic burden of a gluten-free diet."
},
{
"docid": "MED-1743",
"text": "This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional \"chemical\" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating \"substantial non-equivalence\" in compositional characteristics for 'ready-to-market' soybeans. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.",
"title": "Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans."
},
{
"docid": "MED-1179",
"text": "The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture's MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term \"organic,\" reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.",
"title": "Organic foods: health and environmental advantages and disadvantages."
},
{
"docid": "MED-1218",
"text": "There has been a recent increase in community-associated infections linked to methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile. It is established that both pathogens can be recovered from retail pork, although it is unclear to what degree contamination is acquired at the farm in comparison to that acquired during processing. To address this gap, the following study reports on the carriage of MRSA and C. difficile on pigs from birth through to the end of processing. C. difficile was isolated from 28 (93%) of 30 pigs at 1 day of age, but prevalence declined sharply to 1 of 26 by market age (188 days). MRSA prevalence peaked at 74 days of age, with 19 (68%) of 28 pigs testing positive, but declined to 3 of 26 at 150 days of age, with no pig being detected as positive at market age. At the processing facility, C. difficile was isolated from the holding area, with a single carcass testing positive for the pathogen at preevisceration. MRSA was primarily isolated from nasal swabs with 8 (31%) carcasses testing positive at postbleed, which increased to 14 (54%) positive at postscald tanks. Only one carcass (sampled at postbleed) tested positive for MRSA, with no recovery of the pathogen from environmental samples taken. C. difficile ribotype 078 predominated in the longitudinal portion of the study, accounting for all of the 68 isolates recovered from pigs. Only three C. difficile isolates, which were identified as ribotype 078, were recovered at the slaughterhouse. MRSA spa type 539 (t034) predominated in pigs on the farm and samples taken at the slaughterhouse, accounting for 80% of all isolates recovered. The study demonstrated that both C. difficile and MRSA acquired on the farm can be transferred through to processing, although no evidence for significant cross-contamination between carcasses or the slaughterhouse environment was evident.",
"title": "Longitudinal study of Clostridium difficile and Methicillin-resistant Staphylococcus aureus associated with pigs from weaning through to the end of..."
},
{
"docid": "MED-1977",
"text": "Reports have documented colonization of swine in Europe, North America and more recently in China with livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA). Contamination of pig farmers, veterinarians and abattoir workers with these strains has been observed. However, although contamination levels of 10% of retail pork were reported from the Netherlands and Canada, there are limited data of contamination rates of workers handling raw meat. We investigated the rates of MRSA contamination of local butchers working in wet markets, where recently slaughtered pigs are cut up. Nasal swabs collected from 300 pork butchers at markets throughout Hong Kong were enriched in brain heart infusion broth with 5% salt and cultured on MRSASelect(®) . Isolates were confirmed as Staphylococcus aureus and susceptibility testing performed. The presence of mecA was confirmed, SCCmec and spa type determined and relatedness investigated by PFGE. Subjects completed a questionnaire on MRSA carriage risk factors. Seventeen samples (5.6%) yielded MRSA, 15 harbouring SCCmec IVb. Ten strains were t899 (CC9), previously reported from local pig carcasses. Five strains were healthcare associated: SCCmec type II, t701(CC6), colonizing two subjects at the same establishment, and single isolates of t008 (CC8), t002 (CC5) and t123 (CC45). The remaining isolates were t359 (CC97), previously reported from buffaloes, and t375 (CC5), reported from bovine milk. None of these butchers reported recent hospitalization or a healthcare worker in the family. Two had recently received antibiotics, one for a skin infection. Four reported wound infections within the last year. All were exposed to meat for >9 h per day. Carriage of MRSA was higher in butchers than in the general community. Although five strains were probably of healthcare origin, the high incidence of t899 (CC9) suggests that cross-contamination from pork occurs frequently. Washing of hands after touching raw pork is advised. © 2012 Blackwell Verlag GmbH.",
"title": "Colonization of butchers with livestock-associated methicillin-resistant Staphylococcus aureus."
},
{
"docid": "MED-4531",
"text": "Traditional herbal preparations used in Ayurveda, traditional Chinese medicine, traditional Tibetan medicine, and other Asian traditional medicine systems may contain significant amounts of mercury, arsenic or lead. Though deliberately incorporated in Asian traditional herbal preparations for therapeutic purposes, these constituents have caused intoxications worldwide. The aim of this study was therefore to determine mercury, arsenic, and lead levels in Asian traditional herbal preparations on the Dutch market. A total of 292 traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine were sampled between 2004 and 2007. Samples were mostly multi-ingredient traditional herbal preparations containing herbs and minerals. The labeling of less than 20% of the traditional herbal preparations suggested the presence of mercury, arsenic or lead. These elements were shown by inductively coupled mass spectrometry (ICP-MS) in 186 (64%) of 292 traditional herbal preparations. Estimated weekly mercury, arsenic, and lead intake levels were calculated for each traditional herbal preparation from the analytically determined concentrations and the recommended dose. A total of 59 traditional herbal preparations (20%) were likely to result in intakes of these elements significantly exceeding safety limits. Of these 59 traditional herbal preparations, intake estimates for 50 traditional herbal preparations significantly exceeded the safety limit for mercury (range = 1.4-1747 mg week(-1)); intake estimates for 26 traditional herbal preparations significantly exceeded the safety limit for arsenic (range = 0.53-427 mg week(-1)) and intake estimates for eight traditional herbal preparations were significantly above the safety limit for lead (range = 2.6-192 mg week(-1)). It is concluded that the mercury, arsenic, and lead contents of traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine remain a cause for concern and require strict control.",
"title": "Monitoring of mercury, arsenic, and lead in traditional Asian herbal preparations on the Dutch market and estimation of associated risks."
},
{
"docid": "MED-4747",
"text": "In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters (\"anabolics\") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters (\"hormones\") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of \"legal natural levels\" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of \"pour on\" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in \"smart\" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of \"highly\" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily \"normal\" diet.",
"title": "Hormonal growth promoting agents in food producing animals."
},
{
"docid": "MED-5022",
"text": "The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.",
"title": "Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana."
},
{
"docid": "MED-4922",
"text": "The discipline of glycobiology contributes to our understanding of human health and disease through research, most of which is published in peer-reviewed scientific journals. Recently, legitimate discoveries in glycobiology have been used as marketing tools to help sell plant extracts termed \"glyconutrients.\" The glyconutrient industry has a worldwide sales force of over half a million people and sells nearly half a billion dollars (USD) of products annually. Here we address the relationship between glyconutrients and glycobiology, and how glyconutrient claims may impact the public and our discipline.",
"title": "A \"glyconutrient sham\"."
},
{
"docid": "MED-5215",
"text": "Punctal and canalicular plugs are widely used for both temporary and permanent occlusion of the lacrimal puncta in dry eyes. There are many designs and materials available on the market. While their efficacy in improving dry eye symptoms is widely proven, the gamut of complications associated with these devices have never been subject to a general review, although there are numerous case series in the literature associated with one particular device. This review aims to examine the track record of a variety of plugs currently in use, to review the management of complications, and propose strategies for both the prevention of these complications and their treatment.",
"title": "A review of the complications of lacrimal occlusion with punctal and canalicular plugs."
},
{
"docid": "MED-3481",
"text": "The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer approaches for the treatment of obesity have involved inhibition of dietary triglyceride absorption via inhibition of pancreatic lipase (PL) as this is the major source of excess calories. Natural products provide a vast pool of PL inhibitors that can possibly be developed into clinical products. This article reviews various extracts and secondary metabolites from plants and microbial origin with PL inhibitory activity that can be focused for drug development programs.",
"title": "Pancreatic lipase inhibitors from natural sources: unexplored potential."
},
{
"docid": "MED-3693",
"text": "Probiotics are widely used to prevent and treat several diseases. Many commercial products are available worldwide. However, there is no clear international or local legislation about them and previous studies showed that most of the tested products are not in conformity with international guidelines. The aim of this study was to determine if products available in the USA market in 2009 were correctly labeled in terms of quantity of viable bacteria, identification of species and cross contamination by species not on the label. Disturbingly, we found that only 4 of 13 products (31%) were in accordance with label claims. Our results suggest the need for adequate control of probiotic production as well as periodical screenings by competent organizations to monitor the effect of storage on product quality.",
"title": "Microbiological evaluation of commercial probiotic products available in the USA in 2009."
},
{
"docid": "MED-3487",
"text": "Weight loss supplements often contain powerful pharmacoactive ingredients with the potential to cause harm. Trials used to determine product safety and effectiveness, meanwhile, tend to be small, of short duration, and frequently lack financial conflict of interest disclosures. These factors could conspire to place consumers at risk, especially when published research cited in advertising cloaks products with the suggestion that their safety and effectiveness have been proven by science. Examples of current and former weight loss products backed by potentially conflicted or low quality research include Metabolife-356, Hydroxycut, Xenadrine and LeptiCore. Published research, especially in the field of weight loss supplements, needs better conflict of interest disclosure, and regulators should consider how research findings are used in marketing claims.",
"title": "Science of weight loss supplements: Compromised by conflicts of interest?"
},
{
"docid": "MED-4491",
"text": "Dry-cured ham is a traditional product with a strong presence in markets in the Mediterranean area. It is very popular with European consumers and is of enormous economic importance for the meat industry in the Mediterranean area. Although the great palatability of ham largely outweighs other considerations, aspects relating to health and wellbeing are increasingly important factors in consumer decisions. The potential role of ham in a context of healthy nutrition has not been clearly elucidated, especially considering that origins and production methods of dry-cured hams can induce differences in composition. The object of this review was on the one hand to provide an analysis of the components of dry-cured ham and their role in a healthy diet, and on the other hand to suggest possible strategies for improving its nutritional composition. 2009 Elsevier Ltd. All rights reserved.",
"title": "Nutritional composition of dry-cured ham and its role in a healthy diet."
},
{
"docid": "MED-2673",
"text": "Transglutaminase is an enzyme that can be used to cross-link pieces of meat, fish or meat products. The resulting product gives the optical impression of an intact chunk of meat. The usage of transglutaminase as a food additive is permitted in some countries. However, its utilisation has to be declared to ensure transparency for consumers. This paper describes two orthogonal analytical methods suited for the detection of technological relevant transglutaminase concentrations (around 25 mg pure enzyme in 1 kg of product) in meat and meat products. The mass spectrometry-based approach relies on a previous digestion with Achromobacter lyticus protease and LC-MS/MS separation and detection. Sufficient selectivity was obtained by monitoring four different peptides. The orthogonal (complementary and independent), ELISA-based approach relies on two commercially available bacterial transglutaminase-specific antibodies, combined to a sandwich ELISA. The two methods were tested by analysing some 60 samples obtained from the market.",
"title": "Determination of microbial transglutaminase in meat and meat products."
},
{
"docid": "MED-4535",
"text": "Herbal formulations are getting popular throughout the world and commercialized extensively for various medicinal properties. WHO has emphasized the need for quality assurance of herbal products, including testing of heavy metals and pesticides residues. In view of WHO guidelines, single herbal drugs used in herbal formulations were collected from local market, for testing heavy metals and persistent pesticides residue. Therefore, in the present case, we have examined few local samples of certain herbs viz. Emblica officinalis, Terminalia chebula, Terminalia belerica, and Withania somnifera. The present studies were selected for estimation of four heavy metals namely Arsenic, Cadmium, Lead, and Mercury. Apart from these, pesticide residue Viz. Organochlorine pesticides, Organophosphorus pesticides, and Pyrethroids were analyzed in the four samples of single crude drugs. Heavy metals and pesticide residue were found below detection limits in all the samples.",
"title": "Detection of toxic heavy metals and pesticide residue in herbal plants which are commonly used in the herbal formulations."
},
{
"docid": "MED-4870",
"text": "Anatoxin-a is a potent neurotoxin produced by several species of cyanobacteria. This alkaloid may cause fatal intoxication to exposed organisms and this has raised concerns over the increasing popularity of food supplements containing cyanobacteria. These are being marketed with alleged health properties for animal and human consumption. These supplements most commonly contain the genera Spirulina (Arthrospira) and Aphanizomenon and their consumption represent a potential route for anatoxin-a exposure in cases where adequate quality control is not undertaken. In this work, several dietary supplements containing cyanobacteria from different commercial suppliers were evaluated for the presence of anatoxin-a by high performance liquid chromatography with fluorescence detection. Additionally, the presence of the previously derivatized anatoxin-a was confirmed by using Gas chromatography-mass spectrometry. A total of 39 samples were analysed in the study. Results showed that three of the samples (7.7%) contained anatoxin-a, at concentrations ranging from 2.50 to 33 microg g(-1). Quality control of cyanobacterial food supplements is required to avoid potential health effects in humans and animals.",
"title": "First detection of anatoxin-a in human and animal dietary supplements containing cyanobacteria."
},
{
"docid": "MED-1268",
"text": "Most amyotrophic lateral sclerosis (ALS) cases occur sporadically. Some environmental triggers have been implicated, including beta-methylamino-L-alanine (BMAA), a cyanobacteria produced neurotoxin. This study aimed to identify environmental risk factors common to three sporadic ALS patients who lived in Annapolis, Maryland, USA and developed the disease within a relatively short time and within close proximity to each other. A questionnaire was used to identify potential risk factors for ALS among the cohort of patients. One common factor among the ALS patients was the frequent consumption of blue crab. Samples of blue crab from the patients' local fish market were tested for BMAA using LC-MS/MS. BMAA was identified in these Chesapeake Bay blue crabs. We conclude that the presence of BMAA in the Chesapeake Bay food web and the lifetime consumption of blue crab contaminated with BMAA may be a common risk factor for sporadic ALS in all three patients. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Linking β-methylamino-L-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD."
},
{
"docid": "MED-2018",
"text": "A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.",
"title": "Spectrum of gluten-related disorders: consensus on new nomenclature and classification"
},
{
"docid": "MED-2143",
"text": "Many therapeutic agents had been used for the treatment of diabetes mellitus before insulin was discovered and several hundred plants have shown some extent of antidiabetic activity. This study tries to explore which agents were most widely used in Europe in the pre-insulin era. According to the scientific literature and the proprietary drug industry around 1900, more than 100 agents were considered to have hypoglycemic activity. Most of them seem to have been used only occasionally while some others were recommended and marketed to a large extent. Among the medicinal plants, Syzygium cumini (syn. S. jambolanum, Eugenia jambolana), Vaccinum myrtillus and Phaseolus sp. were most common, and other frequently used agents were opium, opium alkaloids, other alkaloids like quinine or Belladonna alkaloids, salicylates, alkaline substances like sodium (bi)carbonate and even strong poisons like arsenic or uranium salts. Syzygium jambolanum seed powder seems to be one of the most intensively studied antidiabetic agents of plant origin.",
"title": "Antidiabetic drugs used in Europe prior to the discovery of insulin."
},
{
"docid": "MED-2726",
"text": "The 2011 UN high-level meeting on non-communicable diseases (NCDs) called for multisectoral action including with the private sector and industry. However, through the sale and promotion of tobacco, alcohol, and ultra-processed food and drink (unhealthy commodities), transnational corporations are major drivers of global epidemics of NCDs. What role then should these industries have in NCD prevention and control? We emphasise the rise in sales of these unhealthy commodities in low-income and middle-income countries, and consider the common strategies that the transnational corporations use to undermine NCD prevention and control. We assess the effectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with these industries and conclude that unhealthy commodity industries should have no role in the formation of national or international NCD policy. Despite the common reliance on industry self-regulation and public-private partnerships, there is no evidence of their effectiveness or safety. Public regulation and market intervention are the only evidence-based mechanisms to prevent harm caused by the unhealthy commodity industries. Copyright © 2013 Elsevier Ltd. All rights reserved.",
"title": "Profits and pandemics: prevention of harmful effects of tobacco, alcohol, and ultra-processed food and drink industries."
}
] |
5110
|
Why does shorting a call option have potential for unlimited loss?
|
[
{
"docid": "281533",
"text": "\"You are likely making an assumption that the \"\"Short call\"\" part of the article you refer to isn't making: that you own the underlying stock in the first place. Rather, selling short a call has two primary cases with considerably different risk profiles. When you short-sell (or \"\"write\"\") a call option on a stock, your position can either be: covered, which means you already own the underlying stock and will simply need to deliver it if you are assigned, or else uncovered (or naked), which means you do not own the underlying stock. Writing a covered call can be a relatively conservative trade, while writing a naked call (if your broker were to permit such) can be extremely risky. Consider: With an uncovered position, should you be assigned you will be required to buy the underlying at the prevailing price. This is a very real cost — certainly not an opportunity cost. Look a little further in the article you linked, to the Option strategies section, and you will see the covered call mentioned there. That's the kind of trade you describe in your example.\"",
"title": ""
}
] |
[
{
"docid": "140371",
"text": "To expand on the comment made by @NateEldredge, you're looking to take a short position. A short position essentially functions as follows: Here's the rub: you have unlimited loss potential. Maybe you borrow a share and sell it at $10. Maybe in a month you still haven't closed the position and now the share is trading at $1,000. The share lender comes calling for their share and you have to close the position at $1,000 for a loss of $990. Now what if it was $1,000,000 per share, etc. To avoid this unlimited loss risk, you can instead buy a put option contract. In this situation you buy a contract that will expire at some point in the future for the right to sell a share of stock for $x. You get to put that share on to someone else. If the underlying stock price were to instead rise above the put's exercise price, the put will expire worthless — but your loss is limited to the premium paid to acquire the put option contract. There are all sorts of advanced options trades sometimes including taking a short or long position in a security. It's generally not advisable to undertake these sorts of trades until you're very comfortable with the mechanics of the contracts. It's definitely not advisable to take an unhedged short position, either by borrowing someone else's share(s) to sell or selling an option (when you sell the option you take the risk), because of the unlimited loss potential described above.",
"title": ""
},
{
"docid": "118633",
"text": "\"There are three ways to do this. So far the answers posted have only mentioned two. The three ways are: Selling short means that you borrow stock from your broker and sell it with the intent of buying it back later to repay the loan. As others have noted, this has unlimited potential losses and limited potential gains. Your profit or loss will go $1:$1 with the movement of the price of the stock. Buying a put option gives you the right to sell the stock at a later date on a price that you choose now. You pay a premium to have this right, and if the stock moves against you, you won't exercise your option and will lose the premium. Options move non-linearly with the price of the stock, especially when the expiration is far in the future. They probably are not for a beginner, although they can be powerful if used properly. The third option is a synthetic short position. You form this by simultaneously buying a put option and selling short a call option, both at the same strike price. This has a risk profile that is very much like the selling the stock short, but you can accomplish it entirely with stock options. Because you're both buying an selling, in theory you might even collect a small net premium when you open. You might ask why you'd do this given that you could just sell the stock short, which certainly seems simpler. One reason is that it is not always possible to sell the stock short. Recall that you have to borrow shares from your broker to sell short. When many people want to short the stock, brokers will run out of shares to loan. The stock is then said to be \"\"hard to borrow,\"\" which effectively prevents further short selling of the stock. In this case the synthetic short is still potentially possible.\"",
"title": ""
},
{
"docid": "307518",
"text": "\"The stock market is not a zero-sum game. Some parts are (forex, some option trading), but plain old stock trading is not zero sum. That is to say, if you were to invest \"\"at random\"\", you would on average make money. That's because the market as a whole makes money - it goes up over time (6-10% annually, averaged over time). That's because you're not just gambling when you buy a stock; you're actually contributing money to a company (directly or indirectly), which it uses to fund activities that (on average) make money. When you buy Caterpillar stock, you're indirectly funding Caterpillar building tractors, which they then sell for a profit, and thus your stock appreciates in value. While not every company makes a profit, and thus not every stock appreciates in true value, the average one does. To some extent, buying index funds is pretty close to \"\"investing at random\"\". It has a far lower risk quotient, of course, since you're not buying a few stocks at random but instead are buying all stocks in an index; but buying stocks from the S&P 500 at random would on average give the same return as VOO (with way more volatility). So for one, you definitely could do worse than 50/50; if you simply sold the market short (sold random stocks short), you would lose money over time on average, above and beyond the transaction cost, since the market will go up over time on average. Secondly, there is the consideration of limited and unlimited gains or losses. Some trades, specifically some option trades, have limited potential gains, and unlimited potential losses. Take for example, a simple call option. If you sell a naked call option - meaning you sell a call option but don't own the stock - for $100, at a strike price of $20, for 100 shares, you make money as long as the price of that stock is under $21. You have a potential to make $100, because that's what you sold it for; if the price is under $20, it's not exercised, and you just get that $100, free. But, on the other hand, if the stock goes up, you could potentially be out any amount of money. If the stock trades at $24, you're out $400-100 = $300, right? (Plus transaction costs.) But what if it trades at $60? Or $100? Or $10000? You're still out 100 * that amount, so in the latter case, $1 million. It's not likely to trade at that point, but it could. If you were to trade \"\"at random\"\", you'd probably run into one of those types of situations. That's because there are lots of potential trades out there that nobody expects anyone to take - but that doesn't mean that people wouldn't be happy to take your money if you offered it to them. That's the reason your 16.66 vs 83.33 argument is faulty: you're absolutely right that if there were a consistently losing line, that the consistently winning line would exist, but that requires someone that is willing to take the losing line. Trades require two actors, one on each side; if you're willing to be the patsy, there's always someone happy to take advantage of you, but you might not get a patsy.\"",
"title": ""
},
{
"docid": "105231",
"text": "The important thing to realize is, what would you do, if you didn't have the call? If you didn't have call options, but you wanted to have a position in that particular stock, you would have to actually purchase it. But, having purchased the shares, you are at risk to lose up to the entire value of them-- if the company folded or something like that. A call option reduces the potential loss, since you are at worst only out the cost of the call, and you also lose a little on the upside, since you had to pay for the call, which will certainly have some premium over buying the underlying share directly. Risk can be defined as reducing the variability of outcomes, so since calls/shorts etc. reduce potential losses and also slightly reduce potential gains, they pretty much by definition reduce risk. It's also worth noting, that when you buy a call, the seller could also be seen as hedging the risk of price decreases while also guaranteeing that they have a buyer at a certain price. So, they may be more concerned about having cash flow at the right time, while at the same time reducing the cost of the share losing in value than they are losing the potential upside if you do exercise the option. Shorts work in the same way but opposite direction to calls, and forwards and futures contracts are more about cash flow management: making sure you have the right amount of money in the right currency at the right time regardless of changes in the costs of raw materials or currencies. While either party may lose on the transaction due to price fluctuations, both parties stand to gain by being able to know exactly what they will get, and exactly what they will have to pay for it, so that certainty is worth something, and certainly better for some firms than leaving positions exposed. Of course you can use them for speculative purposes, and a good number of firms/people do but that's not really why they were invented.",
"title": ""
},
{
"docid": "107045",
"text": "Rich's answer captures the basic essence of short selling with example. I'd like to add these additional points: You typically need a specially-privileged brokerage account to perform short selling. If you didn't request short selling when you opened your account, odds are good you don't have it, and that's good because it's not something most people should ever consider doing. Short selling is an advanced trading strategy. Be sure you truly grok selling short before doing it. Consider that when buying stock (a.k.a. going long or taking a long position, in contrast to short) then your potential loss as a buyer is limited (i.e. stock goes to zero) and your potential gain unlimited (stock keeps going up, if you're lucky!) Whereas, with short selling, it's reversed: Your loss can be unlimited (stock keeps going up, if you're unlucky!) and your potential gain is limited (i.e. stock goes to zero.) The proceeds you receive from a short sale – and then some – need to stay in your account to offset the short position. Brokers require this. Typically, margin equivalent to 150% the market value of the shares sold short must be maintained in the account while the short position is open. The owner of the borrowed shares is still expecting his dividends, if any. You are responsible for covering the cost of those dividends out of your own pocket. To close or cover your short position, you initiate a buy to cover. This is simply a buy order with the intention that it will close out your matching short position. You may be forced to cover your short position before you want to and when it is to your disadvantage! Even if you have sufficient margin available to cover your short, there are cases when lenders need their shares back. If too many short sellers are forced to close out positions at the same time, they push up demand for the stock, increasing price and deepening their losses. When this happens, it's called a short squeeze. In the eyes of the public who mostly go long buying stock, short sellers are often reviled. However, some people and many short sellers believe they are providing balance to the market and preventing it sometimes from getting ahead of itself. [Disambiguation: A short sale in the stock market is not related to the real estate concept of a short sale, which is when a property owner sells his property for less than he owes the bank.] Additional references:",
"title": ""
},
{
"docid": "272547",
"text": "\"Ok, I think what you're really asking is \"\"how can I benefit from a collapse in the price of gold?\"\" :-) And that's easy. (The hard part's making that kind of call with money on the line...) The ETF GLD is entirely physical gold sitting in a bank vault. In New York, I believe. You could simply sell it short. Alternatively, you could buy a put option on it. Even more risky, you could sell a (naked) call option on it. i.e. you receive the option premium up front, and if it expires worthless you keep the money. Of course, if gold goes up, you're on the hook. (Don't do this.) (the \"\"Don't do this\"\" was added by Chris W. Rea. I agree that selling naked options is best avoided, but I'm not going to tell you what to do. What I should have done was make clear that your potential losses are unlimited when selling naked calls. For example, if you sold a single GLD naked call, and gold went to shoot to $1,000,000/oz, you'd be on the hook for around $10,000,000. An unrealistic example, perhaps, but one that's worth pondering to grasp the risk you'd be exposing yourself to with selling naked calls. -- Patches) Alternative ETFs that work the same, holding physical gold, are IAU and SGOL. With those the gold is stored in London and Switzerland, respectively, if I remember right. Gold peaked around $1900 and is now back down to the $1500s. So, is the run over, and it's all downhill from here? Or is it a simple retracement, gathering strength to push past $2000? I have no idea. And I make no recommendations.\"",
"title": ""
},
{
"docid": "363043",
"text": "\"A covered call risks the disparity between the purchase price and the potential forced or \"\"called\"\" sale price less the premium received. So buy a stock for $10.00 believing it will drop you or not rise above $14.00 for a given period of days. You sell a call for a $1.00 agreeing to sell your stock for $14.00 and your wrong...the stock rises and at 14.00 or above during the option period the person who paid you the $1.00 premium gets the stock for a net effective price of $15.00. You have a gain of 5$. Your hypothecated loss is unlimited in that the stock could go to $1mil a share. That loss is an opportunity loss you still had a modest profit in actual $. The naked call is a different beast. you get the 1.00 in commission to sell a stock you don't own but must pay for that right. so lets say you net .75 in commission per share after your sell the option. as long as the stock trades below $14.00 during the period of the option you sold your golden. It rises above the strike price you must now buy that stock at market to fill the order when the counter party choses to exercise the option which results in a REAL loss of 100% of the stocks market price less the .75 a share you made. in the scenarios a 1000 shares that for up $30.00 a share over the strike price make you $5,000 in a covered call and lose you $29,250 in a naked call.Naked calls are speculative. Covered calls are strategic.\"",
"title": ""
},
{
"docid": "69395",
"text": "\"Your plan already answers your own question in the best possible way: If you want to be able to make the most possible profit from a large downward move in a stock (in this case, a stock that tracks gold), with a limited, defined risk if there is an upward move, the optimal strategy is to buy a put option. There are a few Exchange Traded Funds (ETFs) that track the price of gold. think of them as stocks that behave like gold, essentially. Two good examples that have options are GLD and IAU. (When you talk about gold, you'll hear a lot about futures. Forget them, for now. They do the same essential thing for your purposes, but introduce more complexity than you need.) The way to profit from a downward move without protection against an upward move is by shorting the stock. Shorting stock is like the opposite of buying it. You make the amount of money the stock goes down by, or lose the amount it goes up by. But, since stocks can go up by an infinite amount, your possible loss is unlimited. If you want to profit on a large downward move without an unlimited loss if you're wrong and it goes up, you need something that makes money as the stock drops, but can only lose so much if it goes up. (If you want to be guaranteed to lose nothing, your best investment option is buying US Treasuries, and you're technically still exposed to the risk that US defaults on its debt, although if you're a US resident, you'll likely have bigger problems than your portfolio in that situation.) Buying a put option has the exact asymmetrical exposure you want. You pay a limited premium to buy it, and at expiration you essentially make the full amount that the stock has declined below the strike price, less what you paid for the option. That last part is important - because you pay a premium for the option, if it's down just a little, you might still lose some or all of what you paid for it, which is what you give up in exchange for it limiting your maximum loss. But wait, you might say. When I buy an option, I can lose all of my money, cant I? Yes, you can. Here's the key to understanding the way options limit risk as compared to the corresponding way to get \"\"normal\"\" exposure through getting long, or in your case, short, the stock: If you use the number of options that represent the number of shares you would have bought, you will have much, much less total money at risk. If you spend the same \"\"bag 'o cash\"\" on options as you would have spent on stock, you will have exposure to way more shares, and have the same amount of money at risk as if you bought the stock, but will be much more likely to lose it. The first way limits the total money at risk for a similar level of exposure; the second way gets you exposure to a much larger amount of the stock for the same money, increasing your risk. So the best answer to your described need is already in the question: Buy a put. I'd probably look at GLD to buy it on, simply because it's generally a little more liquid than IAU. And if you're new to options, consider the following: \"\"Paper trade\"\" first. Either just keep track of fake buys and sells on a spreadsheet, or use one of the many online services where you can track investments - they don't know or care if they're real or not. Check out www.888options.com. They are an excellent learning resource that isn't trying to sell you anything - their only reason to exist is to promote options education. If you do put on a trade, don't forget that the most frustrating pitfall with buying options is this: You can be basically right, and still lose some or all of what you invest. This happens two ways, so think about them both before you trade: If the stock goes in the direction you think, but not enough to make back your premium, you can still lose. So you need to make sure you know how far down the stock has to be to make back your premium. At expiration, it's simple: You need it to be below the strike price by more than what you paid for the option. With options, timing is everything. If the stock goes down a ton, or even to zero - free gold! - but only after your option expires, you were essentially right, but lose all your money. So, while you don't want to buy an option that's longer than you need, since the premium is higher, if you're not sure if an expiration is long enough out, it isn't - you need the next one. EDIT to address update: (I'm not sure \"\"not long enough\"\" was the problem here, but...) If the question is just how to ensure there is a limited, defined amount you can lose (even if you want the possible loss to be much less than you can potentially make, the put strategy described already does that - if the stock you use is at $100, and you buy a put with a 100 strike for $5, you can make up to $95. (This occurs if the stock goes to zero, meaning you could buy it for nothing, and sell it for $100, netting $95 after the $5 you paid). But you can only lose $5. So the put strategy covers you. If the goal is to have no real risk of loss, there's no way to have any real gain above what's sometimes called the \"\"risk-free-rate\"\". For simplicity's sake, think of that as what you'd get from US treasuries, as mentioned above. If the goal is to make money whether the stock (or gold) goes either up or down, that's possible, but note that you still have (a fairly high) risk of loss, which occurs if it fails to move either up or down by enough. That strategy, in its most common form, is called a straddle, which basically means you buy a call and a put with the same strike price. Using the same $100 example, you could buy the 100-strike calls for $5, and the 100-strike puts for $5. Now you've spent $10 total, and you make money if the stock is up or down by more than $10 at expiration (over 110, or under 90). But if it's between 90 and 100, you lose money, as one of your options will be worthless, and the other is worth less than the $10 total you paid for them both.\"",
"title": ""
},
{
"docid": "232880",
"text": "A long put - you have a small initial cost (the option premium) but profit as the stock goes down. You have no additional risk if the shock rises, even a lot. Short a stock - you gain if the stock drops, but have unlimited risk if it rises, the call mitigates this, by capping that rising stock risk. The profit/loss graph looks similar to the long put when you hold both the short position and the long call. You might consider producing a graph or spreadsheet to compare positions. You can easily sketch put, call, long stock, short stock, and study how combinations of positions can synthetically look like other positions. Often, when a stock has no shares to short, the synthetic short can help you put your stock position in place.",
"title": ""
},
{
"docid": "336541",
"text": "\"There is unlimited risk in taking a naked call option position. The only risk in taking a covered call position is that you will be required to sell your shares for less than the going market price. I don't entirely agree with the accepted answer given here. You would not lose the amount you paid to buy the shares. Naked Call Option Suppose take a naked call option position by selling a call option. Since there is no limit on how high the price of the underlying share can go, you can be forced to either buy back the option at a very high price, or, in the case that the option is exercised, you can be force. to buy the underlying shares at a very high price and then sell them to the option holder at a very low price. For example, suppose you sell an Apple call option with a strike price of $100 at a premium of $2.50, and for this you receive a payment of $250. Now, if the price of Apple skyrockets to, say, $1000, then you would either have to buy back the option for about $90,000 = 100 x ($1000-$100), or, if the holder exercised the option, then you would need to buy 100 Apple shares at the market price of $1000 per share, costing you $100,000, and then sell them to the option holder at the strike price of $100 for $10,000 = 100 x $100. In either case, you would show a loss of $90,000 on the share transaction, which would be slightly offset by a $250 credit for the premium you received selling the call. There is no limit on the potential loss since there is no limit on how high the underlying share price can go. Covered Call Option Consider now the case of a covered call option. Since you hold the underlying shares, any loss you make on the option position would be \"\"covered\"\" by the profit you make on the underlying shares. Again, suppose you own 100 Apple shares and sell a call option with a strike price of $100 at a premium of $2.50 to earn a payment of $250. If the price of Apple skyrockets to $1000, then there are again two possible scenarios. One, you buy back the option at a premium of about $900 costing you $90,000. In order to cover this cost you would then sell your 100 Apple shares at the market price of $1000 per share to realise $100,000 = 100 x $1000. On the other hand, if your option is exercised, then you would deliver your 100 Apple shares to the option holder at the contracted strike price of $100 per share, thus receiving just $10,000 = 100 x $100. The only \"\"loss\"\" is that you have had to sell your shares for much less than the market price.\"",
"title": ""
},
{
"docid": "209359",
"text": "When you short a stock, you can lose an unlimited amount of money if the trade goes against you. If the shorted stock gaps up overnight you can lose more money than you have in your account. The best case is you make 100% if the stock goes to zero. And then you have margin fees on top of that. With long positions, it's the other way around. Your max loss is 100% and your gains are potentially unlimited.",
"title": ""
},
{
"docid": "12542",
"text": "Short selling can be a good strategy to hedge, but you have almost unlimited downside. If a stock price skyrockets, you may be forced to cover your short by the brokerage before you want to or put up more capital. A smarter strategy to hedge, that limits your potential downside is to buy puts if you think the market is going down. Your downside is limited to the total amount that you purchased the put for and no more. Another way to hedge is to SELL calls that are covered because you own the shares the calls refer to. You might do this if you thought your stock was going to go down but you didn't want to sell your shares right now. That way the only downside if the price goes up is you give up your shares at a predetermined price and you miss out on the upside, but your downside is now diminished by the premium you were paid for the option. (You'd still lose money if the shares went down since you still own them, but you got paid the option premium so that helps offset that).",
"title": ""
},
{
"docid": "240215",
"text": "\"The process of borrowing shares and selling them is called shorting a stock, or \"\"going short.\"\" When you use money to buy shares, it is called \"\"going long.\"\" In general, your strategy of going long and short in the same stock in the same amounts does not gain you anything. Let's look at your two scenarios to see why. When you start, LOOT is trading at $20 per share. You purchased 100 shares for $2000, and you borrowed and sold 100 shares for $2000. You are both long and short in the stock for $2000. At this point, you have invested $2000, and you got your $2000 back from the short proceeds. You own and owe 100 shares. Under scenario A, the price goes up to $30 per share. Your long shares have gone up in value by $1000. However, you have lost $1000 on your short shares. Your short is called, and you return your 100 shares, and have to pay interest. Under this scenario, after it is all done, you have lost whatever the interest charges are. Under scenario B, the prices goes down to $10 per share. Your long shares have lost $1000 in value. However, your short has gained $1000 in value, because you can buy the 100 shares for only $1000 and return them, and you are left with the $1000 out of the $2000 you got when you first sold the shorted shares. However, because your long shares have lost $1000, you still haven't gained anything. Here again, you have lost whatever the interest charges are. As explained in the Traders Exclusive article that @RonJohn posted in the comments, there are investors that go long and short on the same stock at the same time. However, this might be done if the investor believes that the stock will go down in a short-term time frame, but up in the long-term time frame. The investor might buy and hold for the long term, but go short for a brief time while holding the long position. However, that is not what you are suggesting. Your proposal makes no prediction on what the stock might do in different periods of time. You are only attempting to hedge your bets. And it doesn't work. A long position and a short position are opposites to each other, and no matter which way the stock moves, you'll lose the same amount with one position that you have gained in the other position. And you'll be out the interest charges from the borrowed shares every time. With your comment, you have stated that your scenario is that you believe that the stock will go up long term, but you also believe that the stock is at a short-term peak and will drop in the near future. This, however, doesn't really change things much. Let's look again at your possible scenarios. You believe that the stock is a long-term buy, but for some reason you are guessing that the stock will drop in the short-term. Under scenario A, you were incorrect about your short-term guess. And, although you might have been correct about the long-term prospects, you have missed this gain. You are out the interest charges, and if you still think the stock is headed up over the long term, you'll need to buy back in at a higher price. Under scenario B, it turns out that you were correct about the short-term drop. You pocket some cash, but there is no guarantee that the stock will rise anytime soon. Your investment has lost value, and the gain that you made with your short is still tied up in stocks that are currently down. Your strategy does prevent the possibility of the unlimited loss inherent in the short. However, it also prevents the possibility of the unlimited gain inherent in the long position. And this is a shame, since you fundamentally believe that the stock is undervalued and is headed up. You are sabotaging your long-term gains for a chance at a small short-term gain.\"",
"title": ""
},
{
"docid": "171819",
"text": "\"There some specific circumstances when you would have a long-term gain. Option 1: If you meet all of these conditions: Then you've got a long-term gain on the stock. The premium on the option gets rolled into the capital gain on the stock and is not taxed separately. From the IRS: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010630 Option 2: If you didn't hold the underlying and the exercise of the call that you wrote resulted in a short position, you might also be able to get to a long-term gain by buying the underlying while keeping your short position open and then \"\"crossing\"\" them to close both positions after one year. (In other words, don't \"\"buy to cover\"\" just \"\"buy\"\" so that your account shows both a long and a short position in the same security. Your broker probably allows this, but if not you, could buy in a different account than the one with the short position.) That would get you to this rule: As a general rule, you determine whether you have short-term or long-term capital gain or loss on a short sale by the amount of time you actually hold the property eventually delivered to the lender to close the short sale. https://www.irs.gov/publications/p550/ch04.html#en_US_2015_publink100010586 Option 1 is probably reasonably common. Option 2, I would guess, is uncommon and likely not worthwhile. I do not think that the wash sale rules can help string along options from expiration to expiration though. Option 1 has some elements of what you wrote in italics (I find that paragraph a bit confusing), but the wash sale does not help you out.\"",
"title": ""
},
{
"docid": "521644",
"text": "Buying the underlying asset will not completely hedge you, only what lies above 155 dollars (strike + price of option) - you still have the risk of losing everything but 5. You have a maximum earnings-potential of 55 dollars (strike of 150 - investment of 100 + option of 5) but you have a risk of losing 95$ (investment of 100 - option of 5). Say chance of winning everything or losing everything is 50-50, your expected outcome is 0.5 x -95 + 0.5 x 55 = -20$. Is this a great investment? Sure you don't know your odds - otherwise it would be a sure thing. You shouldn't sell the call option if you do not expect prices to go up - but in that case - why not just buy the underlying alone? Speculating in options is a dangerous game with infinite earnings-potential but also infinite loss potential. (Consider selling a call option and not buying the underlying and the price goes from 100 to 1.000.000.000).",
"title": ""
},
{
"docid": "22916",
"text": "On expiry, with the underlying share price at $46, we have : You ask : How come they substract 600-100. Why ? Because you have sold the $45 call to open you position, you must now buy it back to close your position. This will cost you $100, so you are debited for $100 and this debit is being represented as a negative (subtracted); i.e., -$100 Because you have purchased the $40 call to open your position, you must now sell it to close your position. Upon selling this option you will receive $600, so you are credited with $600 and this credit is represented as a positive (added) ; i.e., +$600. Therefore, upon settlement, closing your position will get you $600-$100 = $500. This is the first point you are questioning. (However, you should also note that this is the value of the spread at settlement and it does not include the costs of opening the spread position, which are given as $200, so you net profit is $500-$200 = $300.) You then comment : I know I am selling 45 Call that means : As a writer: I want stock price to go down or stay at strike. As a buyer: I want stock price to go up. Here, note that for every penny that the underlying share price rises above $45, the money you will pay to buy back your short $45 call option will be offset by the money you will receive by selling the long $40 call option. Your $40 call option is covering the losses on your short $45 call option. No matter how high the underlying price settles above $45, you will receive the same $500 net credit on settlement. For example, if the underlying price settles at $50, then you will receive a credit of $1000 for selling your $40 call, but you will incur a debit of $500 against for buying back your short $45 call. The net being $500 = $1000-$500. This point is made in response to your comments posted under Dr. Jones answer.",
"title": ""
},
{
"docid": "507828",
"text": "\"I'm adding to @Dilip's basic answer, to cover the additional points in your question. I'll assume you are referring to publicly traded stock options, such as those found on the CBOE, and not an option contract entered into privately between two specific counterparties (e.g. as in an employer stock option plan). Since you are not obligated to exercise a call option you purchased on the market, you don't need to maintain funds on account for possible exercising. You could instead let the option expire, or resell the option, neither of which requires funds available for purchase of the underlying shares. However, should you actually choose to exercise the call option (and usually this is done close to expiration, if at all), you will be required to fund your account much like if you bought the underlying shares in the first place. Call your broker to determine the exact rules and timing for when they need the money for a call-option exercise. And to expand on the idea of \"\"cancelling\"\" an option you purchased: No, you cannot \"\"cancel\"\" an option contract, per se. But, you are permitted to sell the call option to somebody else willing to buy, via the market. When you sell your call option, you'll either make or lose money on the sale – depending on the price of the underlying shares at the time (are they in- or out- of the money?), volatility in the market, and remaining time value. Once you sell, you're back to \"\"no position\"\". That's not the same as \"\"cancelled\"\", but you are out of the trade, whether at profit or loss. Furthermore, the option writer (i.e. the seller who \"\"sold to open\"\" a position, in writing the call in the first place) is also not permitted to cancel the option he wrote. However, the option writer is permitted to close out the original short position by simply buying back a matching call option on the market. Again, this would occur at either profit or loss based on market prices at the time. This second kind of buy order – i.e. made by someone who initially wrote a call option – is called a \"\"buy to close\"\", meaning the purchase of an offsetting position. (The other kind of buy is the \"\"buy to open\"\".) Then, consider: Since an option buyer is free to re-sell the option purchased, and since an option writer (who \"\"sold to open\"\" the new contract) is also free to buy back an offsetting option, a process known as clearing is required to match remaining buyers exercising the call options held with the remaining option writers having open short positions for the contract. For CBOE options, this clearing is performed by the Options Clearing Corporation. Here's how it works (see here): What is the OCC? The Options Clearing Corporation is the sole issuer of all securities options listed at the CBOE, four other U.S. stock exchanges and the National Association of Securities Dealers, Inc. (NASD), and is the entity through which all CBOE option transactions are ultimately cleared. As the issuer of all options, OCC essentially takes the opposite side of every option traded. Because OCC basically becomes the buyer for every seller and the seller for every buyer, it allows options traders to buy and sell in a secondary market without having to find the original opposite party. [...] [emphasis above is mine] When a call option writer must deliver shares to a call option buyer exercising a call, it's called assignment. (I have been assigned before, and it isn't pleasant to see a position called away that otherwise would have been very profitable if the call weren't written in the first place!) Also, re: \"\"I know my counter party cannot sell his shares\"\" ... that's not strictly true. You are thinking of a covered call. But, an option writer doesn't necessarily need to own the underlying shares. Look up Naked call (Wikipedia). Naked calls aren't frequently undertaken because a naked call \"\"is one of the riskiest options strategies because it carries unlimited risk\"\". The average individual trader isn't usually permitted by their broker to enter such an order, but there are market participants who can do such a trade. Finally, you can learn more about options at The Options Industry Council (OIC).\"",
"title": ""
},
{
"docid": "388754",
"text": "\"The question you are asking concerns the exercise of a short option position. The other replies do not appear to address this situation. Suppose that Apple is trading at $96 and you sell a put option with a strike price of $95 for some future delivery date - say August 2016. The option contract is for 100 shares and you sell the contract for a premium of $3.20. When you sell the option your account will be credited with the premium and debited with the broker commission. The premium you receive will be $320 = 100 x $3.20. The commission you pay will depend on you broker. Now suppose that the price of Apple drops to $90 and your option is exercised, either on expiry or prior to expiry. Then you would be obliged to take delivery of 100 Apple shares at the contracted option strike price of $95 costing you $9,500 plus broker commission. If you immediately sell the Apple shares you have purchased under your contract obligations, then assuming you sell the shares at the current market price of $90 you would realise a loss of $500 ( = 100x($95-$90) )plus commission. Since you received a premium of $320 when you sold the put option, your net loss would be $500-$320 = $180 plus any commissions paid to your broker. Now let's look at the case of selling a call option. Again assume that the price of Apple is $96 and you sell a call option for 100 shares with a strike price of $97 for a premium of $3.60. The premium you receive would be $360 = 100 x $3.60. You would also be debited for commission by your broker. Now suppose that the price of Apple shares rises to $101 and your option is exercised. Then you would be obliged to deliver 100 Apple shares to the party exercising the option at the contracted strike price of $97. If you did not own the shares to effect delivery, then you would need to purchase those shares in the market at the current market price of $101, and then sell them to the party exercising the option at the strike price of $97. This would realise an immediate loss of $400 = 100 x ($101-$97) plus any commission payable. If you did own the shares, then you would simply deliver them and possibly pay some commission or a delivery fee to your broker. Since you received $360 when you sold the option, your net loss would be $40 = $400-$360 plus any commission and fees payable to the broker. It is important to understand that in addition to these accounting items, short option positions carry with them a \"\"margin\"\" requirement. You will need to maintain a margin deposit to show \"\"good faith\"\" so long as the short option position is open. If the option you have sold moves against you, then you will be called upon to put up extra margin to cover any potential losses.\"",
"title": ""
},
{
"docid": "578022",
"text": "\"You owe no tax on the option transaction in 2015 in this case. How you ultimately get taxed depends on how you dispose of the position. If it expires, then you will have a short-term capital gain on the option position at expiration. If it is exercised, then the option is \"\"gone\"\" for tax purposes and your basis in the underlying is adjusted. From IRS Publication 550: If a call you write is exercised and you sell the underlying stock, increase your amount realized on the sale of the stock by the amount you received for the call when figuring your gain or loss. The gain or loss is long term or short term depending on your holding period of the stock. In your case, this will be a long-term capital gain. For completeness, if you buy to cover the option back from the market before expiration or exercise, then it is also a short-term capital gain. Also, keep in mind that this all assumes that this covered call is \"\"qualified\"\" so that it does not count as a straddle. You can find more about that in Pub 550. https://www.irs.gov/publications/p550/ch04.html#en_US_2014_publink100010630 All of this is for US tax purposes.\"",
"title": ""
},
{
"docid": "557356",
"text": "\"There are two reasons why most options aren't exercised. The first is obvious, and the second, less so. The obvious: An option that's practically worthless doesn't get exercised. Options that reach expiry and remain unexercised are almost always worthless bets that simply didn't pay off. This includes calls with strikes above the current underlying price, and puts with strikes below it. A heck of a lot of options. If an option with value was somehow left to expire, it was probably a mistake, or else the transaction costs outweighed the value remaining; not quite worthless, but not \"\"worth it\"\" either. The less obvious: An option with value can be cancelled any time before expiration. A trader that buys an option may at some point show a gain sooner than anticipated, or a loss in excess of his tolerance. If a gain, he may want to sell before expiry to realize the gain sooner. Similarly, if a loss, he may want to take the loss sooner. In both cases, his capital is freed up and he can take another position. And — this is the key part — the other end matched up with that option sale is often a buyer that had created (written) exactly such an option contract in the first place – the option writer – and who is looking to get out of his position. Option writers are the traders responsible, in the first place, for creating options and increasing the \"\"open interest.\"\" Anybody with the right kind and level of options trading account can do this. A trader that writes an option does so by instructing his broker to \"\"sell to open\"\" a new instance of the option. The trader then has a short position (negative quantity) in that option, and all the while may be subject to the obligations that match the option's exercise rights. The only way for the option writer to get out of that short position and its obligations are these: Not by choice: To get assigned. That is to say: a buyer exercised the option. The writer has to fulfill his obligation by delivering the underlying (if a call) to the option holder, or buying the underlying (if a put) from the option holder. Not by choice: The option expires worthless. This is the ideal scenario for a writer because 100% of the premium received (less transaction costs) is profit. By choice: The writer is free to buy back exactly the same kind of option before expiry using a \"\"buy to close\"\" order with their broker. Once the option has been purchased with a \"\"buy to close\"\", it eliminates the short position and obligation. The option is cancelled. The open interest declines. Options thus cancelled just don't live long enough to either expire or be exercised.\"",
"title": ""
},
{
"docid": "268802",
"text": "Without commenting on your view of the TV market: Let's have a look at the main ways to get negative exposure: 1.Short the stocks Pros: Relatively Easy Cons: Interest rate, costs of shorting, linear bet 2.Options a. Write Calls b. Buy puts Pros: Convexity, leveraged, relatively cheap Cons: Zero Sum bet that expires with time, theta 3.Short Stock, Buy Puts, Write Calls Short X Units of each stock, Write calls on them , use call premiums to finance puts. Pros: 3x the power!, high kickout Cons: Unlimited pain",
"title": ""
},
{
"docid": "393418",
"text": "By buying the call option, you are getting the benefit of purchasing the underlying shares (that is, if the shares go up in value, you make money), but transferring the risk of the shares reducing in value. This is more apparent when you are using the option to offset an explicit risk that you hold. For example, if you have a short position, you are at unlimited risk of the position going up in value. You could decide you only want to take the risk that it might rise to $X. In that case, you could buy a call option with $X strike price. Then you have transferred the risk that the position goes over $X to the counterpart, since, even if the shares are trading at $X+$Y you can close out the short position by purchasing the shares at $X, while the option counterpart will lose $Y.",
"title": ""
},
{
"docid": "520098",
"text": "\"A derivative contract can be an option, and you can take a short (sell) position , much the same way you would in a stock. When BUYING options you risk only the money you put in. However when selling naked(you don't have the securities or cash to cover all potential losses) options, you are borrowing. Brokers force you to maintain a required amount of cash called, a maintenance requirement. When selling naked calls - theoretically you are able to lose an INFINITE amount of money, so in order to sell this type of options you have to maintain a certain level of cash in your account. If you fail to maintain this level you will enter into whats often referred to as a \"\"margin-call\"\". And yes they will call your phone and tell you :). Your broker has the right to liquidate your positions in order to meet requirements. PS: From experience my broker has never liquidated any of my holdings, but then again I've never been in a margin call for longer then a few days and never with a severe amount. The margin requirement for investors is regulated and brokers follow these regulations.\"",
"title": ""
},
{
"docid": "314478",
"text": "\"And what exactly do I profit from the short? I understand it is the difference in the value of the stock. So if my initial investment was $4000 (200 * $20) and I bought it at $3800 (200 * $19) I profit from the difference, which is $200. Do I also receive back the extra $2000 I gave the bank to perform the trade? Either this is extremely poorly worded or you misunderstand the mechanics of a short position. When you open a short position, your are expecting that the stock will decline from here. In a short position you are borrowing shares you don't own and selling them. If the price goes down you get to buy the same shares back for less money and return them to the person you borrowed from. Your profit is the delta between the original sell price and the new lower buy price (less commissions and fees/interest). Opening and closing a short position is two trades, a sell then a buy. Just like a long trade there is no maximum holding period. If you place your order to sell (short) 200 shares at $19, your initial investment is $3,800. In order to open your $3,800 short position your broker may require your account to have at least $5,700 (according to the 1.5 ratio in your question). It's not advisable to open a short position this close to the ratio requirement. Most brokers require a buffer in your account in case the stock goes up, because in a short trade if the stock goes up you're losing money. If the stock goes up such that you've exhausted your buffer you'll receive what's known as a \"\"margin call\"\" where your broker either requires you to wire in more money or sell part or all of your position at a loss to avoid further losses. And remember, you may be charged interest on the value of the shares you're borrowing. When you hold a position long your maximum loss is the money you put in; a position can only fall to zero (though you may owe interest or other fees if you're trading on margin). When you hold a position short your maximum loss is unlimited; there's no limit to how high the value of something can go. There are less risky ways to make short trades by using put options, but you should ensure that you have a firm grasp on what's happening before you use real money. The timing of the trades and execution of the trades is no different than when you take a plain vanilla long position. You place your order, either market or limit or whatever, and it executes when your trade criteria occurs.\"",
"title": ""
},
{
"docid": "242663",
"text": "\"Some thoughts on your questions in order, Duration: You might want to look at the longest-dated option (often a \"\"LEAP\"\"), for a couple reasons. One is that transaction costs (spread plus commission, especially spread) are killer on options, so a longer option means fewer transactions, since you don't have to keep rolling the option. Two is that any fundamentals-based views on stocks might tend to require 3-5 years to (relatively) reliably work out, so if you're a fundamental investor, a 3-6 month option isn't great. Over 3-6 months, momentum, short-term news, short squeezes, etc. can often dominate fundamentals in determining the price. One exception is if you just want to hedge a short-term event, such as a pending announcement on drug approval or something, and then you would buy the shortest option that still expires after the event; but options are usually super-expensive when they span an event like this. Strike: Strike price on a long option can be thought of as a tradeoff between the max loss and minimizing \"\"insurance costs.\"\" That is, if you buy a deeply in-the-money put or call, the time value will be minimal and thus you aren't paying so much for \"\"insurance,\"\" but you may have 1/3 or 1/2 of the value of the underlying tied up in the option and subject to loss. If you buy a put or call \"\"at the money,\"\" then you might have only say 10% of the value of the underlying tied up in the option and subject to loss, but almost the whole 10% may be time value (insurance cost), so you are losing 10% if the underlying stock price stays flat. I think of the deep in-the-money options as similar to buying stocks on margin (but the \"\"implied\"\" interest costs may be less than consumer margin borrowing rates, and for long options you can't get a margin call). The at-the-money options are more like buying insurance, and it's expensive. The commissions and spreads add significant cost, on top of the natural time value cost of the option. The annual costs would generally exceed the long-run average return on a diversified stock fund, which is daunting. Undervalued/overvalued options, pt. 1: First thing is to be sure the options prices on a given underlying make sense at all; there are things that \"\"should\"\" hold, for example a synthetic long or short should match up to an actual long or short. These kinds of rules can break, for example on LinkedIn (LNKD) after its IPO, when shorting was not permitted, the synthetic long was quite a bit cheaper than a real long. Usually though this happens because the arbitrage is not practical. For example on LNKD, the shares to short weren't really available, so people doing synthetic shorts with options were driving up the price of the synthetic short and down the price of the synthetic long. If you did actually want to be long the stock, then the synthetic long was a great deal. However, a riskless arbitrage (buy synthetic long, short the stock) was not possible, and that's why the prices were messed up. Another basic relationship that should hold is put-call parity: http://en.wikipedia.org/wiki/Put%E2%80%93call_parity Undervalued/overvalued options, pt. 2: Assuming the relationship to the underlying is sane (synthetic positions equivalent to actual positions) then the valuation of the option could focus on volatility. That is, the time value of the option implies the stock will move a certain amount. If the time value is high and you think the stock won't move much, you might short the option, while if the time value is low and you think the stock will move a lot, you might buy the option. You can get implied volatility from your broker perhaps, or Morningstar.com for example has a bunch of data on option prices and the implied components of the price model. I don't know how useful this really is though. The spreads on options are so wide that making money on predicting volatility better than the market is pretty darn hard. That is, the spread probably exceeds the amount of the mispricing. The price of the underlying is more important to the value of an option than the assumed volatility. How many contracts: Each contract is 100 shares, so you just match that up. If you want to hedge 100 shares, buy one contract. To get the notional value of the underlying multiply by 100. So say you buy a call for $30, and the stock is trading at $100, then you have a call on 100 shares which are currently priced at $10,000 and the option will cost $30*100=3,000. You are leveraged about 3 to 1. (This points to an issue with options for individual investors, which is that one contract is a pretty large notional value relative to most portfolios.)\"",
"title": ""
},
{
"docid": "326599",
"text": "Gold's valuation is so stratospheric right now that I wonder if negative numbers (as in, you should short it) are acceptable in the short run. In the long run I'd say the answer is zero. The problem with gold is that its only major fundamental value is for making jewelry and the vast majority is just being hoarded in ways that can only be justified by the Greater Fool Theory. In the long run gold shouldn't return more than inflation because a pile of gold creates no new wealth like the capital that stocks are a claim on and doesn't allow others to create new wealth like money lent via bonds. It's also not an important and increasingly scarce resource for wealth creation in the global economy like oil and other more useful commodities are. I've halfway-thought about taking a short position in gold, though I haven't taken any position, short or long, in gold for the following reasons: Straight up short-selling of a gold ETF is too risky for me, given its potential for unlimited losses. Some other short strategy like an inverse ETF or put options is also risky, though less so, and ties up a lot of capital. While I strongly believe such an investment would be profitable, I think the things that will likely rise when the flight-to-safety is over and gold comes back to Earth (mainly stocks, especially in the more beaten-down sectors of the economy) will be equally profitable with less risk than taking one of these positions in gold.",
"title": ""
},
{
"docid": "142110",
"text": "\"He didn't sell in the \"\"normal\"\" way that most people think of when they hear the term \"\"sell.\"\" He engaged in a (perfectly legitimate) technique known as short selling, in which he borrows shares from his broker and sells them immediately. He's betting that the price of the stock will drop so he can buy them back at a lower price to return the borrowed shares back to his broker. He gets to pocket the difference. He had about $37,000 of cash in his account. Since he borrowed ~8400 shares and sold them immediately at $2/share, he got $16,800 in cash and owed his broker 8400 shares. So, his net purchasing power at the time of the short sale was $37,000 + $16,800 - 4800 shares * $2/share. As the price of the stock changes, his purchasing power will change according to this equation. He's allowed to continue to borrow these 8400 shares as long as his purchasing power remains above 0. That is, the broker requires him to have enough cash on hand to buy back all of his borrowed shares at any given moment. If his purchasing power ever goes negative, he'll be subject to a margin call: the broker will make him either deposit cash into his account or close his positions (sell long positions or buy back short positions) until it's positive again. The stock jumped up to $13.85 the next morning before the market opened (during \"\"before-hours\"\" trading). His purchasing power at that time was $37,000 + $16,800 - 8400 shares * $13.85/share = -$62,540. Since his purchasing power was negative, he was subject to a margin call. By the time he got out, he had to pay $17.50/share to buy back the 8400 shares that he borrowed, making his purchasing power -$101,600. This $101,600 was money that he borrowed from his broker to buy back the shares to fulfill his margin call. His huge loss was from borrowing shares from his broker. Note that his maximum potential loss is unlimited, since there is no limit to how much a stock can grow. Evidently, he failed to grasp the most important concept of short selling, which is that he's borrowing stock from his broker and he's obligated to give that stock back whenever his broker wants, no matter what it costs him to fulfill that obligation.\"",
"title": ""
},
{
"docid": "16747",
"text": "\"The previous answers make valid points regarding the risks, and why you can't reasonably compare trading for profit/loss to a roll of the die. This answer looks at the math instead. Your assumption: I have an equal probability to make a profit or a loss. Is incorrect, for the reasons stated in other answers. However, the answer to your question: Can I also assume that probabilistically speaking, a trader cannot do worst than random? Is \"\"yes\"\". But only because the question is flawed. Consequently it's throwing people in all directions with their answers. But quite simply, in a truly random environment the worst case scenario, no matter how improbable, is that you lose over and over again until you have nothing left. This can happen in sequential rolls of the dice AND in trading securities/bonds/whatever. You could guess wrong for every roll of the die AND all of your stock picks could become worthless. Both outcomes result in $0 (assuming you do not gamble with credit). Tell me, which $0 is \"\"worse\"\"? Given the infinite number of plays that \"\"random\"\" implies, the chance of losing your entire bankroll exists in both scenarios, and that is enough by itself to make neither option \"\"worse\"\" than the other. Of course, the opposite is also true. You could only pick winners, with an unlimited upside potential, but again that could happen with either dice rolls or stock picks. It's just highly improbable. my chances cannot be worse than random and if my trading system has an edge that is greater than the percentage of the transaction that is transaction cost, then I am probabilistically likely to make a profit? Nope. This is where it all falls apart. Just because your chances of losing it all are similarly improbable, does not make you more likely to win with one method or the other. Regression to the mean, when given infinite, truly random outcomes, makes it impossible to \"\"have an edge\"\". Also, \"\"probabilistically\"\" isn't a word, but \"\"probably\"\" is.\"",
"title": ""
},
{
"docid": "147361",
"text": "\"Yes, long calls, and that's a good point. Let's see... if I bought one contract at the Bid price above... $97.13 at expiry of $96.43 option = out of the money =- option price(x100) = $113 loss. $97.13 at expiry of $97.00 option = out of the money =- option price(x100) = $77 loss. $97.13 at expiry of $97.14 option = in the money by 1-cent=$1/contract profit - option price(x100) = $1-$58 = $57 loss The higher strike prices have much lower losses if they expire with the underlying stock at- or near-the-money. So, they carry \"\"gentler\"\" downside potential, and are priced much higher to reflect that \"\"controlled\"\" risk potential. That makes sense. Thanks.\"",
"title": ""
},
{
"docid": "485760",
"text": "\"Do you want to do it pre or post correction? If you're bearish on the market the obvious thing to do is short an index. I would say this is kind of dumb. The main problem is that it may take months or years for the market to crash, and by then it will have gone up so much that even the crash doesn't bring you profit, and you're paying borrowing fees meanwhile as well. You need to watch the portfolio also, when you short sell you'll get a bunch of cash, which you most likely will want to invest, but once you invest it, the market can spike and pummel your short position, resulting in negative remaining cash (since you already spent it). At that point you get a margin call from your broker. If you check your account regularly, not a big deal, but bad things can happen if you treat it as a fire and forget strategy. These days they have inverse funds so you don't have to borrow anything. The fund manager borrows for you. I'd say those are much better. The less cumbersome choice is to simply sell call options on the index or buy puts. These are even cash options, so when you exercise you get/lose money, not shares. You can even arrange them so that your potential loss is capped. (but honestly, same goes for shorts - it's called a stop loss) You could also wait for the correction and buy the dip. Less worrying about shorts and such, but of course the issue is timing the crash. Usually the crashes are very quick, and there are several \"\"pre-crashes\"\" that look like it bottomed out but then it crashes more. So actually very difficult thing to tell. You have to know either exactly when the correction will be, or exactly what the price floor is (and set a limit buy). Hope your crystal ball works! Yet another choice is finding asset classes uncorrelated or even anticorrelated with the broader market. For instance some emerging markets (developing countries), some sectors, individual stocks that are not inflated, bonds, gold and so on can have these characteristics where if S&P goes down they go up. Buying those may be a safer approach since at least you are still holding a fundamentally valuable thing even if your thesis flops, meanwhile shorts and puts and the like are purely speculative.\"",
"title": ""
}
] |
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